Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies.

We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections.

Presence of Non-Diabetic Kidney Diseases in Biopsy Specimens of Diabetic Patients' Single Center Experience.

The complications of type 2 diabetes mellitus (T2DM) are well known and one of them is diabetic chronic kidney disease (DCKD). Over time, it has become clear that patients with T2DM can have nondiabetic chronic kidney diseases (NDCKD), especially those that affect the glomeruli. Clinical indicators for identifying DCKD from NDCKD with high sensitivity and specificity have not yet been identified. Therefore, kidney biopsy remains the golden standard for DCKD diagnosis in patients with T2DM. Despite some indications for kidney biopsy, criteria for a biopsy differ between countries, regions, and doctors. The aim of the study was to analyze the biopsy findings in our T2DM population and the justification of the biopsy according to widely accepted criteria. This single center retrospective study analyzed data from 74 patients with T2DM who underwent kidney biopsy from January 2014 to January 2021. According to the biopsy data, we categorized31 patients in the DN group, patients with typical diabetic glomerulopathy, 11 patients in the mixed group, patients who had pathohistological elements for both DN and non-DN glomerulopathy, and 32 patients in the non-DN group, patients with primary glomerulopathy not linked with DM. In the non-DN and mixed groups, the most frequent glomerulopathy was mesangioproliferative glomerulonephritis, including IgA and non-IgA forms, found in 10 patients, and membranous nephropathy (MN) in 10 patients. We analyzed several parameters and only the amount of proteinuria was found to be significantly linked to biopsy findings related to DN. With the existing criteria for kidney biopsy, we managed to detect changes in the kidneys in about half of our patients with T2DM. These patients required specific treatment, different from that which we use for DCKD patients.

The Qatar 2022 World Cup warm-up: Football goal-scoring evolution in the last 14 FIFA World Cups (1966-2018).

The aim of this study was to elucidate pattern of attacking actions leading up to goal scoring during the 14 FIFA World Cups from 1966 to 2018. The study analysed 1881 goals scored during a total of 732 matches. We employed observational methodology design. Before goal analysis began, it was developed the observing protocol in which data related to selected variables, by system of notation, was entered after reviewing each individual goal scoring action. The analysis of all video material was carried out independently by four experienced examiners (three of them are Ph.D in sports science and one is Ph.D. candidate in sports science with at least 7 years of coaching and experience as analyst in football). The inter-and intra-observer reliability presented good level of agreement. The kappa values ranged from 0.82 (goal scoring through open play) to 1.00 (action leading up to goal), showing a very high agreement for all performance variables. Interclass correlation was very high (ICC = 0.966, 95% upper and lower confidence intervals were between 0.933 and 1.00). A statistically significant trend (p < 0.05) from 1966 to 2018 was identified towards a higher relative frequency of goals scored from set play and collective actions from open play. The Chi-square did not reveal significant differences in the frequency of goal scoring patterns and goal-scoring zones. The results also revealed that the majority of goals were scored between the 76th and 90th minutes of a match (22.7%), from open play (70.5%), inside the penalty area (54.7%), one touch finishing (62.5%), and collective attacks in open play (55.8%). These findings may provide a possible strategic direction for improving goal-scoring performance in football, as well as practical implementation in World Cup tournament preparation.

Significance of acPWV for Survival of Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Abnormal arterial stiffness (AS) is a major complication in end-stage kidney disease (ESKD) patients treated by dialysis. Our study aimed to determine the significance of AS for survival of prevalent dialysis patients, as well as its association with cardiovascular parameters or vascular calcification promoters/inhibitors or both and AS. MATERIALS AND METHODS: The study involved 80 adult hemodialysis patients. Besides standard laboratory analyses, we also determined promoters and inhibitors of vascular calcification (bone biomarkers): serum levels of fibroblast growth factor 23 (FGF23), soluble Klotho, intact parathormone (iPTH), 1,25-dihydroxyvitamin D3, osteoprotegerin, sclerostin, AS measured as ankle carotid pulse wave velocity (acPWV), Ankle Brachial Index (ABI), and vascular calcification (VC) score. Patients were monitored for up to 28 months. According to the median acPWV value, we divided patients into a group with acPWV ≤ 8.8 m/s, and a group with acPWV > 8.8 m/s, and the two groups were compared. RESULTS: Values for bone biomarkers were similar in both groups. Mean arterial blood pressure (MAP), central systolic and diastolic brachial blood pressure, heart rate, and pulse pressure were higher in the group with acPWV > 8.8 m/s than in the group with acPWV ≤ 8.8 m/s. The mortality was higher for patients with acPWV > 8.8 m/s at any given time over 28 months of follow-up. In multivariable analysis, predictors of higher acPWV were age >60.5, higher pulse rate, and higher central systolic or brachial diastolic blood pressure. CONCLUSIONS: According to our results, we advise the measurement of acPWV preferentially in younger dialysis patients for prognosis, as well as intervention planning before the development of irreversible changes in blood vessels. In addition, measuring central systolic blood pressure seems to be useful for monitoring AS in prevalent hemodialysis patients.

Vitamin E-Bonded Membranes Do Not Influence Markers of Oxidative Stress in Hemodialysis Patients with Homozygous Glutathione Transferase M1 Gene Deletion.

BACKGROUND: Increased oxidative stress is a hallmark of end-stage renal disease. Hemodialysis (HD) patients lacking glutathione transferase M1 (GSTM1) enzyme activity exhibit enhanced oxidative DNA damage and higher mortality rate than those with active GSTM1 enzyme. To our knowledge, this is the first study to use the vitamin E-bonded membranes (VEM) in patients with homozygous GSTM1 gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous GSTM1 gene deletion. METHODS: GSTM1 genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with GSTM1-null genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VEM, while the other forty were dialyzed with high-flux same-surface polysulfone dialyzers. Markers of protein and lipid oxidative damage and inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined. RESULTS: Seventy-five patients finished the study. There were no differences at baseline in markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, and thiol groups increased significantly in both groups, but without statistical significance between groups. SOD and C reactive protein (CRP) did not change significantly during the three-month period. IL-6 increased in the control group, and at the same time, decreased in the VEM group, but without statistical significance. Hemoglobin (Hb) value, red blood cells, erythropoiesis resistance index (ERI), serum ferritin and iron did not change significantly within or between groups. Regarding other laboratory parameters, proteins, albumins, triglycerides, serum phosphorus, serum bicarbonate and Kt/V showed significant improvements within groups but with no significant difference between groups. CONCLUSIONS: Our data shows that therapy with VEM over three months had no benefit over standard polysulfone membrane in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking GSTM1 enzyme activity.

Sodium thiosulphate and progression of vascular calcification in end-stage renal disease patients: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Sodium thiosulphate (NaTS) is mostly used in haemodialysis (HD) patients with calcific uraemic arteriolopathy. This double-blind, randomized, placebo-controlled study assessed the effect of NaTS on progression of cardiovascular calcifications in HD patients. METHODS: From 65 screened patients, we recruited 60 patients with an abdominal aorta Agatston calcification score ≥100. Thirty patients were randomized to receive NaTS 25 g/1.73 m2 and 30 patients to receive 100 mL of 0.9% sodium chloride intravenously during the last 15 min of HD over a period of 6 months. The primary endpoint was the absolute change of the abdominal aortic calcification score. RESULTS: The abdominal aortic calcification score and calcification volume of the abdominal aorta increased similarly in both treatment groups during the trial. As compared with the saline group, patients receiving NaTS exhibited a reduction of their iliac artery calcification score (-137 ± 641 versus 245 ± 755; P = 0.049), reduced pulse wave velocity (9.6 ± 2.7 versus 11.4 ± 3.6; P = 0.000) and a lower carotid intima-media thickness (0.77 ± 0.1 versus 0.83 ± 00.17; P = 0.033) and had better preservation of echocardiographic parameters of left ventricular hypertrophy. No patient of the NaTS group developed new cardiac valve calcifications during the trial as compared with 8 of 29 patients in the saline group. By univariate analysis, NaTS therapy was the only predictor of not developing new valvular calcifications. No adverse events possibly related to NaTS infusion were noted. CONCLUSIONS: While NaTS failed to retard abdominal aortic calcification progress, it positively affected calcification progress in iliac arteries and heart valves as well as several other cardiovascular functional parameters.

Impact of Angiotensin-converting Enzyme and Matrix Metalloproteinase-3 Gene Polymorphisms on Risk for Developing Vascular Access Failure in Hemodialysis Patients - A Pilot Study.

For adequate hemodialysis, functional vascular access is obligatory. Neointimal hyperplasia (NIH) has a central role in stenosis and thrombosis development, which represent the most frequent causes of vascular access failure. Polymorphism of different genes that have a significant role in endothelial function may have an impact on NIH development. Therefore, the aim of our study is to determine the effect of angiotensin-converting enzyme (ACE) I/D and matrix metalloproteinase-3 (MMP3) 5A/6A polymorphism on risk for developing vascular access failure in hemodialysis patients. The study included 200 patients on regular hemodialysis at Nephrology Department, University Medical Center Zvezdara. Retrospective analysis included a collection of general and vascular access data from medical records. Genetic analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Patients were divided into two groups: Group 1-patients who have never experienced vascular access failure and Group 2-patients who have at least one spontaneous vascular access failure. There was no difference in age, gender, hemodialysis vintage, main diagnosis, presence of hypertension, and diabetes mellitus between the two groups. There were no statistically significant differences in the frequencies of ACE and MMP3 genotypes between the two groups. Without statistical significance, it was found that homozygotes for I allele had two times higher risk for developing vascular access failure than homozygotes for D allele (OR 2.00; 95%CI: 0.727-5.503; P = 0.180). In addition, patients with 5A allele have 1.7 times higher risk for developing vascular access failure compared with patients without this allele (OR 1.745; 95% CI: 0.868-3.507; P = 0.118). Patients with vascular access failure do not have different genotype distribution regarding ACE gene and MMP3 gene polymorphism as compared with patients without vascular access failure. Still, homozygotes for I allele and homozygotes for 5A allele have higher risk for developing vascular access failure compared with other patients.

Prevalence, clinical characteristics, and predictors of peripheral arterial disease in hemodialysis patients: a cross-sectional study.

BACKGROUND: Peripheral arterial disease (PAD) is common in patients with end-stage renal disease on hemodialysis, but is frequently underdiagnosed. The risk factors for PAD are well known within the general population, but they differ somewhat in hemodialysis patients. This study aimed to determine the prevalence of PAD and its risk factors in patients on hemodialysis. METHODS: This cross-sectional study included 156 hemodialysis patients. Comorbidities and laboratory parameters were analyzed. Following clinical examinations, the ankle-brachial index was measured in all patients. PAD was diagnosed based on the clinical findings, ankle-brachial index < 0.9, and PAD symptoms. RESULTS: PAD was present in 55 of 156 (35.3%; 95% CI, 27.7-42.8%) patients. The patients with PAD were significantly older (67 ± 10 years vs. 62 ± 11 years, p = 0.014), more likely to have diabetes mellitus (p = 0.022), and anemia (p = 0.042), and had significantly lower serum albumin (p = 0.005), total cholesterol (p = 0.024), and iron (p = 0.004) levels, higher glucose (p = 0.002) and C-reactive protein (p < 0.001) levels, and lower dialysis adequacies (p = 0.040) than the patients without PAD. Multivariate analysis showed higher C-reactive protein level (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00-1.06; p = 0.030), vascular access by Hickman catheter (OR, 4.66; 95% CI, 1.03-21.0; p = 0.045), and symptoms of PAD (OR, 5.20; 95% CI, 2.60-10.4; p < 0.001) as independent factors associated with PAD in hemodialysis patients. CONCLUSION: The prevalence of PAD was high among patients with end-stage renal disease on hemodialysis. Symptoms of PAD, higher C-reactive protein levels, and Hickman vascular access were independent predictors of PAD in patients on hemodialysis.

Prognostic value of cardiovascular calcifications in hemodialysis patients: a longitudinal study.

PURPOSE: Cardiovascular calcifications (CVC) are present in up to 70% of non-diabetic dialysis patients. Sparse data are available on predictors of very long-term outcomes of such patients. The Belgrade Aachen Study on Calcification in Hemodialysis patients (BASCH study) aimed to study this using a comprehensive CVC assessment. METHODS: We prospectively analyzed 220 hemodialysis patients followed for a mean of 76 months (median 73 months, range 6-160 months). We compared patients deceased from cardiovascular diseases (CVD) and survivors. Analyses included composite calcification scores (determined by combining ultrasound and X-ray analyses), demographic, clinical and laboratory data and pulse wave velocity (PWV). For survival analysis, patients were divided into group according to quartiles (Q). RESULTS: Compared to survivors, deceased patients from CVD were significantly older, more frequently hypertensive, had shorter dialysis times per week and lower Kt/V values, and they exhibited lower serum fetuin A, osteoprotegerin and hemoglobin as well as higher CRP levels. Composite calcification and Adragao scores were significantly higher in deceased patients from CVD as was PWV. Mean survival was 101 ± 47 months (Q1), 87 ± 51 month (Q2), 66 ± 48 (Q3) and 54 ± 45 months (Q4), p = 0.000. Cox multivariate regression analysis showed that independent predictors for cardiovascular mortality were composite calcification score in the range of third and fourth quartiles. CONCLUSION: Composite calcification score emerged as significant predictors of long-term survival in our group of largely non-diabetic dialysis patient population, finding that should be confirmed by intervention studies.

The 5A Allele of the MMP3-Gene Promoter Polymorphism Is a Risk Factor for Poor Outcome of Hemodialysis Patients.

Cardiovascular morbidity is the leading cause of death in dialysis patients and many risk factors have been involved in its pathogenesis. Genetic susceptibility may be of importance including polymorphism for matrix metalloproteinase 3 (MMP3), which is an enzyme that catalyzes the degradation of collagen, proteoglycans, fibronectin, laminine and elastin. The MMP3 gene promoter contains an insertion/deletion polymorphism characterised by an array of 5 or 6 adenosine residues (5A/6A) at -1612 position. Literature data show that the 5A or 6A allele of the MMP3 gene shows different risk for cardiovascular and overall outcome in general population. The aim was to analyze the -1612 5A/6A promoter polymorphism in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity and 7-year all-cause and cardiovascular mortality. This study included 196 patients on hemodialysis for longer than six months at University Medical Center Zvezdara. The leading causes of end stage renal disease were hypertension and diabetes mellitus. Venous blood was collected on midweek dialysis session and genotype analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method. Among the 198 hemodialysis patients, there were 142 (72%) 5A/6A heterozygotes, 12 (6%) 5A/5A homozygotes, and 44 (22%) 6A/6A homozygotes. These data are consistent with Hardy-Weinberg equilibrium. After 7-year follow-up, the 5A homozygotes showed the lowest all-cause and cardiovascular survival, while the 6A homozygotes showed the highest cardiovascular survival. The 5A allele of the MMP3-gene promoter polymorphism is a potential risk factor in the poor outcome of hemodialysis patients.

Onset of Microscopic Polyangiitis in Binephrectomied Patient on Chronic Hemodialysis-Case Report.

INTRODUCTION: Microscopic polyangiitis (MPA) is one of the causes of the pulmonary-renal syndrome associated with elevated non-specific markers of inflammation and antineutrophil cytoplasmic autoantibody (ANCA) positivity in 50-75%. De novo occurrence of the disease in patients on chronic hemodialysis (HD) has not been described. CASE PRESENTATION: We presented patient who developed MPO-ANCA-associated MPA with lung and musculoskeletal involvement after 4 years on regular HD due to bilateral nephrectomy. After excluding the other causes of MPO-ANCA positivity, diagnosis was confirmed even without renal biopsy. Patient received standard immunosuppression therapy and he is still in remission after 27 months. CONCLUSION: The onset of immune-mediated disease could be observed even after introduction of renal replacement therapy, which may be a diagnostic problem. Early recognition and traditional immunosuppressive regiment may provide successful outcome.

Calcification in arteriovenous fistula blood vessels may predict arteriovenous fistula failure: a 5-year follow-up study.

PURPOSE: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. The impact of vascular calcification process on AVF survival remains unclear and results of several studies about this issue are controversial. In the light of the new knowledge about the different susceptibility for calcification process in different blood vessels, the aim of our study was to analyze whether the calcification of AVF-blood vessels may have an impact on AVF longevity. METHODS: The study included 90 patients, 49 males and 41 females, all of them Caucasians, with a mean age 62 ± 11 years, on regular hemodialysis for more than 1 year with patent primary AVFs. Vascular calcification in AVF-blood vessels or in the anastomotic region was detected using X-ray examination. RESULTS: Calcification in AVF-blood vessels was found in 62% of patients. Binary logistic regression analysis demonstrated that male gender, presence of diabetes mellitus and longer duration of AVF before calcification determination were associated with calcification of AVF-blood vessels. Using a Cox proportional hazard model adjusted for these standardized predicted values revealed that patients with present AVF-blood vessels calcification had increased risk to develop AVF failure with a hazard rate of 3.42 (95% confidence interval 1.00-11.67; P = 0.049). CONCLUSIONS: Calcifications of AVF-blood vessels are found frequently among dialysis patients and may jeopardize the survival of native AVF. We suggested the local X-ray as simple and valid method for detection of patients that are at risk for AVFs failure which should be monitored more closely.

Survival Benefit of Hemodiafiltration Compared With Prolonged High-flux Hemodialysis.

INTRODUCTION:  Patients on dialysis have a high rate of death, mainly of cardiovascular cause. Nephrologists are actively looking for ways to improve patients' outcomes, and alternative dialysis strategies, such as long conventional hemodialysis and hemodiafiltration, are currently being investigated. The aim of this study was to compare anemia, nutrition, inflammation, mineral metabolism, and 3-year survival rates between patients treated with hemodiafiltration and prolonged high-flux hemodialysis (HFH). MATERIALS AND METHODS:  A total of 58 dialysis patients were divided into 2 groups to undergo hemodiafiltration 3 times weekly, 12 hours in total per week, or prolonged duration of HFH (≥ 15 h/w). One-year biochemical parameters were collected retrospectively, together with 36 months patients' survival (prospectively). RESULTS: Patients in the HFH group had longer dialysis vintage; significantly higher levels of hemoglobin (despite less frequent use of erythropoietin-stimulating agents), serum albumin, serum calcium, and serum bicarbonate; and a lower in-tact parathyroid hormone level. Survival rates were comparable between the two groups. The Cox proportional hazard model showed that patients treated with longer HFH had a 32% relative risk reduction of mortality compared to patients treated with hemodiafiltration, but without statistical significance (hazard ratio, 0.68; 95% confidence interval, 0.21 to 2.20; adjusted for diabetes mellitus). CONCLUSIONS: Longer duration of hemodialysis with high-flux membranes had beneficial effects on anemia indexes, mineral metabolism, nutrition parameters, and acidosis in comparison with hemodiafiltration. However, hemodiafiltration did not offer a 36-months survival benefit over prolonged HFH.

PARAMETERS OF HEMODIALYSIS ADEQUACY AND PATIENTS' SURVIVAL DEPENDING ON TREATMENT MODALITIES.

INTRODUCTION: Retrospective studies showed that hemodiafiltration was associated with a reduced risk of mortality compared with standard hemodialysis in the patients with end-stage renal disease. Recently, a few prospective randomized clinical trials found no advantage in survival with hemodiafiltration as compared with high-flux hemodialysis and low-flux hemodialysis. The aim of this study was to compare the parameters of hemodialysis adequacy and two-year survival of patients depending on the modality of hemodialysis. MATERIAL AND METHODS: A total of 159 hemodialysis patients were divided into 3 groups according to the type of hemodialysis treatment: group A - low-flux hemodialysis, group B - high-flux hemodialysis, and group C - hemodiafiltration. All patients had the same duration of hemodialysis sessions. The analysis included average one-year biochemical parameters, and two-year survival of patients. RESULTS: The patients on hemodiafiltration were significantly younger, they had longer dialysis vintage and higher index of dialysis adequancy as compared with the patients on low-flux hemodialysis and high-flux hemodialysis, but without a difference between the two latter groups. Compared to the patients on low-flux hemodialysis, the patients on hemodiafiltration and high-flux hemodialysis had significantly higher hemoglobin value with less frequent erythropoietin stimulating agent use. According to Kaplan-Meier survival analysis, the patients on hemodiafiltration and high-flux hemodialysis had significantly better two-year survival than the patients on low-flux hemodialysis. Cox proportional hazards model confirmed that high-flux hemodialysis caused a significantly lower relative risk of mortality (56% reduction) compared to low-flux hemodialysis (hazard ratio 0.44; P=0.026), and hemodiafiltration caused a 58% reduction in the relative risk of mortality compared to low-flux dialysis (hazard ratio 0.42; P=0.105), but without a statistical significance. CONCLUSION: This study has demonstrated two-year survival benefit with high-flux hemodialysis and hemodiafiltration compared with low-flux hemodialysis. There was no difference in survival between high-flux hemodialysis and hemodiafiltration groups.

Impact of vascular calcifications on arteriovenous fistula survival in hemodialysis patients: a five-year follow-up.

BACKGROUND/AIMS: Vascular calcifications are frequently found among dialysis patients, and the calcification process may influence the patient's outcome. The aim of the present study was to determine the role that vascular calcifications may have on autologous arteriovenous fistula (AVF) survival. METHODS: This study included 90 patients (49 males, mean age 62 ± 11) with a native AVF treated by chronic hemodialysis (HD) for more than one year. The overall vascular calcification scores ranged from 0-11 (Adragao score + vascular access calcification score); patients were categorized into mild (score 0-3; n = 36), moderate (score 4-7; n = 24) and severe (score 8-11; n = 30) calcification groups. AVF survival was then followed for 5 years after calcification measurement or until the patient's death/transplantation. RESULTS: Patients with more pronounced vascular calcifications were more frequently diabetic and male. Multiple linear regression analysis showed a significant relationship between calcification score and male gender, diabetes mellitus, previous duration of AVF, low dialysis flow rate and intact parathormone (iPTH) values. After multivariate adjustment for basal differences, Cox proportional analysis revealed a graded impact of calcification scores on AVF failure: moderate scores (were associated with a hazard rate (HR) of 3.82 (95% confidence interval (CI) 1.10-13.23) and severe scores with an HR of 4.65 (CI 0.97-22.38). CONCLUSION: Vascular calcifications are associated with worse survival of native arteriovenous hemodialysis fistulas.

COLITIS AND "DIAPHRAGM DISEASE" OF THE COLON IN HEMODIALYSIS PATIENT DUE TO PROLONGED USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUG.

INTRODUCTION: The use of non-steroidal anti-inflammatory drugs may lead to stricture of the small intestine and less frequently of the colon. Colonic strictures have not been described in patients on dialysis and the aim of this report is to show the case of dialysis patient who was followed for recurrent and prolonged diarrhea. CASE REPORT: We present the patient on chronic dialysis for 15 years who used non-steroidal anti-inflammatory drugs due to chronic pain and who developed recurrent diarrhea. Diagnosis was made by endoscopy and confirmed by histology. Specific therapy was applied with a good response. CONCLUSION: Although not described in the literature, non-steroidal anti-inflammatory drug-induced colitis and/or diaphragm disease could be a potential reason for recurrent or prolonged diarrhea in dialysis patients.

Influence of hemodialysis duration per week on parameters of dialysis adequacy and cardiovascular morbidity.

INTRODUCTION: The optimal length of dialysis is still under debate and current regimen of 12 hours a week is medically acceptable. The aim of this observational study was to confirm the relationship between different length of dialysis per week and the parameters of dialysis adequacy and cardiovascular morbidity. MATERIAL AND METHODS: The study included 206 patients (128 man and 78 females) who were on maintenance hemodialysis for more than 6 months. They were classified into three groups according to the length of dialysis per week: group I (12 hours), group II (15 hours) and group III (≥17.5 hours). RESULTS: Index of dyalysis adequacy values did not differ among the groups (group I, II, III = 1.32 vs. 1.51 vs. 1.42; p>0.05); however, the patients from group III had the best bicarbonate level (group I, II and III = 22.7; 21.4; 17.6 mmol/L; p<0.001). In comparison with group I (12 hours), longer dialysis duration was associated with significantly higher hemoglobin values (12.2 vs. 11.4 vs. 10.5 g/dL), less frequent use of erythropoietin stimulating agents (26.9% vs. 65% vs. 86.3%), lower stimulating agents weekly dose (median in group I, II, III = 2000 vs. 5000 vs. 4000 I.J.), lower stimulating agents resistance index (4.9 vs. 7.8 vs. 8.8), significantly higher level of serum albumin (42.3 vs. 40.7 vs. 38.2 g/dL), total cholesterol (5.1 vs. 4.7 vs. 4.5 mmol/L) and serum calcium level (2.38 vs. 2.42 vs. 2.28 mmol/L), less frequent use of phosphate binders (53.8% vs. 85% vs. 84.4%) and calcitriol (19.2% vs. 65% vs. 50.6%) and lower intact parathyroid hormone level (336 vs. 363 vs. 446 pg/ml). In addition, longer dialysis duration was associated with lower cardiovascular morbidity score (0.52 vs. 1.05 vs. 1.26). CONCLUSION: Duration of dialysis per week above the current standard positively correlates with parameters of hemodialysis adequacy.

Arteriovenous fistula aneurysm in patients on regular hemodialysis: prevalence and risk factors.

BACKGROUND/AIMS: Compared to all other complications, literature data about vascular access aneurysm (VAA) are the scarcest. The aim of this cross-sectional study was to evaluate the prevalence of arteriovenous fistula (AVF) aneurysms and to confirm the risk factors for their appearance. METHODS: The presence, number and morphological characteristics of AVF aneurysms were confirmed, and according to the score of AVF aneurysm (the sum of the length and width in cm), patients were classified into group 1 (score ≤12) and group 2 (score >12). Analysis included the last data from the medical records including vascular calcifications score. RESULTS: Out of 181 patients, 150 with native fistula were included in this study. Aneurysmatic changes were detected in 90 (60%) patients, and the majority had two or more aneurysms. VAA were more frequent in patients with adult polycystic kidney disease (ADPKD) than in other diagnostic categories. By using forward stepwise logistic regression, we confirmed that patients on high-flux hemodialysis (HD) had 5.3-fold higher risk, and patients with diabetes mellitus had 5.8-fold less risk for developing AVF aneurysm. While vascular calcification score did not influence the incidence of VAA, higher PWV had significant negative influence on formation of AVF aneurysm (OR 1.25, 95% CI 1.003-1.56, p = 0.047). By ROC curve analysis, it was determined that patients who were longer than 5.7 years on HD had greater risk for developing VAA (area = 0.741, p = 0.000). CONCLUSION: This single-center study confirmed the very high prevalence of VAA (60%). Aneurysms were more frequent in patients with ADPKD and in those who had longer dialysis vintage on high-flux membranes with higher blood flow rate.

Application of sentinel lymph node biopsy in cutaneous basosquamous carcinoma.

Basosquamous carcinoma of the skin is a relatively rare cutaneous neoplasm that has significant metastatic potential and a metastatic rate greater than that of basal cell and squamous cell carcinoma. We describe the use of lymphatic mapping and sentinel lymph node biopsy in a 63-year-old man after identification of basosquamous carcinoma. Sentinel lymph node biopsy, which is a standard tool to detect regional lymphatic metastasis in cutaneous melanoma, has been rarely employed to detect lymphatic metastasis of basosquamous carcinoma. The approach was successful in detecting a regional lymphatic metastasis of two nodal basins with minor morbidity. Sentinel lymph node biopsy may be useful for certain high-risk lesions of basosquamous carcinoma.