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May 2017


Original Article

Is Migraine Related to Medial Meningeal Artery and Spinous Foramen Caliber?

Emre Nalbant 1, Hande Nalbant 1, Esra Eruyar 2

1 Radiology Clinic, Dr. Selahattin Cizrelioglu State Hospital, Şırnak, 2 Radiology Clinic, Ankara Numune Training and Research Hospital, Ankara, Turkey

DOI: 10.4328/JCAM.4841 Received: 25.10.2016 Accepted: 20.11.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 252-6

Corresponding Author: Emre Nalbant, Keklikpinari Mahallesi, 873. Sokak Metis Doruk Sitesi, 15/51 Cankaya, Ankara, Turkey. GSM: +905068808047 F.: +90 4866160910 E-Mail: emrenalbant2003@yahoo.com

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Abstract

Aim: Although migraine is one of the headache disorders for which people most often consult a doctor, it still does not have a specific diagnostic labo-ratory or radiologic test. Vasodilation of the medial meningeal artery is wide-ly believed to cause migraines. However, some current hypotheses decrease the role of the vasodilation. If the medial meningeal artery dilates during at-tacks, in the long term it can expand the foramen pass through. Based on this idea, our study investigated whether there is a significant difference between the medial meningeal artery and spinous foramen sizes of migraine patients compared with a control group. Material and Method: Thirty-six migraine patients and 26 tension-type headache (TTH) patients as the control group were involved in the study. Patients were scanned with brain CT (computed tomography) angiography. The medial meningeal artery and spinous foramen sizes of both groups were measured. Results: There was no statistically sig-nificant difference between the measurements of migraine and tension-type headache patients. Discussion: In our study we could not find any evidence to show vasodilation of the dura mater’s vasculature as a factor of migraine pathophysiology. This result indicates the need to continue investigating the different hypotheses for migraine pathophysiology.

Keywords: Migraine; Meningeal Artery; CT Angiography

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Introduction

Migraine, whose prevalence was found as %11,7 by Lipton et al., is a common disease in population [1]. A specific laboratory test or radiological investigation is still not currently available for the diagnosis of migraine. An episodic, unilateral, severe, and throbbing headache is its characteristic property [2]. The disease may be associated with autonomic symptoms, and aura, a focal neurological symptom, may occur in one-third of the patients [3].

For many years, the dura mater and its vasculature have been at the center of the hypotheses trying to explain the pathophysiology of migraine [4,5]. According to the vascular theory, the middle meningeal artery (MMA), which is the primary vasculature of the meninges, plays the most important role in migraine pathophysiology; the general belief about the mechanism of migraine headache is the vasodilation of the meningeal blood vessels [6-8].

With the improvement of technology, it has been possible to visualize extremely thin vessels by Magnetic Resonance Angiography (MRA) and Computed Tomographic Angiography (CTA), and to make reliable measurements [9-11]. Additionally, the spinous foramen, which is the site of the entry of the MMA into the cranium, can also be visualized with the CT angiography.

In the present study, we used multi-slice CT angiography to investigate whether the diameter of the MMA and the area of spinous foramen differed in the patients with migraine.

Material and Method

Although the tension-type headache (TTH) is the most commonly experienced primary headache in the population [12], the role of dural vascular causes in its pathophysiology has not been widely investigated [13,14]. Therefore the cases with TTH have been included in the control group in our study.

Selection of the Patients

A total of 64 patients diagnosed with migraine and TTH were included in the study. The criteria for inclusion in the study were as follows: (i) being in the age range of 18 to 58 years; (ii) being diagnosed with migraine or tension-type headache according to the diagnostic criteria of the International Classification of Headache Disorders (ICHD-II) defined by the International Headache Society (IHS); (iii) a disease course of more than two years; (iv) the frequency of pain being at least two episodes per month; (v) an indication of CT with contrast due to reasons such as a change in the severity of headache or an increased frequency of episodes. The criteria for exclusion were as follows: (i) uncertainty of the diagnosis of migraine or TTH regarding the other diseases associated with headache; (ii) being diagnosed within the previous three years; (iii) recently used vasoactive drugs; (iv) allergy for iodinated contrast material; (v) a previous head-neck surgery.

The study was approved by the local medical ethics committee, and the patients were informed prior to the study (approval number: 923/2014).

CTA

The patients were scanned using a CT scanner with 64 detectors (Aquillon 64, Toshiba Medical Systems, 2011, Japan), and with the following CT scan parameters: collimation 64×0.5, gantry rotation time 0.5 sec, slice thickness 0.5 mm, step value 0.64, 120 kV, and 450 mA. Fifty ml of non-ionic, iodinated contrast material including a high iodine concentration (iodine concentration 350 mg/ml) was administered intravenously through the antecubital vein via a 18- to 20-G catheter and using an automatic pump (Ulrich Medical’s technical version, 2004, Germany), at a rate of 4 ml/sec. Forty cc of serum physiologic was administered following the contrast material. Computed Tomographic Angiography was applied using the bolus tracking method, and the application was initiated when the density in the internal cerebral artery (ICA) was 90 to 100 Hounsfield Units (HU).

Evaluation of the Images

The CTA images were evaluated with the Aquarius (iNtuition Edition v. 4.4.11.82.6784, California, USA) software on the orthogonal and oblique planes, and using multi-planar reconstructions (MPR), volume rendering (VR), and maximum intensity projection (MIP) images.

The area of the spinous canal and the diameter of the middle meningeal artery were measured bilaterally in both groups. The left and the right sides were compared for each patient and between groups. The measurements were made when the patients were not in the course of an episode.

The spinous canal has been commonly visualized as a canal with ovoid shape that extends from anterior to posterior and from medial to lateral. Area measurements were made on the axial sections at the narrowest site of the canal, after the coronal and sagittal MPRs had been made in concordance with the canal’s own axis (Picture 1). The measurements were made on the internal surface of the canal, by the aid of the region of interest (ROI). The diameter of the middle meningeal artery was measured at the site that was about 2 to 3 mm proximal to its level of entry into the spinous canal. On the coronal oblique MPR images which were perpendicular to the long axis of the artery, the out-to-out measurements were made at the area filled with contrast (Picture 2).

Statistics

The data of the study were analyzed using the SPSS 15.0 (Statistical Package for Social Sciences, 15.0, SPSS Inc., Chicago, USA) statistical software.

For the continuous variables, the Mann-Whitney U test and the T-test were used in comparison of the independent groups, and the dependent groups were compared using the Wilcoxon test. The Chi-square test was used in comparing the discrete variables between the groups.

The area of the canal and the arterial diameter were compared in terms of gender using the independent samples test.

A p value <0.05 was accepted to be statistically significant. The descriptive statistical values were expressed in numbers and average percentages.

Results

The two patients who were observed to have atherosclerosis in the ICA after the CT angiography were excluded from the study. The study proceeded with a total of 62 patients. The patients were separated into two groups: 26 cases (41.9%) had TTH, and 36 cases (58.1%) had migraine-type headache. Of the 62 patients, 5 had aplasia of the right spinous canal, and 4 had aplasia of the left spinous canal; therefore the statistical analyses of the right-side measurements included the data of a total of 57 patients, and those of the left-side measurements included the data of a total of 58 patients.

The mean ages of the cases with TTH and migraine headache were 37.42 (18-56) years and 34.19 (18-58) years, respectively; this difference was not found to be significant (p>0.05).

Of the 26 cases with TTH, 22 were female (84.6%) and 4 were male (15.4%); of the 36 cases with migraine-type headache, 32 were female (88.9%) and 4 were male (11.1%). The distributions of genders were similar in the two groups (p >0.05).

The mean durations of the disease in the cases with migraine and TTH were found as 9.3 (2-28) years and 4.6 (2-16) years, respectively.

The area of the right spinous canal in the 25 TTH cases was (mean) 2.182 mm2 (0.51-3.67); this value was measured as (mean) 2.545 mm2 (1.22-6.19) in the 32 migraine cases. The area of the right spinous canal did not differ significantly between the groups (p =0.296).

The area of the left spinous canal in the 25 TTH cases was (mean) 2.484 mm2 (0.39-4.00); this value was determined as (mean) 2.525 mm2 (1.01-5.22) in the 33 migraine cases. The area of the left spinous canal did not differ significantly between the groups (p =0.54).

The results of the measurements regarding the area of the spinous canal are shown in Table 1.

The diameter of the right-side middle meningeal artery was measured as (mean) 1.358 mm (0.77-2.32) in the 25 TTH cases; this value was found as (mean) 1.401 mm (1.01-1.86) in the 32 migraine cases. The diameter of the right-side middle meningeal artery did not differ significantly between the groups (p =0.571).

The diameter of the left-side middle meningeal artery was measured as (mean) 1.344 mm (0.93-2.03) in the 25 TTH cases; this value was (mean) 1.394 mm (0.75-2.14) in the 32 migraine cases. The diameter of the left-side middle meningeal artery did not show significant difference between the groups (p =0.571).

Discussion

The migraine headache is one of the most common reasons among all headache diseases for consulting a doctor. The World Health Organization has considered it among the diseases leading to the greatest disablement. It has been known that about 17.5% of women and 5.6% of men experience migraine headache [1]. Besides its unfavorable effects during episodes, it also has chronic effects such as low performance in school and professional life, and social problems. Nevertheless a specific laboratory test or radiological investigation is still not available currently for the diagnosis of migraine.

Although the pathophysiology of migraine is still not exactly understood, for many years, the middle meningeal artery and the venous system have been at the center of the pathophysiology hypotheses [4,5]. There is a common belief that the underlying mechanism of the migraine headache is the vasodilation of the intracranial blood vessels [15]. In the study of Asghar et al. [16] performed more recently with MR angiography, headache on the same side has been shown to regress with the decrease of the unilateral vasodilation in the MMA in the patients who were administered the vasoconstrictor agent sumatriptan (5HT 1B/1D receptor agonist) during migraine pain. Similarly, in a study of Villalon et al. [6] the level of serotonin, which is a vasoconstrictor and central neurotransmitter, has been shown to decrease during a migraine episode, and the headache has been eliminated with the intravenous infusion of serotonin during the episode. In the same study, ergotamine and other anti-migraine agents have been shown to cause vasoconstriction in the external carotid circulation. This study concludes that the cerebral and meningeal vasodilation is the primary triggering cause of the migraine headache [6].

There are also studies claiming that the meningeal and cerebral vasodilation exists secondary to the release of vasoactive neuropeptides resulting from the activation of the trigeminovascular system, rather than acting as a primary trigger of pain in migraine pathogenesis. In these studies, vasodilation is claimed to play a role in the persistence and worsening of headache [17]. A third consideration claims that the vasodilation is only a harmless audience in the pathogenesis of migraine pain [18,19]. The common point of all three considerations is the existence of vasodilation in migraine headache. However, these hypotheses have mostly been developed due to studies conducted with experimental animals. The reason why there is limited number of studies conducted with humans is because, until recently, invasive methods have been required to make these findings. However, non-invasive sectional imaging methods such as MRA and CTA have been improved, now making it possible to visualize the thin vessels such as the MMA in a sensitive manner [9,10].

More recently, many hypotheses have decreased the role of vasodilation. In the study of Schoonman et al. [20] conducted with 3T MR angiography, an artificial migraine episode was initiated in migraine patients through the infusion of NTG, and the MMA diameters were measured before and during the episodes; the results showed no significant differences. In a study investigating the human MMA microscopically, the dural extravascular tissue surrounding the meningeal arteries was demonstrated to be too rigid to allow a marked expansion of the vessels. It has also been reported that the meningeal arteries are located within grooves at the internal tabula of the calvarium and that 3/4 of their surroundings are composed of bony tissue. As a result, marked vasodilation is impossible [21].

In the chronic phase, the dilation of the arteries may lead to the widening of the canals that they pass through [22]. If any vasodilation had existed during a migraine episode, it might have caused widening of the spinous foramen that the vessel passes through, and this might be considered an indirect finding. To consider this hypothesis, in our study we measured the areas of the spinous canals in the cases experiencing migraine episodes for an average of 9 years. The multi-sectional CT is the most convenient method for visualizing and reliably measuring the spinous canal. When compared to a control group, if a widening is determined in the diameter of the spinous canal that is located at the site of migraine headache, this may indirectly demonstrate the existence of vasodilation in migraine etiopathogenesis. So, the CT may be regarded as a method that helps in the diagnosis of migraine according to the ICD criteria, in cases where initial diagnosis is unclear. Exposure to ionizing radiation is the most important disadvantage of CT; however, this risk can be minimized by investigating only the base of the head.

Knowing whether vasodilation is a mechanism included in the pathophysiology of migraine is extremely important for the development of therapeutic agents. The triptans and ergots are the most effective anti-migraine agents used today. Being potent vasoconstrictors [23], they cause risks for myocardial and cerebral ischemia in patients with vascular diseases [24]. If it is proven that vasodilation does not play a role in pathophysiology, new and safer medications can be developed for these patients [20].

Our study measured both the diameter of the MMA and the area of spinous foramen. The mean value of the MMA diameter was found as 1.38±0.28 on the CT angiography, which was similar to the results of the studies in the literature conducted with MRA [20,25].

The measurements of the MMA diameters and the areas of spinous canal did not show differences in the TTH cases compared to the control group. These results indicate the necessity of considering hypotheses other than vasodilation in the pathogenesis of migraine.

The most important limitation to this study was the measurement of the parameters when the patients were not in the phase of a migraine episode. The difficulties experienced in the admission of the patients to the hospital during an episode, and in the application of procedures during routine intensive work, make it impossible to perform the visualization procedures in the course of an episode. In the literature, similar studies have been conducted during migraine episodes triggered by NTG; however it is not definite that the attacks provoked by NTG are similar to the spontaneous migraine attacks [20]. Not performing the vascular measurements during episodes might have led to the exclusion of changes in diameter that might exist during an attack. This is why we also included the measurement of the spinous canal area in our study.

Conclusion

The area of the spinous canal, which may be indirectly affected by the meningeal arterial dilation that is considered to have an important role in migraine pathophysiology, does not differ in the patients with migraine compared to the group with headache due to non-vascular etiopathogenesis.

We also did not find an increase in the meningeal arterial diameter. This result supports the increasing number of studies reporting that meningeal vasodilation does not play a role in the etiopathogenesis of migraine headache. The present results need to be supported by further studies conducted with a wider series, also including investigations performed during migraine episodes.

Competing interests

The authors declare that they have no competing interests.

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Emre Nalbant, Hande Nalbant, Esra Eruyar. Is migraine related to medial meningeal artery and spinous foramen caliber?. J Clin Anal Med. 2017;8(3):252-256

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The Reasons for Blood Ethanol Concentration Analyses in Patients Admitted to Emergency Department

Kübranur Ünal 1, Turan Turhan 2, Gökçe Atikeler 2, Esin Çalcı 2, Müge Sönmez 3, Fatma Meriç Yılmaz 4

1 Department of Biochemistry, Polatlı Duatepe Public Hospital, 2 Department of Biochemistry, Ankara Numune Training and Research Hospital, 3 Department of Emergency, Ankara Numune Training and Research Hospital, 4 Department of Biochemistry, Yıldırım Beyazıt University, Ankara, Turkey

DOI: 10.4328/JCAM.4794 Received: 28.08.2016 Accepted: 17.11.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 248-51

Corresponding Author: Kübranur Ünal, Department of Biochemistry, Polatlı Duatepe Public Hospital, Ankara, Turkey. E-Mail: dr.kubranur_unal@outlook.com

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Aim: The aim of this study was to obtain reliable data about alcohol con-sumption in Turkey, to evaluate the reasons for blood ethanol concentra-tion (BEC) analyses in patients admitted to emergency departments, and to evaluate the relationship of BEC with age and time of sampling. Material and Method: A total of 801 patients who were admitted for analyses of BEC was included in the study. The results were classified into three groups ac-cording to BEC (<10 mg/dl, 10-50 mg/dl, and >50 mg/dl). BEC levels exceed-ing 10 mg/dl were accepted as ethanol positive (EthPos). The patients were categorized as three groups according to age (<18, 18-40, and >40). The cases were classified according to diagnoses: assault, motor vehicle crashes (MVC), injury, suicide, or occupational accident. In addition the patients were grouped according to their time of sampling, daytime or nighttime. Results: MVC was the most common reason for emergency admissions, while as-sault was the most common cause in EthPos cases. BEC was <10 mg/dL in 72% of emergency admissions. Although BEC levels were in most cases <10 mg/dL at nighttime and daytime, levels >100 mg/dL were seen more frequently at night. Assault was the most common cause at night while MVC was most common during the day. EthPos cases were most often found in ages between 18- 40. Discussion: MVC constitutes the largest portion of all BEC tests among emergency admissions because individuals involved in any traffic accident are required to be tested for BEC. But assaults are the main causes in EthPos emergency admissions, as it is known that ethanol consumption increases tendencies toward offensive behaviors.

Keywords: Blod Ethanol Concentration; Emergency Department; Assault; Motor Vechicle Crashe

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Introduction

Ethanol is the most widely used addictive substance and the incidence of emergency department (ED) admissions due to ethanol intake is gradually increasing all over the world [1]. Additionally, frequent alcohol consumption is a sociomedical problem that affects a significant portion of the population, with >50% of the adult population of the United States (US) reported to be ethanol users. 26% of drug-related ED visits in the US involve ethanol combined with different drugs [2], and alcohol intoxication accounts for 3.6% of deaths worldwide [3].

Alcohol is a Central Nervous System (CNS) depressant with effects proportional to the ethanol concentration in the blood. Deterioration in driving skills that result from alcohol’s CNS depressant effects has been demonstrated at blood ethanol concentrations of as low as ≤50 mg/dL, with progressive impairment at levels >50 mg/dL. Effects on reaction time, visual tracking, mental concentration, attention time, information processing, perception, and psychomotor functions may result from alcohol-related driving impairment [4]. Ethanol reaches peak blood concentrations approximately 60 minutes after ingestion. The ethanol concentration decreases at a rate of approximately 20 mg/dL per hour [5,6].

Ethanol intake increases tendency to accidents (especially motor vehicle crashes–MVC), assault, injury, and suicidal attempts [7]. Our study aimed to obtain reliable and comparable data about alcohol consumption in Turkey, to evaluate the reasons for blood ethanol concentration (BEC) analyses in patients admitted to the ED, and to evaluate the relationships of BEC with age, sex, and time of sampling.

Material and Method

The records of 801 patients who were admitted to Ankara Numune Training and Research Hospital Emergency Biochemistry Laboratory for analyses of BEC between January and June 2014 were retrospectively reviewed. The patients were grouped according to BEC, diagnoses, age, gender, and time of sampling. Data were analyzed as percentages according to each criteria. BEC levels exceeding 10 mg/dl were accepted as ethanol positive (EthPos). The results were classified as three groups according to BEC (<10 mg/dl, 10-50 mg/dl, and >50 mg/dl).The patients were categorized as three groups according to age (<18, 18-40, and >40). The cases were classified according to diagnoses as assault, MVC, injury, suicide occupational accident (OA), and unknown. In addition the patients were grouped according to their emergency sampling time as daytime (08:00-19:59) and nighttime (20:00-07:59).

Venous blood samples of patients were taken to gel containing tubes and centrifuged at 4000 rpm for 10 minutes to analyze the separated serum. Hemolyzed and icteric serum samples were excluded from the study. BEC results were given in two different units: mg/dl and g/L (mg/dl/100= Promil).

In this study, BEC was also measured with the enzymatic method using the Roche P800 autoanalyzer (Roche Diagnostics, Mannheim, Germany) using original commercial kits. Statistical analyses was performed using SPSS 18.0 (SPSS Inc, Chicago, Ill). Pie charts and bar charts were used to depict distributions.

This study was approved by the ethical committee from the research office of Ankara Numune Training and Research Hospital (764 No 12.02.2014).

Results

232 of the 801 patients were EthPos. The number of male cases (87.5%) was significantly higher than female cases (12.5%) (Table 1). In 72.03% of the admissions, ethanol concentrations were <10 mg/dL, while they were >50 mg/dL in 26.09% of the admissions. The distribution of ethanol concentration in all cases is shown in Figure 1. MVC constitutes the largest portion of all BEC tests among emergency admissions. On the other hand, in the overall picture, assault is the main cause of EthPos emergency admissions (Table 2). In terms of overall ethanol concentration, nighttime (20:00-07:59) cases were significantly higher than the daytime (08:00-19:59) cases. Although BEC were in most cases <10 mg/dL at night and daytime, levels >50 mg/dL were seen more often at night. The distribution of ethanol concentration of all cases by daytime or nighttime admission time are shown in Figure 2.

Most of the EthPos cases were found between the ages of 18-39. Ethanol positivity was not observed in the <18 age group (Figure 3).

Discussion

Ethanol is the most frequently encountered toxic substance in both clinical and forensic analytical settings. Ethanol analysis is often requested to evaluate neurological status in life-threatening conditions, to monitor patients undergoing ethanol therapy due to methanol or ethanol toxicity, to monitor those patients enrolled in ethanol and other drug treatment programs, and to evaluate suitability of patients for organ transplantation [8]. Ethanol-related morbidity and mortality result principally from trauma. Traumas often associated with ethanol use include MCV, assault, injury, OA, criminal violence, and suicide. In our study MVC constitutes the largest portion of all BEC tests among emergency admissions.

BEC can be detected in body specimens such as urine and breath. The most commonly used alcohol analysis method in clinical settings is the enzymatic one. Enzymatic methods that are based on the oxidation of ethanol to acetaldehyde with concurrent reduction of nicotinamide adenine allow rapid, automated determination of ethanol in the laboratory setting [9].

Among people under the age of 35, traffic accidents are a leading cause of death. In 2009, 32% of mortal traffic accidents involved a driver or passenger with a BEC exceeding the legal limit [10,11]. The legal BEC limit is currently 50 mg/dL in Turkey for common motor vehicle drivers. The Law Prohibiting Teenagers from Drinking regulates minimum drinking age in Turkey, and people younger than 18 years are prohibited from purchasing and consuming alcohol. We observed BEC exceeding 50 mg/dL in 26.09% of patients.

In 2009, 18.7 million persons over 12 years of age were classified as alcohol abusers in the United States, which represents 7.4% of the related population [2]. Based on the data from another national survey, it can be stated that an estimated 12% of the population had driven under the influence of alcohol at least once during the previous year [12]. Ethanol abuse is common in homicide and domestic violence [13]. 24% of the 11.1 million violent crimes committed annually involve an attacker who had consumed alcohol before the offense in USA [14].

Ethanol intake seems to be a social problem in addition to its known effect on traffic accidents. In the overall picture, assaults are the main causes of EthPos emergency admissions, as it is known that ethanol consumption increases the tendency toward offensive behaviors [15]. In this study, MVC constituted the largest portion of all BEC tests among emergency admissions because individuals involved in any traffic accident are required to be tested for BEC, as these are considered to be judicial cases. Gentilello et al. showed that nearly half of all trauma beds are occupied by patients who were injured while under the influence of alcohol. Alcoholism plays a significant role and should be treated in trauma cases to reduce injury recurrence [16].

Demographics of the patients admitted to our emergency service were similar to the findings of other studies reported from Turkey. Prevalence data will help traffic safety professionals to adequately allocate resources and plan future efforts in reducing drinking-and-driving behavior, thereby reducing traffic accidents [17].

Standardized screening, brief intervention, and referral to treatment (SBIRT) intervention can decrease alcohol consumption, reduce injury, and decrease the number of emergency department visits [18]. However, it is not clear that SBIRT is an effective approach for dangerous alcohol use among patients in care [19]. Additional research, implementation, and interventions are needed to decrease alcohol consumption and admittance to emergency departments.

Finally, in this study, MVC constitutes the largest portion of all BEC tests among emergency admissions because individuals involved in any traffic accident are required to be tested for BEC, as these are considered judicial cases. On the other hand, in the overall picture, assaults are the main causes for EthPos emergency admissions, as it is known that ethanol consumption increases tendencies toward offensive behaviors.

Competing interests

The authors declare that they have no competing interests.

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Kubranur Unal, Turan Turhan, Gokce Atikeler, Esin Calci, Muge Sonmez, Fatma Meric Yilmaz. The reasons for blood ethanol concentration analyses in patients admitted to emergency department. J Clin Anal Med. 2017;8(3):248-251

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Surgical Management of 3 and 4-Part Proximal Humerus Fractures with Locking Plates in Elderly

Emrah Kovalak, Tolga Atay, Y. Barbaros Baykal, Özgür Başal

Department of Orthopaedics and Traumatology, Süleyman Demirel University Medical Faculty, Isparta, Turkey

DOI: 10.4328/JCAM.4834 Received: 12.10.2016 Accepted: 13.11.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 243-7

Corresponding Author: Emrah Kovalak, Ortopedi ve Travmatoloji Anabilim Dalı, Süleyman Demirel Üniversitesi Tıp Fakültesi, 32260 Çünür, Isparta, Türkiye. GSM: +905332346280 E-Mail: emrahkovalak@yahoo.com.

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Aim: Proximal humeral fractures are approximately 5% of all fractures and, %15-20 is displaced and unstable. By the introduction of locking plates there used to be a substantial rise in the osteosynthesis of the 3 and 4-part proxi-mal humeral fractures. But there is still a lack of consensus for the optimal treatment of these complex fractures. In this retrospective study, we aimed to evaluate the functional outcomes and prognostic factors of 3 and 4-part proximal humerus fractures treated with locking plate osteosynthesis in el-derly. Material and Method: 53 patients with displaced 3 and 4-part proximal humeral fractures treated with locking plate osteosynthesis between 2010 and 2015 were included. The fractures were classified according to Neer classification system. Outcomes were assessed by Constant-Murley scoring system (CMS), visual analog pain scale and plain radiographs. In reference to range of motion, forward elevation and abduction of the arm were measured.Results: No statistically significant differences found between the 3- part and 4- part fractures in CMS, forward elevation and, abduction (p>0.05). Pain was significantly higher in 4-part fractures (p=0.035). CMS, forward eleva-tion, and abduction were inversely correlated with age and delay in surgery. There was statistical significance between the patients had complications and those not in terms of CMS, forward elevation and, abduction (p=0.029, p=0.017 and p=0.024). Discussion: Functional outcomes of locking plate fixa-tion of proximal humerus fractures are associated with patient related fac-tors, fracture pattern, surgeon and, the implant. When indications are care-fully selected, locking plate osteosynthesis yield good outcomes in surgical treatment of 3 or 4-part proximal humerus fractures.

Keywords: Angular Stable Plating; Humeral Fracture, Proximal; Locking Plates; Shoulder Fractures

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Introduction

Proximal humeral fractures account for approximately 5% of all fractures and usually affect women over 50 years old with osteoporosis [1-4]. The 15% to 20% of these fractures are displaced, unstable and may negatively affect vascular supply of humeral head [1,2]. In these cases, operative fixation is indicated and the surgical management is usually based on the personal experience and preference of the surgeon [1,5,6].

Various fixation options such as tension bending, intramedullary nailing and plate fixation or hemiarthroplasty had been recommended for the treatment of three, and 4-part fractures of the proximal humerus [4,7-10].

There is a certain consensus on prosthetic replacement of head – split fractures, but out of these, in 3 and 4-part fractures the surgical management based on personal experience [5].

By the introduction of locking plates there used to be a substantial rise in the osteosynthesis of the 3 and 4-part proximal humeral fractures [2,7,10-14]. These plates have some advantages over conventional plates such as, providing high stability allowing early rehabilitation because of angular stable construction and multidirectional locking screws anchored in humeral head, with less dissection of soft tissue and less compromising of periosteal vascularization [2,15-17]. Also, locking plates have superior biomechanical properties under rotational loads than locking intramedullary nails [12,14,18,19]. These specifications made them the preferred choice for the treatment of proximal humeral fractures in elderly, particularly those with osteoporosis [3,4,15,16]. Clinical series have demonstrated some success with the use of locking plates for two part fractures but their clinical utility for 3 and 4-part fractures remain unclear [10].

Still there is a lack of consensus for the optimal treatment of these complex fractures in the written literature [1,5,10,13]. Also, debate goes on patient’s age or timing of the surgery on functional results that are managed with osteosynthesis [6,12,20-22].

With this retrospective study, we aimed to evaluate the functional outcomes and prognostic factors of 3 or 4-part proximal humerus fractures treated with locking plate osteosynthesis.

Material and Method

The retrospective analysis was undertaken on the patients who presented to our hospital between January 2010 and January 2015 with displaced, unstable 3-part and, 4-part proximal humeral fractures treated surgically with locking plate osteosynthesis. All fractures were classified according to Neer [9] classification system. Patient demographics such as age, gender, pre-operative hospitalization time, type of fracture and, union time were gathered from the patient records. Informed consent was obtained from all individual participants included in the study.

The method of surgical treatment was chosen according to the preoperative radiographs and CT images. Osteosytnhesis was preferred for the patients not including the following parameters; articular surface fracture, head-split fracture, anatomic neck displacement > 2 cm, impaction of the head.

Patients were excluded if they had the following: multiple injuries to the same upper extremity or pre-existing upper extremity disability, pathologic fractures, American Society of Anesthesiologists (ASA) grades IV-V and age <50 years old.

All procedures were performed via the standard deltopectoral approach in the beach chair position by two trauma surgeons experienced on shoulder surgery.

After surgery, all patients were treated with same postoperative protocol. Patients were placed in a sling and were encouraged to start early passive range of motion (ROM) exercises and isometric deltoid, biceps and triceps strengthening on postoperative day 1 for 6 weeks. After 6 weeks patients began active ROM exercises in a formal physiotherapy program. Strengthening exercises began 3 months after the operation.

Patients were seen in follow-up at 3, and 6 weeks, 3, 6, and 12 months and assessed on their postoperative outcome by physical and radiological examination. Physical examination was used to determine ROM, pain and discomfort. AP shoulder and axillary views were obtained at each follow-up visit and evaluated for fracture healing, hardware positioning, and osteonecrosis.

Clinical outcomes were assessed at last follow-up visit using Constant-Murley scoring system (CMS; 0-100) [23] without correction for sex and age, and pain via visual analog scale (VAS). In reference to ROM, forward elevation and abduction were measured with long-arm goniometer.

Data were statistically analyzed using SPSS software (v15.0; SPSS Inc. Chicago, IL, USA). Categorical variables were reported as frequencies (percent), and continuous variables were reported as means ± standard deviations (SD). The groups compared for equality by means of an independent samples T-test for continuous variables. Mann-Whitney U test for two unpaired groups were used. Fisher’s exact probability test was used for comparing categorical variables. Spearman’s rank correlation was used when looking for statistical dependence between two variables. A p value <0.05 was considered to be statistically significant.

Results

Fifty- three patients were included in the study with an average follow –up time of 23 (15-60) months. The 38 (71.69%) of the patients were female with a mean age of 68.3±10.3, and, 15 (28.31%) were male with a mean age of 62.0±8.2. Average union time was 12 (10-16) weeks. Patients’ demographics, pre-operative hospitalization and, union time are given in table 1.

There were no statistically significant differences between the 3- part and 4-part fractures in terms of CMS, forward elevation and, abduction (Table 2). Pain was significantly higher, in 4-part fractures (p=0.035) (Table 2). CMS, forward elevation, and abduction were inversely correlated with age and pre-operative hospitalization time (Table 3).

Thirteen (24.5%) patients were sustained various complications; osteonecrosis of the humeral head in 3, screw perforation of the humeral head in 3, nonunion in 2, malunion in 3, subacromial impingement in 2 (Table 4).

Mean CMS of the patients who had complications was 58.72±5.60. When overall complications were enrolled there was statistical significance between the patients had complications and those not in terms of CMS (p=0.029).

The mean forward elevation of the patients who had complication was 128±23.4 and abduction was 87±21.6. There were statistical significance between the patients had complications and those not in terms of forward elevation and abduction (p=0.017 and p=0.024).

There was no dominance of any complication in regards to the fracture type.

A 65 years male old patient with a 3- part fracture had non-union that required conversion to hemiarthroplasty 7 months after the operation, and the other 72 years old female patient with a 4-part fracture did not accept the revision surgery. These 2 patients were considered to be the part of the osteosynthesis group. Of the 3 patients (one 3-part, two 4- part) who had screw perforation, were underwent a second operation to reposition or remove the screw after the initial surgery. The patients who had osteonecrosis had no secondary operation.

The implant failure, screw breakage, infection, or nerve injury was not seen in the study.

Discussion

Surgical treatment of proximal humeral fractures are quite frequently performed procedure in clinical procedure [16]. These fractures usually occur by low-energy trauma in elderly and, manage surgically but generally considered as ‘’surgery of failure’’ due to poor bone quality [4,16]. Additionally, poor bone quality arises arguments over the optimal treatment of these fractures, where as the functional outcome after treatment determines patient’s level of independence [10,21].

In the present study it was found that CMS and ROM were inversely affected by age and longer pre-operative hospitalization time in both 3 and 4- part fractures and, complications were related to the worse functional outcomes. However, there were no significant differences in functional results regard to fracture type, but pain was higher in 4- part fractures.

The affects of the fracture type on functional outcomes are various and, the complications are the major cause of decreased functional status in treatment of proximal humeral fractures [4,16,17,22]. Even though the fracture type not affecting the functional status in non-complicated patients, complication rate seems to be increased by fracture type (more complications in Neer type 4) [22]. Fracture types did not significantly influence the incidence of implant-related complications [24]. The 40% of the complications are seems to be related to the incorrect surgical technique that is mostly related to the experience [4]. Because of high complication rates in 4-part fractures, some authors recommend hemiarthroplasty to avoid seconder surgery despite to lower functional outcomes than locking plates [16,25].

Patient’s age negatively affects the functional results that are managed with osteosynthesis [6,20-22]. Anatomic reduction and restoration of the medial cortical support is harder and found related to the failure in elderly [26]. In the present study, older age and co- morbidities were related to the delay of the surgery and delayed surgery was found positively correlated with poor functional outcomes. Indirect effects of age on fracture such as lower bone mineral density, multifragmentary fracture pattern and age related patient compliance was also stated by Krappinger et al. [26].

Locking plate fixation is associated with some considerable complications [5]. Where as the complications such as avascular necrosis, primary screw perforation, secondary impaction, and secondary dislocation of greater tuberosity are not related to the plate, the complications such as secondary loss of reduction, secondary screw perforation, loosening, screw backing out, and breakage are stated as related to the plate and incidence of implant related complications increases in patients older than 70 years [24].

Avascular necrosis was reported as major and much feared complication in plate fixation, which was related to the worse outcomes and, leading major reason for further revision with secondary arthroplasty [2,5,10,15,17,27]. Locking plate configuration, the surgical technique and, soft tissue preservation allowed by the fixed angled construct lowers the AVN rates when compared with the patients managed with conventional plates [1,24,27]. In some series, the patients in whom osteonecrosis developed had reasonable clinical outcomes and suggest that AVN was well tolerated in elderly population [5,10]. AVN is also well tolerated than malunion or nonunion [28].

Perforation of head screws primarily was one of the most frequent complications in this study with a rate of 5.66%. All of them were related to the initial surgery even with meticulous placement by intraoperative fluoroscopy. In the written literature, perforation of the head screws reported as the most common complication with a range of 2 to 40% with high revision rates [1,13,15,27]. Primarily perforation of head screws is probably related to purchase as much bone as possible coupled with spherical shape of the humeral head [27]. Egol et al. reported that, patients who had screw perforation were on average 6 years older than who had not, without any statistical difference [1]. In our serie, we did not have a correlation like this. Solberg et al. reported that the all screw perforations occurred in the superoposterior quadrant and resulted screw contact with the glenoid but, did not affected the functional results worse than the patients had no screw perforation in contrast with other series [10]. In the present study, we performed screw repositioning in 3 patients immediately in 48 hours after initial surgery, and according to us, they did not affect the functional outcomes.

Secondary screw perforation due to loss of reduction is another complication related to angular stable locking proximal humeral fractures and highly related to reoperations even though slight varus is accepted [5,24,27]. It is reported that missing medial support led to 30% screw perforations compared with 6% intact medial support [24]. It is stated that, the angular stable implant was responsible for screws cutting through osteoporotic humeral heads in elder patients and, was stated as 46% over 65 years old patients [5,21,24]. Anatomic reduction and restoration of the medial cortical support are crucial in order to prevent secondary varus angulation [14,26,27]. In the present study secondary varus angulation occurred in 2 without screw cut-out (Figure 1), where anatomic reduction was achieved and medial support screws were placed but tension band wiring was not performed. In fact tension band wiring was not used in any of the cases. Medial support screws have important contributions to the strength of the medial comminution and, also using of tension band wiring is recommended to neutralize the traction forces of rotator cuff when medial support is insufficient [24,29].

The non-union is another major complication in 3 or 4 -part humeral head fractures [17]. In our series, non-union occurred in 2 (3.77%) patients and required to conversion to hemiarthroplasty and performed in one. In the written literature the rate of non-union is 2,7%- 8% and, related to soft tissue preservation, surgical technique [1,17]. And also complex structure of the fracture is another reason of non-union [21].

Subacromial impingement occurred with a rate of 3.77% in the present study due to high positioning of the plate. Patients did not accept revision surgery. In order to avoid this complication meticulous attention must be paid to correct placement, and use of positioning K-wires is recommended [24].

Retrospective design and, some lack of knowledge such as, the rotator cuff pathologies and functional status of the patients prior to surgery and the physiotherapy performed by the patients by themselves at home are the weak points of the present study.

In conclusion, functional outcomes of locking plate fixation of proximal humerus fractures are associated with many factors, which are related to the patient, fracture pattern, surgeon and the implant. According to our study and in the light of the literature when indications are carefully selected, locking plate osteosynthesis yield good outcomes in surgical treatment of 3 or 4-part proximal humerus fractures.

 Competing interests

The authors declare that they have no competing interests.

 References

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2. Ong CC, Kwon YW, Walsh M, Davidovitch R, Zuckerman JD, Egol KA. Outcomes of open reduction and internal fixation of proximal humerus fractures managed with locking plates. Am J Orthop 2012;41(9):407-12.

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Comparison of Myocardial Perfusion Scintigraphy and Coronary Angiography Results

Umut Elboğa 1, Emre Kuş 2, Tulay Kuş 3, Gökmen Aktaş 3

1 Nükleer Tıp AD, Gaziantep Üniversitesi Tıp Fakültesi, 2 Kardiyoloji Kliniği, Şehitkamil Devlet Hastanesi, 3 Tıbbi Onkoloji BD., Gaziantep Üniverisiyesi Tıp Fakültesi, Gaziantep, Türkiye

DOI: 10.4328/JCAM.4830 Received: 11.10.2016 Accepted: 02.11.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 239-42

Corresponding Author: Umut Elboğa, Nükleer Tıp AD. Gaziantep Üniversitesi Tıp Fak. Gaziantep, Türkiye. T.: +90 3423606060 F.: +90 3423603928 E-Mail: umutelboga@hotmail.com

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Aim: Coronary artery disease (CAD) is one of the most frequent causes of mortality and morbidity worldwide. Coronary angiography is the gold stan-dard for the anatomical diagnosis of coronary artery stenosis. Myocardial Perfusion Scintigraphy (MPS) is a non-invasive imaging modality used for the diagnosis of CAD. In this study, we aimed to compare the findings of MPS and coronary angiogram. Material and Method: Eighty-one patients (37 males, 44 females; mean age 55 ± 10.95 years) with angina and detected perfusion defects on MPS were included in this study. All of the patients underwent coronary angiogram. A narrowing ≥ 50% was considered pathological on the coronary angiography. Results: Findings of the coronary angiogram and MPS were compared and found consistent in 51 (63%) patients. A coronary nar-rowing < 50% was detected by coronary angiogram in 4 (5%) of the remain-ing patients. Coronary angiogram was found to be normal in the remaining 26 patients (32%) and these patients were evaluated as cardiac syndrome X (CSX) known as microvascular angina (MA). Discussion: The findings showed that MPS is superior to coronary angiogram in the early diagnosis of myocar-dial perfusion disorders at the microvascular level. Therefore, we concluded that MPS should be the primary diagnostic tool to begin treatment before an anatomically large narrowing occurs in the coronaries.

Keywords: Coronary Artery Disease; Myocardial Perfusion Imaging; Coronary Angiography

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Introduction

Coronary artery disease (CAD) is a leading cause of morbidity and mortality and accounts for a large share of health costs worldwide. Therefore, diagnosis of CAD before surgery or coronary angiographic intervention is gaining importance to begin preventive treatments and to guide further management. Invasive coronary angiography is a traditional diagnosis modality and the gold standard to indicate coronary artery anatomy. However, it remains insufficient to evaluate the microvascular pathology cardiac syndrome X (CSX) or the functional status of a coronary stenos to predict the functional recovery following revascularization [1]. In this regard, image modalities reflecting microvascular pathology before overt clinical manifestations gain more significance.

Angina appears because of increased oxygen consumption with left ventricular hypertrophy, tachycardia, hypertension or decreased oxygen delivery via anemia, decreased blood flow due to stenosis or vasospasm [2].The ischemic changes starts in the subendocardium and moves toward the epicardium; this can be shown in the delayed enhancement sequences by MRI. Functional assessment of myocard and ischemia can be evaluated by demonstrating perfusion or wall motion abnormalities on cardiac MRI (CMR) including stress CMR and delayed enhancement sequences (stress MRI), stress echocardiography (SE), myocardial perfusion scintigraphy (MPS) with single photon emission CT (SPECT), and positron emission tomography (PET) imaging via adenosine, dipyridamole, exercise, or dobutamine [3]. Thus, ischemia which is not present on the nonstress images can be diagnosed with the post-stress images.The stenotic vessel which is already maximally dilated at rest to maintain myocardial oxygenation is not able to respond to stimulation of vasodilatation due to the loss of it’s vasodilatory reserve. Adenosine and dipyridamole are used as vasodilatoryagents while exercise and dobutamine are used as ionotropic stress agents with imaging modalities to detect perfusion abnormalities.

The commonly used radio-isotopes are thallium-201, Tc-99m sestamibi and Tc-99m tetrofosmin in SPECT. Ischemia is suspected when there is a reduced tracer uptake on the stress acquisition which is reversible on the rest acquisition. Having a defect on both stress and rest acquisitions is suggestive of an infarct when possible attenuation artifacts are exluded [4]. In this study, we aimed to comparethe findings of MPS and coronary angiography in patients with detected myocard perfusion defect and reviewed the value of two tools in the early diagnosis of myocard perfusion defect.

Material and Method

The subjects were selected from patients who had presented to Gaziantep University Nuclear Medicine Department due to chest pain, an abnormal exercise ECG or a failed exercise ECG test between June 2010 and April 2011. Among these subjects, 81 patients (38 male, 44 female, mean age: 55 ± 10.95 years) with ischemia and/or infarct identified with MPS were included in the study. All patients underwent coronary angiography within one month. The patients were informed about the procedure and the radiopharmaceuticals to be administered. This study was approved by the independent ethics committee of the university and aligned with the ethical principles of the Declaration of Helsinki. MPS protocol was applied in the subjects using the SPECT method. Vasodilator-effective drugs were stopped at least 48 hours before investigation. Stress images were acquired at the first day through a treadmill and rest images were acquired on the second day. Intravenous 20 mCi Tc 99m-MIBI was injected in every operation. Low energy high resolution (LEHR) collimator was used in the imaging. After monitoring the patients, the exercise test was implemented with a treadmill using Bruce protocol. The targeted maximal pulse value was calculated according to “210-age” formula. Reaching 85% of the target pulse, collapse of ST segment >2mm, over elevation in blood pressure (systolic>250 mmHg, diastolic >120 mmHg), hypotension, and observation of extreme weakness, shortness of breath and ventricular arrhythmia were accepted as criteria for the termination of the exercise test. Images acquired were evaluated by 3 nuclear medicine specialists with gray scale and colored scale at different times. Detection ofmyocardial perfusion defectswas accepted as a lesion. Perfusion defects were divided into 2 categories reversibledefect (myocardial ischemia) and irreversible defect (severe ischemia/scar tissue).

Coronary angiography was performed in the catheter laboratory of Gaziantep University, Cardiology Clinic. In all patients images were acquired at LAO (left anterior oblique) 45-60° and RAO (right antero-oblique) positions for the left coronary artery and, RAO 30° straight, 30-15° cranial, 30-15° caudal and LAO 45-60° straight, 15° cranial, 15° caudal and also at left lateral, posteroanterior and 20° caudal positions for the left coronary artery. About 6-8 mL of enhancement agent was manually injected during each acquisiton. Coronary angiography was performed by a single operator using similar catheterization equipment. Quantitative coronary analysis was carried out using diameter of the diagnostic catheter for calibration of the magnified image. Vessel diameter, minimal lumen diameter and stenosis diameter percentage were measured using an automated analytic system. The lesions of50% or higher were considered as serious coronary stenosis. Cine images were assessed by an experienced cardiologist.

Results

The mean age of patients was 55 ± 10.95 (range: 41-82). In the assessment of obesity according to BMI, 33(40.7%) patients were obese, 30 (37%) were overweight, and 18 (22.3%) patients were normal weight. Among all patients 2 (2.4%) had an implanted stent and 5 (6.1%) had history of a by-pass operation. Sixty-three (77.7%) cases had hypertension and 42(51.8%) patients were smokers. Twenty-seven (22.2%) patients had a first-degree relative with a history of coronary heart disease. In addition, 48 (59.2%) patients had hyperlipidemia, 30 (37%) patients had diabetes mellitus (DM) and 4 (4.9%) patients have had left bundle branch block. According to history and ECG findings, 13 (22.3) patients were found to have previous myocardial infarction.

Single or multiple artery narrowing of more than 50% according to coronary angiogram was detected in 51 of 81 patients who had pathological findings on myocardial perfusion scintigraphy. Of these 51 patients, 26 (50.9%) patients had a single vessel coronary artery lesion, 17 (33.3%) patients had two vessel lesions, and 5 (15.6%) patients had three vessel lesions. Although only 4 of the remaining 30 patients had narrowing between 30% and 50% in coronary arteries on coronary angiogram, ischemia was found in the regions fed by these vessels on MPS. Of these patients 3 had narrowing in the LAD (35% in 2 cases, 40% in 1 case) and the remaining 1 patient had narrowing in the RCA (40%).There were no soft tissue artifacts on MPS raw images, and the reduction in perfusion occurring in the areas supplied by the vessels with insignificant stenosis was accepted as real ischemia.

Twenty –six of 30 (86.6%) of patients who were detected by MPS as having ischeamia despite normal coronary angiogram finding were identified as microvascular pathology (cardiac syndrome X) according to criteria of typical angina, stress test positivity, normal angiogram, positive MPS results, and a history of obesity, hyperlipidemia, DM, or hypertension. Twelve (46.1%), 14 (53.8), 10 (38.3%) and 16 (61.1%) of these patients had a history of obesity, hyperlipidemia, DM, or hypertension (parameters of metabolic syndrome), respectively.

Discussion

Guidelines recommend the stress electrocardiography (ECG) test as the first-line of investigation inischemic coronary pathology [5]. Stress echocardiography is mostly useful in the case of contraindicated stress ECG. A SPECT is recommended for the diagnosis of CAD in the following conditions: (i) contra-indications to performing stress ECG, (ii) inability to perform stress ECG, (iii) suspicious stress ECG, (iv) abnormal resting ECG.The sensitivity and specificity of SPECT for the diagnosis ofsignificant coronary stenosis (defined as >50% stenosis) are about 86% and 74%, respectively [6]. A false negative result may be seen in the case of three-vessel and left main stem stenosis, because SPECT assesses relative perfusion defects. A study evaluating the accuracy of SPECT on 101 patients who underwent coronary angiograph showed that 13–15% of patients with left main stem stenosis had a normal perfusion with SPECT [7]. Otherwise, attenuation artifacts, for example an elevated diaphragm or breast artifact, may cause a false positive result lowering the specificity [8]. Even than, SPECT is still a valuable tool for predicting cardiovascular events (CVE) indicating a pathology on the microvasculary level. A study performed in patients with stable chest pain syndromes showed that normal stress SPECT images reflect a very low risk of death or non-fatal myocardial infarction (MI) and coronary revascularization can not improve survival in such patients. Otherwise, patients with abnormal images with SPECT had an intermediate to high risk for future cardiac events for about 6.7–7% , annually [9]. Because of the upward trend of annual risk in patients who have high risk factors related to age and sex, stress-induced ECG changes and diabetes mellitus, SPECT should be especially repeated even in the patients with normal stress SPECT so as not to miss syndrome X [4].

Cardiac syndrome X (CSX), also known as microvascular angina (MA), is included among stable coronary syndromes. Gabriele Fragasso et al. showed that patients with CSX and detected inducible myocardial hypoperfusion at MPS had a more severe prognosis with more hospitalizations and symptomatic burden for CAD [10]. Patients with CSX have an annual riskof 2.5% of adverse episodes such as sudden cardiac death, myocardial infarction, stroke, and congestive heart failure [11]. In 1988, Cannon at al. first showed an association between chest pain and electrocardiogram (ECG) changes with changes in microcirculation [12]. Although there is a discussion of whether CSX should be treated as a form of ischemic heart disease, some studies have reported that patients with CSX account for about 10–20% of all patients with symptoms of angina and it was seen that more than 50% of these patients had a persistence of chest pain not responding to short-acting nitrates after exercise [13-15]. Because of the exclusion of MAfrom other classic forms of ischemic main coronary vessels, no standard treatment approach exists. Medications for CAD and non-pharmacological interventions such as lifestyle changes, diet modification and increased physical activity can be applied in patients with suspected CSX.

Patients with MA exhibit only a partial perfusion defect related with a small artery supplying blood (a small muscule area), so it may not cause symptoms of transmural hypoperfusion. Moreover, even if a large area of cardiac muscle is affected, symptoms may not occur, because all the vessels in the area may not be affected. In this regard, although symptoms of ischemia can be masked, it may cause chest pain and ECG changes and it may be detected with a radionuclide test. Currently used methods of imaging in the diagnosis of MA are PET, cardiac MRIi and SPECT [16]. Wojciech Szot et al. conducted a study assessing the effect of cardiac rehabilitation (reducing overweight, regular exercise) on SPECT tests change in patients with MA. Accordingly, improvement in myocardial perfusion in SPECT tests, reduction in the frequency and severity of chest pain and better blood pressure control following cardiac rehabilitation were detected [17]. At rest, patients with MA have a normal or slightly reduced blood flow in vessels. However, it changes during physical exercise or with stress tests because it can not response to increased request. Impaired capacity for vascular relaxation due to low level of nitric oxide released from the endothelial cells of small blood vessels and increased release of vasomotor mediators (endothelin, norepinephrine, renin, angiotensin II, and vasopressin) act in this pathogenesis [18]. İmproving endotelial dysfunction with cardiac rehabilitation was clearly shown with changing SPECT images in that study.

Metabolic syndrome (MetS) is definedas the combination of diabetes mellitus, hypertension, dyslipidemia,central obesity, and microalbuminuria. It is an important risk factor for cardiovascular diseases [19,20]. Kenichi Nakajima et al evaluated the risk of cardiovascular

events of patients who had metabolic syndrome (MetS) without coronary artery disease symptoms (CAD). Accordingly, myocardial perfusion scintigraphy did not differ between patients with and without MetS [21]. This, could arise from including patients without any cardiac symptom in that study. Having symptoms of angina and having ECG changes increase the positivity of MPS. Otherwise, a high MPS defect score was related to cardiovascular events in this study, as mentioned above. In our study,we found normal range (<50 stenosis including 30-50 stenosis) coronary angiogram in 38.1% of patients with detected ischemia in MPS. MetS was recorded in 38.3% of this group. These results indicate the efficiency of MPS in detecting the ischeamia at the areas with smaller than 50% stenosis in coronary vessels. Also, most of these patient were observed to have MetS. Patients who were accepted as normal due to stenosis below 50% in coronary angiogram, but exhibiting ischemia in MPS together with angina symptoms should be considered as high risk cases in terms of CSX. Both preventive medication and non-pharmacological life style changes should be proposed and MPS should be repeated especially in those patients having MetS.

Conclusion

In conclusion, our findings support the inadequacy of coronary angiogram without MPS in the diagnosis of coronary artery disease.

Competing interests

The authors declare that they have no competing interests.

References

1. Tonino PA, Fearon WF, De Bruyne B, Oldroyd KG, Leesar MA, Ver Lee PN, et al. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flowreserveversus angiography in multivessel evaluation. J Am Coll Cardiol 2010;55:2816-21.

2. Crossman DC. The pathophysiology of myocardial ischaemia. Heart 2004;90:576–80.

3. Pakkal M, Raj V, McCann GP. Non-invasive imaging in coronary artery disease including anatomical and functional evaluation of ischaemia and viability assessment. Br J Radiol 2011;84(3):280-95.

4. Hachamovitch R, Hayes S, Friedman JD, Cohen I, Shaw LJ, Germano G, et al. Determinants of risk and its temporal variation in patients with normal stress myocardial perfusion scans: what is the warranty period of a normal scan?J Am Coll Cardiol 2003;41:1329-40.

5. Antman EM, Smith SC, Alpert JS, Gregoratos G, Anderson JL, Hiratzka LF, et al. with Task Force Members. ACC/AHA/ASNC Guidelines for the Clinical Use of Cardiac Radionuclide Imaging executive summary: a report ofthe American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J AmColl Cardiol 2003;42:1318–33.

6.Underwood SR, Anagnostopoulos C, Cerqueira M, Ell PJ, Flint EJ, Harbinson M, et al. Myocardial perfusion scintigraphy: the evidence. Eur J Nucl Med Mol Imaging 2004;31:261–91.

7. Berman DS, Kang X, Slomka PJ, Gerlach J, de Yang L, Hayes SW, et al. Underestimation of extent of ischemia by gated SPECT myocardial perfusion imaging in patients with left main coronary artery disease. J Nucl Cardiol 2007;14:521-8.

8. Dondi M, Fagioli G, Salgarello M, Zoboli S, Nanni C, Cidda C. Myocardial SPECT: what do we gain from attenuation correction (and when)? Q J Nucl Med Mol Imaging 2004;48:181-7.

9. Iskander S, Iskandrian AE. Risk assessment using single-photon emission computed tomographic technetium-99m sestamibi imaging. J Am Coll Cardiol 1998;32:57-62.

10. Gabriele Fragasso, Ludovica Lauretta, Elena Busnardo, Michela Cera, Cosmo Godino, Antonio Colombo, et al. Prognostic role of stress/rest myocardial perfusion scintigraphy in

patients with cardiac syndrome x. Int J Cardiol 2014;173:467-71.

11. Reis SE, Holubkov R, Conrad Smith AJ, Kelsey SF, Sharaf BL, Reichek N, et al.; WISE Investigators. Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J 2001;14:735-41.

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15. Herrmann J, Kaski JC, Lerman A. Coronary microvascular dysfunction in the clinical setting:from mystery to reality. Eur Heart J 2012;33:2771-82.

16. Johnson BD, Shaw LJ, Buchthal SD, Bairey Merz CN, Kim HW, Scott KN, et al. National Institutes of Health-National Heart, Lung, and Blood Institute. Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: results from the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women’s Ischemia Syndrome Evaluation (WISE). Circulation 2004;109:2993-9.

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18. Wu EB. Microvascular dysfunction in patients with cardiacsyndrome X. Heart 2009;95:521.

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21. Nakajima K, Takeishi Y, Matsuo S, Yamasaki Y, Nishimura T. Metabolic syndrome is not a predictor for cardiovascular events in Japanese patients with diabetes mellitus asymptomatic for coronary artery disease: a retrospective analysis of the J-ACCESS-2 study. J Nucl Cardiol 2013;20:234-41.

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Umut Elboga, Emre Kus, Tulay Kus, Gökmen Aktas. Comparison of myocardial perfusion scintigraphy and coronary angiography results. J Clin Anal Med. 2017;8(3):239-242

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Isolated Frontal Sinus Surgery Pathologies

Özer Erdem Gür, Nevreste Didem Sonbay Yılmaz, Nuray Ensari

Department of ENT, Antalya Education and Training Hospital, Antalya, Turkey

DOI: 10.4328/JCAM.4809 Received: 27.09.2016 Accepted: 02.11.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 235-8

Corresponding Author: Nevreste Didem Sonbay Yılmaz, Department of ENT, Antalya Education and Training Hospital, Antalya, Turkey. GSM: +905052692743 E-Mail: didem_ece@yahoo.com

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Aim: Frontal sinus pathologies are seen less often than other paranasal sinus pathologies. However, the close proximity of the frontal sinus to important anatomic structures can cause significant symptoms and complications. The pathologies most frequently seen in the frontal sinus are mucoceles and os-teoma. In this study, a retrospective scan was made of patients operated on for frontal sinus pathology and these patients were evaluated in light of the literature. Material and Method: A retrospective evaluation was made of 1143 patients who underwent endoscopic sinus surgery between September 1999 and March 2016. The patients included in the study were those oper-ated on for a diagnosis of frontal osteoma in 12 cases and for frontal muco-cele in 44 cases. Result: Of the total 1143 patients initially scanned, isolated frontal sinus pathology was determined in only 56 (4.8%). These patients underwent surgery for frontal osteoma in 12 cases and for frontal mucocele in 44 cases. In 12 patients diagnosed with osteoma, surgery was performed with the external approach. Bicoronal flap was applied in 2 patients and in-side eyebrow incision in 10. Of the 44 patients diagnosed with mucocele, surgery was performed with the external approach on 13 patients. In 3 pa-tients with frontal sinus anterior wall defect and frontal recess obliterated on PNS CT, the endoscopic approach was combined with osteoplastic flap. After repair of the dura defect with graft taken from the fascia lata, the frontal sinus ws obliterated with fat tissue taken from the abdomen. Of the 44 pa-tients diagnosed with mucocele, surgery was performed with the endoscopic approach on 28 patients. Discussion: The surgical approaches in frontal sinus pathologies remain a matter of debate. Although endoscopic sinus surgery has been the gold standard among all paranasal surgical approaches since it was first introduced, external approaches still remain current. The general view is that if there is a defect in the frontal sinus anterior wall and there is extension outside the sinus to the orbit wall in particular, if the lesion has lat-eral localisation within the frontal sinus, or if there is a defect in the posterior dura, external surgery should be preferred to external surgery.

Keywords: Frontal Sinus; Surgery; Mucocele; Osteoma

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Introduction

Frontal sinus pathologies are seen less often than other paranasal sinus pathologies [1,2]. However, the close proximity of the frontal sinus to important anatomic structures can cause significant symptoms and complications. Symptoms vary according to the extent of the frontal sinus pathology [2]. If extension is seen towards the inferior of the frontal sinus, there may be ophthalmic symptoms such as propitosis and diplopia. If it is seen to extend to the posterior and enters the head, there can be intracranial pathologies such as meningitis and brain abscess. Finally, if there is exposure towards the anterior there can be cosmetic symptoms [1,3]. Sometimes the pathology in the frontal sinus may itself close the frontal ostium and only cause sinusitic symptoms [3].

The pathologies most frequently seen in the frontal sinus are mucoceles and osteoma. Regarding the paranasal sinuses, mucoceles generally involve the frontal sinus. They are a benign tumour but because of their expansive properties they can show extension to the surrounding tissue by destruction of the bone [4,5]. It is known that they can occur because of any blockage in the frontal ostium. Fu et al. [1] classified mucocele into two main groups according to the etiology. These were identified as secondary mucocele if there was an evident pathology closing the ostium (polyp, tumour, trauma, or surgical-related scar tissue) and as primary mucocele if there was no pathology other than anatomic variation closing the ostium. It has been shown that within all the paranasal sinuses, secondary mucocele are seen particularly in the frontal sinus.

As frontal osteoma are generally asymptomatic, the real incidence is unknown [6]. Of all the paranasal sinuses, the frontal sinus is most often involved. Osteoma are slow-growing benign tumours and very rarely spread to the orbit and intercranial region [7]. Generally they are symptomatic and there is no association between size and symptoms [8]. Sometimes a very small osteoma may cause widespread face and head pain. Apart from Gardner syndrome, in which multiple lesions are seen, frontal osteoma is usually seen as a single lesion [6,7]. Although trauma, inflammation, and heredity are responsible in the etiology, the subject of etiological factors remains controversial [6,7,8].

The treatment for frontal sinus pathologies is surgery [1,2,4,5,8]. However, because of the anatomic character of the frontal sinus, operations are more difficult and complicated than for other paranasal sinuses. During surgery, it should be considered that secondary frontal mucocele may develop following intervention in the frontal recess [1,2].

In this study, a retrospective scan was made of patients operated on for frontal sinus pathology and these patients were evaluated in light of the literature.

Material and Method

A retrospective evaluation was made of 1143 patients who underwent endoscopic sinus surgery between September 1999 and March 2016. The patients included in the study were those operated on for a diagnosis of frontal osteoma in 12 cases and for frontal mucocele in 44 cases. Other cases of pathologies affecting the paranasal sinuses, such as chronic sinusitis and nasal polyposis, were excluded from the study. All the patients were preoperatively evaluated with diagnostic nasal endoscopy and high-resolution paranasal sinus CT.

Surgical Approach:

Intervention to the frontal sinus was performed using an external approach, an endoscopic approach, or a combined approach.

External Approach: For the external approach, a bicoronal flap or an incision within or over the eyebrows is preferred. Leaving the perichondrium intact, the flap is raised as far as the frontal sinus anterior wall inferior border. A template was created by cutting the sinus projections on the Caldwell radiograph taken of the patients. Using this template, the sinus projection of the mass over the frontal sinus periosteum was marked. By making a periosteal incision that was 1-1.5 cm greater in each direction from the marked sinus projection area, the periosteum was carefully elevated. With the aid of the marked area on the Caldwell radiograph, the frontal sinus anterior wall was opened as a cover. In cases of frontal sinus mucocele, the content of the mucocele was aspirated. The frontal sinus ostium was checked and the frontal recess was opened (Figure 1). If a dura defect was determined during the operation, the defect was closed with a graft taken from the fascia lata and to support the graft, the frontal sinus was obliterated with fat tissue taken from the abdomen. In case of frontal sinus osteoma; ıts in the broken base with the help of tour after dilution was tried to be intact.

Endoscopic Approach: A Draft 2 frontal sinusotomy was applied to all the patients. After identification of the frontal recess and ostium, the frontal ostium was widened with curettage and forceps.

Combined Approach: External surgery was combined with the endoscopic approach.

The patients were followed up postoperatively for at least 13 months – 4 years. Endoscopic examination was made for the follow-up. PNS CT was only requested for patients thought to have recurrence.

Results

Of the total 1143 patients initially scanned, isolated frontal sinus pathology was determined in only 56 (4.8%). These patients underwent surgery for frontal osteoma in 12 cases and for frontal mucocele in 44 cases. Of the 44 patients with frontal mucocele, there was no organic pathology closing the frontal ostium in 37 cases and these patients were accepted as primary mucocele. In the 7 patients in the secondary mucocele group, the frontal sinus ostium was obliterated and therefore frontal mucocele developed because of inverted papilloma in 1 case, panpolyposis in 1 case, and transfer to endoscopic sinus surgery in 5 cases.

The 56 patients comprised 32 (57%) females and 24 (43%) males. All the patients presented with the complaint of headache, which was retrobulbar in 20 (36%) cases and in the frontoethmoidal region in 36 (64%). Nasal obstruction was determined in 32 (57%) patients, postnasal discharge in 23 (41%), and sensitivity with pressure on the frontal region in 10 (18%).

In 12 patients diagnosed with osteoma, surgery was performed using the external approach. The form of incision was dependent on the size of the osteoma and patient preference. Bicoronal flap was applied in 2 patients and eyebrow incision in 10. Of the 44 patients diagnosed with mucocele, surgery was performed using the external approach in 13 patients, of whom 7 had a defect in the frontal sinus anterior wall, 4 had intracranial extension, and in 3, the mucocele had a lateral localisation in the frontal sinus. In 3 patients showing frontal sinus anterior wall defect and frontal recess obliterated on PNS CT, the endoscopic approach was combined with osteoplastic flap. After repair of the dura defect with graft taken from the fascia lata, the frontal sinus was obliterated with fat tissue taken from the abdomen. Of the 44 patients diagnosed with mucocele, surgery was performed using the endoscopic approach on 28 patients [Table 1].

All the patients were followed up with endoscopic examinations for 9 months – 4 years. No recurrence was determined in any patient who underwent surgery because of frontal osteoma. Of the 44 patients diagnosed with frontal mucocele, recurrence developed in 1 patient in the 41st month postoperatively. On the preoperative PNS CT taken of this patient, there was panpolyposis together with a lateral frontal mucocele exposing the orbit superior wall. The patient was operated on with the endoscopic approach combined with osteoplastic flap. In the postoperative 41st month, recurrence was determined of both the panpolyposis and the frontal sinus mucocele in the orbit superior wall. The patient was again operated on with a combined approach and in the postoperative 12th month no recurrence was determined.

Discussion

Frontal sinüs surgery is still a matter of debate, with respect both to examination and surgical methods [3,4,9]. As neither the frontal sinus nor the frontal ostium are opened in anterior rhinoscopy or diagnostic nasal endoscopy, it is not possible to evaluate the frontal recess. Paranasal sinus tomography is of critical importance in the diagnosis of frontal sinus pathologies [2,4,7,9]. However, surgical experience is needed to know when and for which disease it should be requested. Sometimes, just as frontal pathology may be revealed to be underlying an atypical headache, no frontal sinus pathology is found in a patient with headache and frontal region sensitivity.

The surgical approaches in frontal sinus pathologies remain a matter of debate [2-5, 7-9]. Although endoscopic sinus surgery has been the gold standard among all paranasal surgical approaches since it was first introduced, external approaches still remain current [4,5,9]. The general view is that if there is a defect in the frontal sinus anterior wall and there is extension outside the sinus to the orbit wall in particular, if the lesion has lateral localisation within the frontal sinus, or if there is a defect in the posterior dura, external surgery should be preferred to endoscopic surgery [1,2,4,5]. This is because dura defects and defects in the orbit roof or in the frontal sinus anterior wall can be repaired in the same session and a better visualisation angle can be obtained with an external approach to laterally located tumours [2,4,9].

In addition, during specification of the osteoma base in frontal osteoma surgery, an external approach is preferred by surgeons over an endoscopic approach because a better visualisation angle is provided. However, there is no definitive criterion as to when an endoscopic approach or external surgery should be applied. An endoscopic approach is less invasive than an external approach and provides better mucociliary clearance, so is therefore more often preferred in frontal mucocele surgery. In an extensive meta-analysis study by Courson et al. [5] no statistically significant difference was found between endoscopic and external approaches with respect to either recurrence or complications. Har-El et al. [10] applied endoscopic-wide marsupialisation in 66 cases of frontal mucocele and no recurrence was determined in any patient. In 1 patient with a defect in the frontal sinus anterior wall, marsupialisation was applied only to the mucocele mucosa. In the 6th month postoperatively the defect was seen to have spontaneously closed.

In our clinic, an external approach was preferred in patients with frontal osteoma because it provides a better visualisation angle. In cases of frontal mucocele, the decision regarding the type of surgery was made according to the condition of the frontal recess. In patients with a defect in the dura or frontal sinus anterior wall, the external approach was used. However, if there was an appearance of obliterated frontal recess on the paranasal sinus tomography, a combined approach was applied by endoscopically widening the frontal recess.

Competing interests

The authors declare that they have no competing interests.

References

1. Fu CH, Chang KP, Lee TJ. The difference in anatomical and invasive characteristics between primary and secondary paranasal sinus mucoceles. Otolaryngol Head Neck Surg 2007;136(4):621-5.

2. Herndon M, McMains KC, Kountakis SE. Presentations and management of extensive fronto-orbital-ethmoid mucoceles. Am J Otolaryngol 2007;28:145-7.

3. Senior BA, Lanza DC. Benign lesions of the frontal sinus. Otolaryngol Clin North Am 2001;34(1):253-67.

4. Gür ÖE, Kaymakcı M, Sonbay Yılmaz ND. Paranasal sinus mucoceles. J Ann Eu Med 2016;4(3):87-92.

5. Courson AM, Stankiewicz JA, Lal D. Contemporary management of frontal sinus mucoceles: A meta-analysis. The Laryngoscope 2014;2:378-86.

6. Keskin İG, İla K, İşeri M, Öztürk M. Paranazal sinüs osteomları. J Med Sci 2013;33:1250-58.

7. Turan Ş, Kaya E, Pınarbaşlı MÖ, Çaklı H. The analysis of patients operated for frontal sinus osteomas. Turk Arch Otorhinolaryngol 2015;53:144-9.

8. Bignami M, Dallan I, Terranova P, Battaglia P, Miceli S, Castelnuovo P. Frontal sinus osteomas: the window of endonasal endoscopic approach. Rhinol 2007;45:315-20.

9. Isa Ay, Mennie J, McGarry GW. The Frontal osteoplastic flap: does it still have a place in rhinological surgery? J Laryngol Otol 2011;125:162-8.

10. Har-El G. Transnasal endoscopic management of frontal mucoceles. Otolaryngol Clin North Am 2001;34:243-51.

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Ozer Erdem Gur, Nevreste Didem Sonbay Yilmaz, Nuray Ensari. Isolated frontal sinus surgery pathologies. J Clin Anal Med. 2017;8(3):235-238

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The Attitudes and Behaviours of Physicians Working in Burdur, Turkey Toward Rational Medicine Use

Özgür Önal 1, Deniz Say Şahin 2, Betül Battaloğlu İnanç 3, Müzeyyen Özcan 4

1 Public Health Exper Dr. Burdur Public Health Directorate, Burdur, 2 Emergency and Disaster Department, Mehmet Akif Ersoy University, Health High School, Burdur, 3 Family Medicine Department, Muğla Sıtkı Koçman Üniversity, Muğla, 4 Association of Public Hospitals, Burdur, Türkiye

DOI: 10.4328/JCAM.4827 Received: 06.10.2016 Accepted: 31.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 230-4

Corresponding Author: Betül Battaloğlu İnanç, Family Medicine Department, Muğla Sıtkı Koçman Üniversity, Muğla, Turkey. T.: +90 252 2141326-28 F.: +90 252 2111345 E-Mail: betulbattaloglu@mu.edu.tr

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Aim: This study aimed to define the manner and behaviour of first line treat-ment physicians’ and general practitionars that work in the second line treat-ment hospitals regarding rational medicine use (RMU) in the centre of Burdur and its surrounding districts. Material and Method:This descriptive study includes first line treatment physicians’ prescribing medication and general practitionars that work in the second line treatment hospitals (total N=102) in the centre of Burdur, Turkey and its surrounding districts. There was no sampling for the study. All the physicians who agreed to participate were reached through a survey taker with a face-to-face interview between April 1, 2015 and July 7, 2015. 98 physicians participated in the study. The data from the study were analysed using the SPSS 17.0 for Windows program. Measurable values were described as arithmetic mean and standard devia-tion, and countable values were calculated as numbers and percentage. Re-sults: In the study including 98 physicians, 78 (79.6%) of them were males, 75 (76.5%) were married, and their average age was 40.77±8.77. The lead-ing factors affecting physicians’ prescriptions were post-graduate studies as cited by 82 (83.7%) and pharmacology lessons for 75 (76.5%). Drug com-pany presentations were the least important factor, cited by 22 physicians (22.4%). The most important criteria for physicians in prescribing were the effectiveness of the drug as cited by 97 (99%) and reliability of the drug for 96 (98%). Also, 98 of the physicians (100%) stated that patients asked them to prescribe certain drugs. However, only eight physicians (8.2%) indicated that they always prescribed the drug demanded by the patient while 88 phy-sicians (89.8%) indicated that they sometimes did this. Discussion: Physi-cians are frequently asked by patients to prescribe painkillers and antibiotics. However, the physicians cannot always meet these demands from the RMU point of view. Our study revealed that physicians should be informed about RMU principles within the scope of continuing medical education. This topic is important for patients’ lives and safety.

Keywords: Rational Medicine Use; Physician; Antibiotics; Painkillers; Burdur; Turkey

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Introduction

A drug is a dosage product that is used to protect humans from diseases, for diagnosis, for treatment, or to fix or change a human function. A drug generally includes an agent or agents formulated with one or more inactive ingredients [1]. While drugs eliminate the negative factors threatening human health and life if used properly, they may cause deaths when used improperly. Thus, proper use of prescription drugs plays an important part in public health [2]. At the same time, there is sample evidence that there is a large missed potential because of the way in which medicines are used: the right medicine does not always reach the right patient, and approximately 50% of all patients fail to take their medicine correctly [3]. For this reason, the World Health Organization (WHO) has emphasized the proper use of drugs and defined rational medicine use in the Nairobi meeting in 1985 [4]. The WHO defines rational medicine use as follows: “Medicine use is rational (appropriate, proper, correct) when patients receive the appropriate medicines, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost both to them and the community. Irrational (inappropriate, improper, incorrect) use of medicines is when one or more of these conditions is not met” [5]. Any mistake that is directly or indirectly related to the use of drugs is defined as irrational use of medicines (IUM). The WHO states that the misuse of drugs has reached a critical dimension. Even the use of some drugs in “medico-legal” borders are known to cause negative results such as drug tolerance, resistance, side effects, and even drug addiction. This is a public problem concerning healthy individuals as well as health teams and patients [6]. Since it is the physicians who chooses and prescribes the best drug among the alternatives following a through evaluation of the patient’s clinical condition, the most important component of rational drug use is the physician’s responsibility and prescribing habits. The success of this process depends on the health authorities’ education of doctors and patients. In Turkey, the Turkish Republic Health Ministry addresses this by informing and training health workers. Because rational knowledge and manner of physicians are significant and no research has been conducted to date in Burdur on this topic, this study has been planned to define physicians’ manners and behaviours related to rational medicine use.

Material and Method

This descriptive and cross-sectional study was planned to include all first line treatment physicians and who wrote prescriptions and general practitionars who works second line treatment health foundations (total N=102) in the centre of Burdur, Turkey and its surrounding districts. To collect data for the research, we prepared a questionnaire including 23 questions aimed at assessing physicians’ descriptive knowledge and manners toward rational medicine use. The study began with the approval numbered 06.03.2015-E.9266 given by the Ethical Committee of Mehmet Akif Ersoy University. In the study there was no sampling. All the physicians willing to participate (98 out of 102) were reached through a survey taker with a face-to-face interview between April 1, 2015 and July 7, 2015. Each face-to-face interview required only 25-35 minutes of the physician’s time. Participants were given information about the questionnaire and their verbal consent was acquired on a volunteer basis. The data from the research were analysed using the SPSS 17.0 for Windows program. Measurable values were described as arithmetic mean and standard deviation, and countable values were calculated as numbers and percentages.

Results

Of the 98 participating physicians, 78 (79.6%) are male, 75 (76.5%) are married, 54 (55.1%) live in surrounding districts and 78 (79.6%) work at first line treatment health foundations. The average age is 40.77±8.77. The average working hours of the physicians is 16.4±10.3. The average number of patients examined by the physicians daily is 71.12±55.06 and the average time period for examining patients is 8.1±4.08 minutes. The physicians were the most knowledgeable about drug application (86.7%, n=85) and daily dosage (82.7%, n=81). They were least knowledgeable about drug price (28.6%, n=28) and interactions (32.7%, n=32) (Table 1). When the physicians were asked to rank the factors influencing their prescribing behaviour, post-graduate studies (83.75%, n=82) and pharmacology class (76.5%, n=75) were reported as the most important factors. In-service education (72.4%, n=71), prescriptions used in the clinic internship (68.4%, n=67), and consulting with colleagues (62.2%, n=61) also were found to be significant factors affecting prescription behaviour. The presentations of drug companies were rated least effective (22.4%, n=22) (Table 1).

Drug effectiveness (99%, n=97) and drug reliability (98%, n=96) were among the significant criteria considered by the physicians when prescribing. The price of the drug was determined to be of little importance (Table 2). When faced with a problem during prescription, 69.4% (n=68) of the physicians referred to medical guidelines, 45.9% (n=45) referred to the opinion of colleagues, and 31.6% (n=31) referred to medical books. Drug company presentations (12.2%, n=12) and senior physician opinion (25.5%, n=25) were the least preferred choices (Table 2). In the survey analysis of the doctors’s behaviour, the drugs they were currently being used or that had used in the past (91.8%, n=90) and pregnancy (86.7%, n=85) were of highest importance. Cost to the patient and the patient’s ability to pay was regarded as important by 22.4% (n=22) of the physicians (Table 2).

All of the physicians (100%, n=98) stated that patients asked them to prescribe certain drugs. However, only 8.2% (n=8) of them reported that they always prescribed the demanded drug, while 89.8% (n=88) stated that they sometimes prescribed the demanded drugs. The most demanded drugs were painkillers, cited by 87.8% (n=86) of physicians, and antibiotics at 50.5% (n=48). The promotions of drug company representatives were stated to be ineffective by 58.2% (n=57) of the physicians. Additionally, it was observed that 76.5% (n=75) of the physicians sometimes asked for examination regarding diagnosis and treatment, 77.6% (n=76) of them gave information about the diagnosis and treatment to the patients, and 58.2% (n=57) of them considered that only informing the patient was sufficient.

Discussion

Important findings about the knowledge, manner, and behaviour of primary and secondary physicians working in Burdur related to RUM were obtained through this research. A study of family physicians conducted by the Turkish Ministry of Health concluded that 61.2% knew the usage of medications well, 55.9% the daily dosage, 52.2% the indications, and 57.4% the side effects [7]. Another study from 2015 relating to the drugs prescribed, physicians were observed to have a full knowledge of posology as well as the method of use (59.8%), side effects (58.6%), indications (56.3%), and drug interaction (44.8%). However, they had only an intermediate level of knowledge about drug prices (50.5%) [8]. In the study of Akıcı, it was determined that 11.6% of the physicians knew the prices of the drugs that they prescribed [9]. By comparison, in Saudi Arabia, physicians either knew “very little” (7%) or knew “nothing at all” (5%) about the drug price and price differences [10]. In accordance with the literature, our study has concluded that during the prescription of drugs, dosage and method of application are consistent with RMU but there is insufficient knowledge about prices. The reason is that the budget for health is restricted in Turkey and in many developing countries. Because they are restricted, the available resources should be used in the best possible way. Thus, in order to use drugs in a rational way, economic evaluations should be made about the medications in addition to general assessment of their effectiveness and reliability [11].

It has been observed in our study that the factors affecting the prescribing behaviour of the physicians include post-graduate studies, pharmacology classes, and in-service education. Similar results were observed in the study made with 157 practitioners in Erzurum. Presentations of drug companies were low-ranking factors, as in our study [12]. In another study including 380 physicians in seven large districts of Ankara, the basic education of the medical faculty and their post-graduate education were observed to be among high ranking factors [13]. Another study including 120 physicians in Kırıkkale determined that 73.6% of the physicians attended in-service education after graduation [8]. It is obvious that physicians are interested in RMU but are in need of training. Results of research into pharmacologists lead us to this opinion. According to this research, 27.8% of the lecturers and assistants were reported to have RMU training [14]. We believe that the physicians working at primary health services and hospitals should be repeatedly informed about the principles of RMU as part of their continuing medical education and that RMU use lectures should be given at medical faculties.

It is stated in our study that the sources of information most frequently referred to by physicians during prescription are medical guidelines (vademecum) (69.4%), opinions of colleagues (45.9%), and scientific publications (37.8%). Similarly, Saygılı’s research identified these sources as vademecum (82.1%), the internet (53.8%), and diagnosis-treatment guidelines (51.3%) (8). Vançelik stated that physicians referred to medical guidelines (73.7%), scientific sources (55.3%), opinions of colleagues (52.0%), medical books (48.7%), and presentation documents of drug companies (33.6%) [12]. Greek doctors rely more on scientific publications and medical textbooks and less on pharmaceutical representatives [15]. It is seen that the sources physicians refer to during prescribing are similar across multiple studies. It can be considered as a process initiating RMU that physicians refer to factual sources when prescribing. We think that this process can be easily handled through appropriate, reliable guidelines considering the most effective drug treatment and the cost. On the other hand, Mahajan et al. found that 83% of the physicians benefited from medical representatives and 69% from the collected articles in journals and from the internet as a source of information [16]. In the study of the Turkish Ministry of Health, the most frequently utilized sources by the physicians during prescription included “research and presentations of pharmaceutical companies” for both family physicians (78.9%) and senior physicians (74.3%) [7]. In Congo, sources of antibiotic prescribing included pharmaceutical companies (73.9%), antibiotic guidelines (66.3%), university courses (63.6%), internet sites (45.7%), and WHO guidelines (26.6%) (17). On the other hand, pharmaceutical representatives were preferred as an information source by 61.14% of Cypriot doctors and 51.99% of Greek doctors (15). The costs of promotions of pharmaceutical companies vary from country to country and generally comprise 15% of the drug expense. As the “information transfer” of promotional studies are considered, it is seen that pharmaceutical companies also attempt to compensate for physicians’ lack of knowledge due to their educational insufficiency [8]. It is observed worldwide that training on RMU is needed and should be continual. We believe that education should be planned according to a country’s conditions and that the needed educational and legal regulations should be enacted in order to maintain and support the newly-achieved manners and behaviours.

According to the findings of our research, the most important factor considered by the physicians during prescription is found to be “the clinical efficiency of the drug” (99%). Similarly, in a study conducted in Ankara, the most effective factor was found to be the efficiency of the drug. In a study including 152 practitioners working in central Erzurum, 90.1% of the physicians stated that the most important criterion during prescription was the efficiency of the drug [13]. Likewise, in the study of Theodorou in Greece and the Greek-populated Southern Cyprus, the most important factor affecting physicians’ prescription behaviour was determined to be the efficiency of the drug [15]. In most cases, choice of medication was based on familiarity and past experience with a drug, because the side-effect profile was influential in choosing a medication with in a particular class [18]. We observe that active ingredient, reliability, and fewer side effects are of significance to the physicians.

In our study, the physicians most often took into account the patient’s medication history (91.8%) and pregnancy (86.7%) and least often the cost to the patient (21.4%). In the study by the Turkish Ministry of Health, 84.2% of the family physicians and 78.5% of the senior physicians took into account the patient’s age as obtained through anamnesis; 83.6% of the family physicians and 78% of the senior physicians took into account pregnancy and breast-feeding status; 67.1% of the family physicians and 65.8% of the senior physicians always referred to the patient’s drug allergies; and 45.7% of the family physicians and 38.6% of the senior physicians frequently considered the cost to the patient [7]. Having the physicians take anamnesis was considered as an advantageous factor for diagnosis. However, the physicians’ consideration of the patient’s ability to purchase the prescribed drugs seemed partially insufficient. For instance, in Singapore, family physicians are highly considerate of the patient’s ability to purchase drugs for the treatment of asthma [19]. We think that inattention to drug cost may cause many more problems in the future, especially in the cases of chronic diseases. Therefore, we believe that physicians should know the financial status of the patient and should act accordingly.

In our study, the physicians stated that while prescribing they provided information about the period of treatment (88.8%), the method of using the drug (87.8%), and daily dosage (85.7%). In the studies of the Turkish Ministry of Health, 59.1% of the family physicians and 66.1% of the senior physicians always informed the patients about the dosage of the drugs; 56.7% of the family physicians and 64.6% of the senior physicians always informed about the period of treatment; 56.5% of the family physicians and 62.3% of the senior physicians always informed about the method of application. In contrast, 88.8% of the family physicians and 85.8% of the senior physicians rarely gave information about the drug price [7]. However, in a study including patients in Mersin, 15.7% of patients did not take all the drugs prescribed, 43.7% stopped using the drugs before the end of the required period, and 9.7% used drugs at a dosage different from what the physician advised [20]. The common irrational medicine use problems in our country are taking medication without consulting a physician, giving and taking advices about drugs from others, stocking drugs at home, taking drugs according to previous experiences with similar complaints, not taking drugs at the time prescribed, using drugs at an improper dosage, and not using drugs for the periods advised by the physician [21]. RMU is not only the responsibility of physicians; the awareness of patients should be raised as well, because patients’ expectations and demands may put pressure on physicians. The way in which the drug is used and the period of drug use is also helpful for active and passive efficiency of RMU. We recommend that visual, written, and audio educational materials and trainings should not be ignored in developing RMU policies.

All of the physicians attending in our study stated that patients demanded prescription of certain drugs, while only 8.2% of the physicians reported that they prescribed the drugs demanded everytime, while 89.8% of them prescribed the demanded drugs sometimes. According to the data of the Turkish Ministry of Health, it was determined that “medical advice for prescription” is at the second frequency (47.5%) for family physicians and at the third frequency for the senior physicians (48.7%). Accordingly, it is notable that the ranking of the reasons for patients to consult physicians “aiming at prescription” is much higher with senior physicians. Similarly, in studies conducted primarily in İzmir in 2003 and in Giresun in 2004, it was reported that “medical advice for prescription” ranked at the top in the patients’ consultations to the community clinics (respectively, 52.5% and 58.1%) [7]. Patient pressure was perceived as a factor contributing to over use of drugs (antibiotics) in the community by nearly two-thirds (61.9%) of respondents, where as only one-third (34.3%) did so in the hospital setting [17]. In other words, we can observe in the literature that physicians may prescribe according to the demands or expectations of patients. This factor seems significant in our country and abroad. We think that the opinions of patients on using drugs for all complaints, apart from the drugs used for chronic diseases, is one of the crucial elements in the scope of RMU.

In our study, the drugs demanded by the patients were firstly painkillers (87.8%) and secondly antibiotics (50.5%). According to the findings of the Turkish Ministry of Health, patients mostly demand “painkillers and rheumatic medications” (respectively 76% and 50.5%). In the second rank of drug demanded from the Family Health Centres are “common cold medications” (49%) and “antibiotic group medications” (26.2%) [7]. According to a study including patients in Mersin, the drugs most frequently found in the houses of patients are painkillers, medical dressing materials and antibiotics. Other studies have found that painkillers (57.8%) are generally or always bought unprescribed and that people without health insurance are most likely to buy unprescribed painkillers [20]. Both of these findings show that the results of our study are consistent with both the data from the Ministry of Health and the findings about patient usage. In India, important factors identified for antibiotic prescriptions by doctors were diagnostic uncertainty, perceived demand and expectation from the patients, practice sustainability and financial considerations, influence from medical representatives, and inadequate knowledge. Doctors also identified certain patient behaviour characteristics and lax regulations for prescribing and dispensing antibiotics as aggravating the problem of antibiotic misuse. A qualitative study conducted in the UK has shown that often general practitioners (GPs) prescribe antibiotics to their patients as they believe it is their duty to do the best for the mandate concerned about more the immediate and serious problems rather than the theoretical complications of increasing antimicrobial resistance [22]. Actually, the frequency of antibiotics use is increasing worldwide, just as in Turkey. Therefore the doctors of other countries also feel themselves under pressure. But in China, the ratio of antibiotics used per prescription was 29.9%, which is close to the WHO’s standard of no higher than 30% [23]. They attribute this relatively low rate of antibiotics use to “education.” Promoting the education of medical knowledge for doctors, reinforcing the promotion of rational drug use to doctors, and initiating performance evaluation for doctors are effective ways for improving prescription quality in Chinese county hospitals. Considering that the share of drug costs among health expenses in Turkey is 25% (7), the results of our findings seem to confirm this results. Although there is some advancement in RMU in Turkey in parallel with the rest of the world, problems about drug use continue [21]. In order to raise awareness about RMU, we think that national educational plans, applications, visual and written guidelines and documents should be prepared and publicized by the social and national media. We consider RMU as a process requiring a public-based approach that includes physicians, patients, and pharmacists.

Conclusion

According to our study, patients demanded that physicians prescribe certain drugs, especially painkillers and antibiotics, but physicians cannot meet these demands according to the principles of RMU. Our findings underscore that physicians should be informed regarding the RMU principles as part of their continuing medical education. The significance of RMU should be emphasized during in-service training. Memorable slogans related to RMU should be displayed in open public spaces, especially in health foundations and in the mass media. We believe that preventing the unprescribed and illegal sales of drugs such as painkillers and antibiotics that may cause negative results due to unconscious use would help to control consumption of such drugs.

Competing interests

The authors declare that they have no competing interests.

References

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Ozgur Onal, Deniz Say Sahin, Betul Battaloglu Inanc, Müzeyyen Ozcan. The attitudes and behaviours of physicians working in Burdur, Turkey toward rational medicine use. J Clin Anal Med. 2017;8(3):230-234

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Evaluation of the Superior Gluteal Nerve During Proximal Femoral Nailing

Mehmet Mesut Sonmez 1, Figen Yilmaz 2, Yunus Oc 1, Ramazan E. Erturer 3, Mustafa F. Seckin 4, Bekir Eray Kilinc 5, Irfan Ozturk 6

1 Department of Orthopaedics, Hamidiye Sisli Etfal Training and Research Hospital, İstanbul, 2 Department of Physical Theraphy, Hamidiye Sisli Etfal Training and Research Hospital, İstanbul, 3 Department of Orthopaedics, Istanbul Liy Hospital, İstanbul, 4 Department of Orthopaedics, Istanbul Bilim University, İstanbul, 5 Department of Orthopaedics, Golhisar State Hospital, Burdur, 6 Department of Orthopaedics, Istanbul University Medical Faculty, İstanbul, Turkey

DOI: 10.4328/JCAM.4824 Received: 03.10.2016 Accepted: 26.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 226-9

Corresponding Author: Bekir Eray Kilinc, M.Akif Mahallesi 23 Nisan Caddesi No:66/2 15300 Bucak, Burdur, Türkiye. GSM: +905306061884 F.: +90 2122360983 E-Mail: dreraykilinc@gmail.com

Abstract
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Abstract

Aim: The superior gluteal nerve may be compromised during hip surgery. We retrospectively evaluated the patients who underwent proximal femoral nail-ing for unstable trochanteric fractures in order to investigate the presence of superior gluteal nerve injury and its clinical findings. Material and Method: Twenty five patients (14 women, 11 men) were included in the study who had femoral nailing between January 2004 and March 2010 at Hamidiye Sisli Etfal Training and Research Hospital Department of Orthopaedics. Two different types of nails which have similar designs and surgical techniques were used for fracture fixation. Patients who had a history of cerebrovascular disease, electromyography findings of polyneuropathy, or degenerative ver-tebral disease were excluded from the study. Patients were evaluated clini-cally and radiologically. Findings related to acute denervation in the gluteus medius muscle and motor unit action potential changes were accepted as signs of superior gluteal nerve injury. Results: Eight patients were using sup-port during walking and three of these patients had positive Trendelenburg sign, but only one patient had acute denervation signs of the superior gluteal nerve. Discussion: Based on the present study the incidence of iatrogenic nerve injury is a rare complication of proximal femoral nailing. Elderly pa-tients, regardless of whether they have nerve injury, may limp and need to use a walking support.

Keywords: Damage; Electromyography; Proximal Femoral Nailing; Superior Gluteal Nerve

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Introduction

Proximal femoral fractures are frequently seen in daily orthopaedic practice [1]. The aim of the treatment is to obtain a stable fixation which allows early mobilization [2].

Intramedullary nails for stabilizing unstable fractures have been available since the early 1980s [3-5]. The nails are inserted percutaneously and allow the surgeon to minimize soft tissue dissection and bone damage, thereby reducing surgical trauma and wound complications and preserving the fracture hematoma that is essential for fracture healing [6-8].

Limping and abduction weakness as a result of damage to the nerves, abductor muscles, or change in neck shaft angle are important complications after hip surgery. Iatrogenic injury of the superior gluteal nerve (SGN) and gluteus medius muscle are most likely contributing factors, as shown in studies using electromyography (EMG). SGN and abductor muscles may be compromised during the surgical procedures. Especially in total hip arthroplasty, the SGN is at risk during the split and retraction of the gluteus medius muscle [9-11]. It may also be compromised during closed antegrade insertion of femoral nails. Although it has been asserted that the nails minimize soft tissue trauma due to percutaneous application, it is known that the entry points of these nails are not within the safe zone for the SGN. Anatomic studies have confirmed that the inferior branch of the SGN follows an oblique course anteriorly and caudally from piriformis fossa in the sagittal plane within the substance of gluteus medius muscle; therefore, injury to the nerve may be inevitable during percutaneous nail insertion [12-15].

In this study we retrospectively evaluated the patients who underwent proximal femoral nailing for trochanteric fractures, in order to investigate the presence of SGN injury and its clinical findings.

Material and Method

This study is based on a retrospective analysis of a prospectively-maintained database to detect superior gluteal nerve (SGN) injury and the effects it might have on the outcome of proximal femoral nailing surgery performed on patients between January 2004 and March 2010 at Hamidiye Sisli Etfal Training and Research Hospital Department of Orthopaedics. The study was approved by the local ethics committee. Our research is being reported aligned with the STROBE statement for case-control studies.

Inclusion criteria were patients who were treated for unilateral unstable intertrochanteric femur fractures (Orthopaedic Trauma Association 31A2 and 31A3) with Proximal Femoral Nail and Proximal Femoral Nail Antirotation (PFN and PFN-A; Synthes, Oberdorf, Switzerland) with a follow-up of at least one year. Exclusion criteria were: patients who had pathological fractures, fractures associated with polytrauma, previous surgery on the ipsilateral hip or femur, advanced osteoarthritis of the affected hip, inability to walk before injury, previous spinal surgery, or a history of cerebralvascular disease. The data of patients were retrieved from their medical files, operative reports, and regular follow-up records. We initially included into the study 51 (28 women and 23 men) patients who agreed to electromyographic investigation (EMG), from an overall total of 349 (193 women and 156 men) patients.

All of the procedures were done by the six regular surgeons.

An initial radiological examination of pelvis with both hips AP view was performed and neck shaft angles were measured for both hips. The neck shaft angle was measured to determine varus/valgus alignment as compared to the unaffected side. Radiographic measurements were performed by two investigators. Of the initial group of 51 patients, 17 patients (13 women and 4 men) who had an avulsion fracture of the greater trochanter or neck shaft angle less then 120 degrees or greater than 140 degrees were excluded because of the secondary varus or valgus deformity.

For clinical evalution, walking ability status was analyzed according to Kyo et al. [16]. In this system, patients are divided into four groups. Group 1 includes patients who can walk unassisted, group 2 includes patients who can walk with assistance, group 3 includes wheelchair-dependent patients, and group 4 includes bedridden patients. Patients were evaluated for Trendelenburg sign. Patients who could balance using finger support only were then asked to stand on one leg, flexing the other leg at the knee, while keeping the hip in extension. The examiner knelt in front of the patient to observe pelvic tilt. The test was negative when the unsupported pelvis was raised normally while standing on one leg and held there for at least 30 seconds [17]. The abductor power of the patients was assessed by the same physician according to the scale proposed by the Medical Research Council (MRC) (Table 1) [18].

EMG was carried out to examine the SGN for the remaining 34 patients (21 women and 13 men). The vastus medialis, gastrocnemius, and extensor hallucis longus muscles were also assessed to determine any evidence of spinal-originated problems. The EMGs were performed by the same neurophysiologist. The mean time between surgery and EMG examination was 18.2 [14-21] months. The muscles were evaluated by the criteria of the American Academy of Electrophysiological Medicine for needle EMG. In order to exclude patients with polyneuropathy, radiculopathy, or plexopathy, nerve conduction studies of both lower extremities were performed. Then, gluteus medius muscles were assessed bilaterally to evaluate the SGN, the vastus medialis muscle for L4 root, extensor hallucis longus muscle for L5 root, and gastrocnemius muscle for S1 root. First, resting activities were assessed for the signs of acute denervation (fibrillation and positive sharp waves), followed by observation of the recruitment pattern, examination of the motor unit action potential (MUAP) amplitudes, and time characteristics. Finally, motor patterns of interferences were investigated during muscle contractions to obtain information about denervation and reinnervation of examined muscles.

Results

After EMG evaluation, 9 patients (7 women and 2 men) with polyneuropathy, radiculopathy, or plexopathy findings were excluded. The remaining 25 patients (14 women and 11 men) were included in the study. The mean age was 59.2 (21-89) years.

The mean collodiaphyseal angle was 131.44° (125-140). Eight patients were walking with support in daily life, of whom only three had positive Trendelenburg sign. The mean age of these patients was 82 (74-89) years and none of them used any walking support before surgery.

Muscle strengths according to the MRC were 2 in one patient, 3 in two patients, and 5 in 22 patients.

Acute denervation signs of the SGN on the affected side was detected in only one patient. This patient’s muscle strength was 2. In addition to the reinnervation MUAPs, discrete, long-duration poliphasic MUAPs were observed in the gluteus medius muscle of this patient. This patient had a positive Trendelenburg test and he was using walking support in daily life. There was no sign of acute denervation in the EMG evaluations of other Trendelenburg sign positive patients. Only sparse MUAPs were detected and there was no sign of poliphasic MUAPs (Table 2).

 Discussion

Although there is no consensus on this point, intramedullary fixation of unstable trochanteric fractures is often considered to be superior to extramedullary fixation because it provides more stable fixation and minimally invasive application [6,13,18]. Deficiency of the abductor mechanism is a well-recognised cause of pain and limping after hip surgery. This can be found incidentally at the time of surgery or it may arise as a result of damage to the SGN intra-operatively due to mechanical failure of the abductor muscle’s detachment from the greater trochanter or malunions resulting in coxa vara or valga [19]. Morbidity attributable to SGN injury is difficult to define. The purpose of the current study was to determine the incidence of the damage to the SGN in patients treated with PFN and PFN-A.

The anatomic course of the SGN has been documented in various anatomical and clinical studies [9-15,20,21]. Branches of the nerve are within the surgical field during the gluteal splitting approach to the piriformis fossa as well as the greater trochanter tip. The average distance from the greater trochanter tip to the lowest branch of the SGN is more than 5 cm farther than the nerve’s distance from the piriformis fossa entry portal [21]. Therefore, using the greater trochanter tip as an entry point may reduce the risk of damage to these nerve branches. Even though the nail is placed with minimally invasive techniques, iatrogenic damage may occur in the bone and soft tissues, especially during the reaming of the entry point. The entry point of PFN AND PFN-A is the tip of the greater trochanter. A 5 cm incision proximal to the greater trochanter has been described for this procedure [6]. The abductor muscles are dissected on the way to the entry point. Out of three patients who had positive Trendelenburg test and were using support while walking, only one patient had evidence of acute denervation in EMG. Muscle strenghts were found in the two patients who had no evidence of nerve injury. Various anatomic studies have also revealed damage to the gluteus medius and minimus muscles with nail insertion at the trochanteric fossa versus minimal damage to these muscles when using the tip of the greater trochanter [22]. In our opinion this can only be a result of tendon or muscle damage.

The fracture of the greater trochanter during trauma or surgery and change in neck shaft angle after fracture union may lead to compromise of the abductor arm. The greater trochanter was intact for all patients in this study and mean collodiaphyseal angle was 131.4°.

There was no evidence of nerve injury or positive Trendelenburg test in 5 of 8 patients who were using support while walking. The mean age of these patients was 82 (74-89) years. When we asked patients why they use support, they declared that they use it to feel confident and because of they are afraid of falling.

The main limitations of this study are its retrospective nature and low number of patients. More extensive follow-up is needed with a larger sample size, including younger patients, to reach more objective and significant results. In addition it is not possible to determine whether the nerve was injured during trauma. However, based on the present study the incidence of iatrogenic nerve injury is a rare complication of proximal femoral nailing. Elderly patients, regardless of whether they have nerve injury, may limp and need to use a walking support.

Competing interests

The authors declare that they have no competing interests.

References

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2. Koval KJ, Zuckerman JD. Intertrochanteric fractures. In: Heckman JD. Bucholz RW, eds. Rockwood and Green’s Fractures in Adults. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:1635–63.

3. Calvert PT. The gamma nail – a significant advance or a passion fashion? J Bone Joint Surg Br 1992;74:329–31.

4. Gupta RK, Sangwan K, Kamboj P, Punia SS, Walecha P. Unstable trochanteric fractures: the role of lateral wall reconstruction. Int Orthop 2010;34:125-9.

5. Schipper IB, Steyerberg EW, Castelein RM, van der Heijden FH, den Hoed PT, Kerver AJ, et al. Treatment of unstable trochanteric fractures. Randomised comparison of the gamma nail and the proximal femoral nail. J Bone Joint Surg Br 2004;86:86-94.

6. Simmermacher RKJ, Bosch AM, Van der Werken CHR. The AO/ASIF proximal femoral nail (PFN): a new device for the treatment of unstable femoral fractures. Injury 1999;30:327–32.

7. Dujardin FH, Benez C, Polle G, Alain J, Biga N, Thomine JM. Prospective randomized comparison between a dynamic hip screw and a mini-invasive static nail in fractures of the tro- chanteric area: preliminary results. J Orthop Trauma 2001;15:401–6.

8. Harrington P, Nihal A, Singhania AK, Howell FR. Intramedullary hip screw versus sliding hip screw for unstable intertrochanteric femoral fractures in the elderly. Injury 2002;33:23–8.

9. Abitbol JJ, Gendron D, Laurin CA, Beaulieu MA. Gluteal nerve damage following total hip arthroplasty: a prospective analysis. J Arthroplasty 1990;5:319-22.

10. Zappe B, Glauser PM, Majewski M, Stöckli HR, Ochsner PE. Long-term prognosis of nerve palsy after total hip arthroplasty: results of two-year-follow-ups and long-term results after a mean time of 8 years. Arch Orthop Trauma Surg 2014;134(10):1477-82.

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12. Basarir K, Ozsoy MH, Erdemli B, Bayramoglu A, Tuccar E, Dincel VE. The safe distance for the superior gluteal nerve in direct lateral approach to the hip and its relation with the femoral length: a cadaver study. Arch Orthop Trauma Surg 2008;128:645-50.

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14. Ozsoy MH, Basarir K, Bayramoglu A, Erdemli B, Tuccar E, Eksioglu MF. Risk of superior gluteal nerve and gluteus medius muscle injury during femoral nail insertion. J Bone Joint Surg Am 2007;89:829-34.

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16. Kyo T, Takaoka K, Ono K. Femoral neck fracture. Factors related to ambulation and prognosis. Clin Orthop Relat Res 1993;215–22.

17. Hardcastle P, Nade S. The significance of the Trendelenburg test. J Bone Joint Surg Br 1985;67:741–6.

18. Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45. London: Her majesty’s Stationary Office; 1976.

19. Parker MJ, Handoll HHG. Gamma and other cephalocondylic intramedullary nails versus extramedullary implants for extracapsular hip fractures in adults. Cochrane Database Syst Rev 2010.

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21. Khan T, Knowles D. Damage to the Superior Gluteal Nerve During the Direct Lateral Approach to the Hip A Cadaveric Study The Journal of Arthroplasty 2007;22(8):1199-200.

22. Stecco C, Macchi V, Baggio L, Porzionato A, Berizzi A, Aldegheri R, et al. Anatomical and CT angiographic study of superior gluteal neurovascular pedicle: implications for hip surgery. Surg Radiol Anat 2013;35:107–13.

23. Ansari Moein C, ten Duis HJ, Oey L, de Kort G, van der Meulen W, Vermeulen K et al. Functional Outcome After Antegrade Femoral Nailing: A Comparison of Trochanteric Fossa Versus Tip of Greater Trochanter Entry Point J Orthop Trauma 2011;25:196-201.

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Mehmet Mesut Sonmez, Figen Yilmaz, Yunus Oc, Ramazan E. Erturer, Mustafa Faik Seckin, Bekir Eray Kilinc, Irfan Öztürk. Evaluation of the superior gluteal nerve during proximal femoral nailing. J Clin Anal Med. 2017;8(3):226-229

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Co-Occurrence of Helicobacter Pylori and Intestinal Metaplasia in Patients with Dyspepsia

Hüseyin Onur Aydın, Abdulcabbar Kartal, Mehmet Oduncu

Department of General Surgery, Sanliurfa Siverek Government Hospital, Sanliurfa, Turkey

DOI: 10.4328/JCAM.4823 Received: 03.10.2016 Accepted: 26.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 223-5

Corresponding Author: Hüseyin Onur Aydın, M. Fevzi Cakmak Av., 53. St., No: 48 P.C.: 06490 Bahcelievler, Cankaya, Ankara, Turkey. T.: +90 3122152629 F.: +90 3122234909 E-Mail: dronuraydin@hotmail.com

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Aim: Helicobacter pylori (HP) is a common gram negative bacteria associ-ated with peptic ulcer disease and malignancy. In this study we evaluated the co-occurrence of helicobacter pylori and intestinal metaplasia (IM) in pa-tients with dyspepsia. Material and Method: We retrospectively evaluated the gastroscopy and antral biopsy results of patients that were admitted to Siverek Government Hospital general surgery outpatient clinic with dys-pepsia between November 2013 and January 2015. Pathology samples were investigated with giemsa for HP and with PAS-AB for intestinal metaplasia. Results: We evaluated 682 patients (304 men, 378 women) with a mean age of 38.22 ±14.64 years (range 18-88 years). We diagnosed 555 (81.4%) with antral gastritis, 81 (11.9%) with pangastritis, and 6 (0.9%) with ulcero-vegetant tumoral lesion. Based on pathology we diagnosed 469 (69.6%) with chronic gastritis, 201 (29.5%) with inactive chronic gastritis, and 6 (0.9%) with adenocarcinoma. HP was detected in 475 (69.6%) patients, intestinal metaplasia was detected in 56 (8.2%) patients, and atrophy was seen in 11 (1.6%) patients. HP was detected in 4 (66.6%) of the 6 patients with adeno-carcinoma. In 48 patients with HP, intestinal metaplasia was also found. In 8 patients with intestinal metaplasia, HP was negative. Co-occurrence of HP and intestinal metaplasia was statistically significant (p: 0.006). Discussion: HP promotes intestinal metaplasia. The prevention and treatment of HP pre-vents precancerous lesions. In particular, patients with dyspepsia resistant to medical treatment should be examined carefully in general surgery practice.

Keywords: Helicobacter Pylori; İntestinal Metaplasia; Dyspepsia; Adenocarcinom

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Introduction

Helicobacter pylori (HP) infection is associated with atrophic gastritis, intestinal metaplasia (IM), and intestinal type gastric cancer. Atrophic gastritis following long chronic inflamation due to HP progresses to IM, displasia, and gastric adenocarcinoma [1]. Early diagnosis and treatment of patients with HP is crucial for prevention of precancerous lesions. Randomised controlled trials reported that eradication of HP prevents precancerous lesions and gastric adenocarcinoma [2]. The few meta-analyses conducted have shown only that HP eradication is not sufficient to prevent gastric adenocarcinoma in patients with intestinal metaplasia and displasia [3]. Early diagnosis and eradication of HP before the development of precancerous lesions has an important role in gastric cancer prevention. Since WHO and IARC (International Agency for Research on Cancer) have defined HP as a group 1 carcinogen, HP eradication has become more important [4,5].

Half of the population of the world is infected with HP and gastric adenocarcinoma is seen in 75% of these patients [6,7]. Peleteiro et al. showed in their prevalence study that incidence of HP infection has increased in every decade in which it has been tracked [8]. In recent years the prevalence of the disease has increased significantly in developing countries like Turkey. In the 2003 TURHEP study, HP infection prevalence was found to be 82.5% in people older than 18 years [9]. Since the prevalence is higher, early diagnosis and eradication are become more important for our country.

As a consequence of chronic HP infection, diffuse antral gastritis (DAG) or multifocal atrophic gastritis (MAG) evolves. As pathogenesis of the infection is not clear yet, the progression of lesions cannot be predicted. In patients who develop DAG, there is more acid secretion and duodenal ulcers are more common. Hypoacidity is seen in patients who develop MAG, and IM is more common [10]. In our study, we aim to detect HP infection in patients with dyspepsia and to evaluate the IM rate due to HP.

Material and Method

We evaluated the patients admitted with dyspepsia to Şanlıurfa Siverek Government Hospital general surgery outpatient clinic between November 2013 and January 2015. We included the patients who had gastroscopy. We retrospectively investigated gastroscopy findings and antral pathology reports. Pathology samples were investigated with giemsa for HP and with PAS-AB for intestinal metaplasia. Statistical analysis was done using the SPSS 21.0 package.

Results

We evaluated 682 patients (304 men, 378 women) with a mean age of 38.22 ±14.64 years (range 18-88 years). Inflamation was detected in 677 (99.3%) patients. There were pathologic findings in 455 of these patients (66.7%). We diagnosed 555 (81.4%) with antral gastritis, 81 (11.9%) with pangastritis, and 6 (0.9%) with ulcero-vegetant tumoral lesion. Based on pathology we diagnosed 469 (69.6%) with chronic gastritis, 201 (29.5%) with inactive chronic gastritis, and 6 (0.9%) with adenocarcinoma. HP was detected in 475 (69.6%) patients, intestinal metaplasia was detected in 56 (8.2%) patients, and atrophy was seen in 11 (1.6%) patients. HP was detected in 4 (66.6%) of the 6 patients with adenocarcinoma. In 48 patients with HP, intestinal metaplasia was also found. In 8 patients with intestinal metaplasia, HP was negative (Table 1). Co-occurrence of helicobacter pylori and intestinal metaplasia was statistically significant (p: 0.006) (Table 2).

Discussion

Chronic HP infection plays a particular role in intestinal type gastric carcinogenesis by promoting atrophic gastritis, intestinal metaplasia, and displasia [11]. These precancerous lesions are important risk factors for gastric adenocarcinoma [12]. In 2006, The American Society for Gastrointestinal Endoscopy (ASGE) reported that routine surveillance programmes for intestinal metaplasia are difficult to implement, but they are important and useful in patients at high risk for gastric cancer [13]. The cost effectiveness and feasibility of these surveillance programmes are still debatable. Zullo et al. recommend endoscopic surveillance for patients with gastric atrophy and intestinal metaplasia once every three years [14]. Because early gastric cancer is usually asymptomatic, 75% of patients are admitted to the hospital in the late stages [15].

Atrophic gastritis, intestinal metaplasia, and displasia are precancerous lesions for gastric cancer. Previous studies have shown that HP infection promotes progression of these precancerous lesions [16]. After the publication of reports with similar results, WHO defined HP infection as a class 1 carcinogen. HP infection is reported to increase the risk of gastric cancer by a factor of 2.8 [17]. In HP patients with certain genotypes, the risk of intestinal metaplasia is higher [18]. HP eradication is important because intestinal metaplasia progresses to displasia and gastric cancer. After IM development, mucosal acidity changes and HP colonisation decreases, at which point HP eradication stops being useful [19]. Although local healing following IM can be seen in the antrum, there was no healing in the corpus in some reports [20]. In type 3 IM patients, the gastric cancer incidence is 28% [21]. In the literature, HP eradication has been shown to be important in gastric cancer prevention [22]. In a study by Sarı et al., 36.31% of 9239 patients were proven to be HP positive by CLO test [23]. In our study we performed gastroscopy in 682 patients; histologically we diagnosed HP in 475 (69.6%) of them. In eastern Anatolia, Olmez et al. detected 560 IM in 4050 patients [24]. In our study we investigated IM development in HP positive patients and diagnosed IM in 48 of 475 HP positive patients. Co-occurrence of helicobacter pylori and intestinal metaplasia was statistically significant (p: 0.006).

In line with other reports, in our study we also detected that HP promotes IM. If HP is positive serologically or histologically, before the development of precancerous lesions, HP eradication should be done to prevent gastric cancer. In HP positive patients, IM may be the irreversible stage in cancer progression. Thus, HP positive patients need close monitoring and aggressive treatment. For prevention of gastric cancer, further studies concerning the healing of IM by HP eradication should be conducted.

Competing interests

The authors declare that they have no competing interests.

References

1. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process–First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer research 1992;52(24):6735-40.

2. Correa P, Fontham ET, Bravo JC, Bravo LE, Ruiz B, Zarama G et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. Journal of the National Cancer Institute 2000;92(23):1881-8.

3. Chen HN, Wang Z, Li X, Zhou ZG. Helicobacter pylori eradication cannot reduce the risk of gastric cancer in patients with intestinal metaplasia and dysplasia: evidence from a meta-analysis. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2016;19(1):166-75.

4. Williams MP, Pounder RE. Helicobacter pylori: from the benign to the malignant. The American journal of gastroenterology 1999;94(11 Suppl):S11-6.

5. Huang JQ, Hunt RH. Review article: Helicobacter pylori and gastric cancer–the clinicians’point of view. Alimentary pharmacology & therapeutics 2000;14(Suppl 3):48-54.

6. Parkin DM. International variation. Oncogene 2004;23(38):6329-40.

7. de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. The Lancet Oncology 2012;13(6):607-15.

8. Peleteiro B, Bastos A, Ferro A, Lunet N. Prevalence of Helicobacter pylori infection worldwide: a systematic review of studies with national coverage. Digestive diseases and sciences 2014;59(8):1698-709.

9. Serin A, Tankurt E, Sarkis C, Simsek I. The prevalence of Helicobacter pylori infection in patients with gastric and duodenal ulcers – a 10-year, single-centre experience. Przeglad Gastroenterologiczny 2015;10(3):160-3.

10. Kapadia CR. Gastric atrophy, metaplasia, and dysplasia: a clinical perspective. Journal of clinical gastroenterology 2003;36(5 Suppl):S29-36.

11. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M et al. Helicobacter pylori infection and the development of gastric cancer. The New England journal of medicine 2001;345(11):784-9.

12. de Vries AC, van Grieken NC, Looman CW, Casparie MK, de Vries E, Meijer GA et al. Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands. Gastroenterology 2008;134(4):945-52.

13. Hirota WK, Zuckerman MJ, Adler DG, Davila RE, Egan J, Leighton JA et al. ASGE guideline: the role of endoscopy in the surveillance of premalignant conditions of the upper GI tract. Gastrointestinal endoscopy 2006;63(4):570-80.

14. Zullo A, Hassan C, Romiti A, Giusto M, Guerriero C, Lorenzetti R et al. Follow-up of intestinal metaplasia in the stomach: When, how and why. World journal of gastrointestinal oncology 2012;4(3):30-6.

15. Cervantes A, Roda D, Tarazona N, Rosello S, Perez-Fidalgo JA. Current questions for the treatment of advanced gastric cancer. Cancer treatment reviews 2013;39(1):60-7.

16. Correa P, Piazuelo MB, Camargo MC. The future of gastric cancer prevention. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2004;7(1):9-16.

17. Cavaleiro-Pinto M, Peleteiro B, Lunet N, Barros H. Helicobacter pylori infection and gastric cardia cancer: systematic review and meta-analysis. Cancer causes & control : CCC 2011;22(3):375-87.

18. Leung WK, Chan MC, To KF, Man EP, Ng EK, Chu ES et al. H. pylori genotypes and cytokine gene polymorphisms influence the development of gastric intestinal metaplasia in a Chinese population. The American journal of gastroenterology 2006;101(4):714-20.

19. Hojo M, Miwa H, Ohkusa T, Ohkura R, Kurosawa A, Sato N. Alteration of histological gastritis after cure of Helicobacter pylori infection. Alimentary pharmacology & therapeutics 2002;16(11):1923-32.

20. Wang J, Xu L, Shi R, Huang X, Li SW, Huang Z et al. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion 2011;83(4):253-60.

21. Meining A, Morgner A, Miehlke S, Bayerdorffer E, Stolte M. Atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach: a reality or merely an hypothesis? Best practice & research Clinical gastroenterology 2001;15(6):983-98.

22. Fuccio L, Zagari RM, Minardi ME, Bazzoli F. Systematic review: Helicobacter pylori eradication for the prevention of gastric cancer. Alimentary pharmacology & therapeutics 2007;25(2):133-41.

23. Sari YS, Sander E, Erkan E, Tunali V. Endoscopic diagnoses and CLO test results in 9239 cases, prevalence of Helicobacter pylori in Istanbul, Turkey. Journal of gastroenterology and hepatology 2007;22(11):1706-11.

24. Olmez S, Aslan M, Erten R, Sayar S, Bayram I. The Prevalence of Gastric Intestinal Metaplasia and Distribution of Helicobacter pylori Infection, Atrophy, Dysplasia, and Cancer in Its Subtypes. Gastroenterology research and practice 2015;2015:434039.

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Huseyin Onur Aydin, Abdulcabbar Kartal, Mehmet Oduncu. Co-occurrence of helicobacter pylori and intestinal metaplasia in patients with dyspepsia. J Clin Anal Med. 2017;8(3):223-225

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Clinical and Demographic Properties of Hand-Foot and Mouth Disease

Alaaddin Yorulmaz 1, Nuran Karaca Onat 2

1 Çocuk sağlığı ve hastalıkları Kliniği, 2 Dermatoloji Kliniği, Konya Beyhekim Devlet Hastanesi, Konya, Türkiye

DOI: 10.4328/JCAM.4821 Received: 05.10.2016 Accepted: 26.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 219-22

Corresponding Author: Alaaddin Yorulmaz, Çocuk Sağlığı ve Hastalıkları Bölümü, Konya Beyhekim Devlet Hastanesi, Konya, Turkey. GSM: +905327806974 T.: +90 3322243060 F.: +90 3322631245 E-Mail:dralaaddin@mynet.com

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Aim: Hand-Foot-and-Mouth Disease (HFMD), which is caused by agents of the enterovirus family, leads to skin and mucosa lesions as well as non-com-plicated systemic infection. In the present review, we aimed to determine clinical characteristics and seasonal distribution of the patients diagnosed with HFMD. Material and Method: The patients referred and diagnosed with HFMD through dermatological and physical examinations between April, 1, 2014 and May, 31, 2016 were reviewed in terms of demographic data, complaints and physical findings. The statistical analysis was performed by “SPSS for Windows 13”, descriptive analysis was performed, and mini-mum-maximum values and standard deviations were calculated. The Mann Whitney U test was used. Values of p<0.05 were accepted as statistically significant. Results: Ninety two patients who were referred to top pediatrics and dermatology departments were diagnosed with HFMD. The mean age of the patients was 5.08 years (10 months-16 years). Fifty seven patients were male (61.90%), and 35 patients were female (38.10%). The most com-mon symptoms at referral were rash (100%) and mild fever (72.82%). Rashes were found on the hands and feet (100% of patients), on the oral mucosa (92.39%), and in the gluteal region (56.52%). The disease appeared most commonly during summer and autumn. Discussion: Hand-Foot-and-Mouth Disease is a viral disease that appears most often in children of 5 years of age and younger. Clinical findings are sufficient for the diagnosis and symp-tomatic treatment is adequate for the cases without severe involvement. The disease is common during the summer but recently, due to seasonal varia-tions, it has also become apparent during autumn, as well. It is important to inform the patients and their relatives about routes of transmission and the isolation methods required.

Keywords: Hand-Foot and Mouth Disease; Seasonal Variations; Rashes

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Introduction

Exanthematous illnesses frequently seen in childhood area group of diseases which have a quite large and important place in the differential diagnosis of childhood disease. The existence of fever with rash increases the likelihood of an infectious diseases. Hand-Foot-and-Mouth Disease (HFMD) is an infection caused by viruses from the enterovirus family It appears with vesicular rash on the skin and mucosa and generally progresses without any complication [1]. Mild symptoms such as lethargy may accompany a mild fever. The disease is generally detected in children between 2 and 10 years of age [2]. The infection may be transmitted through the fecal-oral route, water resources (e.g., a swimming pool), body contact or respiratory tract secretions [3,4]. Small epidemics appear under temperate climate conditions, especially during the summer, the disease has a seasonal progress [5]. Although HFMD is a self-limiting disease with a generally good prognosis, in some cases serious clinical conditions may develop. The approach to the treatment of endemic uncomplicated disease is isolating patients to prevent spread of the disease and treating their symptoms.

The present study was planned to draw attention to HFMD due to the increase in incidence of the disease in our country in recent years. The aim of the present study was to review clinical and demographic characteristics of the patients diagnosed with HFMD and to research the seasonal distribution of the disease.

Material and Method

The medical files of 92 patients who were referred to the Pediatrics and Dermatology polyclinics of Beyhekim Public Hospital between April 1, 2014 and May 31, 2016 and diagnosed with HFMD were reviewed retrospectively. HFMD was diagnosed by detection of the symptoms and findings such as fever; macular, maculopapular, vesicular or petechial rash on the hands, feet, and gluteal area; herpangina; and pharyngitis. Ages and genders of the patients as well as period of referral (month-season), complaints at referral, physical examination findings, and laboratory analyses were recorded from the files. Patients who had Group A β-hemolytic streptococcus detected by throat swab culture were excluded. No viral markers were tested. The statistical analysis was performed by SPSS for Windows 13, descriptive analysis was performed, and minimum-minimum-maximum values and standard deviations were calculated. The Mann Whitney U test was used. Values of p<0.05 were accepted as statistically significant.

Results

The 92 patients included 57 (61.90%) boys and 35 (38.10%) girls, with an average age of 5.08 years (10 months-16 years). The most common symptoms were rash (100%) and subfebrile fever (72.82%). There was rash on the hands and feet in all patients, on the oral mucosa in 92.39%, in the gluteal area in 56.52%, and on the face in 7.60%. The average age of the 52 patients with rash in the gluteal area was 2.90, which is significantly lower than the average for those without gluteal rash (7.90 years) (p<0.05). Furthermore, 41 of 52 patients with rash on the gluteal area were 3 years of age or younger (78.84%). Gastrointestinal symptoms such as nausea, vomiting, and diarrhea were observed in 13.04% of the patients. Demographic and clinical characteristics of these patients are summarized in Table 1. Age difference was not statistically significant.

The disease was most common during summer (16 patients in July, 24 patients in August), and fall (14 patients in September, 17 patients in October) and gradually decreased during late fall. The disease was most common in August (24 patients) during summer and in October (17 patients) during fall. In other words, the disease was detected most often during the summer (44 patients) and fall (35 patients). The numbers of patients according to the months and seasons are shown in Graph 1 and Graph 2, respectively.

White blood counts of 11 (11.95%) patients who had whole blood count analysis were normal. Liver function tests were examined in only three cases (3.26%) and detected within normal range. Two patients (2.17%) were hospitalized and monitored due to severe mucositis, persistent fever, and nutritional problems.

Discussion

Hand-Foot-and-Mouth Disease is a contagious, enteroviral infection characterized by vesicular palmoplantar eruption in the hands and feet and erosive stomatitis. While the disease most frequently occurs with coxsackievirus A16, it also can be caused by coxsackievirus A5, A7, A9, B1, and B3 [6]. The second most common cause is enterovirus 71, which stands out because of its ability to cause epidemics associated with significant mortality and morbidity [6]. The majority of enterovirus infections have a good progress, with fever only, and appear as significant clinical syndromes such as hand-foot-and-mouth disease (HFMD), herpangina, and pleurodynia [6]. However, they also may cause life-threatening infections like meningitis, encephalitis, myocarditis, neonatal sepsis, and acute flaccid paralysis in rare cases.

The majority of HFMD patients are children between 2 and 10 years of age, especially children 5 years of age and younger [1]. The proportion of patients 5 years or younger has been found between 82.60% and 95.60% in different studies [7,8,9]. In the present study, patient ages ranged from 10 months to 16 years of age. The proportion of patients at 5.1 and below 5 years of age was 64.30%. HFMD is quite rare below 1 year of age due to conservation by transplacental antibodies [10,11]. In our study, only 3 patients were 10 months old and 39.13% of the patients were 3 years or younger. Kobayashi et al. has reported cases between 9 months and 9 years of age, with the majority of the cases (75%) during the first 3 years of age [12].

Mirand et al. observed in their study that HFMD was more common in male patients [13]. Similarly, Zhou et al. detected the ratio of boys to girls as 1.4 in their study [7]. Ekinci et al. reported in their study conducted in July 2012 that their 24 patients included 19 boys and 5 girls [14]. We also observed that number of the boys exceeded the number of the girls, with a ratio of 1.62.

HFMD has seasonal characteristics that are affected by changes in climate. High air temperature and humidity increases the incidence of HFMD. Mirand et al. showed that HFMD usually appeared between May and July (77%), peaked in June, and had a secondary acceleration between September and December [13]. A study conducted on the patients diagnosed with HFMD in China showed that the disease peaked in April/May and September/October [9]. Topkarcı et al. reported that the disease was most common in July and August, and secondarily most common in September and October [15]. In line with the literature, in our study HFMD was most common during summer and secondarily most common during fall possible due to the effect of global warming.

The disease is quite communicable and transmitted through close contact with the patients via respiratory and droplet-transmitted infections and the fecal-oral route [1,2]. After an incubation period of 3 to 7 days, the disease progresses with aphthous ulcerovesicular lesions on the oral mucosa and vesicular rash surrounded by a red halo parallel to skin lines on the palm and sole [1,5]. Although the disease is called Hand-Foot-and-Mouth Disease, it may also appear on the knees, elbows, gluteal area, body, and, in rare cases, on the face, although none of these locations may be involved [1]. Rash usually disappears within 7-10 days. Subfebrile fever may also occur, with the rash generally appearing on the second day of the fever [1,2]. In the present study, rash on the hands and feet was detected in all of the patients (100%), while 72.82% had subfebrile fever. Topkarcı et al. reported rash in all patients and subfebrile fever in 76.20% of the patients in their study [15]. We detected oral mucosa involvement in 92.39% of the patients, gluteal area involvement in 56.52%, and vesicular rash in 7.60%.

A significant increase in gluteal area involvement has recently been observed. The average age of the patients with gluteal area involvement was 2.90, compared to 7.90 in those without gluteal area involvement. Involvement of the gluteal area was more common among the patients 3 years or younger who wear diapers.

Hand-Foot-and-Mouth Disease usually has a good progress. However, HFMD epidemics have increased in recent years and severe cases have been reported [7]. A supportive therapy is required for severe cases. In the present study, two male patients (10 and 12 months old) had to be hospitalized due to high fever. The white blood cell count of the two patients was normal in the whole blood count analysis. In the physical examination, the patient with oropharyngeal hyperemia had hyperemic aphthous lesions in patches on the soft palate, oropharyngeal region, and oral cavity mucosa; vesicular lesions appeared on the hands and feet. Both patients were admitted for four days and discharged without any complication. Rarely, the disease may cause fatal complications in the cases with immune system disorder. Findings such as high fever, vomiting, and confusion require examination for viral or aseptic meningitis and encephalitis. The disease may cause cardiac and pulmonary complications; therefore, ECG and radiological examinations such as chest x-ray should be performed [7]. We did not detect any patient with severe symptoms in the present study.

Infectiousness is higher during the first week of the disease. Virus carriage continues for a couple of weeks even after regression of the lesions. Li et al. have reported that viral excretion continued for 30 days in the throat swab and for 54 days in the stool after enterovirus 71 infection and that the lengths of such periods were consistent with the disease severity [16].

Conclusion

Hand-Foot-and-Mouth Disease is a viral disease that appears most often in children at 5 years of age and younger. It is usually observed during summer and fall. Clinical findings are sufficient for the diagnosis and symptomatic treatment is adequate for the cases without severe involvement. It should be considered that rash may not appear only on the hands, feet, and mouth, but also involve the gluteal area and face in younger age groups and severe cases. Usually HFMD ends without complications, but patients should be followed up in terms of cardiac and neurological involvement.

The infectiousness of HFMD is very high and protective precautions are important because there is not any exact treatment or vaccination. Hygiene of the hands; hygiene in food preparation and serving; hand cleaning of small children and their caregivers, particularly after toilet use; and early diagnosis isolation of children with suspicious clinical findings at school nursery or primary care health centers are important for preventing contamination and viral transmission. It is important to inform the patient and their relatives about routes of transmission and the isolation methods required.

Competing interests

The authors declare that they have no competing interests

References

1. Krafchik BR, Tellier R. Viral Exanthems. In: Textbook of Pediatric Dermatology. Harper J, Oranje A, Prove N (Eds). 2nd edition. Massachusetts, Blackwell Publishing, 2006;418-49.

2. Haley JC, Hood AF. Hand-foot-and-mouth disease. Fitzpatrick’s Dermatology in General Medicine. Freedberg IM, Eisen AZ, Wolff K (Eds). 5th edition. New York, McGraw-Hill 1999;2403-07.

3. Keswick BH, Gerba CP, Goyal SM. Occurrence of enteroviruses in community swimming pools. Am J Public Health 1981;71:1026-30.

4. Wong KT, Munisamy B, Ong KC, Kojima H, Noriyo N, Chua KB, et al. The distribution of inflammation and virus in human enterovirus 71 encephalomyelitis suggests possible viral spread by neural pathways. J Neuropathol Exp Neurol 2008;67:162-9.

5. James WD, Berger Tg, Elston DM (Eds). Viral diseases. In: Andrews’ Disease of Skin: Clinical Dermatology.10th edition. Toronto, Saunders Elsevier, 2006:215-367.

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7. Zhou H, Guo SZ, Zhou H, Zhu YF, Zhang LJ, Zhang W. Clinical characteristics of hand, foot and mouth disease in Harbin and the prediction of severe cases. Chin Med J (Engl) 2012;125:1261-5.

8. Ni H, Yi B, Yin J, Fang T, He T, Du Y et al. Epidemiological and etiological characteristics of hand, foot, and mouth disease in Ningbo, China, 2008-2011. J Clin Virol 2012;54:342-8.

9. Zou XN, Zhang XZ, Wang B, Qiu YT. Etiologic and epidemiologic analysis of hand, foot, and mouth disease in Guangzhou city: a review of 4,753 cases. Braz J Infect Dis 2012;16:457-65.

10. Xu W, Jiang L, Thammawijaya P, Thamthitiwat S. Hand, foot and mouth disease in Yunnan Province, China, 2008-2010. Asia Pac J Public Health 2015;27(2):769-77.

11. Peng H, Shu H, Peng-FeiD, Jia-Bin L, Ying Y. Paroxysmal supraventricular tachycardia in an infant with hand, foot, and mouth disease. Ann Dermatol 2012;24:200-2.

12. Kobayashi M, Makino T, Hanaoka N, Shimizu H, Enomoto M, Okabe N, et al. Clinical manifestations of coxsackievirus A6 infection associated with a major outbreak of hand, foot, and mouth disease in Japan. Jpn J Infect Dis 2013;66(3):260-1.

13. Mirand A, Henquell C, Archimbaud C, Ughetto S, Antona D, Bailly JL, et al. Outbreak of hand, foot and mouth disease/herpangina associated with coxsackie virus A6 and A10 infections in 2010, France: a large city wide, prospective observational study. Clin Microbiol Infect 2012;18:110-8.

14. Ekinci AP, Erbudak, E, Baykal, C. 2012 yılı Haziran ayında İstanbul’da el, ayak ve ağız hastalığı sıklığında önemli artış.Türkderm 2013; 47(4):192-3.

15. Topkarcı Z, Erdoğan, B, Yazıcı Z. El-Ayak-Ağız Hastalığının Klinik ve Demografik Özellikleri. Bakırköy Tıp Dergisi 2013;9(1):12-5.

16. Li J, Lin C, Qu M, et al. Excretion of enterovirus 71 in persons infected with hand, foot and mouth disease. Virol J 2013;10:31.

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Alaaddin Yorulmaz, Nuran Karaca Onat. Clinical and demographic properties of hand-foot and mouth disease. J Clin Anal Med. 2017;8(3):219-222

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The Importance of CD56 and CD98 Levels in Patients with Recurrent Implantation Failure

Tevfik Berk Bildacı 1, Bülent Haydardedeoğlu 1, Burcu Kısa Karakaya 1, Filiz Aka Bolat 2, Hulusi Bülent Zeyneloğlu 1

1 Kadın Hastalıkları ve Doğum Anabilim Dalı, Baskent Üniversitesi, 2 Patoloji Anabilim Dalı, Baskent Üniversitesi, Ankara, Türkiye

DOI: 10.4328/JCAM.4820 Received: 30.09.2016 Accepted: 23.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 216-8

Corresponding Author: Tevfik Berk Bildacı, Kadın Hastalıkları ve Doğum Anabilim Dalı, Baskent Üniversitesi, Ankara, Türkiye. GSM: +905325090218 E-Mail: berkbildaci@gmail.com

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Aim: Despite major advances in assisted reproductive techniques, clinical pregnancy rates remain around 31% with fresh embryo transfer and around 41% with oocyte donations. We also know that the implantation process it-self and the window period defined as the ‘’implantation phase’’ are signifi-cantly important for successful in-vitro fertilization (IVF) cycles. With this study we have tried to determine any differences in immunohistochemical staining for CD56 and CD98 within the implantation phase endometrium of patients with recurrent implantation failure and of a control group that even-tually had a successful IVF cycle. Material and Method: This study was ret-rospectively performed on a total of 36 patients selected out of a database of 6260 patients who received their IVF cycles from 2004 to 2010. Patients were defined as implantation failure if they did not have a positive result for b-HCG testing following at least 3 IVF cycles with a total of at least 8 em-bryo transfers. The control group was formed with patients who had success (positive b-HCG testing) on their first IVF treatment. Results: Comparison of means for CD 56 staining percentages, CD 98 staining percentages, CD 98 staining power, and CD 98 staining score showed significant difference between the control group and the study group (p<.001). The endometrium of patients without recurrent implantation failure is significantly more stainable by CD 98 than that of patients with recurrent implantation failure. Discus-sion: We suggest that CD 56 and CD 98 staining for endometrium tissue can be a part of diagnostic testing for patients who are candidates for IVF treatments. We need further studies to determine the correlation between the overall chance for pregnancy and these types of immunohistochemical staining for patients receiving IVF treatment.

Keywords: CD 56; CD 98; In-Vitro Fertilization; Implantation Failure

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Introduction

Implantation is one of the most important parts of the whole process that lies beneath the miraculous event of pregnancy. Implantation is a limiting factor for both natural (unassisted) female reproduction and in-vitro fertilization (IVF) cycles. Despite major advances in assisted reproductive techniques, clinical pregnancy rates remain around 31% with fresh embryo transfer and around 41% with oocyte donations [1].

CD 98 is a type II glycoprotein usually found in ovarian, testicular, and placental tissues. It also can be found in liver, renal, and splenic tissues, participating in the process of amino-acid and hormonal transport [2-3]. CD 98 expression, which is specific to the implantation phase for human reproduction, has a very important role. It was determined that rats with suppressed CD 98 expression with lent viruses showed a diminished blastocyst adhesion. Conversely, increasing CD 98 expression by 2-10 times showed an implantation rate up to 100% [4].

CD 56 positive cells, known as natural killer cells, have been studied extensively to understand their role in both implantation failure and recurrent miscarriages. The principal finding has been elevated numbers of CD 56 + cells in the endometrium of women with implantation failure and recurrent miscarriage compared to control groups [5-7].

As we know, many factors play a role in implantation failure. With this study we have tried to identify any differences of immunohistochemical staining for CD56 and CD98 within the implantation phase in the endometrium of patients with recurrent implantation failure and in the control group who eventually had a successful IVF cycle.

Material and Method

This study was performed retrospectively on a total of 36 patients selected out of a database of 6260 patients who had their IVF cycles between 2004 and 2010. 936 patients were categorized as implantation failure, which was defined as failure to have a positive result for b-HCG testing following at least 3 IVF cycles with a total of at least 8 embryo transfers. Note that the IVF treatments of the patients selected for this study occurred before the national law limiting the number of embryos that may be transferred under different circumstances went into effect.

Patient Selection

586 patients who did not have a hysteroscopy before their IVF cycle and 118 patients whose hysteroscopy revealed polyps, septum, or adhesions were excluded from the study. 41 patients with poor ovarian reserve, defined as the need for r-FSH more than 3000 units and/or patients with metaphase 2-oocyte count less than 6 in an IVF cycle, were also excluded. Additionally, 78 patients who were more than 37 years old were excluded due to advanced maternal age. Of the remaining 113 patients, 67 had a specimen taken from the endometrium but only 21 had 5-10 days post ovulatory characteristics defined by Noyes et al [8].

In selecting the control group, we retrospectively screened 3738 patients who were not successful in having spontaneous pregnancy but had pregnancy over 12 weeks on IVF cycle following an endometrial biopsy collected during the luteal phase. Of these, 2789 patients were excluded because they did not have a hysteroscopy and 403 patients were excluded because of pathological findings in the hysteroscopy. 237 patients were excluded because of advanced maternal age and 117 were excluded for poor ovarian reserve. 15 out of the 192 remaining patients had specimens appropriate for the implantation phase (post ovulatory 5-10 days).

Immunohistochemical Staining and Evaluation

5 μm samples were taken to Poly-L-Lysine covered microscopic slides from paraffin embedded original tissues. Following deparaffinization, ‘’Autostainer Link 48 (DAKO)’’ and as antibody (7.0ml, Ready to use, Code IR 628, Clone 123C3, DAKO, USA) used for staining procedure for CD 56.

Image 1 shows sample images for CD 56 staining.

CD 98 staining was done with the biotin immuneperoxidase method using N1C2 (1/200 dilution, catalogue GTX 104108, Gene Text, Inc.) and incubated at +4°C overnight.

Image 2 shows sample images for CD 98 staining.

CD 56 antibody staining was scored from 0 to 4 according to the percentages of red-brown staining cell diffusiveness from 0%, 1%-25%, 26%-50%, 51%-75%, and 76%-100%, respectively.

CD 98 antibody staining was evaluated for its staining power and diffusiveness. Diffusiveness was scored as it was for CD 56 and the results were multiplied by a power score ranging from 1-3 as weak, moderate, or strong staining. The minimum score for CD 98 was 0 (no staining) and the maximum score was 12 (more than 75% and strong membranous staining). Stromal staining for CD 98 was recorded separately as positive or negative.

Independent samples T test, one-way ANOVA, and chi-square statistical methods were used as appropriate. IBM SPSS 17.0 was used for statistical analysis and a p value less than 0.05 was accepted as statistically significant.

Ethics and Institutional Review Board Approval

Baskent University IRB approved this study; the approval number is KA11/120.

Results

The study group had a mean age of 31.9 ± 2.7, whereas the control group had a mean age of 28.5 ± 3.5 (p=.002). Table 1 compares other IVF cycle parameters.

Comparison of means for CD 56 staining percentages, CD 98 staining percentages, CD 98 staining power, and CD 98 staining scores showed significant difference between groups (p<.001) (Table 2).

There were significant differences between subgroup results of CD 56 staining percentages, CD 98 staining power, and CD 98 staining percentages. No significant difference was observed in CD 98 stromal staining (Table 3). Using a scoring system that included both CD 98 staining percentage and CD 98 staining power (percentage value from 1-4 multiplied by power from 1-3), there was a significant difference between groups (p<0.05).

Discussion

Knowing the limitations of retrospective studies, we excluded possibly important factors for implantation such as poor ovarian reserve, patients with anatomical uterine defects and pathological findings, and advanced maternal age in order to improve the study quality. Also, the study and control groups had quite similar IVF cycle parameters, which contributed to comparability of groups.

There are authors who propose that a similar pathogenesis lies beneath recurrent implantation failure and recurrent pregnancy losses. That is the reason given by most of the leading articles, mostly done by Quenby et al., for recurrent implantation failure was done with CD 56 [7,9]. While Quenby et al. propose that implantation failure relates to oxidative stress on endometrial tissue originating from endometrial edema formation, which is found with increased number of uNK cells and endometrial blood vessels [9]. On the other hand, Matteo et al. found no difference in CD 56 + cells between the recurrent implantation failure group and the control group in a study performed with the flow cytometry technique which also includes CD 56 + cells from blood vessels [10]. Our study showed that the presence of CD 56 + cells in endometrial stromal tissue can be a destructive element for embryo implantation.

Although there is not sufficient published data to draw conclusions about human endometrial tissue, animal studies showed the importance of CD 98 expressing cells for implantation and reproduction. We found that a decreased number of CD 98 expressing cells, resulting in decreased amino-acid and hormonal transportation in endometrial tissue, can be one of the factors for implantation failure.

We suggest that CD 56 and CD 98 staining for endometrium tissue can be a part of diagnostic testing for patients who are candidates for IVF treatments. We need further studies to determine the correlation between the overall chance for pregnancy and these types of immunohistochemical staining for patients receiving IVF treatment.

Competing interests

The authors declare that they have no competing interests.

References

1. Nyboe Andersen A, Goossens V, Bhattacharya S, Ferraretti AP, Kupka MS, de Mouzon J et al. Assisted reproductive technology and intrauterine inseminations in Europe, 2005: results generated from European registers by ESHRE: ESHRE. The European IVF Monitoring Programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod 2009:24(6):1267-87.

2. Chillaron J, Roca R, Valencia A, Zorzano A, Palavin M. Heteromeric amino acid transporters: biochemistry, genetics, and physiology. Am J Physiol Renal Physiol 2001;281(6):995-1018.

3. Fenczik CA, Sethi T, Ramos JW, Hughes PE, Ginsberg MH. Complementation of dominant suppression implicates CD98 in integrin activation. Nature 1997:390(6655):81-5.

4. Dominguez, F, Simon C, Quinonero A, Ramirez MA, Gonzalez-Munoz E, Burghardt H et al. Human endometrial CD98 is essential for blastocyst adhesion. PLoS One 2010;5(10):13380.

5. Ledee-Bataille N, Bonnet-Chea K, Hosny G, Dubanchet S, Frydman R, Chaouat G. Role of the endometrial tripod interleukin-18, -15, and -12 in inadequate uterine receptivity in patients with a history of repeated in vitro fertilization-embryo transfer failure. Fertil Steril 2005:83(3):598-605.

6. Tuckerman E, Laird SM, Prakash A, Li TC. Prognostic value of the measurement of uterine natural killer cells in the endometrium of women with recurrent miscarriage. Hum Reprod 2007:22(8):2208-13.

7. Quenby S, Bates M, Doig T, Brewster J, Lewis-Jones DI, Johnson PM, et al. Pre-implantation endometrial leukocytes in women with recurrent miscarriage. Hum Reprod 1999:14(9):2386-91.

8. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsi. Fertil Steril 1950:1:3-25.

9. Quenby S, Nik H, Innes B, Lash G, Turner M, Drury J, et al. Uterine natural killer cells and angiogenesis in recurrent reproductive failure. Hum Reprod 2009:24(1):45-54.

10. Matteo, MG, Greco P, Rosenberg P, Mestice A, Baldini D, Falagario T, et al. Normal percentage of CD56bright natural killer cells in young patients with a history of repeated unexplained implantation failure after in vitro fertilization cycles. Fertil Steril 2007:88(4):990-3.

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Tevfik Berk Bildaci, Bulent Haydardedeoglu, Burcu Kisa Karakaya , Filiz Aka Bolat, Hulusi Bulent Zeyneloglu. The importance of CD56 and CD98 levels in patients with recurrent implantation failure. J Clin Anal Med. 2017;8(3):216-218

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Evaluation of the Association Between the Neutrophil to Lymphocyte Ratio and Mortality in the Patients Followed up with the Diagnosis of Sepsis

Pınar Korkmaz 1, Sertaş Erarslan 2, Onur Toka 3

1 Department of Clinical Microbiology and Infectious Diseases, Dumlupınar University, Kütahya, 2 Department of Internal Medicine, Dumlupınar University EvliyaÇelebi Training Hospital, Kütahya, 3 Department of Statistics, Hacettepe University, Ankara, Turkey

DOI: 10.4328/JCAM.4816 Received: 28.09.2016 Accepted: 17.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 211-5

Corresponding Author: Pınar Korkmaz, Department of Clinical Microbiology and Infectious Diseases, Dumlupınar University, 43020, Kütahya, Turkey. T.&F.: +90 2742316660, +90 2742316673 E-Mail: drpinarkor@gmail.com.

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Aim: Neutrophil-to-lymphocyte ratio (NLR) is an easily measurable biomarker from complete blood count. NLR has been investigated previously as a po-tential predictor of survival rates in various types of cancers. However, there is a limited number of studies performed regarding the usefulness of NLR for predicting mortality in patients with sepsis. Our aim in this study was to evaluate the association between NLR and mortality of the patients with sepsis in an intensive care unit (ICU). Material and Method: We retrospec-tively assessed the patients who were followed up with the diagnosis of sep-sis in the internal medicine ICU of our hospital between September 1, 2014 and December 31, 2015. Demographic, clinical, and laboratory data were obtained from the patients’ medical records. Results: A total of 104 patients were included in the study. ICU mortality was 57.7% in patients with sepsis. When survivors and non-survivors in theICU were assessed regarding neu-trophil counts, lymphocyte counts, and NLR, no statistically significant dif-ference was determined (p>0.05). While the mortality rate in ICU increased with increasing quartile of NLR, no significant difference was determined in ICU mortality (all p>0.05). Also there was no relationship between NLR and hospital mortality and 6-months mortality in patients with sepsis (p>0.05).Discussion: No significant correlation was found between NLR and mortality rate in the ICU and long-term mortality in patients with sepsis.

Keywords: Neutrophil-To-Lymphocyte Ratio; Sepsis; Mortality

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Introduction

Sepsis, a major public health concern, is described as a syndrome of physiological, pathological, and biochemical abnormalities induced by infection. Although the true incidence is unknown, sepsis is among the leading causes of mortality and critical illness worldwide [1]. Despite modern ICU treatments and antibiotic treatments, the mortality associated with sepsis remains high. The pathophysiology of sepsis is not clearly understood [2]. Many biomarkers, including acute phase proteins and cytokines, are used both in clinical practice and in research to determine the underlying inflammatory conditions in the ICUs [3].

In sepsis, polymorphonuclear neutrophils mediate major antimicrobial activities on the one hand and contribute to the development of multiple organ failure on the other hand [4]. The physiological immune response of circulating white blood cells to a wide range of stressful events such as tissue injury, severe trauma, major surgery, burns, and sepsis syndrome is characterized by elevation of neutrophils and decline in lymphocyte counts [5]. Zahorec [5] showed that changes occur in neutrophil and lymphocyte counts as a response of the immune system to surgical stress, systemic inflammation, or sepsis, and, there was a correlation between the degree of neutrophilia and lymphocytopenia and the severity of the disease.

Neutrophil-to-lymphocyte ratio (NLR) is an easily measurable biomarker from complete blood count; Zahorec has stated that it can be used in clinical practice in the ICU [5]. NLR has been investigated previously as a potential predictor of survival rates in various types of cancers [5-9]. However, there are not many studies regarding the usefulness of NLR in predicting mortality in patients with sepsis [3,10]. Our aim in this study was to evaluate the association between NLR and mortality of the patients with sepsis in the ICU.

Material and Method

We retrospectively assessed the patients followed up with the diagnosis of sepsis in the internal medicine ICU of our hospital between September 1, 2014 and December 31, 2015. The study was approved by the local ethics committee. Patients aged ≥ 18 years admitted to the ICU with a diagnosis of sepsis were included in the study. Assessment of sepsis, severe sepsis, and septic shock were performed according to American College of Chest Physicians/Society of Critical Care Medicine Conference definitions [11].

Patients aged ≤ 18 years, pregnant women, patients with known hematological disease, patients with diseases causing trauma, intoxication, and immunosuppressive disease, receiving immunosuppressive therapy, previous chemotherapy (within the last 6 months) were excluded from the study. Demographic, clinical, and laboratory data were obtained from the patients’ medical records. Age, gender, comorbid diseases (Charlson comorbidity index score) [12], Simplified Acute Physiology Score II [13], and Glasgow coma score values measured during admission to the ICU were obtained from the patients’ medical records. Circulating neutrophil and lymphocyte counts and NLR were obtained from the values measured at the time of admission. The value range considered to be normal for leukocyte were 5.2-12.4 x103µL for neutrophil and 0.9-5.2 x103µL for lymphocyte.

Our primary aim was to evaluate the association between NLR and ICU mortality and secondary aim was to evaluate the association between NLR and the hospital mortality and 6-month mortality in patients with sepsis. Mortality data were obtained from the patients’ medical records.

The SPSS 20 program was used for statistical analysis. Mean and standard deviation and additionally median and minimum-maximum values of quantitative data of variables were given. Frequency and percentage values were given for qualitative observations. Interclass differences of qualitative observations were interpreted using Chi-square analysis. The intergroup differences of quantitative data were interpreted using Mann Whitney U test during dual comparisons and Kruskal Wallis test during multiple comparisons. The quartile values were obtained for NLR values and the difference was investigated in the classes created according to the quartile values. A multiple logistic regression model was obtained to investigate the mortality based on NLR classification and the odds ratio was interpreted. Statistical significance was evaluated at a confidence level of 95%.

Results

A total of 104 patients were included in the study. Fifty-two of 104 patients (50%) were males and their mean age was 75.12±12.25 years (min 18-max 92). Baseline demographic data of the patients are shown in Table 1. While vasopressor support was performed in 88 patients (84.6%) during follow-up in ICU, mechanical ventilation support was provided in 44 patients (42.3%) during follow-up in ICU. Again, hemodialysis was performed in 25 patients (24%). Total parenteral nutrition was used in 98 patients (94.2%). Bacteria could be identified bacteriologically in 44 patients (42.3%). Gram-positive cocci, gram-negative bacilli, and yeasts were identified in 31.8%, 68.2%, and 2.3% of the patients, respectively.

ICU mortality was 57.7% in patients with sepsis. When survivors and non-survivors in the ICU were assessed regarding neutrophil counts, lymphocyte counts, and NLR, no statistically significant difference was determined (p>0.05). When survivors and non-survivors were evaluated, red cell distribution width (RDW), C reactive protein (CRP), total bilirubin, and INR values were found to be statistically significant between the two groups (p<0.05) (Table 2). No significant difference was determined between the two groups regarding platelet counts, hemoglobin, mean corpuscular volume, mean platelet volume, and albumin/globulin ratio (p>0.05).

When NLR was divided into quartiles, no significant difference was determined between quartiles regarding age, gender, SAPS score, and comorbid diseases (Table 3). While mortality rate in the ICU increased with increasing quartile of NLR, no significant difference was determined in ICU mortality (first quartile=reference value; second quartile=0.368 (95% Cl, 0.116 to 1.173); third quartile=0.502 (95% Cl, 0.157 to 1.61); fourth quartile=0.368 (95% Cl, 0.116 to 1.173); all p>0.05).

The hospital mortality rate was 66.3%. No significant difference was determined between NLR and hospital mortality (p>0.05). When NLR was divided into quartiles, no significant difference was determined in hospital mortality rate (first quartile=reference value; second quartile=0.773 (95% Cl, 0.274 to 2.622); third quartile=0.773 (95% Cl, 0.274 to 2.622); fourth quartile =0.361 (95% Cl, 0.522 to 5.969); all p>0.05).

The six-month mortality rate was 70.2%. No significant difference was determined between NLR and mortality (p>0.05). When NLR was divided into the quartiles, no significant difference was determined in 6-months mortality (first quartile=reference value; second quartile 0.515 (95% Cl, 0.77 to 3.437); third quartile=0.288 (95% Cl, 0.52 to 1.598); fourth quartile =0.227 (95% Cl, 0.40 to 1.282); all p>0.05).

Discussion

White blood cell count is a commonly used parameter for the diagnosis and follow-up of the diseases encountered in daily practice. Jilma et al. [14] determined that circulating neutrophil counts increased and circulating lymphocyte counts decreased as a general immune response to endotoxemia. Four to six hours after endotoxemia, circulating neutrophil counts increased by 300% and circulating lymphocyte counts decreased by 85% [14]. Decrease in lymphocyte counts results from increased catecholamine, prolactin, and cortisol levels, migration of lymphocytes toward the reticuloendothelial system, and apoptosis [15,16].

The hypothesis of an association between NLR and neutrophilia and lymphocytopenia developing in systemic inflammatory and stress conditions and the severity of the clinical course was demonstrated for the first time by Zahorec [5]. In this study, Zahorec defined a correlation between the severity of clinical course and the severity of neutrophilia and lymphocytopenia in 90 oncological patients who were followed up with a diagnosis of stress, systemic inflammation, and sepsis. Consequently, he stated that the ratio of neutrophil and lymphocyte counts was an easily measurable parameter for determining prognosis during ICU follow-up of the patient and it could be used routinely in daily clinical practice.

The authors of another study stated that NLR measured at the time of admission to the hospital due to acute decompensated heart failure was associated with 30-day mortality and it could be used for risk classification [17]. Again, Suliman et al. [18] found that increasing quartile of NLR was associated with increased mortality and Azab et al. [19] found that NLR was associated with admission to ICU and prolonged hospitalization in the patients with acute pancreatitis.

Following from these research studies, in our study we investigated the association between NLR measured at the time of admission to ICU of the patients followed up with a diagnosis of sepsis in the ICU and the mortality rate of patients with sepsis; no correlation was found. Similarly, in the study performed by Salciccioli et al. [3], no correlation was determined between NLR and 28-day mortality in patients with sepsis. Our patients followed up in the ICU were divided into quartiles with respect to NLR (<8.21, 8.21-16.7, 16.7-27.75, >27.75) and while an increase was observed with increasing quartile of NLR, no statistical significance was determined. Similarly, the patients in the study performed by Salciccioli et al. [3] were also divided into quartiles regarding NLR, but no correlation was found between the quartiles with respect to mortality in patients with sepsis.

Contrary to this, in the study performed by Riche et al., NLR measured at the time of admission to ICU of the patients followed up with a diagnosis of septic shock was found to be significantly lower in the patients who died before the fifth day of admission [10]. However, one of the limitations of this study is that long-term mortality (14 day or 28 day) was not investigated. Again, reduced level of circulating neutrophils determined in the study performed by Bermejo-Martin et al. [4]. is associated with mortality. The aforementioned study proceeded from the hypothesis that low neutrophil count might cause difficulty in developing sufficient initial immunity. In sepsis, neutrophil adhesion to vascular endothelium and leukocyte aggregates occur and, as a result, circulating neutrophil count may decrease. In patients with multiple organ failure due to sepsis, localization of neutrophils ranging from an intense infiltration of the lung to sequestration and aggregation in renal blood vessels were seen [20]. Neutrophils in the circulation can exist in varying functional states and consequently a cross-sectional assessment relating to the neutrophil or lymphocyte counts may be inadequate to understand the effect of these parameters on diseases such as sepsis [3].

In our study, when NLR and 6-month mortality rate was evaluated, no significant correlation was determined. Again when NLR was divided into the quartiles, no significant correlation was found between NLR and 6-month mortality. In the study performed by Salciccioli et al. [3], a correlation was found between NLR and 1-year mortality in the critically ill patients followed up in the ICU, but a separate classification for sepsis patients was performed only for 28-day mortality. Although NLR, hospital mortality, and 6-month mortality were defined to be an independent factor in the study performed by Akilli et al. [21]. a separate subgroup analysis was not performed for patients with sepsis, who comprised 9.4% of the cases in this study. In both of the studies, the correlation between long-term mortality and NLR was defined for critically ill patients and not for patients with sepsis. In our study, the correlation between long-term mortality and NLR in patients with sepsis was defined for the first time.

In conclusion, no significant correlation was found between NLR and mortality rate in the ICU and long-term mortality in patients with sepsis. When the pathophysiology of sepsis is considered to be due to varying functional states of neutrophils or lymphocytes, we think that the neutrophil or lymphocyte count alone may not be adequate to understand the effects of these blood cells in sepsis. Since there are not many studies performed on this subject, further studies are required to investigate the correlation between NLR and sepsis.

Competing interests

The authors declare that they have no competing interests.

References

1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315(8): 801-10.

2. Muller Kobold AC, Tulleken JE, Zijlstra JG, Sluiter W, Hermans J, Kallenberg CG, et al. Leukocyte activation in sepsis; correlations with disease state and mortality. Intensive Care Med 2000;26(7):883-92.

3. Salciccioli JD, Marshall DC, Pimentel MA, Santos MD, Pollard T, Celi LA, et al. The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study. Crit Care 2015;19:13.

4. Bermejo-Martín JF, Tamayo E, Ruiz G, Andaluz-Ojeda D, Herrán-Monge R, Muriel-Bombín A et al. Circulating neutrophil counts and mortality in septic shock. Crit Care 2014;18(1):407.

5. Zahorec R. Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001;102(1):5-14.

6. Sarraf KM, Belcher E, Raevsky E, Nicholson AG, Goldstraw P, Lim E. Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg 2009;137(2):425-8.

7. Cho H, Hur HW, Kim SW, Kim SH, Kim JH, Kim YT, et al. Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother 2009;58(1):15-23.

8. Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, Terjanian T, et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol 2012;19(1):217-4.

9. Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 2005;91(3):181-4.

10. Riché F, Gayat E, Barthélémy R, Le Dorze M, Matéo J, Payen D. Reversal of neutrophil-to-lymphocyte count ratio in early versus late death from septic shock. Crit Care 2015;19:439.

11. Levy MM, Artigas A, Phillips GS, Rhodes A, Beale R, Osborn T, et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012;12(12): 919-24.

12. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40(5):373-83.

13. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36(5):309-32.

14. Jilma B, Blann A, Pernerstorfer T, Stohlawetz P, Stohlawetz P, Eichler HG, Vondrovec B, et al. Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin. Am J Respir Crit Care Med 1999;159(3):857-63.

15. Dionigi R, Dominioni L, Benevento A, Giudice G, Cuffari S, Bordone N, et al. Effects of surgical trauma of laparoscopic vs. open cholecystectomy. Hepatogastroenterology 1994;41(5):471-6.

16. Ayala A, Herdon CD, Lehman DL, Ayala CA, Chaudry IH. Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators. Blood 1996;87(10):4261-75.

17. Uthamalingam S, Patvardhan EA, Subramanian S, Ahmed W, Martin W, Daley M, et al. Utility of the neutrophil to lymphocyte ratio in predicting long-term outcomes in acute decompensated heart failure. Am J Cardiol 2011;107(3):433-8.

18. Muhmmed Suliman MA, Bahnacy Juma AA, Ali Almadhani AA, Pathare AV, Alkindi SS, et al. Predictive value of neutrophil to lymphocyte ratio in outcomes of patients with acute coronary syndrome. Arch Med Res 2010;41(8):618-22.

19. Azab B, Jaglall N, Atallah JP, Lamet A, Raja-Surya V, Farah B, et al. Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis. Pancreatology 2011;11(4): 445-52.

20. Brown KA, Brain SD, Pearson JD, Edgeworth JD, Lewis SM, Treacher DF. Neutrophils in development of multiple organ failure in sepsis. Lancet 2006;368(9530):157-69.

21. Akilli NB, Yortanli M, Mutlu H, Gunaydin YK, Koylu R, Akca HS, et al. Prognostic importance of neutrophil-lymphocyte ratio in critically ill patients: short- and long-term outcomes. Am J Emerg Med 2014;32(12):1476-80.

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Pinar Korkmaz, Sertas Erarslan, Onur Toka. Evaluation of the association between the neutrophil to lymphocyte ratio and mortality in the patients followed up with the diagnosis of sepsis. J Clin Anal Med. 2017;8(3):211-215

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The Prognostic Value of Hematological Parameters in Patients with Pulmonary Embolism

Şule Taş Gülen 1, Onur Yazıcı 1, İmran Kurt Ömürlü 2

1 Chest Disease Department, 2 Biostatistics Department, Adnan Menderes University, Aydın, Turkey

DOI: 10.4328/JCAM.4800 Received: 05.09.2016 Accepted: 12.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 207-10

Corresponding Author: Şule Taş Gülen, Department of Chest Diseases, Adnan Menderes University School of Medicine, Aydin, Turkey. GSM: +90 5056919099 E-Mail: dr_suletas@yahoo.com.tr

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Aim: By analyzing the hemogram values of patients with PE during and fol-lowing the treatment, the relationships of hematological parameters with response to treatment and prognosis of the disease were investigated. Ma-terial and Method: Forty-eight patients, who were hospitalized and treated with the diagnosis of PTE in the Pulmonary Diseases Clinic of our hospital between December 2014 and December 2015, were included in the study. The patients’ charts, located in the digital archive system, were analyzed ret-rospectively and demographic characteristics, clinical evaluations, and their hemogram results during and following the treatment were retrospectively evaluated. Among the hemogram parameters, the values of WBC,NLR and MPV were statistically analyzed. For statistical analysis, SPSS 17.0 software and the Kolmogorov-Smirnov test, Mann-Whitney U test and independent sample t test were used. Results: The average age of the 48 patients included in our study was 62.68, and 27 (56.2%) of them were males. The average duration of hospitalization was 9.2 days. The median values of NLR, MPV, and WBC at the time of diagnosis were 4.82 (3.04-9.32), 10.2 (7.40-11.8), and 9215 (6507.5-13255), respectively. Following treatment, these values were 2.60 (1.82-3.74), 9.3 (7-12.9), and 7265 (6125-8872.5), respectively. It was determined that the NLR, MPV, and WBC values were statistically significant-ly reduced following treatment (p <0,001). Discussion: Our study suggested that NLR,MPV and WBC can be used as prognostic inflammatory indicators for diagnosing and treating pulmonary embolism.

Keywords: Pulmonary Embolism; White Blood Cell Count; Neutrophil Lymphocyte Ratio; Mean Platelet Volume

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Introduction

Pulmonary embolism (PE) is a preventable, important clinical problem with high morbidity and mortality [1]. Simple tests can be used to determine prognosis and to evaluate patients’ responses to treatment. Hemogram parameters such as white blood cell count (WBC), platelet count, neutrophil lymphocyte ratio (NLR), and mean platelet volume (MPV) have been recently investigated as inflammatory indicators in numerous disorders [2,3]. In recently conducted studies on patients with PE, the elevation of NLR has been found to be correlated with early mortality [4]. Studies that examine MPV have determined that MPV was increased, platelet count was reduced in pulmonary embolism and these values were associated with the diameter of the right ventricle [5,6 ].

As far as we know there is no study in the medical literature that investigates the effect of PE treatment on hematological parameters. In this study, by analyzing the hemogram values of patients with PE during and following treatment, the relationships of hematological parameters with response to treatment and prognosis of the disease were investigated.

Material and Method

Forty-eight patients, who were hospitalized and treated with the diagnosis of PE in the Pulmonary Diseases Clinic of our hospital between December 2014 and December 2015 were enrolled in the study. Patients who did not have any clinical signs of infection (such as fever, cough, or sputum) or high laboratory parameters (such as C-reactive protein and procalcitonin) and whose patient charts were available for investigation, were included in the study. Following approval of the local ethics committee, patients’ charts were retrospectively analyzed via the digital archive system. Their demographic data (age, gender, medical history), duration of hospital stay, comorbidities, chronic treatments administered, and the units in which they had been followed-up for acute phase and maintenance embolism treatments (clinic/intensive care unit) were recorded. The patients were classified as low mortality (stable hemodynamic status and absence of right ventricular dysfunction); intermediate mortality risk group (stable hemodynamic status and presence of right ventricular dysfunction in radiological or laboratory investigations); and high mortality (unstable hemodynamic status), according to the Turkish Thoracic Society 2015 Consensus Report on Diagnosis and Treatment of Pulmonary Thromboembolism. Patients with low mortality risk were named as Group 1, and patients having intermediate-low, intermediate-high, and high risks were joined into one group and named as Group 2.

The hemogram results of patients who had no identified infections, obtained at the time of diagnosis and as part of discharge from the hospital were retrospectively evaluated. The routine hemogram parameters, white blood cell count (WBC), neutrophil and lymphocyte counts were recorded together with the mean platelet volume (MPV). By dividing the neutrophil count by the lymphocyte count, the neutrophil lymphocyte ratio, which is one of the nonselective inflammatory markers, was calculated.

Statistical analysis

For statistical analysis, SPSS software (Statistical Package for Social Sciences) version 17.0 was used. The Kolmogorov-Smirnov test was used to assess the normality of numeric variables. For the numeric variables that were normally distributed, comparison between two groups was made by independent sample t test and descriptive statistics are presented as mean±standard deviation. For the numeric variables that were not normally distributed, comparison between the two groups was made by the Mann–Whitney U test and descriptive statistics are presented as median (25-75 percentiles). The p values below 0.05 were considered statistically significant.

Results

The average age of the 48 patients enrolled in the study was 62.68 ± 15.88 (30-84), of whom 27 (56.2%) patients were male. The average duration of hospitalization was 9.2 ± 4.64 (1-22) days. When frequencies of risk factors and comorbidities were analyzed, 35 (62.6%) patients were determined to have at least one pathology (Table 1).

When grouped in terms of early mortality, 30 patients were in the low-risk group (Group 1), 13 patients were in the intermediate-risk group, and five patients were in the high-risk group for embolism (Group 2) (Table 2). No statistically significant differences were found between the two groups in terms of NLR, MPV, and WBC values at the time of diagnosis (Table 3).

The median values of NLR, MPV, and WBC were 4.82 (3.04-9.32), 10.2 (7.40-11.8) , and 9215 (6507.5-13255), respectively, at the time of diagnosis. Since one patient died at the second hour of treatment, the results of 47 patients were available following treatment. Post-treatment median values of NLR, MPV, and WBC were 2.60 (1.82-3.74), 9.3 (7-12.9), and 7265 (6125-8872.5), respectively; these were statistically significantly lower when compared to the results at the time of diagnosis (Table 4).

Discussion

Pulmonary embolism is a disorder with high mortality when left untreated. Establishment of the prognosis and the choice of treatment are made according to the classification based on early mortality risk 1. Until now, clinical scorings such as Geneva scoring, and pulmonary embolism severity index or cardiac markers such as troponin and natriuretic peptide have been used to determine prognosis [7-9 ].

Although the role of systemic inflammation in PE has been known, its association with prognosis has not been clearly identified. In conducted studies, leucocytes were shown to participate in venous thrombosis by creating endothelial injury [9]. Additionally, NLR is considered to be a simple indicator of subclinical inflammation and is used for prediction of mortality in diseases such as coronary artery disease and cancer [10]. Our study investigated not only clinical scoring systems but also the relationships of laboratory tests, such as NLR, MPV, and WBC, simply determined by complete blood count, with the PE prognosis. When classification was made according to early mortality, no significant differences were found between the low-mortality PE group and the intermediate-high mortality PE group at the time of diagnosis, in terms of NLR, MPV, and WBC. The study conducted by Ermiş et al. on 209 patients with acute pulmonary embolism (APE) and 162 healthy controls, investigated whether MPV was a prognosticindicator in high-risk pulmonary embolism; MPV was found to be unrelated to the severity of embolism (massive, submassive, nonmassive) [11]. Similarly, in our study, a relationship between severity of embolism and MPV was not found. In the study conducted by Kostrubiec et al. on 192 APE patients and 100 healthy controls, no difference was found between the two groups in terms of MPV value. However, when the patients were classified according to low, intermediate and high mortality risks, the MPV values were significantly higher in the intermediate and high-risk groups when compared to the low-risk group. In addition, there was no significant difference between the MPV values of the intermediate and high-risk group and those of healthy controls [12]. Similar to the study by Ermiş et al., they determined that MPV value was higher in patients who died when compared to patients who survived. In both studies, this situation was explained by the possible relationship of MPV with the right ventricular dysfunction and myocardial injury [11,12]. Varol et al., in their study on 107 APE that patients and 70 healthy controls, showed that MPV was higher in APE and this was correlated with the diameter of the right ventricle [13]. We had no healthy control group in our study and therefore, comparisons with a control group were not possible. However, when patients were grouped according to the mortality risk, no significant differences were found between groups in terms of NLR, MPV, and WBC. This situation might be explained by the small number of patients in our study and the fact that the groups were nonhomogeneous.

A study by Kayrak et al. on 359 APE patients, investigated whether NLR was a prognostic indicator for early mortality in APE. In the group that died at the end of the first month of treatment, NLR and WBC were found to be significantly higher when compared to patients who survived. For this reason, it was emphasized that NLR and WBC were simple and cheap tests that predict early mortality (4). In another study conducted by Yeşildağ et al., the relationships of computerized tomography obstruction score (Qanadli obstruction score) with NLR and MPV were investigated in 95 patients, who were diagnosed with PE by computerized tomography pulmonary angiography (CTPA). In this study, when right ventricle / left ventricle short axis ratios and NLR were compared with survival rate and mortality, mortality was significantly related to NLR and MPV [14]. In our study, radiological findings were not evaluated. Since mortality had occurred in only one patient at the second hour of treatment, evaluation was not possible in terms of mortality.

Currently, the issues of whether NLR, MPV, and WBC are increased in APE and are indicators of mortality is being investigated; however, there have not been sufficient studies evaluating post-treatment response. In the study conducted by Eren et al. on 209 patients who received treatment for acute coronary syndrome, poor cardiovascular results of NLR and its characteristics for mortality prediction were investigated. The cut-off value of NLR was taken as 4.7 in terms of mortality and the patients were grouped as low (<3.0), intermediate (3.0-4.7) and high (>4.7). Their in-admission, in-hospital, 6th month, and follow-up NLR values were compared to the risk scores named GRACE (Global Registry of Acute Coronary Events) and TIMI (Thrombolysis in Myocardial Infarction); no differences were found between groups in cardiac-related hospitalizations [15]. In our study, it was determined that following treatment, the values of NLR, MPV, and WBC were significantly reduced when compared to the pre-treatment values.

The Limitations of the Study

The retrospective characteristics of our study and the relatively small number of patients when group analysis was performed constituted the limitations of the study. Also, we didn’t include healthy control groups in the study; instead, we compared the before-treatment and after-treatment values of NLR, MPV, and WBC in patients with an indication of pulmonary embolism.

Conclusion

The values of NLR, MPV, and WBC were found to be significantly reduced following treatment. We suggest that these parameters are simple, cheap, and easily accessible indicators for demonstrating the response to the treatment of the disease. Since the number of patients is small in our study, more comprehensive, prospective studies are required in order to support our suggestion.

Competing interests

The authors declare that they have no competing interests.

References

1. Arseven O, Okumus NG, Ongen G, Müsellim B. Turkish Thoracic Society Consensus Report on Diagnosis and Treatment of Pulmonary Thromboembolism in 2015. Istanbul, 2015.

2. Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Review of Cardiovascular Therapy 2013;11:55-9.

3. Celik A, Ozcan IT, Gündes A, Topuz M, Pektas I, Yesil E, et al. Usefulness of admission hematologic parameters as diagnostic tools in acute pulmonary embolism. Kaohsiung Journal of Medical Sciences 2015;31:145-9.

4. Kayrak M, Erdoğan HI, Solak Y, Akilli H, Gül EE , Yildirim O, et al. Prognostic Value of Neutrophil to Lymphocyte Ratio in Patients with Acute Pulmonary Embolism: A Restrospective Study. Heart Lung Circ 2014;23:56-62.

5. Varol E, Icli A, Uysal BA, Ozaydin M. Platelet indices in patients with acute pulmonary embolism. Scand J Clin Lab Invest 2011;71:163-7.

6. Talay F, Ocak T, Alcelik A, Erkuran K, Akkaya A, Duran A, et al. A New Diagnostic Marker For Acute Pulmonary Embolism In Emergency Department: Mean Platelet Volume. African Health Sciences 2014;14:94-9.

7. Aujesky D, Perrier A, Roy PM, Stone RA, Cornuz J, Meyer G, et al. Validation of a clini¬cal prognostic model to identify low-risk patients with pulmonary embolism. J Intern Med 2007;261:597-604.

8. Wicki J, Perrier A, Perneger TV, Bounameaux H, Junod AF. Predicting ad¬verse outcome in patients with acute pulmonary em¬bolism: a risk score. ThrombHaemost 2000;84:548-552.

9. Jo JY, Lee MY, Lee JV, Rho BH, Choi W. Leukocytes and systemic inflammatory response syndrome as prognostic factors in pulmonary embolism patients. BMC Pulm Med 2013;13:74-81.

10. AlkhouriN, Stiff GM, Campbell C, Lopez R, Tamimi TAR, Yerian L, et al. Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. Liver International 2012;32:297-302.

11. Ermis H, Yucel N, Gulbas G, Turkkan S, Aytemur ZA. Does the mean platelet volume have any importance in patients with acute pulmonary embolism? Wien Klin Wochenschr 2013;125:381-5.

12. Kostrubiec M, Labyk A, Pedowska-Wlosek J, Hrynkiewicz-Szymanska A, Pacho S, Jankowski K, et al. Mean platelet volume predicts early death in acute pulmonary embolism. Heart 2010;96:460-5.

13. Varol E, Icli A, Uysal BA, Ozaydin M. Platelet indices in patients with acute pulmonary embolism. Scandinavian Journal of Clinical and Laboratory Investigation 2011;71:163-7.

14. Yesildag M, Keskin S, Güler I, Keskin Z. Correlation of Computerized Tomography Angiographic Pulmonary Artery Obstruction Score with Hematologic Outcome and Mortality in Patients with Acute Pulmonary Embolism. TurkiyeKlinikleri J Med Sci 2013;33:952-7.

15. Eren M, Ozpelit E, Aytemiz F, Güngör H, Güneri S. Neutrophil to Lymphocyte Ratio on Admission: Is a Predictor of Cardiovascular Outcome in Patients with Acute Coronary Syndrome as it Predicts Mortality? Koşuyolu Heart Journal 2014;17:153-8.

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Sule Tas Gulen, Onur Yazici, Imran Kurt Omurlu. The prognostic value of hematological parameters in patients with pulmonary embolism. J Clin Anal Med. 2017;8(3):207-210

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Alterations of Thyroid Hormone Levels in Cadmium Exposure

Evren Akgöl 1, Engin Tutkun 2, Hinc Yilmaz 3, Fatma Meric Yilmaz 4, Meside Gunduzoz 3, Ceylan Demir Bal 4, Ali Unlu 5, Sedat Abusoglu 5

1 Deparatment of Biochemistry, Birecik State Hospital, Birecik, Sanliurfa, 2 Department of Public Health, Bozok University Faculty of Medicine, Yozgat, 3 Department Occupational Diseases Service, Occupational Diseases Hospital, Ankara, 4 Department of Biochemistry, Yildirim Beyazit University Faculty of Medicine, Ankara, 5 Department of Biochemistry, Selcuk University Faculty of Medicine, Konya, Turkey

DOI: 10.4328/JCAM.4802 Received: 07.09.2016 Accepted: 04.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 202-6

Corresponding Author: Evren Akgol, Department of Biochemistry, Birecik State Hospital, Urfa, Turkey. GSM: +905057656775 F.: +90 4146524775 E-Mail: akgolevren@yahoo.com

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Aim: Environmental chemicals and heavy metals may alter thyroid hormone levels via several mechanisms, including disruption of iodine (I) transport, thyroid peroxi¬dase, thyroid hormone-binding proteins, hepatic catabolism, deiodinases, and receptor binding. Our aim was to investigate the change in thyroid hormone levels in cadmium exposure. Material and Method: Painters, welders, miners, and smelters with an occupational exposure of more than 10 years, aged between 18-70 years, were divided into six groups according to whole blood cadmium levels (Group 1: 0-0.5 μg/L; Group 2: 0.5-1 μg/L; Group 3: 1-1.5 μg/L; Group 4: 1.5-2 μg/L; Group 5: 2-2.5 μg/L; Group 6: >2.5 μg/L).Results: There was a positive correlation between cadmium and serum free thyroxine and triiodothyronine levels. There was a negative correlation be-tween cadmium and serum alanine aminotransferase and vitamin B12 levels. Discussion: Cadmium exposure was found to lead to an increase in thyroid hormone levels.

Keywords: Cadmium Toxicity; Thyroid Functions; Thyroxine; Workers

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Introduction

From the physiological point of view, cadmium does not have a functional role in living organisms. It probably enters the cell via voltage-sensitive Ca+2 and Mg+2 channels of the plasma membrane. Due to its chemical similarity with zinc, it interferes with the physiological functions of zinc [1]. Cadmium (Cd2+) is a heavy metal that is produced due to pollution from several sources. Occupational exposure can result from the amounts released into the environment and from the end-products related to mining, smelting, and electroplating. Also, exposure results from the profound use of consumer products such as nickel/ Cd2+ batteries, pigments, and plastics. Cadmium toxicity is associated with elevated incidences of chronic kidney disease, hypertension, osteoporosis, and leukemia, as well as cancers of the lung, kidney, urinary bladder, pancreas, breast, and prostate [2]. Thyroid hormones (THs) play a critical role in the functions of nervous, reproductive, and cardiovascular systems in both children and adults [3]. Iodothyronine deiodinases constitute a group of selenoproteins which initiate or terminate thyroid hormone action. Three iodotronine deiodinases, D1 and D2, were identified and they are functional in catalyzing the outer and/or the inner ring deiodination in mammals. The Type 1 Deiodinase (D1) is responsible for the removal of iodines from iodothyronines [4]. Although it is highly expressed in various tissues, hepatic D1 activity is generally considered to be the most important source of plasma triiodothyronine (T3) [5].

In recent years, the endocrine-disrupting property of cadmium has been observed many times in animal studies [6,7]. It has been demonstrated that type I 5’-deiodinase (5’ DI) levels decrease with exposure to cadmium and other heavy metals [8].

The molecular mechanisms of toxic effects of cadmium have not yet been completely understood [9]. The overall effect is likely to be the synergism of several proposed mechanisms such as oxidative stress [10], apopitosis [11], and interference with cell functions [12].

It has been concluded that cadmium has the affinity to concentrate in the thyroid gland in addition to the liver, kidneys, and pancreas. Whole blood cadmium levels have a positive correlation with thyroid gland accumulation. Cadmium causes oxidative stress and affects the tissue by indirect mechanisms. Mitochondria are considered to be the main intracellular targets for cadmium [13]. Also, the thyroid-disrupting effect of cadmium has been reported as structurally degrading the rough endoplasmic reticulum of this tissue. This process may also lead to inflation in mitochondria [14].

In our study, our aim was to determine the serum thyroid hormone levels and metabolic status of cadmium-exposed workers in several industrial sectors and provide information about cadmium toxicity.

Material And Method

Study Population

The patients who were admitted to Ankara Occupational Diseases Hospital with a suspicion of cadmium exposure ,between January 2011 and December 2013 were included in this study. A total of 1724 participants (517 painters, 344 welders, 431 miners, and 432 smelters) with an occupational exposure more than 10 years and for whom blood cadmium levels for the previous 3-year period were obtained from patient records were included in the study. The subjects with diagnosis of a chronic illness including chronic renal failure, acute or chronic hepatitis, or thyroid disease were excluded. The age range was 18 to 70 years, with a median age of 38 years. The study was approved by the Kecioren Training and Education Hospital Ethics Committee on 22.02.2012 (Approval number: B.10.4.ISM.4.06.68.49).

Sampling and Laboratory Procedures

Fasting whole blood samples were collected from the participants into ethylenediaminetetraacetic acid (EDTA) containing tubes. Whole blood cadmium levels were determined using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) (Agilent 7700 series, Tokyo, Japan). Blood samples were digested by the microwave induced acid digestion method. A standard solution of cadmium was prepared by dilution of certified standard solutions (High-Purity Standards, Charleston, SC, USA). Two levels of quality control materials were used (Seronorm, Billingstad, Norway) [15]. The results were expressed as micrograms per liter. Biochemical parameters (Free T3, T4, TSH, folic acid, vitamin B12, AST, and ALT) were analyzed in Roche Cobas 6000 e601/c501 electrochemiluminescence hybride analyzer (Roche, USA).

All the participiants of this study gave informed consent. The participiants were classified into six groups according to the whole blood cadmium levels. Group 1: 0-0.5 µg/L; Group 2: 0.5-1 µg/L; Group 3: 1-1.5 µg/L; Group 4: 1.5-2 µg/L; Group 5: 2-2.5 µg/L; Group 6: >2.5 µg/L.

Statistical Analysis

The statistical analysis was performed using SPSS v16 software. The statistical data consists of the median, minimum and maximum blood levels. Kolmogorov-Smirnov test was performed to verify normality and differences between the groups were compared using Kruskal-Wallis and Mann Whitney U tests for non-parametric variables. p<0.05 was considered to be significant. Spearman correlation test was performed for whole blood cadmium and serum free T3, thyroxine (T4), Vitamin B12, and ALT.

Results

Biochemical and demographic parameters are presented in Table 1. There was no significant difference for serum thyroid-stimulating hormone (TSH), aspartate aminotransferase (AST), and folic acid levels between the six groups (p=0.187, p=0.193 and p=0.467, respectively). Serum vitamin B12 and serum ALT levels were higher in Group 1 compared to other groups. Serum free T3 and T4 levels were significantly lower in Group 1 compared to other groups (p<0.001) (Figure 1).

There was a positive correlation between cadmium and serum free T4 and T3 levels (r=0.167, p<0.001and r=0.159, p<0.001, respectively) (Figure 2).

There was no correlation between whole blood cadmium and serum TSH levels (Figure 2) (r=0.026, p=0.826). There was a negative correlation between cadmium and serum vitamin B12 levels (Figure 2) (r= -0.112, p<0.001).

Discussion

Increasing use of metals in anthropogenic activities have led to toxic metal exposure. In recent years, many environmental and industrial chemicals have been identified as having a disrupting effect on the human endocrine system [16]. Even though the underlying mechanism of toxic effects of cadmium on thyroid functions is unknown, several studies have demonstrated the endocrine-disrupting effect of cadmium on thyroid hormones. There are several animal studies on cadmium-related thyroid dysfunction. Gupta et al. administered cadmium chloride to chickens for 15 days and demonstrated that this exposure decreased serum T3 concentration and hepatic 5’-monodeiodinase (5’D-I) and superoxide dismutase (SOD) activities (68.75%, 90.47%, and 20.81%, respectively). Administration of the antioxidant vitamin E (α-tocopherol, 5 mg/kg weight on alternate days) was reported as preventing cadmium-induced increase in lipid peroxidation [17]. In another experimental study, there were inconsistent results. Assessing the effect of lead and cadmium on endocrine status in cows naturally exposed to lead and cadmium in different industrial areas, the correlation between thyroidal hormones and the whole blood cadmium concentrations were found to be not significant (r = – 0.079 and – 0.48; P > 0.05). However, there was a positive correlation between blood lead and plasma T3 (r = 0.287) and T4 (r = 0.173) [18]. In a study to determine the effect of long-term, low-dose cadmium administration on thyroid functions in sheep, it was found that serum levels of T3, T4, free T3, free T4, and TSH significantly decreased in cadmium-treated sheep compared to a control group (p<0.05) [19] (Table 2).

Although the age range for this study was wide (18-70 years), there has been no specific reference range of thyroid hormone levels. In human studies there are some conflicting results among different studies. In a study group with a goiter diagnosis, cadmium was detected only in nodular goiter samples (n=65) [20]. In another study, cadmium in cord blood and TSH concentrations in neonatal blood were found to be significantly negatively correlated [21]. In a Japanese study, 35 inhabitants of the cadmium-polluted Kakehashi River area in Ishikawa Prefecture were compared to 60 inhabitants of a non-polluted area. T4 levels of females were found to be significantly lower while T3 levels of both genders were significantly higher than in controls [22]. Another study reported no association between concentrations of heavy metals and thyroid hormone levels [23]. In Germany, as part of an epidemiological study on exposure to a toxic waste incineration plant, Osius’s group investigated the relation between blood concentrations of polychlorinated biphenyls (PCBs), lead, cadmium, mercury, and thyroid hormone status. Blood cadmium concentration was associated with increasing TSH and diminishing FT4 [24]. In an evaluation of the relationship between cadmium exposure and thyroid hormones in the National Health and Nutrition Examination Survey (NHANES) 2007-2008, urinary cadmium was found to be positively associated with total T3, total T4, free T3, and thyroglobulin (Tg) [3] (Table 3).

In this study, we found a positive correlation between whole blood cadmium levels and serum thyroid hormones. Serum vitamin B12 levels were inversely correlated with cadmium exposure. This finding may indicate that high levels of cadmium can accelerate the elimination process of vitamin B12 [25]. This might be an explanation for the lower serum vitamin B12 levels in cadmium-exposed groups. Also in this study, there was a negative and positive correlation between cadmium and serum ALT. Further studies must be performed to establish this association.

Conclusion

This study found a positive correlation between whole blood cadmium levels and serum thyroid hormones. The alterations in these hormone levels might be due to a blockage in the peripheral conversion step. Although serum TSH levels were found not to be statistically significant between groups, a counter-activation of thyroid stimulation and thyroid hormone (free T3 and free T4) release may occur as a compensation mechanism.

Acknowledgements

No funding from any pharmaceutical firm was received for this project, and the authors’ time on this project was supported by their respective employers.

Competing interests

The authors declare that they have no competing interests.

References

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8. Wade MG, Parent S, Finnsan KW, Foster W, Younglai E, McMahon A, et al. Thyroid toxicity due to subchronic exposure to complex mixture of 16 organochlorines, lead and cadmium. Toxicol Sci 2002;67(2):207-18.

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20. Błazewicz A, Dolliver W, Sivsammye S, Deol A, Randhawa R, Orlicz-Szczesna G, et al. Determination of cadmium, cobalt, copper, iron, manganese, and zinc in thyroid glands of patients with diagnosed nodular goitre using ion chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2010;878(1):34-8.

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Evren Akgol, Engin Tutkun, Hinc Yilmaz, Fatma Meric Yilmaz, Meside Gunduzoz, Ceylan Demir Bal, Ali Unlu, Sedat Abusoglu. Alterations of thyroid hormone levels in cadmium exposure. J Clin Anal Med. 2017;8(3):202-206

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Processes Petrolingualis of the Foramen Lacerum and Relationship with the Internal Carotid Artery

Enis Kuruoglu

Department of Neurosurgery, Ondokuz Mayis University, Medical Faculty, Samsun, Türkiye

DOI: 10.4328/JCAM.4798 Received: 03.09.2016 Accepted: 03.10.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 198-201

Corresponding Author: Enis Kuruoglu, Department of Neurosurgery, Ondokuz Mayis University, Medical Faculty, 55139 Samsun, Turkey. T.: +90 3623121919/2629 F.: +90 3624576041 E-Mail:drenis@hotmail.com

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The superior border of the petrolingual ligament is the marker for differen-tiating the cavernous part of the internal carotid artery from the lacerum part. To evaluate the presence or absence of intracranial aneurysms, the pa-tients included in this study were evaluated with computerized tomographic angiography. Imaging data were stored in digital imaging and communica-tions in medicine (DICOM) format and subsequently converted using imag-ing software into three-dimensional volume rendered neurovascular images. These images of the 54 patients (27 male and 27 female) were evaluated to analyze the processes of the petrolingualis. In all cases, the processes of the petrolingualis were determined on the medial (petrous portion of the temporal bone) and lateral (sphenoid bone) side. This bony process may be used in the classification of internal carotid artery in patients who underwent three-dimensional computerized tomographic angiography. In the present study, the shape of the process and its relationship with the carotid artery were described.

Keywords: Processes Petrolingualis; Carotid Canal; Carotid Foramen; Volume Rendering Technique; Microsurgical Anatomy; Three-Dimensional Images; Computerized Tomography

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Introduction

The foramen lacerum is different from other foramina located at the cranial base because no anatomically important neural or vascular structures pass through it. The foramen lacerum is located just inferior to the opening of the carotid canal. The internal carotid artery does not travel through the foramen lacerum. The segment of the internal carotid artery travels above the foramen lacerum. Bouthillier at al. [1] have proposed a classification system that describes the entire internal carotid artery, uses a numerical scale in the direction of blood flow, and identifies the segments of the internal carotid artery according to the anatomy surrounding the internal carotid artery and the compartments through which it travels. According to this classification, the internal carotid artery has seven segments as follows: C1, cervical; C2, petrous; C3, lacerum; C4, cavernous; C5, clinoid; C6, ophthalmic; and C7, communicating.

The internal carotid artery leaves from the carotid canal and travels above the foramen lacerum as the lacerum segment of the internal carotid artery. This segment ends at the superior border of the petrolingual ligament and enters the cavernous sinus as a cavernous segment. There is a carotid impression on the lingual part of the sphenoid bone. At the starting point of the carotid sulcus, there are two bony processes incompletely covering the sulcus. One of them is located on the petrous apex and the other is located on the sphenoid bone. The petrolingual ligament is located between the processes to cover the superior border of the internal carotid artery. The bony process located at the petrous apex is referred to as the petrous part of the processus petrolingualis, while the process located at the sphenoid bone is referred to as the sphenoid part of the processus petrolingualis.

In the present study, the shape and location of the processus petrolingualis were evaluated based on the three-dimensional volume rendered neurovascular images in order to describe their micro-vascular properties in view of the literature.

Material and Method

To evaluate the presence or absence of intracranial aneurysms, the patients included in this study were evaluated with computerized tomographic angiography. When an aneurysm was detected, the optimal appropriate management, either surgical clipping or endovascular coiling, was chosen and offered to the patients and their families.

The images analyzed in this study were obtained using the Aquilion ONE multidetector row computerized tomography scanner (Toshiba, Medical Systems, Tokyo, Japan). All patients were given detailed instructions to lie on the table with mouth and eyes closed. A suitable external fixation device was used when necessary to stabilize the patient’s head. After obtaining a frontal and lateral scanogram, a conventional unenhanced computerized tomography was performed if clinically necessary (120 kV, 200 mAs).

Computerized tomographic angiography images were acquired following intravenous timed injection of contrast agent (Visipaque [Iodixanol] 270 mg/100 ml, OPAKIM) using an auto-triggered mechanical injector. The injection rate was 4 ml/s to a total injection volume of 40 ml of contrast agent followed by injection of 20 ml of contrast agent at 3 ml/s. Transverse scans were acquired in the helical mode with radiation parameters 120 kV and 300 mA, matrix size 512 x 512, field of view (FOV) 28-32 cm, slice thickness 1 mm, pitch 1.0, and isotropic voxel size 0.5 mm. The acquisition time was 11-16 s.

Imaging data were stored in digital imaging and communications in medicine (DICOM) format and subsequently analyzed with OsiriX imaging software (OsiriX Foundation, Geneva, Switzerland). Three-dimensional reconstruction of the data was performed to permit viewing of the anatomical area of interest. Settings for the three-dimensional reconstruction algorithm were established as follows: The database window of the program was opened to find the patient’s two-dimensional computerized tomographic angiography images sequence. The imaging cluster was unpacked to the front window. 3D Volume Rendering option was selected to create three-dimensional volume rendered image after the opening of 2D/3D Reconstruction Tools from the dashboard. Following automatic opening of the next window including the volume rendered image graphics processing unit (GPU) engine was selected to render the image at the best resolution. If it was necessary to remove the artifact from the head fixation device, the Sculpt function could be selected to remove the artifact from the working window. The button for rotating around the focal point was selected among the Mouse button functions to rotate the images to view the region from a point perpendicular to the anatomic area of interest. The button for the zoom function could also be selected for magnification of the image. Then Window-Level section was selected to arrange the opacity of the image for maximal reconstruction of the vascular and/or bone structures. The Measurement button was selected to measure diameter, width, and length of the structures as well as to measure the distance between two different points.

Results

To evaluate the presence or absence of intracranial aneurysms, the bilateral courses of the internal carotid artery at the foramen lacerum of 53 patients (26 male and 27 female) were evaluated with computerized tomographic angiography. The mean age of the patients was 57.92±9.7 years. Three-dimensional volume rendered neurovascular images based on the computerized tomographic angiography were evaluated to analyze the course of the internal carotid artery at the foramen lacerum and at the carotid sulcus on the sphenoid bone and processes petrolingualis.

The internal carotid artery enters into the skull via the carotid canal. The artery enters the canal through the carotid foramen located at the inferior aspect of the skull base. The internal carotid artery exits the carotid canal via the internal foramen located at the site of the foramen lacerum. The segment of the internal carotid artery located inside the carotid canal is called the petrous segment. The segment of the artery between the internal foramen of the carotid canal and the superior border of the petrolingual ligament is classified as the lacerum segment. The level of the petrolingual ligament is important in the determination of the segments of the internal carotid artery and posterolateral border of the cavernous sinus. The sites and bony marks of the petrolingual ligament attachments were evaluated using three-dimensional volume rendering technique.

The petrous part of the petrolingual process has a wider range of base in comparison with sphenoidal part. Processes petrolingualis with its petrous and sphenoidal parts incompletely cover the internal carotid artery at the end of the lacerum segment. This structure creates a bony skeleton for the petrolingual ligament (Figure a).

Discussion

The foramen lacerum is a generally triangular shaped bony foramen located between the sphenoid, apex of the petrous temporal, and basilar part of the occipital bones. The petrous portion of the internal carotid artery and carotid sympathetic nerve plexus pass through the carotid canal to reach the foramen lacerum. The lacerum segment of the internal carotid artery passes over the foramen lacerum to reach the cavernous sinus. The anatomic location of the foramen lacerum is perpendicular.

Recently, Bouthillier at al. [1] proposed a classification system that describes the entire internal carotid artery, uses a numerical scale in the direction of blood flow, and identifies the segments of the internal carotid artery according to the anatomy surrounding the internal carotid artery and the compartments through which it travels. According to this classification, the internal carotid artery has seven segments as follows: C1, cervical; C2, petrous; C3, lacerum; C4, cavernous; C5, clinoid; C6, ophthalmic; and C7, communicating. Ziyal et al. [12] and Rhoton [7] have also classified the segments of internal carotid artery without mentioning the lacerum segment.

The volume rendering technique may be used in the three-dimensional evaluation of some anatomical structures such as the internal carotid artery. Volume rendering technique is a group of modalities in the converting of two-dimensional images to the three-dimensional images [2,4,6]. The two-dimensional images acquired by computerized tomography and magnetic resonance imaging is used to create the volume rendered images [2,3,6]. Computerized tomographic angiography with its three-dimensional advantage is a commonly used diagnostic application to detect intracranial aneurysms. In the literature, the diagnostic sensitivity of computerized tomographic angiography has been reported between 70% and 96% depending on the size and location of the pathology [5,8,9,10,11]. A three-dimensional viewer provides modern rendering modes such as multiplanar reconstruction, surface rendering, volume rendering, and maximum intensity projection. In the present study, we used OsiriX software in the processing of DICOM images. This software may show the basal cerebral arteries and cervical segment of the internal carotid arteries together with the bone structures of the cranial base including the carotid canal.

The internal carotid artery passes through two foramen during its course through the carotid foramen. One of them is located in the external surface of the cranial base. The other foramen is located at the posterior border of the foramen lacerum. The internal carotid artery passes over the foramen lacerum to reach the cavernous sinus. The posterior border of the cavernous sinus is created by the petrolingual ligamentous structure. There are two bony marks in the determination of the posterior border of the cavernous sinus. Three-dimensional computerized tomographic evaluation may provide the visualization and determination of the bony structures such as the petrous and sphenoidal parts of processes petrolingualis in the evaluation of cases.

In this study, two anatomical bony landmarks were used to determine the internal carotid artery entrance to the cavernous sinus. These two processes are the processes petrolingualis. This process has two parts. One of them is located on the petrous part of the temporal bone. This part covers the internal carotid artery medially and superiorly. The other part is located on the sphenoid bone and named the pars sphenoidalis of processes petrolingualis.

The petrous segment of the internal carotid artery is covered with the bony structure of the temporal bone. The Latin term of the canal describes a tubular shape of passage with two openings. Like other canals, the carotid canal has two exits. The first opening is the entrance foramen of the internal carotid artery. This foramen faces the inferior external aspect of the cranial base. The second opening is located at the foramen lacerum. The internal carotid artery leaves the carotid canal via this foramen. This foramen faces the foramen lacerum and is referred to as the anterior carotid foramen. It is anatomically located in front of the other foramen, which is referred to as the inferior carotid foramen. The inferior carotid foramen is perpendicularly located at the cranial base. The anterior carotid foramen is vertically located at the base of the cranium facing the foramen lacerum. The anatomic location of the foramen lacerum is perpendicular. The carotid foramen has two portions inside the petrous portion of the temporal bone—the vertical part and the horizontal part. The vertical part follows the inferior carotid foramen. The vertical part turns sharply to the anterior direction until reaching the foramen lacerum via the anterior carotid foramen. The course of the horizontal part of the internal carotid artery has an antero-medial direction. It continues its course until reaching the anterior portion of the foramen lacerum. At this point, there is another semi-canal. The bridge over the internal carotid artery creates the petrolingual ligament. This semi-canal continues with the carotid impression over the sphenoid wing.

The results of this study show that the three-dimensional volume rendering technique can be used in the evaluation of cranial base structures, including micro-vascular surgical anatomy. It is necessary to further evaluate the biomechanics, flow dynamics, and interaction with perivascular neural cranial base structures.

Competing interests

The authors declare that they have no competing interests.

References

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Enis Kuruoglu. Processes petrolingualis of the Foramen Lacerum and relationship with the internal carotid artery. J Clin Anal Med. 2017;8(3):198-201

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Prevalence of Carotid Canal Dehiscence Facing with Middle Ear and its Relationship with Tinnitus

Mehmet Emre Sivrice 1, Hasan Yasan 2, İsmail Çoban 3, Mustafa Kayan 4

1 Department of Otorinolaringology, Tavsanlı Docent Doktor Mustafa Kalemli State Hospital, Kutahya, 2 Department of Oto-Rhino-Laryngology and Head&Neck Surgery, Faculty of Medicine, S.Demirel University, Isparta, 3 Department of Oto-Rhino-Laryngologyand Head&Neck Surgery, Antalya Atatürk State Hospital, Antalya, 4 Department of Radiology, Faculty of Medicine, S.Demirel University, Isparta, Turkey

DOI: 10.4328/JCAM.4805 Received: 09.09.2016 Accepted: 29.09.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 195-7

Corresponding Author: Mehmet Emre Sivrice, Department of Otorinolaringology, Tavsanlı Doc. Dr. Mustafa Kalemli State Hospital, 43300, Kutahya, Turkey. GSM: +905447724319 F.: +90 2746151425 E-Mail: emresivrice@gmail.com

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Aim: To assess the frequency of carotid canal dehiscence facing with middle ear cleft and its relationship with pulsatile tinnitus. Material and Method: High resolution computed tomography scans (reformatted from the axial plane images taken for paranasal sinus investigations) of 1026 temporal bone images of 513 patients were retrospectively examined for the presence of dehiscent internal carotid artery. The presence of pulsatile tinnitus com-plaint was noted. The relationship between carotid canal dehiscence in the middle ear and pulsatile tinnitus was investigated. Results: One thousand and twenty-six (1,026) temporal bone images of 513 patients were investigated for the presence of carotid canal dehiscence in the middle ear(30.9 %). Three hundred and eighteen (318) out of 1026 temporal bone images proved to present carotid canal dehiscence in the middle ear. There were 16 ears with pulsatile tinnitus at the site of dehiscent carotid canal. There were 19 ears with pulsatile tinnitus at the site of the temporal bone without carotid canal dehiscence. There was no statistically significant correlation between the carotid canal dehiscence and pulsatile tinnitus. Discussion: Neither age nor gender is a determining factor for the presence of carotid canal dehiscence. Pulsatile tinnitus seems not to be related with carotid canal dehiscence.

Keywords: Carotid Artery; Pulsatile Tinnitus; Temporal Bones

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Introduction

Internal carotid artery and the jugular bulb are two major vascular structures that pass through the temporal bone, and if dehiscent, face with the middle ear cavity. It is well known that the dehiscence of the jugular bulb may cause pulsatile tinnitus. Although carotid canal dehiscence (CCD) has been documented in previous studies, its relationship with pulsatile tinnitus has not been established [1,2,3]. Here we have evaluated the frequency of carotid canal dehiscence in the middle ear and its relationship with pulsatile tinnitus.

Material and Method

The outpatient and inpatient charts of all patients who underwent computed tomographic (CT) evaluation of the paranasal sinuses from March 2008 through September 2010 were reviewed. CT evaluation of the paranasal sinuses was performed in the axial projection without the administration of intravenous contrast material. We performed the CT examinations with the patient supine on the scanner bed with the head in extension. Multi-slice 128 CT scanning (Definition AS, Siemens Medical Solutions, Forchheim Germany) was obtained in the axial plane with the following parameters:120 kV, gantry rotation of 1 second and 110 mA second, 0.8 pitch factor, and mean total acquisition time 5 seconds. Examinations were evaluated using both bone and soft tissue windows. The axial CT scans of patients with paranasal sinus evaluation were reformatted to obtain coronal plane images. Temporal bones were normally visualized in the paranasal sinus being investigated. Reformatted images of temporal bone (axial and coronal plane images) were investigated for carotid canal dehiscence in the middle ear(Figure 1). This evaluation was carried out by one radiology specialist and one ENT specialist. Clinical findings of all patients were taken from charts. In cases of discrepancy or insufficient information in the files, then the patients were asked by phone about the nature of complaints and clinical history. Exclusion criteria were as follows: patients who had a history of previous ear operation, known cardiovascular disease, ototoxic drug usage, head trauma, aberrant internal carotid artery (ICA), intratemporal or intratympanic mass and/or fluids, and age older than 50 years. During the evaluation, CCD is accepted as positive if any part of the carotid canal is facing with the middle ear cleft, and the petrous and eustachian part has dehiscence. Dehiscence of the carotid canal on the base of cranium was not evaluated as CCD.

Statistical analyses were carried out by independent sample T-test and correlation was investigated by Pearson correlation test. P value less than 0.05 was accepted as significant.

Results

The number of patients included in this study was 513 and the number of temporal bone images was 1206. The mean age and range of age of patients were 32.80 ± 12.39 and 10-50 years, respectively. The numbers of male and female patients were 263 (51.3%) and 250 (48.7%) respectively. Three hundred and eighteen (318) out of 1026 temporal bone images (30.99%) showed the presence of CCD in the middle ear. There were 16 ears with pulsatile tinnitus at the side of CCD. There were 19 ears with pulsatile tinnitus at the side of temporal bone without CCD. One hundred and thirty-nine patients have had bilateral CCD (278 temporal bones), 28 patients have had only right-sided CCD, and 12 patients have had only left-sided CCD. That is, 167 out of 513 right-sided temporal bones have had CCD in the middle ear (32.6%), and 151 out of 513 left-sided temporal bones have had CCD in the middle ear (29.4%). There were 30 patients in the pulsatile tinnitus group. Five of these 30 patients had bilateral pulsatile tinnitus. In the pulsatile tinnitus group, 21 right-sided ears and 14 left-sided ears were involved. Fifteen of the right-sided pulsatile tinnitus and eight of the left-sided pulsatile tinnitus patients had high jugular bulb with dehiscence. The etiology of pulsatile tinnitus in the remaining 12 ears was not diagnosed by the present findings. Right-sided pulsatile tinnitus was seen in nine ears with CCD, and 12 ears without CCD. Left-sided pulsatile tinnitus was seen in seven ears with CCD, and seven ears without CCD(Table 1).

There was no statistically significant difference between involvement of right-sided versus left-sided temporal bones. There were no statistically significant correlations between CCD and pulsatile tinnitus, CCD and age, or CCD and gender(Table 2).

Discussion

The carotid canal starts to develop as two laminae of the petrous bone in the 18th fetal week. In cases of incomplete closure of these laminae the carotid canal occupies dehiscence[4]. There is a wide range reported for the frequency of CCD. This discrepancy may be attributable to differences in the criteria used to define case selection and in the evaluation technique (radiologic or histologic) for identifying the dehiscence[1]. Our study results may reveal some differences from the literature due to case selection. We have included the cases only with radiologic CCD in the middle ear space. Normally, the ICA enters the petrous bone medial to styloid process via the carotid canal. The initial vertical segment is anterior to the cochlea and separated from the tympanic cavity by a thin plate of bone. Disappearance of the bony plate between the ICA and the middle ear results in dehiscence of the carotid artery in the middle ear. Sometimes this dehiscence may result in aberrant ICA in the middle ear[3].CT can be used to investigate the CC. The best plane is the coronal, through the horizontal portion of the canal, with which one can clearly see the abnormalities of its walls[5]. We have evaluated the presence of CCD in the middle ear both in coronal and axial CT planes of temporal bones. Although there are some studies investigating the frequency of carotid canal dehiscence, most of them are related to both the ventral and dorsal carotid canals. The origin of CCD in the middle ear may be explained by failures in ossification, congenital anomaly, persistence of embryonic vessels, bone absorption throughout the years, middle ear inflammatory processes, and traumatic injuries of the temporal bone[1,2,3,4,5,6]. We have excluded the cases with a history of temporal bone trauma or middle ear inflammatory processes.

Penido et al. [2] investigated CCD in the middle ear by microanatomic study. They have found 35.2% CCD in the middle ear. We have found the frequency of radiologic CCD in the middle ear as 30.9%. This finding is consistent with the literature. Previous studies are mostly related only to the frequency of CCD. Because jugular bulb dehiscence is a known cause of pulsatile tinnitus, we researched the relationship between CCD and pulsatile tinnitus. Patients who have carotid canal dehiscence also have high jugular bulb at a prevalence of more than 60%[7]. In this case, the reasons for pulsatile tinnitus may not be clear. However, our study indicates that CCD does not cause pulsatile tinnitus by itself. The prevalence of carotid canal dehiscence decreases with increasing temporal bone age[6]. In our study there is no statistically significant correlation between patient age and CCD frequency. This could be due to case selection criteria.

The differential diagnosis of pulsatile tinnitus includes: middle ear (effusion, chronic otitis media), neoplasm (glomus jugulare or glomus tympanicum, geniculate ganglion hemangioma), arterial (arterio-venous fistulas, internal auditory vascular loops), venous (benign intracranial hypertension, sigmoid or jugular diverticulum, high jugular bulb) pathologies, and aneurysm of the internal carotid artery[8,9]. Dehiscent jugular bulb is one cause of pulsatile tinnitus. It is usually asymptomatic, but when symptoms are present, tinnitus is the most common complaint[10].

ICA-related pulsatile tinnitus can be caused by carotid artery aneurysm, carotico-jugular or carotico-cavernous fistula, or aberrant ICA. The aberrant ICA is another cause for pulsatile tinnitus. Aberrant ICA can be identified on CT scan by the following features: intratympanic mass, enlarged inferior tympanic canaliculus, absence of the vertical segment of the ICA canal, and the absence of bone covering the tympanic portion of the ICA[3].

This is the first study that investigates the radiologic frequency of carotid canal dehiscence in the middle ear cleft and its relationship with pulsatile tinnitus.

Conclusion

The frequency of carotid canal dehiscence in the middle ear cleft was 30.99% (318 dehiscences in 1026 temporal bone images). Neither age nor gender is a determining factor for the presence of CCD. Dehiscence of the carotid canal facing withmiddle ear cleft seems not to be one of the causes of pulsatile tinnitus.

Competing interests

The authors declare that they have no competing interests.

References

1. Hearst MJ, Kadar A, Keller JT, Choo DI, Pensak ML, Samy RN. Petrous carotid canal dehiscence: an anatomic and radiographic study. Otol Neurotol 2008;29(7):1001-4.

2. Penido Nde O, Borin A, Fukuda Y, Lion CN. Microscopic anatomy of the carotid canal and its relations with cochlea and middle ear. Braz J Otorhinolaryngol 2005;71(4):410-4.

3. Sauvaget E, Paris J, Kici S, Kania R, Guichard JP, Chapot R, Thomassin JM, Herman P, Tran Ba Huy P. Aberrant internal carotid artery in the temporal bone: imaging findings and management. Arch Otolaryngol Head Neck Surg 2006;132(1):86-91.

4. Tóth M, Medvegy T, Moser G, patonay L. Development of the protympanum. Ann Anat 2006;188(3):267-73.

5. Pastor Vázquez JF, Gil Verona JA, García Porrero M. Carotid canal dehiscence in the human skull. Neuroradiology 1999;41(6):447-9.

6. Moreano EH, Paparella MM, Zelterman D Goycoolea MV. Prevalence of carotid canal dehiscence in the human middle ear: a report of 1000 temporal bones. Laryngoscope 1994;104(5 Pt 1):612-8.

7. Wang CH, Shi ZP, Liu DW,Wang HW, Huang BR, Chen HC. High Computed Tomographic Correlations between Carotid Canal Dehiscence and High Jugular Bulb in the Middle Ear. Audiol Neurootol 2010;16(2):106-12.

8. Mattox DE, Hudgins P. Algorithm for evaluation of pulsatile tinnitus. Acta Otolaryngol 2008;128(4):427-31.

9. Palacios E, Gómez J, Alvernia JE, Jacob C. Aneurysm of the petrous portion of the internal carotid artery at the foramen lacerum: anatomic, imaging, and otologic findings. Ear Nose Throat J 2010 ;89(7):303-5.

10. El-Begermy MA, Rabie AN. A novel surgical technique for management of tinnitus due to high dehiscent jugular bulb. Otolaryngol Head Neck Surg 2010;142(4):576-81.

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Mehmet Emre Sivrice, Hasan Yasan, Ismail Coban, Mustafa Kayan. Prevalence of carotid canal dehiscence facing with middle ear and its relationship with tinnitus. J Clin Anal Med. 2017;8(3):195-197

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Secondary Vascular Access Procedures for Hemodialysis After Primary Snuff-Box Arteriovenous Fistula

Mahir Kırnap, Tugan Tezcaner, Gökhan Moray

From the Departments of General Surgery and Transplantation, Baskent University Faculty of Medicine, Ankara, Turkey

DOI: 10.4328/JCAM.4799 Received: 03.09.2016 Accepted: 30.09.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 190-4

Corresponding Author: Mahir Kırnap, Baskent University, Taskent Caddesi No: 77, Bahcelievler, Ankara 06490, Turkey. T.: +90 3122127393 F.: +90 3122150835 E-Mail: mahirkir@hotmail.com

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Aim: To investigate the secondary arteriovenous fistulas constructed after a snuff-box fistula. Material and Method: We reviewed data on 95 arterio-venous fistulas that were created as a secondary vascular access between January 2007 and December 2015. Of those 95 fistulas, 37 (39%) were ip-silateral elbow brachial-cephalic arteriovenous fistulas and 58 (61%) were ipsilateral wrist radial-cephalic arteriovenous fistulas; all were created after a primary snuff-box fistula. Results: All arteriovenous fistulas had matured. The primary patency rates for elbow brachial-cephalic arteriovenous fistulas and radial-cephalic arteriovenous fistulas were as follows: 1-year rate, 88% to 87% and 4-year rate, 70% to 61%. The secondary patency rates for were as follows: 1-year rate, 91% to 93%; 4-year rate, 72% to 63%. No early failure occurred. There were 15 late failures. The most common causes of failure were stenosis within the vein (n=8 patients), aneurysm (n=5 patients), and central vein stenosis (n=2 patients). Discussion: These data suggest that before a radial-cephalic or brachial-cephalic arteriovenous fistula is cre-ated, the construction of a snuff-box fistula enable the vascular structures to dilate, and may so fascilitate the success rate of seconder AVFs. For this reason a radial-cephalic arteriovenous fistula or an elbow brachial-cephalic arteriovenous fistula should be the second choice.

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Introduction

The original and recently updated national kidney foundation dialysis outcomes quality initiative practice guidelines (NKF-DOQI) recommend to increase the placement of native arteriovenous fistulas (AVFs) for the first choice of vascular access for hemodialysis. These guidelines also recommend that the order of preference for AVF creation should be the wrist radial-cephalic (RC) type as the primary AVF and then the elbow brachial-cephalic (BC) type as the secondary AVF. If either of these is not viable, then another type of fistula made of synthetic material should be used. The RC type of AVF is recommended as the primary and best option for vascular access[1].

The first AVF should be created as distally as possible to provide a long segment of arterialized vein for repeated venipuncture and to save alternative sites for creation of additional fistulas. Distal AVFs have the lowest complication rates[2,5]. A radial-cephalic AVF in the anatomical snuff-box is the other alternative to a wrist RC AVF, and the most distal site of the forearm has been recommended by several authors as the primary option for an AVF.[2-5]The main advantage of the snuff-box AVF is that preserving the proximal vessels to create additional AVFs also provides a long segment of vein for needling. In case of failure of a snuff-box AVF after maturation, creation of a secondary arteriovenous access site is often facilitated by the presence of an already arterialized vein[5,6].

It has been informally suggested that creating a snuff-box AVF before an RC or a BC AVF may dilate the veins of the forearm and upper arm and improve the outcome of subsequent AVF construction in the ipsilateral arm. That this suggestion? suggestion has never been systematically studied, and little is known or has been published about it[6].

The aims of this retrospective study were to investigate the types of fistulas and the patency, maturation rates, complications, and late results of ipsilateral AVFs created after a snuff-box fistula.

Material and Method

Between January 2007 and December 2015, 323 snuff-box AVFs for hemodialysis were created at our institution. Sufficient data were was available for 75 patients (95 fistulas) with secondary AVFs created after primary functional snuff-box fistulas. When a snuff-box AVF failed, a standard ipsilateral RC AVF was constructed if possible, or a contralateral snuff-box AVF or a contralateral wrist access was created. If the contralateral wrist was not suitable for both a snuff-box and an RC AVF, then an ipsilateral BC AVF was created in the same extremity. All fistulas in this study were secondary ipsilateral RC AVFs (n=58) or BC AVFs (n=37). Moving to the contralateral extremity for creation of the secondary vascular access was the exclusion criterion. All AVFs were constructed with the same surgical technique by general surgeons experienced in vascular access. Thirty-seven ipsilateral BC AVFs and 58 ipsilateral RC AVFs were created after 95 primary snuff-box fistulas.

Fistula patency and maturation time were obtained from dialysis unit and hospital medical records.

Demographic factors and comorbid conditions (the duration of treatment with hemodialysis; and the frequency of hemodialysis) were also assessed. The time until fistula failure occurred was determined from dialysis unit notes.

Before the operation, the adequacy of the cephalic vein and the arterial supply of the upper limb (brachial, radial, ulnar pulses) were determined by clinical examination. All secondary accesses were created under local anesthesia. All operations were performed as outpatient procedures.

A palpable thrill or a bruit on auscultation was taken as an indicator of good fistular function. Primary failure was defined as those fistulas that failed within 6 weeks, before the fistula

could be used for hemodialysis, including those that were technical failures. Primary patency refers to the duration of access patency until the first intervention to maintain patency or until fistula failure. Cumulative secondary patency refers to fistulas functioning for dialysis, regardless of the number of interventions required to maintain patency. Fistula failure was defined as an inability to use the fistula for hemodialysis owing to a cause other than transplant or death. Operative ligations were classified as failures. Patients who underwent renal transplant were considered as lost to follow-up, not as failures. Deaths being unrelated to fistula failure also were treated as lost to follow-up. A fistula was considered to have matured when it provided adequate dialysis. Complication rates refer to fistula-related problems only and include the causes of fistula failure.

The mean ± SD was the descriptive statistic used to express results for quantitative variables. A Kaplan-Meier survival analysis was performed according to primary and secondary patency rates. Differences in patency rates between RC and BC AVFs were assessed using the log-rank test. A p value <0.005 was considered statistically significant for all comparisons.

Results

Seventy-five patients underwent the creation of a total of 95 snuff-box fistulas. Demographic data are listed in Table I. The most common cause of renal failure was diabetes in 32 patients (42% of total). The other causes of renal failure were hypertension in 18 (24%), glomerulonephritis in 12 (16%), unknown etiology in 7 (9%), and chronic pyelonephritis 6 (8%).

Of those 95 secondary AVFs, 37 (39%) were ipsilateral BC AVFs and 58 (61%) were ipsilateral RC AVFs. Forty-five RC AVFs (77%) and 30 BC AVFs (81%) were placed on the left side.

Thirty-seven BC AVFs were constructed after a primary snuffbox AVF. The reasons for creating the BC AVFs were, extensive thrombosis in 20 patients (54%), stenosis (needle sites) of forearm cephalic outflow vein in 9 patients (24%), aneurysm formation of forearm cephalic outflow vein in 8 patients (21%). Those complications changed the operative plan to creation of a BC AVF. In 37 BC AVFs created at our institution, extensive disease within the outflow vein was the main cause of BC AVFs procedures.

Maturation and complications

There were no primary failures among 95 secondary access procedures. The median follow-up for the patients studied was 50 months (range, 3-65 months). All of the AVFs matured, and the median maturation time was 19.5 ± 3.2 days (range, 15-30 days) for RC AVFs and 19.4 ± 2.9 days (range, 15-30 days) for BC AVFs. All of the secondary accesses were matured and functional.

Postoperative complications included 2 infections (none of which required drainage) that were treated with antibiotics, and 4 hematomas (none of which required drainage). One patient presented with minimal “steal” symptoms after a left-sided RC fistula operation. Those symptoms resolved spontaneously within 1 week of their onset. The overall morbidity rate was 6%, and no patient died during the 30 days after the procedure.

Patency

Figures 1 and 2 show the primary and secondary patency rates determined with the Kaplan-Meier survival analysis for RC AVFs and BC AVFs. The primary patency rates for BC AVFs and RC AVFs were as follows: 1-year rate, 91% to 89%; 2-year rate, 82% to 74%; 3-year rate, 65% to 67%; and 4-year rate, 60% to 62%. The difference in primary patency between the 2 groups was not significant (p=0.9, log rank). The secondary patency rates for BC AVFs and RC AVFs were as follows: 1-year rate, 96% to 93%; 2-year rate, 90% to 83%; 3-year rate, 83% to 73%; and 4-year rate, 76% to 62%. The difference in secondary patency between the 2 groups was not significant (p=0.4, log rank).

There were 12 late failures among 95 functional AVFs. The most common cause of failure was stenosis within the vein in 9 patients (9.4%) (6 RC AVFs and 3 BC AVFs) and an aneurysm in 3 patients (3%) (2 RC AVFs and 1 BC AVF).

Secondary patency (successful recanalization) was attempted in 22 fistulas (11 RCs and 11 BCs) and was successful in the 15 AVFs (68%) (6 RC and 9BC). Of these thrombectomies, 13 were surgical and 9 were performed via interventional radiology. Subclavian vein stenoses, which were confirmed by venographic studies, developed in 4 patients. We attempted to correct the stenoses with percutaneous transluminal angioplasty, but the interventions were unsuccessful because 2 of the stenoses were not elastic.

Discussion

The number of patients worldwide with end-stage renal disease receiving hemodialysis treatment increases every year[7]. By 2001, more than 1 million patients were undergoing dialysis, and the annual global average rate of increase was 7%[7,8]. In Europe, 80% of hemodialysis patients have an autogenous AVF as a vascular access, but only 24% of patients in the United States have an autogenous AVF[9]. According to the Turkish Nephrology Society Registry, which records data for 25 321 patients at 388 hemodialysis centers in Turkey, of patients who had started hemodialysis treatment for the first time, 35.6% have an autogenous AVF as the first intravenous route in; and in individuals treated with regular hemodialysis, 90.1% have an autogenous AVF[10]. Of those AVFs, 42% were localized 1/3 distal region of the forearm, 25% were localized 1/3 mid region of the forearm and 8.5% had a snuff-box AVF[10]. .

The NKF-K/DOQI clinical practice guidelines for vascular access suggest placement of an autogenous AVF for primary vascular access for hemodialysis[1]. An autogenous RC AVF is regarded as the first and best choice for vascular access. In our study, all secondary fistulas were native after the initial snuff-box AVF, which led to a reduction in the number of more complicated secondary access procedures such as AV prosthetic grafts.

The present study shows that 58 RC AVFs (61%) and 37 BC AVFs (39%) were feasible after primary snuff-box AVFs. Multiple stenoses may develop at the site of multiple venipunctures. Stenosis and aneurysm formation at the inflow vein can lead to thrombosis. Multiple stenotic areas are associated with unsuccessful thrombectomy and the need for additional BC AVFs instead of RC AVFs. There was no immediate failure and all AVFs were functional after 30 days. These 2 types of secondary vascular access procedures that were made after a primary snuff-box AVF were successful.

“Failure to mature” is defined as the inability to use a fistula for hemodialysis at 6 weeks after its construction[11]. However, 10% to 24% of RC AVFs are either compromised by a thrombosis directly after surgery or do not function adequately because of a failure to mature[12,16]. RC AVFs have a reported maturation rate of 25% to 80%[17]. Rao and colleagues reported that failure to mature was as high as 38%, although most other authors have not reported such high rates as this[18]. In our report, maturation rates and times were better than those cited in the literature[11]. Arterialized vein segments resulted in better maturation rates and shorter maturation times. However, the study group was young and the mean hemodialysis time was short, these factors could influence the maturation rate.

A review of the literature showed that the primary patency rate of RC AVFs ranges from 70% to 91% at 1 year, although a recent meta-analysis reported that the primary patency rate may be as low as 62.5% and the secondary patency rate may be as low as 66.0% at 1 year after the creation of the fistula[11,19,20]. The 1-year primary patency rates of BC AVFs and forearm prosthetic arteriovenous grafts have been reported to range from 70% to 84% and 62% to 87% respectively[12,21,25].

In this study, the primary and secondary patency rates of RC AVFs are better than the rates listed in a recent meta-analysis of radial-cephalic patency and better than the patency rates for prosthetic arteriovenous grafts. The primary and secondary patency rates of BC AVFs are better than the patency rates of both BC AVFs and prosthetic grafts[11,12].

The main reason for the failure of functional secondary RC AVFs in this study was multiple needle puncture site stenoses in the outflow vein.

One of the most commonly performed alternative secondary fistulas is the prosthetic graft. This type of fistula results in high rates of infection, steal symptoms, high-output cardiac failure, aneurysm formation, and thrombosis[26,27].

According to the Turkish Nephrology Society Registry, in 25.7% of the patients receiving the routine hemodialysis treatment for the first time, the initial intravenous route is the temporary (nontunneled) subclavian catheterization[28]. Subclavian vein occlusion or stenosis can occur in up to 50% in patients who have had an indwelling subclavian catheter[29]. Subclavian vein occlusion confirmed by venography, contributed to 2 AVF failures in this study.

These data suggests that it is more vital to create a snuff-box fistula, if possible, for primary vascular access before construction of an RC AVF is attempted. By doing so, a long vein segment is well preserved for needling, and this segment also preserves proximal vessels for further AVF creation. An RC AVF should be the secondary choice in 61% of patients undergoing creation of a secondary access after a snuff-box AVF. This operation is often facilitated by the presence of arterialized vein segment. This type of secondary AVF is associated with better outcomes, although additional studies are required.

The limitations of our study were that there were no randomized trials in literature, from which conclusions could be drawn. For that reason, this paper is the only report analyzing the secondary vascular access procedures created after functional snuff-box fistulas. It is clear that well-planned randomized trials are needed to provide additional information about access surgery.

Competing interests

The authors declare that they have no competing interests.

References

1. Clinical Practice Guidelines for Vascular Access: update 2000. Am J Kidney Dis 2001 Jan; 37(1 Suppl 1): S137-81.

2. Almasri J, Alsawas M, Mainou M, Mustafa RA, Wang Z, Woo K, Cull DL, Murad MH. Outcomes of vascular access for hemodialysis: A systematic review and meta-analysis. J Vasc Surg 2016;64(1):236-43.

3. Bonalumi U, Civalleri D, Rovida S, Adami GF, Gianetta E, Griffanti-Bartoli F. Nine years’ experience with end-to-end arteriovenous fistula at the ‘anatomical snuff-box’ for maintenance hemodialysis. Br J Surg 1982;69(8): 486-8.

4. Bartova V, Vanecek V, Valek A. Snuffbox fistula – better vascular access for hemodialysis. Dial Transplant 1984;13:631-2.

5. Sekar N. Snuff-box arteriovenous fistulas. Int Surg 1993;78(3):250-1.

6. Wolowczyk L, Williams AJ, Donovan KL, Gibbons CP. The snuff-box arteriovenous fistula for vascular access. Eur J Vasc Endovasc Surg 2000;19(1):70-6.

7. Lysaght MJ. Maintenance dialysis population dynamics: current trends and long-term implications. J Am Soc Nephrol 2002;13 Suppl1:S37-40.

8. Moeller S, Gioberge S, Brown G. ESRD patients in 2001: global overview of patients, treatment modalities and development trends. Nephrol Dial Transplant 2002;17(12): 2071-6.

9. Pisoni RL, Young EW, Dykstra DM, Greenwood RN, Hecking E, Gillespie B, Wolfe RA, Goodkin DA, Held PJ. Vascular access use in Europe and the United States: results from the DOPPS. Kidney Int 2002;61(1):305-16.

10. Nephrology, Dialysis and Transplantation in Turkey, Registry 2004 (English) Central Registry Committee: Ekrem Erek, Gültekin Süleymanlar, Kamil Serdengeçti. Publisher: Turkish Society of Nephrology, number of pages:91.

11. Rooijens PP, Tordoir JH, Stijnen T, Burgmans JP, Smet de AA, Yo TI. Radiocephalic wrist arteriovenous fistula for hemodialysis: meta-analysis indicates a high primary failure rate. Eur J Vasc Endovasc Surg 2004;28(6):583-9.

12. Coburn MC, Carney WI Jr. Comparison of basilic vein and polytetrafluoroethylene for brachial arteriovenous fistula. J Vasc Surg 1994;20(6):896-902;discussion 903-4.

13. Reilly DT, Wood RF, Bell PR. Arteriovenous fistulas for dialysis: blood flow, viscosity, and long-term patency. World J Surg 1982;6(5):628-33.

14. Tordoir JH, Kwan TS, Herman JM, Carol EJ, Jakimowicz JJ. Primary and secondary access surgery for hemodialysis with the Brescia-Cimino fistula and the polytetrafluoroethylene (PTFE) graft. Neth J Surg 1983;35(1):8-12.

15. Wedgwood KR, Wiggins PA, Guillou PJ. A prospective study of end-to-side vs. side-to-side arteriovenous fistulas for hemodialysis. Br J Surg 1984;71(8):640-2.

16. Kherlakian GM, Roedersheimer LR, Arbaugh JJ, Newmark KJ, King LR. Comparison of autogenous fistula versus expanded polytetrafluoroethylene graft fistula for angioaccess in hemodialysis. Am J Surg 1986;152(2):238-43.

17. Palder SB, Kirkman RL, Whittemore AD, Hakim RM, Lazarus JM, Tilney NL. Vascular access for hemodialysis. Patency rates and results of revision. Ann Surg 1985;202(2): 235-9.

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Kanayama HO, Minakuchi J, Tsuchida K. Vascular access for long-term hemodialysis/hemodiafiltration patients. J Vasc Access 2015;16 Suppl.

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26. Manafov EN, Batrashov VA, Sergeev OG, Yudaev SS. [Permanent vascular access for haemodialysis]. Angiol Sosud Khir 2015;21(3):187-93.

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29. Rowse JW, Kirksey L. Surgical Approach to Hemodialysis Access. Semin Intervent Radiol 2016;33(1):21-4.

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Mahir Kirnap, Tugan Tezcaner, Gokhan Moray. Secondary vascular access procedures for hemodialysis after primary snuff-box arteriovenous fistula. J Clin Anal Med. 2017;8(3):190-194

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Low Prognostic Nutritional Index Before Radiotherapy is a Poor Prognostic Factor for Rectum Cancer

Neslihan Kurtul¹, Celalettin Eroğlu²

¹Dept. of Radiation Oncology, University of Sütçü İmam, Faculty of Medicine, Kahramanmaraş, ²Dept. of Radiation Oncology, University of Erciyes, Faculty of Medicine, Kayseri, Turkey

DOI: 10.4328/JCAM.4796 Received: 02.09.2016 Accepted: 29.09.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 185-9

Corresponding Author: Neslihan Kurtul, Dept. of Radiation Oncology, University of Sütçü İmam, Faculty of Medicine, Kahramanmaraş, Turkey. GSM: +905067872841 F.: +90 3442803409 E-Mail: drneslihankurtul@gmail.com

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Aim: The aim of this study was to examine the effect of the prognostic nu-tritional index (PNI) value on survival in patients with rectum cancer who received postoperative chemoradiotherapy. Material and Method: The study included 65 patients who received adjuvant chemoradiotherapy. Radiother-apy of 5040 cGy and simultaneous 5-FUFA chemotherapy was given to the patients. The patients were divided into two groups as PNI ≤46 and PNI >46 according to the ROC analysis. The differences in survival between the groups were calculated using the log rank test. The univariate and multivari-ate hazard ratios were calculated using the Cox proportional hazard model.Results: The patients included 22 (33.8%) females and 43 (66.2%) males. The low PNI group comprised 28 (43.1%) patients and the high PNI group, 37 (56.9%). According to the Kaplan-Meier analysis, mean survival was 59 months (95% CI; range, 44.95-73.08 months) in the low PNI group and 80 months (95% CI; range 66.53- 94.82 months) in the high PNI group. The 5-year survival rate was 49% in the low PNI group and 65% in the high PNI group. In the univariate analysis, T stage, N stage, tumor diameter, and PNI had an effect on overall survival (p<0.05). In the multivariate Cox regression analysis, T stage (p=0.014), tumor diameter (p=0.023), and PNI (p=0.045) were found to be prognostic factors affecting overall survival, independent of the other variables. Discussion: The results of the study showed that the PNI value before radiotherapy is a poor prognostic factor for rectum cancer.

Keywords: Prognostic Nutritional Index; Radiotherapy; Rectum Cancer

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Introduction

Colorectal cancers are the third most frequently seen cancers in both males and females [1]. Although they are the same organ, normal colon and rectum tissue are different structures embryologically, histologically, and functionally. Similarly, rectum cancers demonstrate some differences from colon cancers and have a worse prognosis [2]. The most important prognostic factors in rectum cancer are the degree of bowel wall penetration by the tumor, lymph node involvement, and the presence of distant metastasis. Tumor differentiation shows an effect on survival by increasing the risk of lymph node metastasis which is related to increased lymphovascular invasion [3]. Circumferential tumors, tumors with deep central ulceration, and fixed tumors have a worse prognosis compared to those that do not have these properties.

In the prognosis of rectum cancer, it is necessary to evaluate not only the prognostic indicators associated with the tumor but also patient-related factors. Although age, gender, and ethnicity are slightly related with survival, they can affect the choice of treatment [4].

Determination of cancer prognosis through nutritional and immunological status of the patients has been emphasized recently. PNI is a marker calculated from the serum albumin and lymphocyte count values in the peripheral blood that shows the preoperative nutritional and immunological status of the patient. It was first described by Buzby et al. to evaluate the risks of surgery to the gastrointestinal system [5]. Onedera et al. then evaluated the effect of PNI in cancer patients and a correlation was determined between low PNI and poor survival [6]. As a result of subsequent studies, it was shown to be a simple and effective method that could be used preoperatively to determine the optimum medical treatment, define the most appropriate time for surgery,and to predict cancer prognosis [7].

The PNI value has been examined before curative or palliative surgery in colorectal cancers, but the prognostic importance of the value before adjuvant radiotherapy is not known. In this study, the PNI values were examined in patients undergoing adjuvant chemoradiotherapy because of rectum cancer, which is different from colon cancer in respect to treatment and survival. To the best of our knowledge, this is the first study to evaluate the effect of PNI value before chemoradiotherapy on disease-free survival and overall survival in surgically treated rectum cancers.

Material and Method

Patients

This retrospective study included patients who underwent surgery because of rectum cancer between January 2007 and December 2011 and received adjuvant chemoradiotherapy. The clinical, pathological, and blood sample data of the patients were obtained retrospectively from the hospital records. Patients without survival data or serum albumin and lymphocyte values, those receiving radiotherapy <50Gy, those who could not receive chemotherapy, those having secondary malignancy, and those receiving neoadjuvant chemoradiotherapy were excluded from the study. After the application of the exclusion criteria, a total of 65 patients were included in the study.

TNM classification was determined according to the AJCC. All the patients were administered 5040 Gy radiotherapy and, simultaneously, two cycles 425mg/m2 fluorouracil with 20 mg/m2 folinic acid chemotherapy. After the radiotherapy, the patients were followed up at 3-month intervals for the first two years, then every six months up to five years and annually thereafter. Adjuvant chemotherapy was continued after the chemoradiotherapy. All the blood samples were taken before the chemoradiotherapy was started. The PNI value was calculated using the formula of 10 x serum albumin +0.005 x total lymphocyte count. This study was approved by the Local Ethics Committee.

Statistical analysis

For the statistical analyses of the study data, SPSS version 20.0 (IBM; SPSS Inc. Chicago, IL) software was used. Data were expressed as frequency, percentage, mean± standard deviation, and median (min-max). A value of p<0.05 was accepted as statistically significant.

ROC analysis was applied to determine the best predictive value of PNI for 5-year survival. The cutoff value was determined as 46 with 70% sensitivity and 57% specificity (Figure 1). The area under the curve was 0.632. The patients were separated into two groups, as low PNI ≤46 and high PNI >46. The Chi-square test was used to compare the low PNI group and the high PNI group with respect to age, gender, T stage, N stage, stage, grade, perineural invasion, lymphovascular invasion, and tumor diameter.

The differences in survival between the groups were calculated with the log rank test. The survival curves were created using the Kaplan-Meier method. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Significant values in the univariate Cox regression analysis were included in the multivariate analysis.

Results

The patients included 22 (33.8%) females and 43 (66.2%) males with a median age of 63 years (range, 28-81 years). The low PNI group comprised 28 (43.1%) patients and the high PNI group, 37 (56.9%). The median follow-up period was 58 months (range, 4-112 months). The median overall survival (OS) rate was 92 months (95% CI; range, 61-122 months). The disease-free survival (DFS) rate was 90 months (95% CI; range, 55-124 months). At the end of the follow-up period, 31 (47.7%) patients had died, and 32 (49.2%) patients had developed local recurrence and/or distant metastasis.

A statistically significant relationship was determined between PNI and advanced age (p=0.04). No statistically significant relationship was determined between PNI and gender, T stage, N stage, perineural invasion, lymphovascular invasion, tumor diameter, or grade (Table 1).

In the Kaplan-Meier analysis, the T stage (p=0.019), N stage (p=0.26), grade (p=0.005), PNI (p=0.028), and tumor diameter (p=0.018) of the clinicopathological features were determined to have an effect on OS. The DFS rate was found to be affected by the T stage (p=0.021), N stage (p=0.007), stage (p=0.019), perineural invasion (p=0.011), grade (p=0.008), and tumor diameter (p=0.035).

According to the Kaplan-Meier analysis, OS was median 54 months (95% CI; range, 26-81 months) in the low PNI group, and while the median OS could not be calculated in the high PNI group, the mean value was 81±14 months (95% CI; range 67-95 months) (p=0.028, Figure 2). The 5-year OS rate was 49% in the low PNI group and 65% in the high PNI group. The 9-year OS rate was 20% in the low PNI group and 58% in the high PNI group. The DFS was determined as 41 months (95% CI; range, 1-101 months) in the low PNI group and the median DFS was calculated as 74±15 months (95% CI; range, 59-89 months) in the high PNI group. The 5-year DFS was found to be 45% in the low PNI group and 64% in the high PNI group. The 9-year DFS rates were 26% in the low PNI group and 52% in the high PNI group. Although the DFS was correlated with high PNI, it was not statistically significant (p=0.114).

In the univariate Cox regression analysis, T stage, N stage, tumor diameter, and PNI were found to have a statistically significant effect on overall survival (p<0.05). In the multivariate Cox regression analysis, T stage (p=0.014), tumor diameter (p=0.023), and PNI (p=0.045) were found to be prognostic factors affecting overall survival, independent of the other variables. The factors affecting OS and DFS in the Cox regression analysis are shown in Table 2 and Table 3.

Discussion

In the tumor environment, inflammation is a key element and plays a significant role in tumor development, metastasis, and response to treatment [8]. It is known that systemic inflammation raises the level of C-reactive protein and changes the relative proportion of white blood cells, thereby elevating the neutrophil count and decreasing the lymphocyte count [9, 10]. Lymphopenia is often observed in cancer patients at an advanced stage, and the reduced lymphocyte count is strongly associated with a poor prognosis of progression-free survival and OS in advanced cancer patients [11]. Kitayama et al. [12] found a correlation between the lymphocyte value measured in peripheral blood and better tumor response in non-metastatic rectum cancer treated with neoadjuvant chemoradiotherapy.

A previous study of Stage III CRC patients showed better OS and DFS in patients with high lymphocyte levels that had infiltrated the tumor micro-environment compared to patients with low levels [13]. A correlation was also shown in nasopharynx cancer patients between low percentage of lymphocyte and poor survival [14]. In addition to albumin being a good marker showing the nutritional status of the patient, it has recently been used as a marker of inflammatory response. Heys et al. [15] first determined a relationship between hypoalbuminemia and increased risk of mortality in a study of 431 patients with localized colorectal cancer. Current studies of colorectal cancer patients have shown a linear relationship between serum albumin level and postoperative morbidity and mortality [16]. On the basis of these studies, it can be said that there is a close correlation between low albumin and lymphocyte values and poor cancer survival. Therefore, to predict the prognosis of patients, scoring scales have been developed that include the albumin and lymphocyte values such as the Glasgow Prognostic Score, the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, and PNI.

PNI is a simple, cost-effective, and well-validated tool that is calculated from the serum albumin and total lymphocyte count to show the immuno-nutritional status of patients. It was first used by Onedera et al. [6] to determine the nutritional status of patients who had undergone surgery for gastrointestinal cancer. Although a cutoff value of 45 for PNI is accepted as malnutrition, some authors have defined a cutoff value of 40 based on the study of Onedera et al. and others have used different cutoff values of 44.7, 48, and 44.6. In the current study, the cutoff value was defined as 46 using ROC curve analysis as in the study by Jiang et al. [17].

In a study of 219 CRC patients, Nozoe et. al. [18] showed an increase in depth of tumor invasion and, accordingly, an increased tumor stage with low PNI. Although there was a relationship between low PNI and advanced age, which was close to statistical significance (p=0.06), no relationship was determined between gender, lymph node metastasis, lymphatic permeation, venous invasion, and PNI, which is consistent with the findings of the current study. When the survival analysis was examined, tumor stage, PNI, and venous invasion had an effect on survival, independent of other factors.

Mohri et al. [19] determined that low PNI was a poor prognostic factor for postoperative complications and OS, especially in Stage II-III CRC. However, this correlation was not seen at Stage IV. As Stage IV disease was not included in the current study, the conclusion was reached of a correlation between low PNI and poor OS in locally advanced disease. Furthermore, in the Mohri et al. study, low PNI was more often seen in patients aged over 65 years, with large tumor size, and a higher TNM stage. In the current study, low PNI was also seen more often in patients over 65 years of age, but there was no correlation with tumor size and stage. These results are supported by a large cohort study that showed that rates of low PNI increased at an advanced age and, in contrast to Stage IV, reduced survival at Stages II-III [20].

In the current study, no relationship was found between tumor diameter, T stage, and N stage in the postoperative pathology evaluation; this is thought to be due to the absence of a tumor. However, low PNI was still correlated with poor OS. This result can be explained by the relationship of the low PNI in the preoperative period with the tumor-systemic immune/inflammatory response, as it has been suggested that a larger volume of tumor cells leads to higher production of proinflammatory cytokines, which in turn suppresses the hepatic production of albumin [16, 21].

The PNI in the postoperative period can have a negative effect on OS through different routes such as impaired nutrition, nutritional or inflammatory changes that can develop after surgery, or patient tolerance to adjuvant treatments. Previous studies have shown that malnutrition has weakened the immune system, lowered the response to chemotherapy, and consequently has caused poor survival [22, 23]. In addition to these factors, albumin itself may increase the efficacy of associated chemotherapeutic drugs [24]. Therefore, the PNI value must initially be calculated before CRT, and nutritional support must be considered for patients with low albumin and PNI levels.

In conclusion, in contrast to studies where the PNI value was examined preoperatively in patients with colorectal cancer, the PNI value before radiotherapy in patients undergoing postoperative adjuvant chemoradiotherapy because of rectum cancer was found to be a poor prognostic factor. However, as this was the first study and was retrospective, further prospective studies with a high number of patients are needed to better clarify this subject.

Competing interests

The authors declare that they have no competing interests.

References

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2. Li M, Li J, Zhao A, Gu J. Colorectal cancer or colon and rectal cancer? Oncology 2008;73(1-2):52-7.

3. Brodsky JT, Richard GK, Cohen AM, Minsky BD. Variables correlated with the risk of lymph node metastasis in early rectal cancer. Cancer 1992;69(2):322-6.

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5. Buzby GP, Mullen JL, Matthews DC, Hobbs CL, Rosato EF. Prognostic nutritional index in gastrointestinal surgery. The American Journal of Surgery 1980;139(1):160-7.

6. Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi 1984;85(9):1001-5.

7. Sun K, Chen S, Xu J, Li G, He Y. The prognostic significance of the prognostic nutritional index in cancer: a systematic review and meta-analysis. J Cancer Res Clin Oncol 2014;140(9):1537-49.

8. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454(7203):436-44.

9. Epstein FH, Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. New England Journal of Medicine 1999;340(6):448-54.

10. Song A, Eo W, Lee S. Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients. World J Gastroenterol 2015;21(43):12410.

11. Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Research 2009;69(13):5383-91.

12. Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H. Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer. Radiation Oncology 2010;5(1):1.

13. Huh JW, Lee JH, Kim HR. Prognostic significance of tumor-infiltrating lymphocytes for patients with colorectal cancer. Archives of Surgery 2012;147(4):366-72.

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16. Chiang J, Chang C, Jiang S, Yeh C, You J, Hsieh P, et al. Pre‐operative serum albumin level substantially predicts post‐operative morbidity and mortality among patients with colorectal cancer who undergo elective colectomy. Eur J Cancer Care (Engl). 2015. doi: 10.1111/ecc.12403.

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Neslihan Kurtul, Celalettin Eroglu. Low prognostic nutritional index before radiotherapy is a poor prognostic factor for rectum cancer. J Clin Anal Med. 2017;8(3):185-189

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Retrospective Analysis of 513 Cases Diagnosed with Rib Fracture Secondary to Blunt Thorax Trauma

Serdar Özkan 1, Gözde Besi Tetik 2, Rezan Tahtacı 2, Osman Uzundere 3, Gökçe Cinli 3

1 Department of Thoracic Surgery, 2 Department of Emergency Medicine, 3 Department of Anesthesiology and Reanimation, Siirt State Hospital, Siirt, Turkey

DOI: 10.4328/JCAM.4788 Received: 24.08.2016 Accepted: 16.09.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 181-4

Corresponding Author: Serdar Özkan, Department of Thoracic Surgery, International Medicana Konya Hospital, Konya, Turkey. T.: +90 3322218080 E-Mail: drozkan78@yahoo.com

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Aim: This study aimed to analyze blunt chest trauma cases who were diag-nosed with rib fracture and to examine the regional differences likely to ap-pear in trauma cases and treatment approaches. Material and Method: 513 cases who applied to the Emergency Service and Department of Thoracic Surgery between October 2013 and December 2014 due to blunt trauma and were diagnosed with rib fracture were retrospectively examined. The cases were evaluated in terms of etiological factors, thoracic, and other system injuries accompanying the rib fracture, prognosis, and the treatments ap-plied. Results: Isolated rib fracture was present in 266 of the cases. Thoracic organ injuries such as pneumothorax, hemothorax, hemopneumothorax, lung contusion, or laceration and sternal fracture accompanying the rib fracture were present in 247 of the cases. While one or two rib fractures were detect-ed in 298 cases, six or more rib fractures were present in 28 cases. 78.2% of hemothorax cases, 85.3% of pneumothorax cases, 95.4% of hemopneu-mothorax cases, 81.8% of bilateral pneumothorax cases, 26% of bilateral hemothorax cases, and 71.4% of bilateral hemopneumothorax cases were treated by applying tube thoracostomy. 129 cases diagnosed with thoracic organ injury in addition to rib fracture but not subjected to surgical interven-tion, and 266 cases diagnosed with isolated rib fracture were discharged with full recovery after appropriate medical treatment. Discussion: Most of the rib fractures occurring due to blunt trauma are treated successfully with medical treatments and conservative approaches and do not need advanced surgical treatments.

Keywords: Trauma; Rib; Fracture

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Introduction

It is known that severe chest trauma constitutes 1/3 of the cases hospitalized due to trauma, and that thorax trauma is responsible for 20-25% of the mortalities [1]. Blunt chest traumas are increasing as a result of today’s living standards. Many are due to traffic accidents. Traumas resulting from playing sports and from falling are more frequently seen than the penetrating traumas. As in all traumas, immediate evaluation, accurate diagnosis, and appropriate and rapid treatment are essential to reduce morbidity and mortality due to thorax traumas.

The objective of our study is to analyze the cases who applied due to chest trauma and were diagnosed with rib fracture and to determine the regional differences likely to appear in trauma cases.

Material and Method

This study retrospectively examined 513 cases who applied to the Emergency Service and Department of Thoracic Surgery of Siirt State Hospital between October 2013 and December 2014 due to blunt trauma and were diagnosed with rib fracture.

The cases were divided into seven different groups according to the way the trauma occurred: traffic accident inside a vehicle, traffic accident outside a vehicle, pounding, falling, sports accident, occupational accident, and other accidents. We evaluated the radiological examinations that were performed when the cases applied to our hospital and those that were performed in the hospital during their treatment. The cases were examined in terms of etiological factors, thoracic and other system injuries accompanying the rib fracture, prognosis, and the treatments applied. The patients treated by hospitalization were categorized into two groups: those being followed under service and those in intensive care conditions. The cases were evaluated in three groups according to the treatment approach: a conservative approach with medical treatment, those having tube thoracostomy, and those having thoracic surgery. A conservative approach with appropriate medical treatment and without surgical intervention was performed in the cases who were diagnosed with radiologically localized, linear, or minimal pneumothorax or hemothorax, but whose current pathology was not evident in their physical examination and did not affect their general condition. All the other cases were treated with tube thoracostomy and surgical procedures. Thoracic epidural catheter application was performed in the cases continuing to have severe pain despite the analgesic treatment.

Results

Of 513 cases included in the study, 341 (66.4%) were male and 172 were female. The average age of the cases was 37.2 (3-76).

The cases were mainly composed of those diagnosed with rib fracture after traffic accidents or pounding (Table 1). Isolated rib fracture was present in 266 of the cases. Thoracic organ injuries such as pneumothorax, hemothorax, hemopneumothorax, lung contusion or laceration, and sternal fracture accompanying the rib fracture were present in 247 (48.1%) of the cases (Table 2). The second most frequently observed injuries were musculoskeletal system injuries (33.7%) (Table 3). While one or two rib fractures were detected in 298 (58%) cases, six or more rib fractures were present in 28 (5.4%) cases (Table 4). Flail chest was not detected in any cases with multiple rib fracture.

Parenteral analgesic treatment was administered as standard to all the cases who were hospitalized; intercostal nerve blockage was applied to the cases whose pain could not be controlled completely despite the treatment. In addition to medical treatment and intercostal nerve blockage, thoracic epidural catheter application for analgesia was performed in 48 of 215 cases with severe pain in whom three or more rib fractures were monitored.

Of the 84 cases in which lung contusion was monitored, 55 (65.4%) were due to traffic accidents, 9 (10.7%) were due to pounding, 6 (7.1%) were due to occupational accident, 11 (13%) were due to falling, and 3 (3.5%) were due to other traumas (Table 2). There was pneumothorax in 18 cases diagnosed with contusion, hemopneumothorax in ten cases, and bilateral hemothorax in eight cases which were detected as comorbidities.

Thoracotomy plus a surgical repair operation were performed in three of the cases included in the study due to lung laceration. One case who was operated on due to lung laceration plus hemopneumothorax after a traffic accident out of the vehicle also had abdominal organ injury and died intraoperatively. One case in whom lung contusion was monitored was operated on due to the rupture of the traumatic pseudocyst observed in the contusion area after three days. Of the 34 cases having abdominal organ injury accompanying the rib fracture, liver injury was detected in 22 and spleen injury in 12. Three cases diagnosed with spleen injury were operated on by general surgery.

327 (63.1%) of the 513 cases included in the study were treated by hospitalization. Nineteen cases were followed under intensive care conditions and 308 cases were followed under service conditions. 78.2% of hemothorax cases, 85.3% of pneumothorax cases, 95.4% of hemopneumothorax cases, 81.8% of bilateral pneumothorax cases, 26% of bilateral hemothorax cases, and 71.4% of bilateral hemopneumothorax cases were treated by applying tube thoracostomy (Table 5). 129 cases diagnosed with thoracic organ injury in addition to rib fracture but not subjected to surgical intervention and 266 cases diagnosed with isolated rib fracture were discharged with full recovery after appropriate medical treatment.

The average hospitalization duration of the cases was 3.6 (2-7) days in isolated rib fracture cases and 5.2 (4-11) days in the other cases. Average hospitalization durations were 4.2 (2-6) for those under service care and 7.8 (4-11) for intensive care.

Discussion

Thorax traumas are involved in a substantial portion of the patients applying to emergency service due to trauma, and it is reported that thorax traumas constitute about 1/3 of the cases hospitalized [2].

The most frequently observed complication is rib fractures in blunt thorax trauma. Generally, it is observed in the 4th-9th ribs. Fracture in the first or second ribs indicates that the trauma is very severe [3]. In the fractures occurring in the 9th-12th ribs, liver, and spleen injuries may occur. Surgical intervention is very rarely needed in rib fractures. The cases having more than three fractures or elderly cases should be hospitalized and receive treatment for preventing complications.

Of the 513 cases included in the study, 266 (51.8%) were diagnosed with isolated rib fracture. 116 (43.6%) of these cases were due to traffic accidents while 150 (56.3%) had other traumatic etiologies. Isolated rib fracture cases mainly had an outpatient follow-up with medical treatment without needing hospitalization. Rib fractures may lead to a wide range of complications, from simple pain to life-threatening organ injuries. However, as in our study, most cases can be treated with conservative approaches. Major surgical interventions such as thoracotomy or sternotomy are required in 10% of the blunt trauma cases while emergency thoracotomy is required in 1-2% [4]. Rates of thoracotomy due to trauma are reported between 1.2-12.7% in the studies conducted in our country [2]. The rate of thoracotomy in our study was 0.7%. We believe this lower rate of thoracotomy is because only the cases with rib fracture were included in the study; it may also be due to the high rate of cases with rib fracture due to pounding and falling.

At 54%, extremity injuries are the injuries most frequently accompanying thorax trauma [5]. With similar results, musculoskeletal system injuries were monitored as the most frequently accompanying injury in our study.

Pulmonary contusion is frequently seen in the posttraumatic period and paves the way for complications such as pneumonia and ARDS [6]. Contusion especially occurs during in-vehicle traffic accidents, and its mortality rate can reach 40% [7]. In our study the pulmonary contusion rate was 16.3%. We believe this high rate of contusion is probably because most of the traffic accident cases might be caused by vehicles locally known as “pat pats”, manufactured in local factories and without safety features. These vehicles, which make a thudding sound, are commonly used in the region in which our hospital give service. The injuries that occur in accidents involving these vehicles are similar to those that occur from motorcycle accidents.

It is stated that traffic accidents are among the most frequent causes of death, especially for those below the age of 40, and the majority of those exposed to such injuries are male [8]. Likewise, in our study there were more males than females.

In a study conducted in our country, while traffic accidents constitute most of the chest traumas, chest traumas due to falling rank second [2]. In our study, however, pounding cases ranked second. Moreover, we strongly suspect that some of the cases reported during anamnesis as resulting from sports accidents or falls actually occurred due to pounding. However, to avoid revealing the situation as a judicial case, an incorrect anamnesis was given deliberately. We think that this result is due to the different sociocultural understanding of life in different regions of our country.

The most frequently observed intrathoracic pathologies are hemothorax and pneumothorax in blunt thorax traumas [1,9]. Regarding pneumothorax in thorax trauma cases, studies can be found that absolutely suggest tube thoracostomy for preventing serious complications such as tension pneumothorax [10]. In our study, tube thoracostomy was applied to 126 of 144 cases diagnosed with pneumothorax while 18 cases were radiologically followed with continuous oxygen support by 2 l/m without applying tube thoracostomy due to monitoring minimal/linear pneumothorax line. Clinical and radiological progression was not observed in any of the 18 cases and they were discharged with full recovery.

Pain control and follow-up and respiratory physiotherapy have important roles in thorax trauma cases. Therefore, in our study, medical treatment and respiratory physiotherapy were applied to all of the cases for pain control and secretion retention. Some studies suggest stabilization of rib fractures with operative methods for shortening the hospitalization duration and for preventing complications [11]. No operation was performed for rib fractures in any of our study cases. In addition to medical treatment, thoracic epidural catheter application for analgesia was performed in 48 of 215 cases in whom three or more rib fractures were monitored due to severe pain. In all of the cases to whom a thoracic epidural catheter was applied, there was a significant decrease in pain and a significant increase in mobilization and respiratory exercise capacities.

 Conclusions

Most of the rib fractures occurring due to blunt trauma can be treated with medical treatments and conservative approaches and do not need advanced surgical treatments. We suggest that, apart from operations to be performed for preventing thoracic organ injury in displaced rib fractures, it is appropriate to try alternative methods such as thoracic epidural catheter application. This should be used primarily for intercostal blockage or analgesia for rib stabilization operations that are performed, but only if there is a pain indication. Additionally, we recommend that cases of minimal pneumothorax and hemothorax occurring secondary to blunt trauma should be treated with close clinical and radiological follow-up instead of performing tube thoracostomy. Larger-scale research studies should explore surgical intervention application for cases where pneumothorax and hemothorax continue to progress.

Competing interests

The authors declare that they have no competing interests.

References

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Serdar Ozkan, Gozde Besi Tetik, Rezan Tahtaci, Osman Uzundere, Gokce Cinli. Retrospective analysis of 513 cases diagnosed with rib fracture secondary to blunt thorax trauma. J Clin Anal Med. 2017;8(3):181-184

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Treatment of Hallux Valgus with Hyaluronic Acid: A Pilot Study

İlhan Sezer 1, Meral Bilgilisoy Filiz 2, Sibel Çubukçu Fırat 3

1 Department of Physical Medicine and Rehabilitation, Division of Rheumatology, Antalya Training and Research Hospital, 2 Department of Physical Medicine and Rehabilitation, Antalya Training and Research Hospital, 3 Department of Physical Medicine and Rehabilitation, Division of Algology, Akdeniz University, Faculty of Medicine, Antalya, Turkey

DOI: 10.4328/JCAM.4786 Received: 17.08.2016 Accepted: 14.09.2016 Printed: 01.05.2017 J Clin Anal Med 2017;8(3): 177-80

Corresponding Author: Meral Bilgilisoy Filiz, Department of Physical Medicine and Rehabilitation, Antalya Training and Research Hospital, 07100 Antalya, Turkey. T.: +90 2422494400-4287 GSM: +905056475840 F.: +90 2422494462

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Abstract

Aim: Hallux valgus is the deformity of the first metatarsophalangeal (MTP) joint with abduction and valgus rotation of the great toe, combined with a medially prominent first metatarsal head. Hyaluronic acid injection has been used in the treatment of degenerative disorders of several joints success-fully. In this research, we aimed to investigate the effectiveness of hyaluronic acid injection in patients with hallux valgus. Material and Method: Eleven female and two male patients with hallux valgus were included in this pilot study. Only patients with mild and moderate hallux valgus were included in the study. 1 cc hyaluronic acid was injected into the affected MTP joint three times, at one-week intervals. Visual analogue scale(VAS) score, walking time without pain, walking distance, and daily analgesic needs of the patients were recorded. All clinical outcomes were assessed before, and then one and three months after the first injection. Results:The mean VAS score was 83.08±4.58. One month after the first injection, VAS scores of patients had decreased sig-nificantly (30±4.38, P: 0.001). Also, increased walking time and distance and decreased daily analgesic need were observed at the first month of postin-jection follow-up (P: 0.001). After 3 months, the positive outcomes remained significant compared to preinjection evaluations. Discussion: According to our preliminary results, we suggest thathyaluronic acid injectionsmay be ef-fective in reducing pain and increasing walking time and distance in patients with hallux valgus.Future studies are needed to clarify the beneficial effects of hyaluronic acid injection in patients with hallux valgus.

Keywords: Hallux Valgus; Hyaluronic Acid; Osteoarthritis

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Introduction

Hallux valgus deformity is one of the most common foot problems seen by clinicians. It is defined as a deformity at the first metatarsophalangeal (MTP) joint with abduction and valgus rotation of the great toe, combined with a medially prominent first metatarsal head [1]. The etiology can be related to occupational, genetic, and extrinsic factors. Heredity seems to be the major predisposing factor with up to 68% of patients showing a familial tendency [2].Extrinsic factors, such as wearing high-heeled shoes may also be important in the development of hallux valgus [3].Although nonsurgical approaches have been recommended as the first treatment choice, there are a few conservative treatment alternatives for patients with hallux valgus deformity [4].The source of pain in patients with hallux valgus may be the peripheral soft tissue or secondary degenerative changes in the joint.

Hyaluronic acid injection has been used in the treatment of degenerative disorders of several joints successfully [5-7].However, to the best of our knowledge, there are no trials concerning the effects of hyaluronic acid injections in hallux valgus. Therefore, in this research, we aimed to investigate the effectiveness of hyaluronic acid injection in patients with hallux valgus by carrying out a pilot study.

Material and Method

Eleven female and two male consecutive patients with hallux valgus were recruitedbetween July and November 2007. All the subjects gave their informed consent prior to their inclusion in the study.The principles outlined in the Declaration of Helsinki were followed.Weight-bearing anteroposterior radiographs of both feet were obtained from each patient to assess the hallux valgus angle (HVA) and the intermetatarsal angle (IMA). The HVA is formed by the intersection of the longitudinal axes of the proximal phalanx and the first metatarsal,and the IMA is formed by the intersection of the longitudinal axes of the first and second metatarsals (Figures 1-2) [8].The severity of the deformity was classified using the following radiological criteria: normal (HVA<15°, IMA<10°); mild (HVA 15 to 20°, IMA 10 to 14°); moderate (HVA 20° to 40°, IMA 15° to 20°), and severe (HVA>40°; IMA>20°) [9].Using this classification, the grading of hallux valgus by radiographs was performed by the same experienced researcher. Patients with mild and moderate hallux valgus were included in this study. Patients were excluded if they had severe hallux valgus, hallux rigidus or any other foot deformities,orsystemic or neuropathic disorders that affect the foot and ankle such as rheumatoid arthritis, gout, or polyneuropathy. Patients taking anticoagulant or analgesic drugs and patients whohad a previous intra-articular injection inthe affected MTP joint were also excluded from the study. The contraindications for the injections were infection or inflammation of the joint, skin disease or skin infection at the injection site, pregnancy, and related hypersensitivities.

A 25-gauge needle was used to inject1.2 million dalton weight 1 cc hyaluronic acid (sodium hyaluronat) into the affectedMTP joints three times, at one-week intervals. All hyaluronic acid injections were applied inthe first MTP joint using the standard dorsal approach by the same physician [10].No analgesic was allowed except paracetamol (maximum 2000 mg/day) during the study. Paracetamol use was stopped 8 hours before the clinical evaluations. For clinical evaluation, VAS score, walking time without pain (minutes), walking distance (the number of blocks that can be walked without pain), and daily analgesic needs of the patients were recorded. All clinical outcomes of the patients were assessed before, and then one and three months after the first injection by a differentresearcher.

The statistical analysis was performed using the SPSS 11.0 for Windows program. The clinical outcomes of the patients were analyzed using the Wilcoxon Signed Ranks Test. P<0.05 was considered as being statistically significant.

Results

All patients completed the study. Systemic or local adverse effects did not occur during or shortly after intra-articular injection. The mean age of the patients was 49.69±1.15 years and mean disease duration was 5.08 ±0.30 years. The mean hallux valgus angle was 29.230 (min:160, max:400) and mean intermetatarsal angle was 13.080 (min:100, max:170). In three patients, hallux valgus was in the mild form,whereas moderate form was determined in ten patients. One month after the first hyaluronic acid injection, VAS scores and the amount of daily analgesic needs of patients were found to be significantly decreased (P:0.001) (Table1). Also, increased walking time and distance were observed at the first month of postinjection follow-up (P: 0.001). After 3 months, the positive outcomesfor the patients remained significant compared to preinjection evaluations (P: 0.001). No statistical difference was determined between the first and third monthassessments.

Discussion

Although hallux valgus is a frequently seen musculoskeletal disorder in general, its treatment protocolhas not yet been clarified. A consensus has not been reached on several surgical techniques and their rates of success [11,12].Conservative treatment options which are widely preferred, are limited. In our study, VAS values and daily analgesic needs of patients decreased and walking distance and walking time increased significantly one month after the hyaluronic acid injection. There were no significant differences between the first and third months’ mean values of walking time and distance after injection, reflecting unchanged positive effects of administration. Also, since these findings are similar after three months of the hyaluronic acid delivery,the possibility of a placebo effect is minimized.Similar to our results, several studiesoffirst metatarsophalangeal joint osteoarthritishave reported that HA injections resulted in statistically significant reductions in patients’symptoms [13,14].Pons et al. compared the effectiveness of HAand triamcinolone injections in first metatarsophalangeal joint osteoarthritis in 37 patients, and found that both treatments were successfulin terms of pain at rest or with palpation and pain on passive mobilization, without any significant differences between groups [13].Petrella et al. [14]assessed the efficacy of HA injections into the first MTP joint in golfers toe patients who reported osteoarthritis-associated pain, loss of MTP joint ROM, and disability that interfered with golf participation. They reported that HA injection was significantly effective for pain tolerance[14].However, the results of thethesestudies could not be confirmed by placebo-controlled randomized trials.

The source of pain in patients with hallux valgus has not been clearly determined. Peripheral soft tissue or articular reasons are possible pain sources. Stephens has defined a degenerative process with erosions in the pathogenesis of hallux valgus [15].The tissue damage in the medial line of the MTP joint and erosion in the head of metatarsal and medial or lateral sesamoid bones can be seen even in the early stage of the disorder. The deformation can be initiated with the loss of the cartilage in the head of metatars. Erosion in the MTF joint was determined in studies on patients and cadavers with hallux valgus [16]. Also it has been reported that any disorder resulting in first MTP joint inflammation may weaken MTP soft tissue restraints, predisposing to bunion formation [17].In a study thatevaluated 265 patients with hallux valgus, cartilage degeneration was reported in 73.2% of the patients and a significant correlation between the grade of this degeneration and hallux valgus angle was determined [18].These results of clinical and histopathological studies suggestthat hallux valgus might be considered as a degenerative disorder which can affect the MTP joint and peripheral soft tissue with a process similar to osteoarthritis. Our observational study which indicated the effectiveness of hyaluronic acid in patients with hallux valgus may also support these results. The positive effect of hyaluronic acid in patients with hallux valgus may be the results of its analgesic, anti-inflammatory, and viscoelastic features [5-7].Because of frequent recurrences, high complication rates, and the ineffective results of surgical interventions which have been reported, new conservative treatment alternatives are needed [19].

The main weakness of our study is the limited number of patients, the absence of a control group, and the absence of a specific evaluation method to ratethe functioning of the first toe. Because of these important limitations, our results should be carefully considered.

Conclusions

Despite several important limitations, based onour results, we believethat hyaluronic acid injection may be an effectiveconservative therapy choice for the treatment of hallux valgus.Future controlled studies with larger sample sizesand control groupsare needed to clarify the beneficial effects of hyaluronic acid injection in patients with hallux valgus.

Competing interests

The authors declare that they have no competing interests.

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How to Cite

Ilhan Sezer, Meral Bilgilisoy Filiz, Sibel Cubukcu Firat. Treatment of hallux valgus with hyaluronic acid: A pilot study. J Clin Anal Med. 2017;8(3):177-180

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