The Economic Impact of Obesity in Turkey: A Micro-Costing Analysis.

Background: Turkey currently has the highest obesity prevalence among its European counterparts. 32% and 61% of the population live with obesity and overweight, respectively. Overweight and obesity are linked to non-communicable diseases that incur incremental health and economic costs. The significant public health concern warrants an assessment of the cost of obesity. Methods: A micro-costing approach from the public payer perspective was conducted to estimate direct healthcare costs associated with ten obesity-related comorbidities (ORCs) in Turkey. Clinical practice guidelines and a systematic literature review informed ORCs and the respective cost categories. This was subsequently validated by a steering committee comprising seven experts. Seventy public sector physicians were surveyed to estimate healthcare resource use. Unit costs were derived from Social Security Institute's Healthcare Implementation Communique. Cost items were summed to determine the annual cost per patient per ORC, which was validated by the steering committee. Medical inflation was considered in a scenario analysis that varied resource unit costs. Results: Chronic kidney disease, heart failure and type 2 diabetes are the costliest ORCs, incurring an annual cost of 28,600 TRY, 16,639 TRY and 11,993 TRY, respectively. Individuals in Turkey with any ORC triggered direct healthcare costs ranging 1857-28,600 TRY annually. Costs were driven by tertiary care resources arising from treatment-related adverse events, disease complications and inpatient procedures. In the scenario analysis, medical resource unit costs were inflated by 18.7% and 39.4%, triggering an average increase in cost across all ORCs of 1998 TRY and 4210 TRY, respectively. Conclusion: Our findings confirm that obesity and its complications result in significant financial burden to the public healthcare system. By quantifying the burden of obesity across a comprehensive spectrum of ORCs, our study aims to support the economic case for investing in appropriate obesity interventions.

Magnetic resonance imaging based kidney volume assessment for risk stratification in pediatric autosomal dominant polycystic kidney disease.

Introduction: In the pediatric context, most children with autosomal dominant polycystic kidney disease (ADPKD) maintain a normal glomerular filtration rate (GFR) despite underlying structural kidney damage, highlighting the critical need for early intervention and predictive markers. Due to the inverse relationship between kidney volume and kidney function, risk assessments have been presented on the basis of kidney volume. The aim of this study was to use magnetic resonance imaging (MRI)-based kidney volume assessment for risk stratification in pediatric ADPKD and to investigate clinical and genetic differences among risk groups. Methods: This multicenter, cross-sectional, and case-control study included 75 genetically confirmed pediatric ADPKD patients (5-18 years) and 27 controls. Kidney function was assessed by eGFR calculated from serum creatinine and cystatin C using the CKiD-U25 equation. Blood pressure was assessed by both office and 24-hour ambulatory measurements. Kidney volume was calculated from MRI using the stereological method. Total kidney volume was adjusted for the height (htTKV). Patients were stratified from A to E classes according to the Leuven Imaging Classification (LIC) using MRI-derived htTKV. Results: Median (Q1-Q3) age of the patients was 6.0 (2.0-10.0) years, 56% were male. There were no differences in sex, age, height-SDS, or GFR between the patient and control groups. Of the patients, 89% had PKD1 and 11% had PKD2 mutations. Non-missense mutations were 73% in PKD1 and 75% in PKD2. Twenty patients (27%) had hypertension based on ABPM. Median htTKV of the patients was significantly higher than controls (141 vs. 117 ml/m, p = 0.0003). LIC stratification revealed Classes A (38.7%), B (28%), C (24%), and D + E (9.3%). All children in class D + E and 94% in class C had PKD1 variants. Class D + E patients had significantly higher blood pressure values and hypertension compared to other classes (p > 0.05 for all). Discussion: This study distinguishes itself by using MRI-based measurements of kidney volume to stratify pediatric ADPKD patients into specific risk groups. It is important to note that PKD1 mutation and elevated blood pressure were higher in the high-risk groups stratified by age and kidney volume. Our results need to be confirmed in further studies.

A case of crescentic glomerulonephritis with exacerbation of pre-existing IgA nephropathy after COVID-19.

BACKGROUND: Relapses or new-onset IgA nephropathy (IgAN) have been documented in patients after vaccination against SARS-CoV-2; however, only one adult patient has been reported in whom pre-existing IgAN worsened during coronavirus disease 2019 (COVID-19). CASE: We present the first pediatric case with biopsy-proven IgAN and genetically confirmed Alport syndrome, who developed end-stage kidney disease after an exacerbation of IgAN associated with COVID-19. The patient`s basal serum creatinine was 0.7-0.9 mg/dL before infection. He had not been vaccinated against COVID-19. He was admitted to the hospital with edema, hypertension, an elevated serum creatinine of 4.7 mg/ dL, and massive proteinuria. Three months before admission, he had been admitted to another hospital with COVID -19 and an elevated serum creatinine (1.9 mg/dL), but no biopsy had been performed at that time. The kidney biopsy revealed IgAN with 50% fibrocellular crescents with sclerosed glomeruli, tubular atrophy, and interstitial fibrosis. His serum creatinine did not decrease even after five administrations of pulse steroids, and hemodialysis was initiated. CONCLUSION: In conclusion, COVID -19 may pose a high risk for exacerbation of pre-existing glomerular disease. It is therefore necessary to closely monitor the kidney function of patients with underlying glomerulonephritis during and after COVID-19 and consider an early biopsy if serum creatinine does not return to baseline levels. In addition, this case report highlights the clinical importance of the co-occurence of IgAN and Alport syndrome.

Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study.

BACKGROUND: Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. METHODS: Data from children aged 0-19 years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1 year of age without pre-existing kidney abnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15 ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. RESULTS: A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13 years old (range 2-18 years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15 years old. CONCLUSION: MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.

COVID-19 associated thrombotic microangiopathy.

A limited number of cases of thrombotic microangiopathy (TMA) have previously been reported in association with COVID-19. Our report describes two cases of TMA associated with COVID-19, one of which was successfully treated with eculizumab. The first case was a 23-month-old girl, and the second case was a 9-month-old boy. PCR tests for SARS-CoV-2 were positive in both cases, and laboratory results showed microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. No known aetiology for TMA was found in either case. Stool tests for Shigatoxin-producing Escherichia coli were negative. Coagulation tests, ADAMTS13 activity, serum complement levels, and homocysteine levels were all within the normal range. No known genetic mutation was found, including mutations of complement, diacylglycerol kinase epsilon, and cobalamin C. In the first case, eculizumab was administered due to persistent haemolysis and prolonged anuria. In conclusion, TMA may be associated with COVID-19 infection. Treatment with eculizumab may be beneficial in selected patients because of the potential activation of the complement system.

Combination treatment of bortezomib and epirubicin increases the expression of TNFRSF10 A/B, and induces TRAIL-mediated cell death in colorectal cancer cells.

Colorectal cancer is one of the most common cancers worldwide, affecting the colon and rectum. A major problem in the treatment of colorectal cancer is acquired chemoresistance, including resistance against death receptor-induced apoptosis. Therefore, investigating new biomarkers for the treatment of the disease and sensitization strategies against TRAIL might be of high clinical importance. TNFRSF10A/B are known as death receptors for TRAIL-induced apoptotic cell death. In this study, we used multiple bioinformatic tools and experimental analyses to investigate the role of TRAIL receptors TNFRSF10A and TNFRSF10B in colorectal cancer. We also identified the potential effect of bortezomib and epirubicin in the induction of TRAIL-mediated apoptotic cell death. Here, we showed that TNFRSF10 A/B expressions are upregulated in various tumor types, including COAD, and its high expression is decreased with the different clinicopathological parameters in COAD. We also found an association between TNFRSF10 A/B expression and tumor molecular subtypes. We further detected the association between the expression of TNFRSF10 A/B and immune cell tumor infiltration, including B cells, CD8+ T cells, neutrophils and dendritic cells. In addition, we showed that combining bortezomib and epirubicin treatment leads to the upregulation of TNFRSF10 A/B in colorectal cancer cells in vitro. The increase in the expression of death receptors was correlated with higher active caspase-3 levels following the incubation of cells with recombinant TRAIL protein, which is a ligand for TNFRSF10 A/B receptors. Our results suggest that TNFRSF10 A/B may be a marker to differentiate tumor molecular subtypes in colorectal cancer. The expression of TNFRSF10 A/B may be associated with the recruitment of immune cells into tumors and the development of tumor suppression. The combination of bortezomib and epirubicin treatment might sensitize colorectal cancer cells to TRAIL-induced apoptosis via the upregulation of death receptor.

A novel homozygous missense variant in TBC1D31 in a consanguineous family with congenital anomalies of the kidney and urinary tract (CAKUT).

Congenital anomalies of the kidney and urinary tract (CAKUT) is the leading cause of chronic kidney disease in the first three decades of life. Until now, more than 180 monogenic causes of isolated or syndromic CAKUT have been described. In addition, copy number variants (CNV) have also been implicated, however, all of these causative factors only explain a small fraction of patients with CAKUT, suggesting that additional yet-to-be-discovered novel genes are present. Herein, we report three siblings (two of them are monozygotic twin) of a consanguineous family with CAKUT. Whole-exome sequencing identified a homozygous variant in TBC1D31. Three dimensional protein modeling as well as molecular dynamics simulations predicted it as pathogenic. We therefore showed for the first time an association between a homozygous TBC1D31 variant with CAKUT in humans, expanding its genetic spectrum.

The Effects of Virtual Reality Glasses on Vital Signs and Anxiety in Patients Undergoing Colonoscopy: A Randomized Controlled Trial.

Colonoscopy is a painful procedure that causes anxiety and changes in vital signs. Pain and anxiety may cause patients to avoid colonoscopy, which is a preventive and curative healthcare service. The aim of this study was to examine the effects of virtual reality glasses on the vital signs (blood pressure, pulse, respiration, oxygen saturation, and pain) and anxiety in patients undergoing colonoscopy. The population of the study consisted of 82 patients who underwent colonoscopy without sedation between January 2, 2020, and September 28, 2020. Post-power analysis was performed with 44 patients who agreed to participate in the study, met the inclusion criteria, and were followed up for pre- and post-tests. The experimental group participants (n = 22) watched a 360° virtual reality video through virtual reality glasses whereas the control group participants (n = 22) underwent a standard procedure. Data were collected using a demographic characteristics questionnaire, the Visual Analog Scale-Anxiety, Visual Analog Scale-Pain, Satisfaction Evaluation Form, and monitoring of vital signs. The experimental group participants had significantly lower levels of pain, anxiety, systolic blood pressure, and respiratory rate and significantly higher peripheral oxygen saturation during colonoscopy than the control group participants. The majority of the experimental group participants were satisfied with the application. Virtual reality glasses have a positive effect on vital signs and anxiety during colonoscopy.

Evaluation of Second Primary Cancer Risk Among Chronic Lymphocytic Leukemia Patients: Multicenter Study.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary cancers (SPC). The aim of this study is to determine the frequency of SPC in CLL patients and determine the relationship between these cancers and their treatment status, cytogenetic factors, and other risk factors. METHODS: The study was designed as multicenter and retroprospective. The sample comprised 553 subjects with a CLL diagnosis. Data collection commenced in August 2016, and completed at May 2021. RESULTS: Fifty one of 553 patients followed for CLL, had a history of SPC. SPC development rate was 9.2%. Epithelial tumors were mostly observed. According to the incidence skin, lymphoma, renal, breast, lung, gastrointestinal system, thyroid, malignant melanoma, prostate, Kaposi's sarcoma, neuroendocrine tumor, ovarian, larynx and salivary gland cancers were detected respectively. The 13q deletion was the most common genetic abnormality in those who developed SPC, and the frequency of 13q deletion was found to be increased statistically significant in those with malignancy, compared to those who did not. CONCLUSION: In CLL patients with SPC, the age of diagnosis, 13q and CD38 positivity, and treatment rates with fludarabine and monoclonal antibodies were found to be higher. Also, we determined that SPC frequency increased independently from hemogram values (except hemoglobin values), ß2 microglobulin level on admission, number of treatment lines, and genetic mutations other than 13q, in CLL patients. In addition, the mortality rate was higher in CLL patients with SPC and they were prone to be in advanced stages at the time of diagnosis.

Cardiometabolic Risk Factors in Pediatric Kidney Transplant Recipients.

OBJECTIVE: There is an increased risk of obesity and metabolic syndrome among kidney transplant recipients, which adversely affects cardiovascular and renal outcomes in these patients. The present study aims to investigate the prevalence of metabolic syndrome in pediatric kidney transplant recipients and the associations of metabolic syndrome with cardiovascular disease and graft function. MATERIALS AND METHODS: This cross-sectional, single-center study included 52 kidney transplant recipients (27 males) transplanted before 18 years of age. All subjects underwent a comprehensive assessment that included anthropometric and blood pressure measurements and laboratory tests. Metabolic syndrome was defined based on the recent recommendations of the Pediatric Renal Nutrition Taskforce. Left ventricular hypertrophy was assessed as a risk factor for cardiovascular disease, and estimated glomerular filtration rate was assessed to determine graft function. RESULTS: The median age of patients was 15.9 (13.8;18.4) years, and the median follow-up time was 35.5 (20.0;62;0) months after transplantation. Nineteen patients (36.5%) were obese or overweight, 43 (83%) had hypertension or controlled hypertension, 23 (44%) had dyslipidemia, and 9 (17%) had hyperglycemia. Ten patients (19.2%) were diagnosed with metabolic syndrome. Twenty-eight patients (54%) had left ventricular hypertrophy. The prevalence of left ventricular hypertrophy was higher in patients with metabolic syndrome than in those without metabolic syndrome (90% vs. 45%, P = .014), whereas estimated glomerular filtration rate did not differ between the 2 groups. CONCLUSION: Cardiometabolic risk factors are common in pediatric kidney transplant recipients. Approximately one-fifth of patients have metabolic syndrome, and left ventricular hypertrophy is much more common among patients with metabolic syndrome. However, there is no relationship between metabolic syndrome and graft dysfunction.

Effect of Blood Groups on Clinical Presentations and Treatment Outcomes in Immune Thrombotic Thrombocytopenic Purpura Patients with Severe ADAMTS13 Deficiency: A Multi-Center Experience.

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by accumulation of ultra-large von Willebrand factor (vWF) due to the significantly reduced activity ADAMTS13. Limited studies have been published examining the blood group as an epidemiological factor that can contribute to development of TTP. It has been suggested that due to low vWF levels, the distribution of the "O" blood group among TTP patients may be lower than anticipated compared to the blood group distribution rates in the normal population. The aim of this study was to explore the relationship between blood groups and the clinical outcome of immune TTP (iTTP). Methods: Thirty patients with iTTP with severe ADAMTS13 deficiency were enrolled. Data collection commenced in January 2011 and was completed by June 2020. It was analyzed whether there was a difference between the blood groups in terms of frequency of iTTP, response to treatment, frequency of relapse, and clinical and laboratory results. Results and Conclusions: The distribution of group "A" among patients with iTTP was higher than expected. Although not statistically significant, patients with blood group "O" required more TPE for the treatment and relapse rate was statistically higher than other blood groups. Mortality rate in all patients was 6.7%. Although blood group "A" is a risk factor for iTTP, the frequency of relapse is higher in the blood group "O."

Profile of psychotropic agents used in autism spectrum disorder according to comorbidities in Turkey: A 4-year evaluation.

It is known that the use of psychotropic pharmaceuticals is common in comorbidities seen in autism spectrum disorder (ASD). We have very limited knowledge about which psychotropic drugs are prescribed when comorbidities are diagnosed in patients with ASD. It is aimed to determine the profile of psychotropic agents in patients diagnosed with ASD associated with comorbidities between the ages of 0-24 in Turkey over 4 years. Data belonging to ASD in Prescription Information System (PIS) was obtained from the 'Turkish Medicines and Medical Devices Agency'. A total of 34 066 prescriptions including 45 624 psychotropic drugs were analyzed. A total of psychotropic drugs prescribed for patients with ASD was 75.4%. The following psychotropic drugs were prescribed for the patients with ASD and its comorbidities; risperidone (28.6%), aripiprazole (13.7%), and valproic acid (11.3%) are the most preferred psychotropics. The percentage of pharmaceuticals containing psychotropic active substances in prescriptions with ASD and its comorbidities is 7.5%. This study is the first research in which psychotropics used in ASD were evaluated over a wide period and nationwide. Antipsychotics were most commonly prescribed with the diagnosis of ASD. In the presence of ASD and its comorbidities, risperidone was most frequently prescribed.

Humoral and cellular immune response to SARS-CoV-2 mRNA BNT162b2 vaccine in pediatric kidney transplant recipients compared with dialysis patients and healthy children.

BACKGROUND: Compared with the general population, the immune response to COVID-19 mRNA vaccines is lower in adult kidney transplant recipients (KTRs). However, data is limited for pediatric KTRs. In this study, we aimed to assess humoral and cellular immune responses to the COVID-19 mRNA vaccine in pediatric KTRs. METHODS: This multicenter, prospective, case-control study included 63 KTRs (37 male, aged 12-21 years), 19 dialysis patients, and 19 controls. Humoral (anti-SARS-CoV2 IgG, neutralizing Ab (nAb)) and cellular (interferon-gamma release assay (IGRA)) immune responses were assessed at least one month after two doses of BNT162b2 mRNA vaccine. RESULTS: Among COVID-19 naïve KTRs (n = 46), 76.1% tested positive for anti-SARS-CoV-2 IgG, 54.3% for nAb, and 63% for IGRA. Serum levels of anti-SARS-CoV-2 IgG and nAb activity were significantly lower in KTRs compared to dialysis and control groups (p < 0.05 for all). Seropositivity in KTRs was independently associated with shorter transplant duration (p = 0.005), and higher eGFR (p = 0.007). IGRA titer was significantly lower than dialysis patients (p = 0.009). Twenty (43.4%) KTRs were positive for all immune parameters. Only four of 11 seronegative KTRs were IGRA-positive. COVID-19 recovered KTRs had significantly higher anti-SARS-CoV-2 IgG and nAb activity levels than COVID-19 naïve KTRs (p = 0.018 and p = 0.007, respectively). CONCLUSIONS: The humoral and cellular immune responses to SARS-CoV-2 mRNA BNT162b2 vaccine are lower in pediatric KTRs compared to dialysis patients. Further prospective studies are required to demonstrate the clinical efficacy of the mRNA vaccine in KTRs. This prospective study was registered in ClinicalTrials.gov (NCT05465863, registered retrospectively at 20.07.2022). A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical and subclinical acute kidney injury in children with mild-to-moderate COVID-19.

BACKGROUND: Our aim was to identify acute kidney injury (AKI) and subacute kidney injury using both KDIGO criteria and urinary biomarkers in children with mild/moderate COVID-19. METHODS: This cross-sectional study included 71 children who were hospitalized with a diagnosis of COVID-19 from 3 centers in Istanbul and 75 healthy children. We used a combination of functional (serum creatinine) and damage (NGAL, KIM-1, and IL-18) markers for the definition of AKI and subclinical AKI. Clinical and laboratory features were evaluated as predictors of AKI and subclinical AKI. RESULTS: Patients had significantly higher levels of urinary biomarkers and urine albumin-creatinine ratio than healthy controls (p < 0.001). Twelve patients (16.9%) developed AKI based on KDIGO criteria, and 22 patients (31%) had subclinical AKI. AKI group had significantly higher values of neutrophil count on admission than both subclinical AKI and non-AKI groups (p < 0.05 for all). Neutrophil count was independently associated with the presence of AKI (p = 0.014). CONCLUSIONS: This study reveals that even children with a mild or moderate disease course are at risk for AKI. Association between neutrophil count and AKI may point out the role of inflammation in the development of AKI. IMPACT: The key message of our article is that not only children with severe disease but also children with mild or moderate disease have an increased risk for kidney injury due to COVID-19. Urinary biomarkers enable the diagnosis of a significant number of patients with subclinical AKI in patients without elevation in serum creatinine. Our findings reveal that patients with high neutrophil count may be more prone to develop AKI and should be followed up carefully. We conclude that even children with mild or moderate COVID-19 disease courses should be evaluated for AKI and subclinical AKI, which may improve patient outcomes.

Comparison of the efficacy of mud-pack and hot-pack treatments in chronic non-specific neck pain: A single-blind, randomized-controlled study.

Objectives: This study aims to compare the short-term efficacy of mud-pack (MP) and hot-pack (HP) treatments with the same temperature and duration on sleep, function, depression, and quality of life for chronic non-specific neck pain (CNNP) patients. Patients and methods: Between December 2018 and September 2019, a total of 70 patients with CNNP diagnosis (12 males, 58 females; mean age: 50.2±9.4 years; range, 24 to 65 years) were included. The patients were divided into two groups. The MP group (n=35) had a total of 15 sessions of MP for 20 min + transcutaneous electrical nerve stimulation (TENS) for 20 min + home exercise (HE) on five days per week for three weeks. The HP group (n=35) had 15 similar sessions of HP for 20 min + TENS for 20 min + HE. The patients were assessed with the Visual Analog Scale (VAS-pain), VAS physician's and patient's global assessments, modified Neck Disability Index (mNDI), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), and Short Form-36 (SF-36) measures before treatment, at the end of post-treatment third week and one month later. Results: In the MP group, there were statistically significant improvements in all parameters at the end of treatment three-week and one-month follow-up (p<0.05), apart from SF-36 Vitality/Energy (SF-36V/E) at the end of treatment and SF-36 General Health (SF-36GH) at one month. In the HP group, there were statistically significant improvements observed for all parameters (p<0.05), apart from the SF-36 Physical Role and SF-36GH at the end of treatment third week and SF-36V/E at the first-month assessment. The VAS-pain(p<0.001), mNDI (p=0.019), BDI (p=0.002), SF-36GH (p<0.001), SF-36V/E (p<0.001) and SF-36 mental health (p<0.001) showed statistically significantly superior improvements in the MP group (p<0.05). Conclusion: In CNNP patients, both MP and HP treatments are effective. However, MP therapy has more positive effects on pain, function, depression, and quality of life parameters. The MP treatment may be used in addition to TENS treatment for CNNP patients.

Transgenic Expression of Haemonchus contortus Cytochrome P450 Hco-cyp-13A11 Decreases Susceptibility to Particular but Not All Macrocyclic Lactones in the Model Organism Caenorhabditis elegans.

The number of reported macrocyclic lactones (ML) resistance cases across all livestock hosts is steadily increasing. Different studies in the parasitic nematode Haemonchus contortus assume the participation of cytochrome P450s (Cyps) enzymes in ML resistance. Still, functional data about their individual contribution to resistance or substrate specificity is missing. Via microinjection, transgenic Caenorhabditis elegans expressing HCON_00141052 (transgene-Hco-cyp-13A11) from extrachromosomal arrays were generated. After 24 h of exposure to different concentrations of ivermectin (IVM), ivermectin aglycone (IVMa), selamectin (SEL), doramectin (DRM), eprinomectin (EPR), and moxidectin (MOX), motility assays were performed to determine the impact of the H. contortus Cyp to the susceptibility of the worms against each ML. While transgene-Hco-cyp-13A11 significantly decreased susceptibility to IVM (four-fold), IVMa (2-fold), and SEL (3-fold), a slight effect for DRM and no effect for MOX, and EPR was observed. This substrate specificity of Hco-cyp-13A11 could not be explained by molecular modeling and docking studies. Hco-Cyp-13A11 molecular models were obtained for alleles from isolates with different resistance statuses. Although 14 amino acid polymorphisms were detected, none was resistance specific. In conclusion, Hco-cyp-13A11 decreased IVM, IVMa, and SEL susceptibility to a different extent, but its potential impact on ML resistance is not driven by polymorphisms.

Anti-vascular endothelial growth factor therapy in diabetic macular edema: real-life outcomes from a multicenter study in Turkey over 36 months.

PURPOSE: This study aimed to report the visual and anatomical outcomes of intravitreal anti-VEGF treatment for diabetic macular edema (DME) in a real-world clinical setting from Turkey over 36 months. METHODS: This is a retrospective, multicenter (7 sites) study. The medical records of 1072 eyes (both previously treated and naive eyes) of 706 consecutive patients with visual impairment due to center-involving DME treated with intravitreal anti-VEGF injections between April 2007 and February 2017 were reviewed. The eyes were divided into mutually exclusive three groups based on the duration of follow-up (12, 24, or 36 months). Primary outcome measures were changes in visual acuity (VA) and central macular thickness (CMT) from baseline to final visit in each cohort, frequency of visits and intravitreal anti-VEGF injections. As secondary endpoints, VA outcomes were assessed in subgroups stratified by baseline VA [<70 ETDRS letters and ≥70 ETDRS letters] and loading dose status of anti-VEGF injections. RESULTS: VA increased by a mean of 8.2 letters (12-month cohort, p < 0.001), 5.3 letters (24-month cohort, p < 0.001), and 4.4 letters (36-month cohort, p = 0.017) at final visits. The eyes with <70 VA letters achieved more significant VA improvement at final visits in all cohorts compared with eyes with >70 VA letters (p < 0.001). The mean decreases in CMT from baseline to last visits at 12-, 24-, and 36- month cohorts were -100.5 µm, -107.7 µm, and -114.3 µm, respectively (p < 0.001). The mean number of injections given were 4.6, 2.3, and 1.8 during years 1 to 3, respectively. Patients who received loading dose showed greater VA gains than those who did not in all follow-up cohorts. CONCLUSION: Our study revealed that anti-VEGF treatment improved VA and CMT over a follow-up of 36 months. Although these real-life VA outcomes following anti-VEGF therapy for DME were similar to other real-life studies, they were inferior to those noted in randomized controlled trials, mainly due to undertreatment.

[The Role of Anti-HBc Testing on Donor Selection and Its Contribution to Current Alghorithms; Can the Gülhane Experience Be a Model for Turkey?] / Anti-HBc Testinin Bagisçi Seçimindeki Rolü, Güncel Algoritmaya Katkisi; Gülhane Deneyimi Türkiye için Örnek Model Olur Mu?

Additional or different test procedures can be applied to maximize transfusion safety by reducing the risk of transfusion-transmitted infections. Antibodies to hepatitis B core antigen (anti-HBc) is one of the most commonly used serologic marker in this context. The aim of the study was to analyse anti-Hbc test results performed within the scope of routine screening tests in our center and to examine the effect of the donor re-entry protocol established. A total of 57191 people who applied to Gülhane Regional Blood Center to donate blood between 2014-2019 were included in the study. All blood donations were screened for anti-HBc by chemiluminescense immunoassay (Architect i2000 SR, AXSYM, Abbott, IL, USA). Hepatitis B surface antibody (anti-HBs) and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) (ABI Prism 7500 Real time PCR system, Applied Biosystems, USA) tests were performed in accordance with the donor recovery protocol for those who could be reached among those with positive for anti-HBc test results. Samples with > 100 IU/ml of anti-HBs levels and negative for HBV DNA test were included in the donor pool. Of the 57 191 blood donors involved in the study, 5125 (8.5%) were found as positive for anti-HBc. Of the donors, 54 035 (94.4%) were male and 3156 (5.5%) were female. The difference was found to be statistically significant in terms of gender distribution between the years of the study (p<0.001). The highest anti-HBc positivity rate (35.7%) was in the age group of 60 years and over while the lowest positivity rate (3.8%) was in the age group of 18-30 years (r= 0.549, p= 0.0001). The year with the highest anti-HBc seroprevalance (10.1%) was 2017, while the year with the lowest (7.9%) was 2014. The distribution of seropositivity over the years was statistically significant (p<0.001). In the study, anti-HBs and HBV-DNA test results of 439 donors were accessible and of which 301 (68.5%) were considered eligible to donate again according to the re-entry protocol. The isolated anti-HBc positivity and HBV-DNA positivity rates were 7.5% (33/430) and 0.2% (1/439) respectively,in blood donors to whom re-entry protocol was performed. The seroprevalance of anti-HBc below 10% during the six-year period in which the study was conducted is a critical data for the evaluation of this test within the scope of routine microbiological screening tests. Moreover, we have observed that donor losses due to the antiHBc testing can be significantly reduced with the implementation of donor re-entry protocols. Anti-HBc screening strategy should be decided by considering of HBV epidemiology, cost-effectivity and possible blood donor losses.

Comparison of infants and children with urolithiasis: a large case series.

We evaluated the demographic features, etiologic risk factors, treatment strategies, and outcome of the infants and children with urolithiasis (UL). A retrospective multicenter study was conducted including 23 Pediatric Nephrology centers in Turkey. The medical records of 2513 children with UL were reviewed. One thousand, three hundred and four boys and 1209 girls (1.1:1) were reported. The mean age at diagnosis was 39.5 ± 35 months (0.4-231 months), and 1262 patients (50.2%) were in the first year of life (infants). Most of the cases with infantile UL were diagnosed incidentally. Microlithiasis (< 3 mm) was found in 794 patients (31.6%), and 64.5% of the patients with microlithiasis were infants. Stones were located in the pelvis-calyces in 63.2% (n: 1530) of the cases. The most common stone type was calcium oxalate (64.6%). Hypocitraturia was the most common metabolic risk factor (MRF) in children older than 12 months, but in infancy, hypercalciuria was more common. Fifty-five percent of the patients had received at least one medical treatment, mostly potassium citrate. At the end of a year's follow-up, most of the patients with microlithiasis (85%) showed spontaneous remission. The rate of spontaneous stone resolution in infants was higher than in children. Spontaneous remission rate was higher in cases with MRF ( - ) stones than in MRF ( +) stones. However, remission rate with medical treatment was higher in cases with MRF ( +) stones. This study represents the results of a large series of infants and children with UL and showed that there are several differences such as underlying metabolic and anatomic abnormalities, clinical course, and stone remission rates between infants and children with urinary stone disease.