Metformin: A stroke of luck

http://www.ejgm.co.uk/Metformin-A-stroke-of-luck,108679,0,2.htmlMetformin is an oral glucose-lowering drug that has been widely used for more than half a century. Both the American Diabetes Association and the European Association for the study of Diabetes recommend metformin as the first line therapy for the treatment of type II diabetes mellitus. Metformin has considerably evolved from being an antidiabetic into a drug with a wider potential of therapeutic uses such as anticancer, antiaging, treatment of gestational hypertension, preeclampsia and weight loss. In addition to the in-label use of metformin as an anti-hyperglycemic medication, it is widely prescribed as an off label therapy for young women with Poly Cystic Ovary Syndrome for the treatment of symptoms associated with the disorder. This article is a brief summary that lists and briefly discusses current and potential non-hyperglycemic uses and effects of metformin

Dynamics of hospital admissions and all-cause mortality of HIV infected patients in Kazakhstan: data from unified nationwide electronic healthcare system 2014–2019

Background and objectivesAlthough global HIV pandemic has stabilized, it continues to rise in Eastern Europe and Central Asia due to exponential growth of newly acquired cases. Based on UNAIDS, there are currently 35,000 people living with HIV (PLWH) in Kazakhstan. This alarming HIV epidemiologic situation mandates urgent investigation of causes, routes of transmission and other characteristics in order to halt the epidemic. We aimed to analyze the data of all hospitalized patients for the period of 2014–2019 who tested positive for HIV from the Unified National Electronic Health System (UNEHS) of Kazakhstan.MethodsThis cohort study extracted data for all HIV positive patients during 2014–2019 from UNEHS of Kazakhstan to apply descriptive, Kaplan–Meier estimation, and Cox proportional hazards regression model. Crosscheck of the target population data was conducted with tuberculosis, viral hepatitis, alcohol abuse and intravenous drug user (IDU) cohorts in order to create a comprehensive database. All survival functions and factors associated with mortality were tested for significance.ResultsThe cohort population (n = 2,213) mean age was 33.3 ± 13.3 years with 1,375 males (62.1%) and 838 females (37.9%). Incidence rate decreased from 2.05 in 2014 to 1.88 in 2019, however, prevalence and mortality continues to escalate every year, the mortality raised significantly from 0.39 in 2014 to 0.97 in 2019. People aged >50 years, males, retired people, patients from tuberculosis hospital profile had much lower survival probabilities than the corresponding groups. Adjusted Cox regression model death hazard showed strong association of HIV patients with tuberculosis coinfection (HR 1.4, 95% CI 1.1; 1.7, p < 0.001).ConclusionThe results of this study demonstrate high rates of HIV mortality, strong association of HIV with TB coinfection, regional, age specific, gender, hospital profile and social status differences that significantly affect HIV prevalence. Since the prevalence of HIV is continuing to increase, more information is necessary for evaluation and implementation of prevention procedures

Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease: A Pilot Study

Biomarkers; Chronic kidney disease; ProteinuriaBiomarcadores; Enfermedad renal crónica; ProteinuriaBiomarcadors; Malaltia renal crònica; ProteinúriaProteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19–53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49–117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes.The authors acknowledge funding from the Nazarbayev University Collaborative Research Program (CRP) for 2020–2022 (Funder Project Reference: 091019CRP2105)

PATIENTS RECEIVING HEMODIALYSIS DO NOT LOSE SARS-COV-2 ANTIBODIES MORE RAPIDLY THAN NON-RENAL CONTROLS: A PROSPECTIVE COHORT STUDY

Background Patients with end-stage kidney disease receiving maintenance hemodialysis (HD) are at increased risk for mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with the general population. However, it is currently unknown whether the long-term SARS-CoV-2 humoral and cellular immune responses in patients receiving HD are comparable to individuals with normal kidney function. Method The prospective cohort study included 24 patients treated with maintenance HD and 27 non-renal controls with confirmed history of coronavirus disease (COVID-19). In all participants the levels of specific IgG were quantified at three timepoints: 10, 18, and 26 weeks from disease onset. In a subgroup of patients, specific T-cell responses were evaluated. Results The seropositivity rate declined in controls over time and was 85% and 70.4% at weeks 18 and 26, respectively. All HD patients remained seropositive over the study period. Seropositivity rate at week 26 was greater among patients receiving HD: RR = 1.4 [95%CI: 1.17–1.94] (reciprocal of RR = 0.7 [95% CI: 0.52–0.86]), p = 0.0064. In both groups, IgG levels decreased from week 10 to week 26, but antibodies vanished more rapidly in controls than in HD group (ANOVA p = 0.0012). The magnitude of T-cell response was significantly lower in controls than in HD patients at weeks 10 (p = 0.019) and 26 (p = 0.0098) after COVID-19 diagnosis, but not at week 18. Conclusion Compared with non-renal adults, patients receiving HD maintain significant long-term humoral and cellular immune responses following natural COVID-19

SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS) FOR PROTEIN DETERMINATION IN HUMAN URINE

Excessive protein excretion in human urine is an early and sensitive marker of diabetic nephropathy, primary and secondary renal disease. Kidney problems, particularly chronic kidney disease, remain among the few growing causes of mortality in the world. Therefore, it is important to develop efficient, expressive, and low-cost method for protein determination. Surface-enhanced Raman spectroscopy (SERS) methods are potential candidates to achieve those criteria. In this paper, the SERS method was developed to distinguish patients with proteinuria and the healthy group. Two types of commercial gold nanoparticles with a diameter of 60 nm and 100 nm were employed to prepare substrates for the analysis of 78 samples of unique patients. Data analysis by the PCA-LDA algorithm, and the ROC curves, gave results for diagnostic figures of merits. Sensitivity, specificity, accuracy, and AUC were 0.79, 0.89, 0.85, and 0.90 for the set with 60 nm Au NPs, respectively. Sensitivity, specificity, accuracy, and AUC were 0.79, 0.98, 0.90, and 0.91 for the set with 100 nm Au NPs, respectively. The results show the potential of SERS spectroscopy in differentiating between patients with proteinuria and healthy individuals for clinical diagnostics

INCIDENCE AND MORTALITY RATES OF STROKES IN KAZAKHSTAN IN 2014–2019

There is a lack of information on the epidemiology of acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in developing countries. This research presents incidence and mortality rates of stroke patients based on hospital admission and discharge status in one of the Central Asian countries by analysis of large-scale healthcare data. The registry data of 177,947 patients admitted to the hospital with the diagnosis of stroke between 2014 and 2019 were extracted from the National Electronic Health System of Kazakhstan. We provide descriptive statistics and analyze the association of socio-demographic and medical characteristics such as comorbidities and surgical treatments. Among all stroke patients, the incidence rate based on hospital admission of AIS was significantly higher compared to SAH and ICH patients. In 5 year follow-up period, AIS patients had a better outcome than SAH and ICH patients (64.7, 63.1 and 57.3% respectively). The hazard ratio (HR) after the trepanation and decompression surgery was 2.3 and 1.48 for AIS and SAH patients; however, it was protective for ICH (HR = 0.87). The investigation evaluated an increase in the all-cause mortality rates based on the discharge status of stroke patients, while the incidence rate decreased over time

Pre-ESRD Depression and Post-ESRD Mortality in Patients with Advanced CKD Transitioning to Dialysis.

Background and objectivesDepression in patients with nondialysis-dependent CKD is often undiagnosed, empirically overlooked, and associated with higher risk of death, progression to ESRD, and hospitalization. However, there is a paucity of evidence on the association between the presence of depression in patients with advanced nondialysis-dependent CKD and post-ESRD mortality, particularly among those in the transition period from late-stage nondialysis-dependent CKD to maintenance dialysis.Design, setting, participants, &amp; measurementsFrom a nation-wide cohort of 45,076 United States veterans who transitioned to ESRD over 4 contemporary years (November of 2007 to September of 2011), we identified 10,454 (23%) patients with a depression diagnosis during the predialysis period. We examined the association of pre-ESRD depression with all-cause mortality after transition to dialysis using Cox proportional hazards models adjusted for sociodemographics, comorbidities, and medications.ResultsPatients were 72±11 years old (mean±SD) and included 95% men, 66% patients with diabetes, and 23% blacks. The crude mortality rate was similar in patients with depression (289/1000 patient-years; 95% confidence interval, 282 to 297) versus patients without depression (286/1000 patient-years; 95% confidence interval, 282 to 290). Compared with patients without depression, patients with depression had a 6% higher all-cause mortality risk in the adjusted model (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.09). Similar results were found across all selected subgroups as well as in sensitivity analyses using alternate definitions of depression.ConclusionPre-ESRD depression has a weak association with post-ESRD mortality in veterans transitioning to dialysis

Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease : A Pilot Study

Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19-53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49-117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcome