The prevalence of Fabry disease in a Turkish population with chronic kidney patients.

BACKGROUND AND OBJECTIVES: Fabry disease (FD) is an X-linked lysosomal storage disease with various clinical symptoms due to a deficiency of an enzyme called alpha-galactosidase A. The likelihood of nephropathy increases with age and the severity of the mutation in Fabry patients. Fabry disease is difficult to diagnose. The exact incidence and prevalence of Fabry disease are unknown due to its atypical or oligosymptomatic forms. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: GLA gene mutations were examined in patients over the age of 18 who were followed up on with a diagnosis of chronic kidney disease and who had or did not receive renal replacement therapy from October 2017 to December 2019. RESULTS: A total of 18 sites in 8 locations around Turkey volunteered to participate in the study, including people aged 18 and older with stages 1-5 of chronic kidney disease (CKD) or getting renal replacement therapy. 1904 patients were screened in total. In 13 cases, a D313Y pseudo mutation in the GLA gene was discovered. GLA gene mutations were found and pathologically assessed in four of the tested cases. CONCLUSIONS: The range of clinical symptoms of Fabry disease, as well as the frequent delays in diagnosis, result in treatment being too late. We believe that screening chronic renal patients at high risk for Fabry disease is warranted.

[A case of Peritonitis Caused by Wickerhamomyces anomalus (Candida pelliculosa) Related to Peritoneal Dialysis]. / Wickerhamomyces anomalus (Candida pelliculosa)'un Etken Oldugu Periton Diyalizi Iliskili Bir Peritonit Olgusu.

Fungal peritonitis is less commonly seen than bacterial peritonitis in patients undergoing peritoneal dialysis (PD), but it is a serious complication with high morbidity and mortality. It often results in catheter loss and modifying therapy from PD to hemodialysis. The causative organisms are often Candida species. In this report, a PD-associated peritonitis caused by Wickerhamomyces anomalus (Candida pelliculosa), a rare fungal infection agent with increasing clinical importance by causing different clinical pictures was presented. An outpatient peritoneal fluid culture was sent from a 48-yearold male patient, who had been undergoing continuous peritoneal dialysis (CAPD) for 9 years, due to abdominal pain and blur in peritoneal fluid during dialysis. The patient admitted to the emergency department four days later due to the persistence of his complaints. A sample of peritoneal fluid was taken in the emergency department and sent to the laboratory for microbiological analysis. In the direct microscopical examination of the peritoneal fluid; cell number was determined as 210/mm3, and no microorganisms were seen in the Gram and methylene blue staining. The patient was admitted to the nephrology service with a pre-diagnosis of PD-associated peritonitis. Enterobacter aerogenes was grown in the peritoneal fluid culture which was sent from the dialysis outpatient clinic four days ago. The peritoneal fluid sample sent from the emergency department was inoculated on 5% sheep blood , EMB and chocolate agars and no growth was detected. As the patient's complaints and peritoneal fluid leukocyte count continued to increase, peritoneal fluid cultures were repeated and recurrent growth of yeast was detected in cultures. The yeast was identified as Candida pelliculosa by matrix assisted laser desorption ionization time-of-flight mass spectrofotometry (MALDI-TOF) VITEK®MS (bioMerieux, France). The species identification was confirmed by sequencing the target ITS gene regions on the rRNA and the isolate was identified as 100% Wickerhamomyces anomalus (sexual reproduction form of Candida pelliculosa, teleomorph). The reference microdilution method was performed according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI) in order to test the antifungal susceptibility. After 24 hour incubation, the minimal inhibitory concentrations (MIC) were determined as 0.03 µg/ml for amphotericin B, 0.125 µg/ml for caspofungin 0.125 µg/ml for voriconazole, 0.03 µg/ ml for itraconazole and 4 µg/ml for fluconazole. Fluconazole and anidulafungin were started for the treatment of fungal peritonitis. The patient's peritoneal dialysis catheter was removed and hemodialysis was applied to the patient. Clinical and laboratory symptoms regressed with antifungal therapy and the patient's anidulafungin treatment was discontinued for 14 days after the catheter removal. In conclusion, in patients undergoing CAPD, as in our case, fungal pathogens should also be considered although it is rare, when there is no laboratory and clinical improvement, and the response to treatment is not complete in PD-associated peritonitis to prevent delays in diagnosis and treatment.

Gamma-glutamyl transferase to albumin ratio can predict severity of coronary artery disease detected by coronary computed tomography angiography.

OBJECTIVE: Gamma-glutamyl transferase (GGT) to albumin ratio (GAR) has been shown to be helpful to diagnose and determine the severity of coronary artery disease (CAD). Coronary computed tomography angiography (CCTA) is a guide recommended non-invasive test that provides information about the presence, severity, and morphology of coronary plaques. In this study, our main aim was to investigate the relationship between the presence, morphology, and severity of coronary plaques detected via CCTA and GAR in patients with low to moderate risk for undiagnosed CAD. METHODS: Nine hundred and sixty six patients were included who underwent CCTA. The severity of CAD and plaque morphology were investigated. CT-adapted Leaman score (CT-LeSc) was calculated to determine the extent of the CAD. The study population was further evaluated in three groups according to tertiles of GAR. RESULTS: Atherosclerotic plaques were more common in the male gender and older patients with conventional cardiovascular risk factors. GAR was significantly lower in patients with normal CCTA than in patients with a non-obstructive plaque or obstructive plaque on CCTA. Patients in upper GAR tertiles had a higher coronary calcium score (CACS) and CT-LeSc. GAR was one of the independent predictors to predict severe stenotic plaque and high CACS. CONCLUSION: GAR can independently predict the presence, extent, and severity of CAD determined by CT-LeSc. We believe as a cheap, safe, and widely available tool, GAR would be useful in the diagnosis of CAD.

A novel human ex-vivo burn model and the local cooling effect of a bacterial nanocellulose-based wound dressing.

BACKGROUND: Burn wound progression is a significant problem as burns initially thought to be superficial can actually become full thickness over time. Cooling is an efficient method to reduce burn wound conversion. However, if the cooling agent is below room temperature, depending on the wound size the patient is at risk of hypothermia. Additionally, tissue perfusion is reduced leading to an aggravation of burn wound progression. We investigated if wound dressings based on non-pre-cooled bacterial nanocellulose (BNC) with a high water content cool a burn just by evaporation and reduce the intradermal damages in the skin. MATERIAL AND METHODS: In a human ex-vivo model, skin explants underwent contact burns using a 100 °C hot steel block. The burned areas were divided into two groups of which one was cooled with a BNC-based wound dressing. Intradermal temperature probes measured temperature in cooled and uncooled burn sites over 24 h. For histological assessments of the burned areas biopsies were taken at different time points. High mobility group box-1 (HMBG1) staining served as marker for cell vitality and necrosis in the different skin layers. RESULTS: Intradermal temperature measurement showed that application of the BNC-based wound dressing reduced temperature significantly in burned skin. This cooling effect resulted in a maximum temperature difference of 6.4 ± 1.9 °C and a significant mean reduction of the area under the curve in the first hour after burn of 62% (p < 0.0001). The histological results showed less necrosis and less dermal-epidermal separation in the cooled areas. The HMGB1 staining revealed more vital cells in the cooled group than in the uncooled group. CONCLUSION: Based on our results, BNC-based wound dressings cool a burn. Intradermal temperature as well as thermal damage of the tissue was reduced. The tested BNC-based wound dressing can be used without pre-cooling to cool a burn as well as to reduce the burn BNC-based wound progression through its evaporation cooling effect.

The effect of rituximab on encapsulated peritoneal sclerosis in an experimental rat model

Background/aim: Peritoneal sclerosis may be observed in varied manifestations. However, the most serious form is the encapsulated peritoneal sclerosis. We researched the effect of rituximab on peritoneal fibrosis in an experimental rat model. Materials and methods: Twenty-four Wistar Albino rats were divided into 4 equal groups. During weeks 0­3; group I received isotonic saline (IS) solution, group II, group III, and group IV received chlorhexidine gluconate (CG) via intraperitoneal (i.p.) route. In the next 3 weeks nothing adminestred to both group I and group II but IS solution was adminestred to group III via i.p. route and 375 mg/m2/week rituximab was applied intravenously on days 21, 28, and 35 to group IV. Fibrosis, peritoneal thickness, and inflammation were evaluated. Immunohistochemical methods used for the detection of matrix MMP-2, TGF-ß1, and VGEF expressions. Results: The rituximab (group IV) had significantly lower fibrosis and peritoneal thickness scores than the group II and III (P < 0.001). TGF-ß1 and VEGF expressions were significantly lower in the rituximab group than in the group II and III (P < 0.001). Conclusion: We found that rituximab had a significant effect on the peritoneal thickness, total fibrosis, TGF-ß1 and VGEF scores which were induced by CG.

Abatacept as a therapeutic option in the treatment of encapsulated peritoneal sclerosis: an experimental rat model.

PURPOSE: Encapsulated peritoneal sclerosis (EPS) is a rare complication of long-term peritoneal dialysis (PD) and is usually associated with mortality. Inflammation is a leading factor for developing EPS. This study aimed to investigate the effect of abatacept on peritoneal fibrosis and inflammation using the EPS rat model. METHODS: Twenty-four Wistar albino rats were randomly divided into four equal groups. Group I (control group) was administered isotonic saline (IS) via the intraperitoneal (ip) route during weeks 0-3. Chlorhexidine gluconate (CG) ip was administered to group II (CG group) during weeks 0-3. Group III (CG + IS group) received CG for the first 21 days and IS solution for the following 3 weeks. Group IV (abatacept group) received CG during weeks 0-3, and subsequently, 50 mcg/day abatacept during weeks 4-6. Peritoneal thickness, fibrosis, and inflammation were examined using light microscopy. Expressions of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta 1 (TGF-ß1) were detected by immunohistochemical staining. RESULTS: Lesser peritoneal thickness and lower inflammation score were observed in the abatacept group than in the CG and CG + IS groups (p < 0.05). Furthermore, the abatacept group had a lower fibrosis score than the CG + IS group (p < 0.05). MMP-2 and TGF-ß1 scores were lower in the abatacept group than in the CG + IS group (p < 0.05). CONCLUSIONS: The results revealed that abatacept had a histopathological beneficial effect on peritoneal fibrosis, inflammation, MMP-2, and TGF-ß1 scores, which were induced by CG. Abatacept could be a new therapeutic option for treating EPS.

Renal Late Effects After the Treatment of Unilateral Nonsyndromic Wilms Tumor.

Wilms tumor is the most common renal malignancy of childhood. Because of the improvement in prognosis and the increase in survival rates, long-term consequences of the treatment for Wilms tumor are of greater concern. We investigated late renal effects of the treatment on 50 survivors of nonsyndromic unilateral Wilms tumor. After the second year since the cessation of treatment, the glomerular filtration rate (GFR), urinary protein excretion, urinary ß2 microglobulin levels, and blood pressure as well as the general health status were assessed. Results were analyzed for correlation with clinical variables, chemotherapy, and radiotherapy as possible risk factors. At a median follow-up time of 8.8 years (mean=10.9; range, 2.3 to 35.4 y), none of the patients developed end-stage renal disease. Compensatory hypertrophy was observed in 68% of the cases. The median maximum bipolar length was significantly higher in patients diagnosed after the age of 36 months. Eleven (22%) and 2 (4%) of the 50 patients were hypertensive at the time of the diagnosis and the study, respectively. Similarly, median GFR values were significantly lower at the time of diagnosis, although at the time of the study, all patients had normal GFR values. With longer follow-up intervals, especially after 10 years, a significant decreasing trend in the GFR was observed (P=0.002).