Immunotactoid hepatopathy: A novel entity with histologically proven recurrence post liver transplantation.

Immunotactoid deposition is a rare fibrillary deposition disease that is primarily seen in the kidney and is associated with paraproteinemia. Here, we report a case of hepatic immunotactoid deposition in a 67-year-old male with a history of smoldering myeloma and chronic kidney disease who underwent liver transplantation for metabolic dysfunction-related cirrhosis. Immunotactoid deposition was first identified in the explanted liver and recurred in the allograft within only 7 weeks following transplantation, presenting as ascites with normal liver function tests. The patient's posttransplant course was complicated by proteinuria and renal failure requiring dialysis. Histologic examination of both native and allograft livers demonstrated pink amorphous material occupying sinusoidal spaces that were Congo-red negative and immunoglobulin M Kappa-restricted. Electron microscopy revealed characteristic deposits of electron-dense bundles of hollow microtubules with a 40 nm diameter within the sinusoids and space of Disse, consistent with immunotactoids. Therapy of the patient's underlying plasma-cell dyscrasia utilizing a daratumumab-based regimen showed decreased serum paraproteins, resolution of ascites, and improved kidney function, no longer requiring dialysis, without inducing rejection. The patient continues to respond to treatment 10 months posttransplant.

Outcomes of therapeutic plasma exchange for the treatment of patients with multiple myeloma cast nephropathy.

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy. Eighty patients were included in this analysis, of whom 72.5% had ≥50% drop in their initial involved sFLC. At 3 months from TPE initiation, the overall hematologic response rate (ORR) was 67.5% with a very good partial response or better (≥VGPR) rate of 40%. At 6 months, ORR was 57.5%, with ≥VGPR rate of 49%. The renal response rate at 3 and 6 months was 47.5% and 43.75%, respectively; the overall renal response rate was 48.75%. On multivariable analysis, every one unit increase in baseline creatinine (odds ratio [OR] 0.76, p = 0.006), and achievement of ≥VGPR (OR 21.7 p < 0.0001) were significantly associated with renal response. Also, a ≥50% drop in sFLC was favorably associated with renal response (OR 3.39, p = 0.09). With a median follow-up of 36.4 months, the median overall survival (OS) was 11 months. On multivariable analysis, achievement of renal response (hazard ratio [HR] 0.3, p < 0.0001) and newly diagnosed disease (NDMM; HR 0.43, p = 0.0055) were associated with improved OS. Among NDMM patients, those treated with daratumumab-based regimens had a trend for better OS (p = 0.15), compared to other regimens, but the difference was not significant. At the end of follow-up, an estimated 40.4% of patients who were on dialysis were able to become dialysis independent. In conclusion, our study highlights the poor survival of patients with MCN. Achievement of early renal response is crucial for prolonged OS, with daratumumab-based therapies showing promise.

Impact of the COVID-19 Pandemic on Nephrology Fellow Training and Well-Being in the United States: A National Survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic's effects on nephrology fellows' educational experiences, preparedness for practice, and emotional wellbeing are unknown. METHODS: We recruited current adult and pediatric fellows and 2020 graduates of nephrology training programs in the United States to participate in a survey measuring COVID-19's effects on their training experiences and wellbeing. RESULTS: Of 1005 nephrology fellows-in-training and recent graduates, 425 participated (response rate 42%). Telehealth was widely adopted (90% for some or all outpatient nephrology consults), as was remote learning (76% of conferences were exclusively online). Most respondents (64%) did not have in-person consults on COVID-19 inpatients; these patients were managed by telehealth visits (27%), by in-person visits with the attending faculty without fellows (29%), or by another approach (9%). A majority of fellows (84%) and graduates (82%) said their training programs successfully sustained their education during the pandemic, and most fellows (86%) and graduates (90%) perceived themselves as prepared for unsupervised practice. Although 42% indicated the pandemic had negatively affected their overall quality of life and 33% reported a poorer work-life balance, only 15% of 412 respondents who completed the Resident Well-Being Index met its distress threshold. Risk for distress was increased among respondents who perceived the pandemic had impaired their knowledge base (odds ratio [OR], 3.04; 95% confidence interval [CI], 2.00 to 4.77) or negatively affected their quality of life (OR, 3.47; 95% CI, 2.29 to 5.46) or work-life balance (OR, 3.16; 95% CI, 2.18 to 4.71). CONCLUSIONS: Despite major shifts in education modalities and patient care protocols precipitated by the COVID-19 pandemic, participants perceived their education and preparation for practice to be minimally affected.

Mesenchymal Stem Cells Ameliorate Cuprizone-Induced Demyelination by Targeting Oxidative Stress and Mitochondrial Dysfunction.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. The main causes of MS disease progression, demyelination, and tissue damage are oxidative stress and mitochondrial dysfunction. Hence, the latter are considered as important therapeutic targets. Recent studies have demonstrated that mesenchymal stem cells (MSCs) possess antioxidative properties and are able to target mitochondrial dysfunction. Therefore, we investigated the effect of transplanting Wharton's jelly-derived MSCs in a demyelination mouse model of MS in which mice were fed cuprizone (CPZ) for 12 weeks. CPZ is a copper chelator that impairs the activity of cytochrome oxidase, decreases oxidative phosphorylation, and produces degenerative changes in oligodendrocytes, leading to toxic demyelination similar to those found in MS patients. Results showed that MSCs caused a significant increase in the percentage of myelinated areas and in the number of myelinated fibers in the corpus callosum of the CPZ + MSC group, compared to the CPZ group, as assessed by Luxol fast blue staining and transmission electron microscopy. In addition, transplantation of MSCs significantly increased the number of oligodendrocytes while decreasing astrogliosis and microgliosis in the corpus callosum of the CPZ + MSC group, evaluated by immunofluorescence. Moreover, the mechanism by which MSCs exert these physiological effects was found to be through abolishing the effect of CPZ on oxidative stress markers and mitochondrial dysfunction. Indeed, malondialdehyde significantly decreased while glutathione and superoxide dismutase significantly increased in CPZ + MSC mice group, in comparison witth the CPZ group alone. Furthermore, cell therapy with MSC transplantation increased the expression levels of mitochondrial biogenesis transcripts PGC1α, NRF1, MFN2, and TFAM. In summary, these results demonstrate that MSCs may attenuate MS by promoting an antioxidant response, reducing oxidative stress, and improving mitochondrial homeostasis.

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression.

BACKGROUND: The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy. METHODS: Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR < 60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk. RESULTS: 25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P = 0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P = 0.71). CONCLUSIONS: Use of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy.

"What do you think about nephrology?" A national survey of internal medicine residents.

BACKGROUND: Interest in nephrology has been declining among internal medicine residents but the reasons behind this observation are not well characterized. Our objective was to evaluate factors influencing residents' choice of subspecialty. METHODS: This is a mixed-method QUAL-QUAN design study that used the results of our previously published qualitative analysis on residents' perception of nephrology to create and pilot a questionnaire of 60 questions. The final questionnaire was distributed to 26 programs across the United States and a total of 1992 residents. We calculated response rates and tabulated participant characteristics and percentage of participant responses. We categorized choice of fellowship into 2 medical categories (Highly Sought After vs. Less Sought After) and fitted a logistic regression model of choosing a highly vs. less sought after fellowship. RESULTS: Four hundred fifteen out of 1992 (21%) US residents responded to the survey. Of the 268 residents planning to pursue fellowship training, 67 (25%) selected a less sought after fellowship. Female sex was associated with significantly higher odds of selecting a less sought after fellowship (OR = 2.64, 95% CI: 1.47, 4.74). Major factors deterring residents from pursuing nephrology were perception of inadequate financial compensation, broad scope of clinical practice and complexity of patient population. We observed a decline in exposure to nephrology during the clinical years of medical school with only 35.4% of respondents rotating in nephrology versus 76.8% in residency. The quality of nephrology education was rated less positively during clinical medical school years (median of 50 on a 0-100 point scale) compared to the pre-clinical years (median 60) and residency (median 75). CONCLUSION: Our study attempts to explain the declining interest in nephrology. Results suggest potential targets for improvement: diversified trainee exposure, sub-specialization of nephrology, and increased involvement of nephrologists in the education of trainees.

DNA methylation signatures of Prostate Cancer in peripheral T-cells.

BACKGROUND: Prostate Cancer (PCa) is the second most common cancer in men where advancements have been made for early detection using imaging techniques, however these are limited by lesion size. Immune surveillance has emerged as an effective approach for early detection and to monitor disease progression. In recent studies, we have shown that host peripheral blood immune cells undergo changes in DNA methylation in liver and breast cancer. METHODS: In the current study, we examined the DNA methylation status of peripheral blood T cells of men with positive biopsy for PCa versus men with negative biopsy having benign prostate tissue, defined as controls. T cells DNA was isolated and subjected to Illumina Infinium methylation EPIC array and validated using Illumina amplicon sequencing and pyrosequencing platforms. RESULTS: Differential methylation of 449 CG sites between control and PCa T cell DNA showed a correlation with Gleason score (p < 0.05). Two hundred twenty-three differentially methylated CGs between control and PCa (Ƨ +/- 10%, p < 0.05), were enriched in pathways involved in immune surveillance system. Three CGs which were found differentially methylated following DMP (Differentially methylated probes) analysis of ChAMP remained significant after BH (Benjamini-Hochberg) correction, of which, 2 CGs were validated. Predictive ability of combination of these 3 CGs (polygenic methylation score, PMS) to detect PCa had high sensitivity, specificity and overall accuracy. PMS also showed strong positive correlation with Gleason score and tumor volume of PCa patients. CONCLUSIONS: Results from the current study provide for the first-time a potential role of DNA methylation changes in peripheral T cells in PCa. This non-invasive methodology may allow for early intervention and stratification of patients into different prognostic groups to reduce PCa associated morbidity from repeat invasive prostate biopsies and design therapeutic strategy to reduce PCa associated mortality.

Conference Report on First Certificate Course in Health Professions Educationat College of Medicine, University of Kerbala, Iraq.(September 2019).

The current status of medical education in Iraq requires complete transformation to conform to the latest trends of modern education. Presently it is compromised due to the influence of political factors, finances, weakness or fragility of planning and security. It has to be re-shaped for the future of medical education to produce good and efficient medical professionals. It is necessary to reform and revise the curriculum as accreditation in accordance with international medical universities. The initial requirement is faculty development in areas including but not limited to, curriculum development, teaching and learning improvement, research capacity building, and leadership development. The capacity building of faculty at College of Medicine, University of Kerbala (CMUCK) has been initiated in collaboration with Medics International at a local and the government level. Medics International conducted the current Course on Certificate in Health Professions Education (CHPE) programme in September, 2019 to facilitate the faculty to revise their curriculum and improve their current educational practices. Further steps will be taken to develop the faculty for Masters in Medical Education (MME), PhD, and fellowship programmes. To face the on-going challenges in the medical and health care system, continous efforts are required for faculty education. Medics International has volunteered to begin a series of Webinars through its global faculty to reach out to the Iraqi Board followed by engagement of the Arab Board covering 18 countries.

Frequency, Timing, and Types of Medication Ordering Errors Made by Residents in the Electronic Medical Records Era.

OBJECTIVES: To describe associations between resident level of training, timing of medication orders, and the types of inpatient medication ordering errors made by internal medicine residents. METHODS: This study reviewed all inpatient medication orders placed by internal medicine residents at a tertiary care academic medical center from July 2011 to June 2015. Medication order errors were measured by pharmacists' reporting of an error via the electronic medical record during real-time surveillance of orders. Multivariable regression models were constructed to assess associations between resident training level (postgraduate year [PGY]), medication order timing (time of day and month of year), and rates of medication ordering errors. RESULTS: Of 1,772,462 medication orders placed by 335 residents, 68,545 (3.9%) triggered a pharmacist intervention in the electronic medical record. Overall and for each PGY level, renal dose monitoring/adjustment was the most common order error (40%). Ordering errors were less frequent during the night and transition periods versus daytime (adjusted odds ratio [aOR] 0.93, 95% confidence interval [CI] 0.91-0.96, and aOR 0.93, 95% CI 0.90-0.95, respectively). Errors were more common in July and August compared with other months (aOR 1.05, 95% CI 1.01-1.09). Compared with PGY2 residents, both PGY1 (aOR 1.06, 95% CI 1.03-1.10), and PGY3 residents (aOR 1.07, 95% CI, 1.03-1.10) were more likely to make medication ordering errors. Throughout the course of the academic year, the odds of a medication ordering error decreased by 16% (aOR 0.84, 95% CI 0.80-0.89). CONCLUSIONS: Despite electronic medical records, medication ordering errors by trainees remain common. Additional supervision and resident education regarding medication orders may be necessary.

Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC. Although VHL mutations are considered as drivers of ccRCC, they are not sufficient to cause the disease. Recent genome-wide sequencing studies of ccRCC have revealed that mutations of genes coding for epigenome modifiers and chromatin remodelers, including PBRM1, SETD2 and BAP1, are the most common somatic genetic abnormalities after VHL mutations in these tumors. Moreover, recent research has shed light on the extent of abnormal epigenome alterations in ccRCC tumors, including aberrant DNA methylation patterns, abnormal histone modifications and deregulated expression of non-coding RNAs. In this review, we discuss the epigenetic modifiers that are commonly mutated in ccRCC, and our growing knowledge of the cellular processes that are impacted by them. Furthermore, we explore new avenues for developing therapeutic approaches based on our knowledge of epigenome aberrations of ccRCC.

Reversible cerebral vasoconstriction syndrome: a comprehensive update.

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiological syndrome characterized by recurrent thunderclap headache, with or without neurologic symptoms, and reversible vasoconstriction of cerebral arteries. RCVS affects patients in various racial and ethnic groups and in all age groups, although most commonly in the fourth decade of life. Many conditions and exposures have been linked to RCVS, including vasoactive drugs and the peripartum period. Disturbance of the cerebral vascular tone is thought to contribute to the disease's pathophysiology. RCVS generally follows a monophasic course. Associated strokes and cerebral hemorrhages are not uncommon. In this review we will attempt to provide a comprehensive overview of RCVS, with emphasis on the controversies in the field and the newest findings in the reported literature.

Cardiac Surgery Outcomes in Patients Receiving Hemodialysis Versus Peritoneal Dialysis.

Rationale & Objective: We sought to compare outcomes of patients receiving dialysis after cardiothoracic surgery on the basis of dialysis modality (intermittent hemodialysis [HD] vs peritoneal dialysis [PD]). Study Design: This was a retrospective analysis. Setting & Participants: In total, 590 patients with kidney failure receiving intermittent HD or PD undergoing coronary artery bypass graft and/or valvular cardiac surgery at Cleveland Clinic were included. Exposure: The patients received PD versus HD (intermittent or continuous). Outcomes: Our primary outcomes were in-hospital and 30-day mortality. Secondary outcomes were length of stay, days in the intensive care unit, the number of intraoperative blood transfusions, postsurgical pericardial effusion, and sternal wound infection, and a composite of the following 4 in-hospital events: death, cardiac arrest, effusion, and sternal wound infection. Analytical Approach: We used χ2, Fisher exact, Wilcoxon rank sum, and t tests, Kaplan-Meier survival, and plots for analysis. Results: Among the 590 patients undergoing cardiac surgery, 62 (11%) were receiving PD, and 528 (89%) were receiving intermittent HD. Notably, 30-day Kaplan-Meier survival was 95.7% (95% CI: 93.9-97.5) for HD and 98.2% (95% CI: 94.7-100) for PD (P = 0.30). In total, 75 patients receiving HD (14.2%) and 1 patient receiving PD (1.6%) had a composite of 4 in-hospital events (death, cardiac arrest, effusion, and sternal wound infection) (P = 0.005). Out of 62 patients receiving PD, 16 (26%) were converted to HD. Limitations: Retrospective analyses are prone to residual confounding. We lacked details about nutritional data. Intensive care unit length of stay was used as a surrogate for volume status control. Patients have been followed in a single health care system. The HD cohort outnumbered the PD cohort significantly. Conclusions: When compared with PD, HD does not appear to improve outcomes of patients with kidney failure undergoing cardiothoracic surgery. Patients receiving PD had a lower incidence of a composite outcome of 4 in-hospital events (death, cardiac arrest, pericardial effusion, and sternal wound infections).

Patients receiving peritoneal dialysis (PD) are frequently switched to hemodialysis (HD) around the time of an open-heart surgery. More times than not, this is driven by the preference of nonkidney doctors, because HD is perceived to control toxins and fluids better. PD is, however, more advantageous and can achieve similar results while being gentler. In an effort to keep patients on their home PD, we analyzed how they fared when compared with their HD counterparts. Patients maintained on PD did just as well if not better around and after their open-heart surgery. Given the expected increase in patients treated with PD, efforts should be made to maintain them on their home modality even around major surgeries.

Immunoinformatic Analysis of Leishmania Major gp46 Protein and Potential Targets for Vaccination against Leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis (CL) is a parasitic disease with a significant burden in the Old World countries. OBJECTIVE: In the current study, some of the primary biochemical properties and IFN-γ inducing epitopes with specific binding capacity to human and mouse MHC alleles were predicted for Leishmania major gp46 antigenic protein. METHODS: Several online servers were used to predict physico-chemical traits, allergenicity, antigenicity, transmembrane domain and signal peptide, subcellular localization, post-translational modifications (PTMs), secondary and tertiary structures, tertiary model refining with validations. Also, IEDB web server was used to predict mouse/human cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes. RESULTS: The 33.25 kDa protein was stable, hydrophilic, antigenic, while non-allergenic, with enhanced thermotolerance and 45 PTM sites. The secondary structure encompassed a random coil, followed by extended strands and helices. Ramachandran-based analysis of the refined model showed 73.1%, 21.6%, 3.4% and 1.9% of residues in the most favored, additional allowed, generously-allowed and disallowed regions, respectively. Epitope screening demonstrated 4 HTL epitopes against seemingly protective HLA alleles, 5 HTL epitopes against the HLA reference set, 3 human CTL epitopes and a number of mouse MHC-restricted epitopes. CONCLUSION: This paper provides insights into the bioinformatics characteristics of the L. major gp46 protein as a promising vaccine candidate.

Virtual Nephron: Evaluation of a Novel Virtual Reality Educational Tool.

Introduction: Recent technological advancements allowed the development of engaging technological tools. Using ASN funding from the ASN, we developed a 3D Virtual Reality (VR) physiology course entitled DiAL-Neph (Diuretic Action and eLectrolyte transport in the Nephron). We hereby present its evaluation. Methods: The study consisted of 2 parts: evaluation of knowledge gain, and qualitative evaluation of platform reception. Internal medicine PGY1 residents were randomly assigned into 2 groups: a VR group and a conventional group. Knowledge acquisition was assessed with a post-test administered at the end of the course and repeated within 6 to 12 weeks. Independent t-tests were used to compare the number of correct answers between the groups. A survey and focus groups composed of medicine residents evaluated the platform. Sessions were recorded and transcribed verbatim. Data was analyzed through the content analysis approach by two independent reviewers. Results: Of 117 PGY1 resident participants, 64 were randomized to the VR group and 53 were randomized to the traditional group. Initial test results showed higher scores among VR compared to the traditional group (76.5% correct vs. 68.8%). Seventy-eight PGY1s participated in the follow up testing (46 VR group vs. 32 traditional group) and results showed no significant difference in test results. Greater than 90% of the residents rated the platform positively and 77% preferred it as a teaching method. Conclusion: The DiAL-Neph VR platform appeared to improve short-term learning but not long-term retention. Further studies are needed to investigate the impact of such teaching platforms on overall interest in nephrology.

The boiled-egg technique: a new method for obtaining femoral head autograft used in acetabular defect reconstruction.

Primary total hip arthroplasty can be complicated by acetabular bony defects, threatening the biomechanical integrity of the prosthesis. Traditionally, when autologous bone is used to pack these defects, it is obtained from thin slices of femoral head in addition to acetabular reamings. We report a novel technique for the acquisition of autologous femoral head bone graft used in the reconstruction of acetabular defects during primary total hip arthroplasty.

C3 glomerulopathy.

C3 glomerulopathy (C3G) is a rare kidney disease that causes kidney dysfunction as a result of dysregulation of the complement system alternate pathway (AP). C3G encompasses 2 separate disorders, C3 glomerulonephritis and dense deposit disease. The presentation and natural history is variable and kidney biopsy is needed to confirm the diagnosis. The overall prognosis is poor with high recurrence rates after transplant. A better understanding of C3G is needed as is high-quality evidence to guide therapy, which currently includes mycophenolate mofetil and steroids for moderate to severe disease, and terminal complement blockade with anti-C5 therapy in unresponsive cases.

IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world. The etiology is unknown but a dysregulated T-cell immune response to viral, bacterial, and food antigens activating mucosal plasma cells to produce polymeric IgA has been proposed. No serological test exists to diagnosis IgAN. A definitive diagnosis requires kidney biopsy which is not always necessary. Kidney failure occurs in 20% to 40% of patients within 10 to 20 years.

Effect of serum albumin level on high-dose methotrexate induced toxicities in acute lymphoblastic leukemia patients.

Objectives: Methotrexate (MTX) is a key therapeutic agent for leukemias. When given in high doses, leucovorin rescue is added to reduce its toxicity. It has been postulated that low albumin levels are associated with delayed clearance and increased toxicity of MTX. Hence, this prospective cohort study was proposed to evaluate the correlation between serum albumin level and HDMTX toxicity in acute lymphocytic leukemia (ALL) patients and to compare the MTX toxicity in hypo and normoalbuminemic patients. Methods: Forty-six ALL patients of either gender aged 2-40 years receiving HDMTX for 1st time were included in the study. The serum albumin levels were measured before chemotherapy before each cycle. The patients received 24-h infusion of HDMTX on days 8, 22, 36, and 50 (four cycles). The serum concentration of MTX was measured after first cycle only. The patients were followed for toxicities that were graded according to CTCAE-V4.0. Results: There was a negligible correlation between cumulative albumin levels of all four cycles and cumulative toxic events. The median toxic events were 19 (16-23). The Spearmen correlation coefficient ρ was 0.055 (P = 0.460). No association was found between albumin level and MTX toxicity in cycle wise analysis also. In each cycle, there was no significant difference in the toxicities between the hypo and normoalbuminemic patients. Only vomiting showed significant (P < 0.05) inverse correlation with albumin levels. Hypoalbuminemic patients showed significantly (P < 0.01) higher grade of nausea compared to normoalbuminemia. Conclusion: There was negligible correlation between albumin levels and MTX toxicity despite delayed clearance supporting the safety of MTX in mildly hypoabuminemic patients.

Treatment and practical considerations of diabetic kidney disease.

Diabetic kidney disease (DKD) is a complication of diabetes that can lead to kidney failure. Over the years, several drugs have been developed to combat this disease. In the early 90s, angiotensin blockade (ACEi and ARBs) was introduced, which revolutionized the treatment of DKD. In recent years, newer drugs such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin antagonists, and mineralocorticoid receptor antagonists (MRA) have shown great promise in reducing albuminuria and protecting the kidneys. These drugs are being used in combination with lifestyle modifications, patient education, and risk factor modification to effectively manage DKD. In this review, we will explore the latest pharmacological options, their efficacy, and their potential to revolutionize the management of this debilitating disease.

Improving the durability of cobaltite cathode of solid oxide fuel cells - a review.

Solid oxide fuel cells (SOFCs) are highly efficient, low-emission, and fuel-flexible energy conversion devices. However, their commercialization has lagged due to the lack of long-term durability. Among several performance degradation mechanisms, cathode degradation and elemental inter-diffusion of the electrolyte and cathode has been identified as the predominant factors. In the most common SOFC systems, a cobalt-based perovskite material is used, for example LSC or LSCF. These cobalt-based materials offer mixed conductivity and higher concentration of oxygen vacancies as compared to LSM at lower operating temperature leading to favorable reduction kinetics. However, the presence of cobalt results in higher cost, higher thermal expansion co-efficient (TEC) mismatch and most importantly leads to rapid degradation. Various elements like strontium, cobalt, cerium, chromium, or zirconium accumulate or deposit at the electrode-electrolyte interface, which results in sluggish reaction kinetics of the oxygen reduction reaction (ORR). These elements react to form secondary phases that have lower ionic and electronic conductivity, cover active reaction sites, and eventually lead to cell and system deterioration. Over the past decade, several studies have focused on preventative and protective measures to prolong SOFC lifetime which includes novel fabrication techniques, introduction of new layers, addition of thin films to block the cation transport. Such efforts to prevent the formation of insulating phases and decomposition of the cathode have resulted in a remarkable improvement in long-term stability. In this review paper, current research on leading mechanisms responsible for the degradation of cobaltite cathode of solid oxide fuel cell has been summarized and durability improvement strategies of cobalt-based SOFC cathodes have been discussed.