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Hemoglobin variability (Hb-var) in patients with chronic kidney disease has been stipulated to be a result of exogenous treatment with erythropoiesis stimulating agents (ESA) and has been related to mortality in dialysis patients. We hypothesized the existence of Hb-var independent of ESA administration and compared it to that in healthy adults using data from the Scripps-Kaiser and NHANES III databases. We studied the Hb-var in 1571 peritoneal dialysis patients which included 116 patients not requiring treatment with erythropoietin. We systematically studied the differences between the groups that needed ESA therapy and those who did not. White race and male sex were significant predictors of need for erythropoietin therapy. We found peritoneal dialysis patients to exhibit significantly increased Hb-var independent of treatment with exogenous erythropoietin (0.99 gm/dL vs. 1.17 gm/dL, p-value<0.001). We found age to be a significant determinant of Hb-var in the ESA treated group. Hb-var in younger patients (<30 years) was increased by 50% compared to young healthy adults. The Hb-var in elderly (>60 years) peritoneal dialysis patients was similar to that seen in healthy elders, suggesting similarity with anemia of aging. We conclude that exogenous ESA administration does not explain Hb-var entirely but may enhance it. Intrinsic factors affecting erythropoiesis including age may be the major determinants of Hb-var.

A fundamental challenge in emulating kidney tissue formation through directed differentiation of human pluripotent stem cells is that kidney development is iterative, and to reproduce the asynchronous mix of differentiation states found in the fetal kidney we combined cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and heterochronic organoids were well vascularized when engrafted under the kidney capsule. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed, but despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study. We propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop similar stromal overgrowth when engrafted under the kidney capsule. Ashwani Gupta et al. report an improved protocol for kidney organoid differentiation from pluripotent stem cells. The authors simulate the condition of the fetal kidney by mixing cells differentiated at different times from the same organoid, thereby promoting nephrogenesis in vitro and vascularization after engraftment under the kidney capsule in mice.

Thromboembolism is more common in kidney transplant recipients (KTRs) than in the general population. Studies evaluating arterial and venous thromboembolism (VTE) in KTRs are scarce and the magnitude and risk factors are mostly undefined. A nested control study was conducted from January 1, 2007, to December 31, 2019. Adult KTRs who were detected to have VTE events during this period were included. The primary outcome was to assess the prevalence of VTE in this population. Secondary outcomes were the assessment of the time to occurrence of the thromboembolic events after transplantation and assessing the risk factors and patient survival. For each subject studied, 4 controls were matched from the data set. Amongst 2158 patients, 97 (4.5%) were found to have VTE. The median follow-up time was 3.9 years (6-156 months). A total of 101 VTE events were recorded. The most common site of VTE was the lower limb deep vein thrombosis in 79 patients (0.03%)).In multivariate Cox regression analysis, serum creatinine of more than 3 mg/dl [HR 1.30, 95% CI (1.03-1.38)] was independently associated with increased VTE risk. Patients who developed a VTE had higher mortality as compared to patients who did not develop VTE. No increased risk of graft failure was found in VTE patients. This study suggests that kidney transplantation surgery is a moderate risk factor for VTE, and VTE is associated with higher morbidity and mortality. However, prospective studies are needed to establish a definite role of VTE in outcomes in KTRs.

Objectives: The present study was conducted with the aim to compare the sodium (Na) and  potassium (K) results on arterial blood gas (ABG) and electrolyte analyzers both of which use direct ion selective electrode technology. Materials and Methods: This was a retrospective study in which data were collected for simultaneous ABG and serum electrolyte samples of a patient received in Biochemistry Laboratory during February to May 2015. The ABG samples received in heparinized syringes were processed on Radiometer ABL80 analyzer immediately. Electrolytes in serum sample were measured on ST-100 Sensa Core analyzer after centrifugation. Data were collected for 112 samples and analyzed with the help of Excel 2010 and  Statistical software for Microsoft excel XLSTAT 2015 software. Results: The mean Na level in serum sample was 139.4 ± 8.2 mmol/L compared to 137.8 ± 10.5 mmol/L in ABG (P < 0.05). The mean difference between the results was 1.6 mmol/L. Mean K level in serum sample was 3.8 ± 0.9 mmol/L as compared to 3.7 ± 0.9 mmol/L in ABG sample (P < 0.05). The mean difference between the results was 0.14 mmol/L. Statistically significant difference was observed in results of two instruments in low Na (<135 mmol/L) and normal K (3.5-5.2 mmol/L) ranges. The 95% limit of agreement for Na and K on both instruments was 9.9 to −13.2 mmol/L and 0.79 to −1.07 mmol/L respectively. Conclusions: The clinicians should be cautious in using the electrolyte results of electrolyte and ABG analyzer in inter exchangeable manner.

Background Studies have shown that the incidence of atrial fibrillation (AF) in cancer is most likely due to the presence of inflammatory markers. The purpose of our study is to determine the association of AF with different cancer subtypes and its impact on in‐hospital outcomes. Methods Data were obtained from the National Inpatient Sample database between 2005 and 2015. Patients with various cancers and AF were studied. ICD‐9‐CM codes were utilized to verify variables. Patients were divided into three age groups: Group 1 (age < 65 years), Group 2 (age 65‐80 years), and Group 3 (age > 80 years). Statistical analysis was performed using Pearson chi‐square and binary logistic regression analysis to determine the association of individual cancers with AF. Results The prevalence of AF was 14.6% among total study patients (n = 46 030 380). After adjusting for confounding variables through multivariate regression analysis, AF showed significant association in Group 1 with lung cancer (odds ratio, OR = 1.92), multiple myeloma (OR = 1.59), non‐Hodgkin lymphoma (OR = 1.55), respiratory cancer (OR = 1.55), prostate cancer (OR = 1.20), leukemia (OR = 1.12), and Hodgkin's lymphoma (OR = 1.03). In Group 2, the association of AF with multiple myeloma (1.21), lung cancer (OR = 1.15), Hodgkin lymphoma (OR = 1.15), non‐Hodgkin lymphoma (OR = 1.12), respiratory cancer (OR = 1.08), prostate cancer (OR = 1.06), leukemia (OR = 1.14), and colon cancer (OR = 1.01) were significant. In Group 3, AF showed significant association with non‐Hodgkin lymphoma (OR = 1.06), prostate (OR = 1.03), leukemia (OR = 1.03), Hodgkin's lymphoma (OR = 1.02), multiple myeloma (OR = 1.01), colon cancer (OR = 1.01), and breast cancer (OR = 1.01). The highest mortality was found in lung cancer in age <80 and prostate cancer in age >80. Conclusion In patients age <80 years, AF has significant association with lung cancer and multiple myeloma, whereas in patients age >80 years, it has significant association with non‐Hodgkin lymphoma and prostate cancer. In patients age <80 years, increased mortality was seen in AF with lung cancer and in patients age >80 years, increased mortality was seen in those with AF and prostate cancer. Twitter In age <80, lung cancer and multiple myeloma have a strong association with AF while thyroid and pancreatic cancers have no association with AF at any age. In age greater than 80, NHL and prostate cancer have a significant association with AF. Our study found that in age <80, lung cancer and multiple myeloma have a strong association with AF while thyroid and pancreatic cancers have no association with AF at any age. In age greater than 80, NHL and prostate cancer have a significant association with AF. The highest mortality incidence in age <80 was found in lung cancer and in age >80 was seen in prostate cancer

Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (p<0.05 for all). The injected fetal kidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (p<0.05 for both). In addition, the kidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (p<0.05 for all). Our data shows that culture expanded fetal kidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.

Background The association between atrial fibrillation (Afib) and sinus and AV nodal dysfunction has previously been reported. However, no data are available regarding the association between Afib and bundle branch block (BBB). Methods Patient data were obtained from the Nationwide Inpatient Sample (NIS) database between years 2009 and 2015. Patients with a diagnosis of Afib and BBB were identified using validated International Classification of Diseases, 9th revision, and Clinical Modification (ICD‐9‐CM) codes. Statistical analysis using the chi‐square test and multivariate linear regression analysis were performed to determine the association between Afib and BBB. Results The total number of patients with BBB was 3,116,204 (1.5%). Patients with BBB had a mean age of 73.5 ± 13.5 years, 53.6% were males, 39.1% belonged to the age group ≥80 years, and 72.9% were Caucasians. The prevalence of Afib was higher in the BBB group, as compared to the non‐BBB group (29% vs 11.8%, p value<.001). This association remained significant in multivariate regression analysis with an odds ratio of 1.25 (CI: 1.24‐1.25, P < .001). Among the subtypes of BBB, Afib was comparatively more associated with RBBB (1.32, CI 1.31‐1.33, p value<.0001) than LBBB (1.17, CI 1.16‐1.18, p value<.0001). The mean cost was higher among Afib with BBB, compared with Afib patients without BBB ( $15 795 vs $ 14 391, p value<.0001). There was no significant difference in the mean length of stay (5.6 vs 5.9 days, p value<.0001) or inpatient mortality (4.9% vs 4.8%). Conclusion This study demonstrates that prevalence of Afib is higher in patients with BBB than without BBB. Cost are higher for Afib patients with BBB, compared to those without BBB, with no significant increase in mortality or length of stay. This study demonstrates that prevalence of Afib is higher in patients with BBB than without BBB. Cost are higher for Afib patients with BBB, compared to those without BBB, with no significant increase in mortality or length of stay.

Background Neurotoxicity is a common side effect of treatment with calcineurin inhibitors. Tremors are frequently reported as the most common manifestation. Variable presentations can include headaches, seizures, visual hallucinations or blindness. Sixth nerve palsy has been reported in previous cases of bone marrow and cardiac transplant patients receiving calcineurin inhibitors. In many of these previously reported cases, the drug was administered intravenously and very high drug levels were found. Case presentation We report the first case of isolated diplopia in a patient being treated for idiopathic membranous glomerulonephritis. This is also the first report where the neurotoxicity induced by initial tacrolimus therapy persisted with subsequent cyclosporine therapy, two structurally different calcineurin inhibitors which share a common mechanism of action. In our case toxicity occurred after 3 months of therapy despite low serum concentrations and the symptoms resolved completely after discontinuation of the drugs. Conclusion Our case provides further evidence that the neurotoxicity is a result of calcineurin inhibition. Monitoring of serum concentrations of these drugs has not been correlated with toxicity. The mean duration to onset of symptoms can be as much as 70 days suggesting accumulation of the drug in the central nervous system plays a role. Recognition of this condition is important for prompt diagnosis and appropriate management.

Mesenchymal stem cells (MSCs) are promising cells for cardiovascular regenerative medicine. However, their potential may be limited, because of their restricted cardiovascular differentiation potential and decline in their number and functional characteristics with increasing donor age. We have previously shown that rat fetus heart harbors primitive MSCs and administration of these cells improved left ventricular (LV) function after ischemia/reperfusion injury in rats. To evaluate their potential as a new cell type for clinical cardiovascular cell therapy, we have undertaken this study on the isolation and characterization of human fetal cardiac MSCs (hfC-MSCs). MSCs were isolated from the heart of five 14-16-week-old aborted human fetuses and studied for their growth characteristics, karyotypic stability and senescence over successive passages, expression of mesenchymal and embryonal markers by flow cytometry and immunocytochemistry, constitutive expression of cardiovascular genes by RT-PCR, differentiation into cells of the cardiovascular lineage and their immunomodulatory properties. The hfC-MSCs grew as adherent monolayer with spindle shaped morphology and exhibited rapid proliferation with an average population doubling time of 34 hours and expansion to up to more than 80 population doublings with maintenance of a normal karyotype and without senescence. Immunophenotyping showed that they had similar phenotype as human bone marrow mesenchymal stem cells (hBM-MSCs) expressing CD73, CD90, CD105 and lacking expression of CD31, CD34, CD45, HLA-DR. However, hfC-MSCs expressed significantly higher levels of CD117 and SSEA-4 compared to hBM-MSCs. In addition, hfC-MSCs expressed the embryonal markers Oct-4, Nanog and Sox-2 as compared to hBM-MSCs. Further, hfC-MSCs had significantly higher expression of the cardiovascular genes viz. ISL-1, flk-1, GATA-4, NKX2.5 and MDR-1 as compared to hBM-MSCs, and could be differentiated into major cardiovascular cells (cardiomyocytes, endothelial cells, smooth muscle cells). Interestingly, hfC-MSCs markedly reduced T-lymphocyte proliferation with an increased secretion of TGF-β and IL-10. Our results show that human fetus heart is a novel source of primitive MSCs with cardiovascular commitment which may have a potential therapeutic application in cardiovascular regenerative medicine.

BK virus is a polyoma virus which remains in latent phase in the urinary tract, particularly in the renal tubular epithelial cells. In immunosuppressed patients, it is activated and manifests as tubule-interstitial nephritis causing renal allograft dysfunction. A total of 402 patients who underwent renal allograft biopsy from 2013 to 2016 were included in this study; six patients were diagnosed to have BK virus nephropathy. Histopathology showed ground glass intra-nuclear inclusions accompanied by acute tubular injury, interstitial inflammation, and varying degree of interstitial fibrosis and tubular atrophy. Patients were managed with reduction in the overall immunosuppression. Only one patient progressed to graft failure on follow-up. The overall prevalence of polyoma virus at our center is 1.49%.