Murat Gunay

Comparison of Bevacizumab, Ranibizumab, and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity in Turkey

ABSTRACT Purpose: To evaluate the efficacies and treatment outcomes following intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and laser photocoagulation (LPC) in retinopathy of prematurity (ROP). Methods: This was a retrospective interventional case series study including the data of 134 infants (264 eyes) who were treated with IVB, IVR, or LPC for ROP. The data were collected from two major ROP treatment centers in Turkey without any randomization or masking. Regression of ROP, recurrence profile, complications after each treatment modality, and indications for retreatment were evaluated. The main outcome measures included the total inactivation of ROP with anatomic and refractive outcomes at 1.5 years of adjusted age. Results: There were 55 infants (41.1%) in the IVB group, 22 infants (16.4%) in the IVR group, and 57 infants (42.5%) in the LPC group. All but 3 infants (5.5%) in the IVB group and 11 infants (50%) in the IVR group showed recurrence to stage 1 and 2 ROP following IVB and IVR (p < 0.001). Retreatment was performed in three infants in both IVB and IVR groups (p = 0.098). At 1.5 years of adjusted age, all infants showed favorable anatomic outcome except one infant in the LPC group. No significant difference of the mean spherical equivalent (SE) was observed between the groups (p = 0.131). In Zone I ROP, laser treated infants had significantly higher rates of myopia and high myopia than IVB and IVR treated infants (p = 0.040 and p = 0.019, respectively). Conclusions: Both IVB and IVR treated infants had significantly better refractive outcomes in Zone I ROP as compared to LPC treated infants at 1.5 years of adjusted age. The higher rate of disease recurrence was associated with IVR. Gestational age (GA) and the zone of ROP were also predictive factors for recurrence of ROP in the study.

Heart-type fatty acid-binding protein as a potential biomarker of acute carbon monoxide poisoning☆☆☆

BACKGROUNDnThe aim of this study was to investigate the role of serum heart-type fatty acid-binding protein (H-FABP) in the evaluation of patients with carbon monoxide (CO) poisoning.nnnMETHODSnForty patients with acute CO poisoning admitted to the emergency department and 15 healthy adults as the control group were included in the study. Serum H-FABP levels of patients were studied on admission and at the 6th, 12th, and 18th hours. Patients were divided into 3 groups according to clinical severity as mild, moderate, and severe. Patients were also divided into 2 groups according to treatment with hyperbaric oxygen (HBO) or normobaric oxygen.nnnRESULTSnSerum H-FABP levels of the patients were higher than those of the control group. There was a negative correlation between H-FABP levels and Glasgow Coma Scale score on admission. Heart-type fatty acid-binding protein levels were significantly higher in patients in the severe compared with mild group. Heart-type fatty acid-binding protein levels in patients treated with HBO were significantly higher than in those treated with normobaric oxygen. The cutoff value of serum H-FABP as an indicator for HBO treatment was determined as 1.5 ng/mL or higher, with a sensitivity of 85.7% and specificity of 69.7%. Serial measurement revealed that H-FABP level peaked at the sixth hour and reduced over time but remained higher than in the control group at the 18th hour.nnnCONCLUSIONnHeart-type fatty acid-binding protein may be a promising novel biomarker in the evaluation of clinical severity and in the selection of patients for HBO therapy in acute CO poisoning.

New inflammatory markers for prediction of non-dipper blood pressure pattern in patients with essential hypertension: Serum YKL-40/Chitinase 3-like protein 1 levels and echocardiographic epicardial adipose tissue thickness

Abstract The aim of the present study was to investigate whether YKL-40 levels and epicardial adipose tissue (EAT) thickness were associated with non-dipping pattern in essential hypertension (HT). Age- and sex-matched 40 dipper hypertensive patients and 40 non-dipper hypertensive patients were included in the study. Non-dippers had significantly increased EAT thickness and higher YKL-40 and high-sensitivity C-reactive protein levels than dippers. Multivariate logistic regression analysis showed that the EAT thickness and serum levels of YKL-40 and high-sensitivity C-reactive protein were independent predictors of non-dipping pattern in essential HT. In essential HT, presence of non-dipping pattern is associated with increased inflammatory response.

The Relationship between Serum Oxalic Acid, Central Hemodynamic Parameters and Colonization by Oxalobacter formigenes in Hemodialysis Patients

Background/Objective: Elevated pulse wave velocity (PWV) and central aortic blood pressures are independent predictors of increased cardiovascular morbidity and mortality in hemodialysis (HD) patients. Oxalic acid is a uremic retention molecule that is extensively studied in the pathogenesis of calcium oxalate stones. Oxalobacter formigenes, a member of the colon microbiota, has important roles in oxalate homeostasis. Data regarding the colonization by and the exact role of O. formigenes in the pathogenesis of oxalic acid metabolism in HD patients are scant. Hence, we aimed to determine the relationship between fecal O. formigenes colonization, serum oxalic acid and hemodynamic parameters in HD patients with regard to the colo-reno-cardiac axis. Methods: Fifty HD patients were enrolled in this study. PWV and central aortic systolic (cASBP) and diastolic blood pressures (cADBP) were measured with a Mobil-O-Graph (I.E.M. GmbH, Stolberg, Germany). Serum oxalic acid levels were assessed by ELISA, and fecal O. formigenes DNA levels were isolated and measured by real-time PCR. Results: Isolation of fecal O. formigenes was found in only 2 HD patients. One of them had 113,609 copies/ml, the other one had 1,056 copies/ml. Serum oxalic acid levels were found to be positively correlated with PWV (r = 0.29, p = 0.03), cASBP (r = 0.33, p = 0.001) and cADBP (r = 0.42, p = 0.002) and negatively correlated with LDL (r = -0.30, p = 0.03). In multivariate linear regression analysis, PWV was independently predicted by oxalic acid, glucose and triglyceride. Conclusions: This is the first study that demonstrates the absence of O. formigenes as well as a relation between serum oxalic acid and cASBP, cADBP and PWV in HD patients. Replacement of O. formigenes with pre- and probiotics might decrease serum oxalic acid levels and improve cardiovascular outcomes in HD patients.

Neutrophil-Lymphocyte ratio and Platelet-Lymphocyte ratio as useful predictive markers of prediabetes and diabetes mellitus

AIMSnChronic inflammation plays a central role in the development and progression of diabetes, and in the pathogenesis of its complications. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are indicators of subclinical inflammation. Mean platelet volume (MPV) is one of the platelet function indices. We investigated the association of NLR, PLR and MPV with prediabetes and type 2 diabetes mellitus and determine whether or not these are reliable markers for diagnosis.nnnMATERIALS AND METHODSnParticipants were divided into four groups; 1: normal glucose tolerance, 2: impaired glucose tolerance (prediabetic), 3: newly diagnosed diabetic by OGTT. 4: group is previously diagnosed diabetic without complication. Outcomes were compared between groups.nnnRESULTSnThere are significant differences between all groups in NLR (p=0.004) and PLR (p=0.021) values. NLR values are significantly higher in prediabetic (1.60±0.85), firstly diagnosed diabetic (1.58±0.78) and clear diabetic (2.07±0.95) groups compared to normal group (1.37±0.69) (mean, SD). PLR values are significantly lower in prediabetic (90.35±44.34) and firstly diagnosed diabetic (86.38±45.24) groups compared to normal group (100.55±48.14) but significantly higher in clear diabetic group (122.45±37.43). There are no significant differences between all groups in MPV values.nnnCONCLUSIONnInflammation marker NLR significantly increases in prediabetic and diabetic patients. PLR significantly decreases in prediabetes and early stages of diabetes but increases in later stages. NLR and PLR values may be reliable predictive markers in prediabetes and diabetes mellitus.

Serum YKL-40/chitinase 3-like protein 1 level is an independent predictor of atherosclerosis development in patients with obstructive sleep apnea syndrome.

OBJECTIVEnThe inflammatory process plays an important role in the development of cardiovascular complications in patients with obstructive sleep apnea syndrome (OSAS). YKL-40/chitinase 3-like protein 1 is a novel biomarker of systemic inflammation. This study aimed to investigate whether carotid intima-media thickness (CIMT), a useful marker for early atherosclerosis, is associated with serum YKL-40/chitinase 3-like protein 1 levels in patients with normotensive and nondiabetic OSAS.nnnMETHODSnThe study included 40 OSAS patients and 40 age- sex- and body mass index-matched healthy controls. Serum YKL-40 levels were detected by enzyme-linked immunosorbent assay. CIMT was measured by B-mode ultrasound.nnnRESULTSnThe patients with OSAS had significantly increased CIMT and higher YKL-40 and high sensitivity C-reactive protein (hsCRP) levels than those of the controls. CIMT was strongly correlated with serum YKL-40 levels (r=0.694, p<0.001), hsCRP (r=0.622, p<0.001), age (r=0.525, p=0.001), and weakly correlated with apnea-hypopnea index (AHI) (r=0.365, p=0.021) and the percentage of recording time spent (PRTS) of oxygen saturation<90% (r=0.488, p=0.001). Moreover, it was detected that serum YKL-40 levels were strongly correlated with AHI (r=0.617, p<0.001), and weakly correlated with SaO2<90% of PRTS (r=0.394, p=0.012) and hsCRP (r=0.486, p=0.001). In multiple regression analyses, age and serum levels of YKL-40 and hsCRP were found to be independent predictors of CIMT.nnnCONCLUSIONnIn patients with OSAS, CIMT was increased. This increase was associated with serum YKL-40 level. Increased serum level of YKL-40 may be an early predictor of atherosclerosis development in patients with OSAS.

Association between serum fetuin‐A level and erectile function

Recent studies have shown that ED is an early symptom of atherosclerosis. Fetuin‐A, a glycoprotein secreted by the liver, kidneys and choroid plexus, has been linked to systemic fibrosis and calcification in human and rat studies. Deficiency of this compound may play a role in atherosclerosis and cardiovascular disease progression. The aim of the study was to examine whether serum fetuin‐A level is related to erectile function or severity of ED. Sixty ED patients without cardiovascular disease were assigned to one of the three groups (mild, moderate or severe ED) depending on ED severity. Twenty healthy volunteers were included as the control group. The International Index of Erectile Function‐5 questionnaire was used to measure erection quality in all four groups. Mean age, body mass index, total testosterone, low‐ and high‐density lipoprotein cholesterol, and triglyceride levels did not significantly differ between the three erectile dysfunction and control groups (P > 0.05). The group with severe ED had a significantly lower mean fetuin‐A level than the mild ED and control groups. For both mild and moderate ED groups, the mean serum fetuin‐A level was significantly lower in comparison with the control group (P < 0.001). Serum fetuin‐A level may be used as a supplemental biochemical parameter in preliminary evaluation of ED.

The Effects of Diabetes Mellitus on Ovarian Injury and Reserve: An Experimental Study.

Objective: The study aims to investigate the effects of diabetes mellitus (DM) on ovarian injury and reserve in a rat model. Study Design: In this prospective experimental study, 16 female Sprague-Dawley albino rats (12 weeks, 220-240 g) were randomly divided into 2 groups. Group 1 included 8 normal healthy rats as controls. No drug was administered to the controls. Group 2 included the other 8 rats in which diabetes was induced by intraperitoneal injections of streptozotocin (STZ). After overt DM occurred (blood glucose >250 mg/dl), all the animals were euthanized and blood samples were collected by cardiac puncture for biochemical analysis. Bilateral oophorectomy was performed for histopathological examination. Immunoexpressions of nuclear factor-kappa B (NF-kB) and caspase-3 as well as anti-Müllerian hormone (AMH) levels were assessed. Values were analyzed by t test. Results: Immunoexpressions of NF-kB and caspase-3 were significantly higher in non-treated diabetic rats than in the control group (p = 0.011 and p = 0.010, respectively). In healthy control group, AMH levels (3.22 ± 0.58 ng/ml) were significantly higher than in the non-treated diabetic group (1.41 ± 0.25 ng/dl; p = 0.024). Conclusion: Hyperglycemia causes severe ovarian injury via NF-kB pathway and caspase-3 apoptotic pathway, leading to the decrease in ovarian reserve in STZ-induced diabetic rats.

Novel Zinc Finger Protein Gene 469 (ZNF469) Variants in Advanced Keratoconus

ABSTRACT Purpose: Common polymorphic variants upstream of Zinc finger protein gene 469 (ZNF469) have been associated with central corneal thickness. Rare ZNF469 variants have been shown in keratoconus patients. The aim of the current study was to investigate the frequency of ZNF 469 gene variants in rapidly progressive advance keratoconus patients who underwent corneal transplant surgery by the age of 30, compared to their frequency in the normal Turkish population. Methods: A search in a patient database was performed to identify patients with a rapidly progressive keratoconus requiring corneal transplant surgery by the age of 30 in at least one eye. Twenty-six advance keratoconus patients (study group) and 109 health subjects (control group) were included in the study. Blood samples were donated, and genomic DNA was extracted. The entire coding sequence of the ZNF469 gene including the 84 bp of the putative intron was amplified using PCR primers and analyzed using next generation sequencing (NGS). Results: Fifteen single nucleotide polymorphisms previously reported and registered to the dbSNP database were detected in the study group. The allele frequencies of these polymorphisms were higher in the keratoconus group compared to the control group and to the ExAC genome database. Three new missense heterozygote variants and one new synonym variant were detected in keratoconus group. According to prediction software, the P873T and Q2188H variants were shown to be non-tolerated, whereas G3424S could be tolerated. The synonymous variant R1060R is not predicted to lead to abnormal splicing by Human Splicing Finder in silico analysis. Conclusion: New detected ZNF 469 P873T and Q2188H heterozygote coding variants in isolated advance keratoconus patients may be associated with the disease pathogenesis.

An experimental study of ascorbic acid effects in acute renal failure under general anesthesia

PURPOSEnTo evaluate the preventive effect of ascorbic acid on sevoflurane-induced acute renal failure in an experimental rat model.nnnMETHODSnTwenty-four adult male Wistar rats were randomly distributed into three groups. Subjects were allocated into 3 groups: Group I received sevoflurane only, whereas Groups II and III had moderate (150 mg/kg) and high (300 mg/kg) doses of AA in addition to sevoflurane, respectively. Rhabdomyolysis and myohemoglobinuric ARF was formed by intramuscular administration of glycerol on the upper hind limb on the 15th minute of inhalation anesthesia. Biochemical parameters consisted of serum levels of blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), total antioxidant capacity (TAC), and protein carbonyl content. Histopathological variables were tubular necrosis, fibrin, and cast formation.nnnRESULTSnNGAL levels were significantly lower in Group III than Group II and Group I. On the other hand, TAC, PCO, urea and creatinine levels were notably higher in Group I compared with Groups II and III. There was a significant difference between 3 groups on frequencies of acute tubular necrosis (p=0.003), fibrin (p<0.001) and cast (p<0.001). Acute tubular necrosis and fibrin formation were more prominent in Group I. Casts were more common in Groups II and III.nnnCONCLUSIONSnThe ascorbic acid serve as a prophylactic agent against renal damage in patients receiving sevoflurane anesthesia and higher doses were associated with more apparent protective effects.