Semaglutide-associated kidney injury.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are multipurpose agents effective in improving glycemic control in patients with type 2 diabetes while also achieving weight loss and risk reduction of major cardiovascular (CV) events and chronic kidney disease progression. With their increased utility in diabetes, obesity, CV health and renal protection, the use of GLP-1RAs has increased. However, with this increased use, there have also been increased reports of associated kidney adverse events, including case reports of acute interstitial nephritis (AIN) associated with GLP-1RA use. We report the data from the Food and Drug Administration adverse event reporting system (FAERS) in relation to GLP-1RA use and adverse kidney events, with acute kidney injury being the most common. In addition, we report two cases of semaglutide-associated biopsy-proven AIN and one with associated podocytopathy. To our knowledge, this is the first case of biopsy-proven AIN with podocytopathy associated with semaglutide use. Both patients experienced complete remission shortly after discontinuing semaglutide and undergoing immunosuppressive therapy. Further analysis of the FAERS database revealed 17 cases of proteinuria and 1 case of glomerulonephritis associated with semaglutide in the FAERS database, however no further information was available. While further research is needed to establish causality, this case series adds to the growing body of literature that semaglutide is associated with AIN and adds a new association, semaglutide with AIN and podocytopathies. While the overall clinical and mortality benefits of GLP-1RAs may outweigh the rarer risks, prescribers need to be aware of these associations, particularly as the use of GLP-1RAs continues to expand.

ANCA-Associated Vasculitis.

ANCA-associated vasculitis (AAV) is a necrotizing, small-to-medium vessel vasculitis associated with significant morbidity and mortality. AAV is a systemic autoimmune disease affecting kidneys, eyes, sinuses, peripheral nerves, skin, and upper and lower respiratory tracts. AAV tends to present in characteristic phenotypes categorized clinically as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA). Kidney involvement is a common feature of AAV, and has important implications on disease prognosis and management. Existing therapies have been refined and improvements in our understanding of the pathophysiology of AAV has led to approval of novel therapies. In this review, we provide an overview of epidemiology, disease mechanisms, clinical presentation and review therapeutic strategies for induction and maintenance of remission.

Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019.

Importance: Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. Objective: To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. Design, Setting, and Participants: An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. Exposures: In this study, no particular exposure was specifically targeted. Main Outcomes and Measures: The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. Results: In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). Conclusions and Relevance: In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Anti-microbial efficacy of a scientifically developed and standardized herbal-alcohol sanitizer.

Hands are the primary mode of transmission of microbe-based infections, as they harbor normal microbiota and pathogenic microbes. SARS-CoV-2 has endangered lives worldwide, and WHO has recommended good hygiene practices, especially hand hygiene. In addition, other infectious diseases like diphtheria, measles, tuberculosis, HIV, malaria, etc. are spreading in the shadow of the COVID-19 pandemic. The anti-microbial efficiency of two in-house developed herbal-alcohol based hand sanitizers containing Azadirachta indica, Citrus limon, Zingiber officinale, and Aloe vera (HS1) and Zingiber officinale replaced with Ocimum sanctum (HS2) was evaluated. HS1, with Zingiber officinale, and HS2, with Ocimum sanctum, herbal sanitizers showcased in-vitro anti-viral activity on MDCK cells using the reference strain of influenza A virus, A/PR/8/34 (H1N1), and reduced 99.99% of microbial load within 30 s of contact time, estimated by the Antimicrobial Susceptibility Testing Method. On volunteers, HS1 and HS2 were more effective than alcohol-based WHO sanitizers. Moreover, HS2 sanitizer is more effective against viruses and has better efficiency and hedonic qualities in volunteers than HS1. These sanitizers don't irritate or dry up the skin and have a longer shelf life. Overall, findings reveal that herbal-alcohol-based sanitizers are promising hand hygiene products with the capability of reducing microbial load.

Management of Hepatitis C Virus and Hepatitis B Virus Infection in the Setting of Kidney Disease.

Treatment of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection poses unique challenges in patients with kidney disease. Direct-acting antivirals have been a major breakthrough in eradicating HCV infection, and several pangenotypic regimens are available for patients with chronic kidney disease or end-stage kidney disease requiring dialysis with high cure rates and no need for dose adjustment. Direct-acting antiviral therapy alone can treat HCV-associated cryoglobulinemic glomerulonephritis; concurrent antiviral and immunosuppressive therapy is needed for cases of severe, organ-threatening manifestations of cryoglobulinemia. Immunosuppression may be needed for HBV-associated kidney disease (polyarteritis nodosa or membranous nephropathy) when there is evidence of severe immune-mediated injury while weighing the risk of potential viral activation. Most HBV antiviral agents need to be dose-adjusted in patients with chronic kidney disease or end-stage kidney disease requiring dialysis, and drug-drug interactions need to be carefully evaluated in patients with kidney transplants. Considerations for accepting HCV- and HBV-infected donors for kidney transplantation are discussed.

Atypical Anti-Glomerular Basement Membrane Disease.

Atypical anti-glomerular basement membrane (anti-GBM) disease is characterized by linear immunoglobulin G (IgG) deposition along the GBM without circulating IgG anti-GBM antibodies. Compared to classic anti-GBM disease, atypical anti-GBM disease tends to be milder with a more indolent course in certain cases. Moreover, pathologic disease pattern is much more heterogenous in atypical anti-GBM disease than in the classic type, which is uniformly characterized by diffuse crescentic and necrotizing glomerulonephritis. Although there is no single well-established target antigen in atypical anti-GBM disease, the target antigen (within the GBM) and the autoantibody type are hypothesized to be different from the classic type. Some patients have the same antigen as the Goodpasture antigen that are detected only by a highly sensitive technique (biosensor analysis). Some cases of atypical anti-GBM disease have autoantibodies of a different subclass restriction like IgG4, or of monoclonal nature. Antibodies targeting antigen/epitope structure other than the Goodpasture antigen can be detected using modified assays in some cases. Patients with IgA- and IgM-mediated anti-GBM disease are known to have negative circulating antibodies because conventional assays do not detect these classes of antibodies. A significant proportion of cases with atypical anti-GBM disease do not have any identifiable antibodies despite extensive evaluation. Nevertheless, extensive evaluation of atypical autoantibodies using modified assays and sensitive techniques should be attempted, if feasible. This review summarizes the recent literature on atypical anti-GBM disease.

Securing Optical Networks Using Quantum-Secured Blockchain: An Overview.

The deployment of optical network infrastructure and development of new network services are growing rapidly for beyond 5/6G networks. However, optical networks are vulnerable to several types of security threats, such as single-point failure, wormhole attacks, and Sybil attacks. Since the uptake of e-commerce and e-services has seen an unprecedented surge in recent years, especially during the COVID-19 pandemic, the security of these transactions is essential. Blockchain is one of the most promising solutions because of its decentralized and distributed ledger technology, and has been employed to protect these transactions against such attacks. However, the security of blockchain relies on the computational complexity of certain mathematical functions, and because of the evolution of quantum computers, its security may be breached in real-time in the near future. Therefore, researchers are focusing on combining quantum key distribution (QKD) with blockchain to enhance blockchain network security. This new technology is known as quantum-secured blockchain. This article describes different attacks in optical networks and provides a solution to protect networks against security attacks by employing quantum-secured blockchain in optical networks. It provides a brief overview of blockchain technology with its security loopholes, and focuses on QKD, which makes blockchain technology more robust against quantum attacks. Next, the article provides a broad view of quantum-secured blockchain technology. It presents the network architecture for the future research and development of secure and trusted optical networks using quantum-secured blockchain. The article also highlights some research challenges and opportunities.

Use of TIMP-2 and IGFBP-7 for prediction of postoperative acute kidney injury after cardiac surgery.

BACKGROUND: The following cell cycle arrest urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7), have been used for early detection of acute kidney injury (AKI) in critically ill patients. The purpose of this study is to validate the use of these urinary biomarkers in patients undergoing open heart surgery. MATERIALS AND METHODS: In a single-center prospective observational study, urine samples were collected in 108 consecutive patients who underwent open heart surgery immediately after separation from cardiopulmonary bypass and on postoperative day 1, and were sent for the biomarker [TIMP-2]*[IGFBP7] analysis. Acute kidney injury was defined based on KDIGO criteria, and levels of [TIMP-2]*[IGFBP7] were analyzed for the ability to predict AKI. RESULTS: Of the 108 patients, 19 (17.6%) patients developed postoperative AKI within 48 hours of surgery. At the threshold of > 0.3 (ng/mL)2/1,000, post-cardiopulmonary bypass [TIMP-2]*[IGFBP-7] had a sensitivity of 13% and specificity of 82% for predicting postoperative AKI. Postoperative day-1 [TIMP-2]*[IGFBP-7] had a sensitivity of 47% and a specificity of 59% for predicting postoperative AKI. There were no differences in [TIMP-2]*[IGFBP-7] values at either timepoint between patients who developed postoperative AKI as compared to those who did not. CONCLUSION: Urinary [TIMP-2]*[IGFBP7] was not predictive of the risk of AKI after cardiac surgery in this single-center study population.

Efficacy of Aqueous Extract of Chinese Caterpillar Mushroom Ophiocordyceps sinensis (Ascomycota) Against Simulated Altitude Stress and Subacute Toxicity Studies.

Exposure to high altitude severely impacts performance of unacclimatized individuals and contraindications associated with synthetic drugs ascertain the need for development of herbal drugs. Thus, the present study investigated the adaptogenic potential of Ophiocordyceps sinensis aqueous extract (CSAQ) using simulated altitude stress models such as severe hypoxia (SH) in hermetic vessel, cold restraint (CR) at 4°C, and hypobaric hypoxia (HBH) at 7,620 meter, ~ 282 mm Hg. To further address safety limits of extract, subacute toxicity studies were conducted in rats orally administered with CSAQ (0, 100, 500 and 1000 mg/kg) in a single dose/day for 28 days. Results revealed that animals administered with CSAQ increased convulsion time and core body temperature during SH and CR stress. CSAQ modulated thermogenic response by upregulating uncoupling protein 1 and maintaining metabolic homeostasis. Further, CSAQ improved antioxidant status (glutathione and 2,3-diposhphoglycerate), attenuated pro-inflammatory cytokine NF-κB, and augmented hypoxia inducible factor and nuclear erythroid 2 related factor 2 in HBH exposed animals. Toxicity studies revealed no observed adverse effect level with 1000 mg/kg extract in body weight gain, organ/body weight ratio, hematological variables, biochemical parameters and histoarchitecture of vital organs. In conclusion, CSAQ initiated dose dependent adaptive response and exhibited high safety margins, which strongly suggests the therapeutic potential of CSAQ in mitigating high altitude maladies.

Recurrent chylous ascites in patient with previous retroperitoneal radiation treatment.

Chylous ascites is the accumulation of lymphatic fluid in the peritoneal cavity due to disruption of lymphatic drainage caused due to obstruction or trauma. We report a man in his 60s who was previously treated for diffuse large B cell lymphoma with radiation to bulky abdominal/mesenteric lymphadenopathy. He was later found to have recurrent chylous ascites several years later, requiring multiple paracentesis. Recurrent lymphoma was ruled out with negative cytology of peritoneal fluid as well as lymph node biopsy with no evidence of malignancy. We believe that the patient had obstruction of lymphatic drainage due to previous radiation therapy causing fibrosis. The patient underwent lymphangiography which did not visualise the central lymphatic duct within the abdomen raising suspicion for obstruction of the ducts secondary to previous radiation.

Symptomatic leptomeningeal carcinomatosis: a rare presentation of chronic lymphocytic leukaemia relapse.

Central nervous system (CNS) involvement in patients with chronic lymphocytic leukaemia (CLL) is very rare and, when present, it is frequently asymptomatic. Rather, CNS involvement is more common in other haematological malignancies such as mantle cell lymphoma or diffuse large B cell lymphoma. The paucity of literature on CNS involvement in CLL underscores the importance of increasing awareness about its presentation, diagnosis and optimal management. We describe a case of symptomatic leptomeningeal leukaemic involvement as an atypical presentation of CLL relapse. A favourable clinical response was observed following systemic monotherapy with venetoclax.

Glomerular Disease in Liver Disease.

Glomerular diseases are an important cause of kidney disease in patients with liver disease. Although kidney involvement due to tubular or vascular disease is more common, glomerular diseases became more prevalent as hepatitis infections increased and then subsequently decreased with the widespread availability of hepatitis A and B vaccines and the development of effective antiviral treatments for hepatitis B and C. In this review, we discuss the common glomerular pathologies that are seen in patients with liver disease and the current treatment options available to them.

Acute-onset heart failure secondary to biventricular non-compaction cardiomyopathy and atrial septal defect in a woman presenting in the seventh decade.

We present a case of a previously asymptomatic 63-year-old woman who presented with worsening dyspnoea for 3 weeks. Initial transthoracic and later transoesophageal echocardiography confirmed biventricular non-compaction cardiomyopathy and a large secundum atrial septal defect (ASD) measuring 1.4 cm. Additionally, there was a haemodynamically significant left to right shunt causing acute decompensated systolic heart failure. She eventually underwent closure of the septal defect using a AMPLATZER Septal Occluder device. Decision to close the defect was made as the left to right shunt was causing severe pulmonary hypertension and acute heart failure. Since most heart failure treatments involve lowering of the LV afterload there was consideration that this could cause right to left shunting and could cause an Eisenmenger physiology. Hence the AMPLATZER Septal Occluder device was placed to eliminate the shunt through the ASD. The ASD combined with the non-compaction posed significant treatment challenge in this case.

Oxalate nephropathy: a review.

This review describes the clinical and pathological features of oxalate nephropathy (ON), defined as a syndrome of decreased renal function associated with deposition of calcium oxalate crystals in kidney tubules. We review the different causes of hyperoxaluria, including primary hyperoxaluria, enteric hyperoxaluria and ingestion-related hyperoxaluria. Recent case series of biopsy-proven ON are reviewed in detail, as well as the implications of these series. The possibility of antibiotic use predisposing to ON is discussed. Therapies for hyperoxaluria and ON are reviewed with an emphasis on newer treatments available and in development. Promising research avenues to explore in this area are discussed.

Burkitt lymphoma: interpreting FISH testing for MYC gene rearrangements.

Burkitt lymphoma is a highly aggressive B cell non-Hodgkin's lymphoma characterised by translocation of MYC gene on chromosome 8. This translocation is usually detected by fluorescent in-situ hybridisation (FISH) studies as part of routine diagnostic work-up and prognostication. FISH testing is commonly done with the break-apart probe (BAP). This case illustrates how this testing can be falsely negative. This patient is a young male diagnosed with Stage I low-risk Burkitt with FISH negative for MYC translocation initially on BAP testing. Additional testing with dual FISH probe detected MYC/IGH translocation. FISH testing using BAPs alone may be falsely negative for MYC translocations creating a diagnostic challenge and compromising the treatment approach and assessment of prognosis.

Nanobioremediation: A sustainable approach towards the degradation of sodium dodecyl sulfate in the environment and simulated conditions.

Nanotechnology has gained huge importance in the field of environmental clean-up today. Due to their remarkable and unique properties, it has shown potential application for the remediation of several pesticides and textile dyes. Recently it has shown positive results for the remediation of sodium dodecyl sulfate (SDS). One of the highly exploited surfactants in detergent preparation is anionic surfactants. The SDS selected for the present study is an example of anionic linear alkyl sulfate. It is utilized extensively in industrial washing, which results in the high effluent level of this contaminant and ubiquitously toxic to the environment. The present review is based on the research depicting the adverse effects of SDS in general and possible strategies to minimizing its effects by bacterial degradation which are capable of exploiting the SDS as an only source of carbon. Moreover, it has also highlighted that how nanotechnology can play a role in the remediation of such recalcitrant pesticides.

CRRT-associated ketoacidosis: A series of 5 cases.

Continuous renal replacement therapy (CRRT) is a dialysis modality used in critically ill patients with acute kidney injury (AKI). Although most dialysate and replacement fluids are dextrose-containing, CRRT-associated hypophosphatemia sometimes warrants the use of phosphorus-containing solutions which are dextrose free. The other less commonly used dextrose-free dialysate solutions are certain formulations of Prismasol and Prismasate. As glucose is a small molecule, which is readily cleared with dialysis, use of these solutions can result in increased caloric loss, net glucose deficit, and shifting of the metabolic pathway towards gluconeogenesis and ketogenesis. Starvation ketosis is usually a benign entity, however when combined with factors such as stress of critical illness, can produce metabolic acidosis which at times can be severe. We describe five patients who developed worsening metabolic acidosis despite adequate clearance from CRRT and were diagnosed with CRRT-associated ketoacidosis. Administration of dextrose-containing fluids or tube feeds promptly resulted in resolution of ketonemia and acidosis. Recognition of this entity is of great importance as the reflexive reaction to increase the prescribed dose of CRRT to improve the acidosis, in fact worsens the problem.

Advances in Understanding of Pathogenesis and Treatment of Immune-Mediated Kidney Disease: A Review.

There continues to be rapid advancement in our understanding of the pathogenesis of immune-mediated kidney disease. This progress has culminated in the development of multiple therapeutic agents that have consistently improved renal and patient outcomes. The focus of this review is to discuss these recent advancements in immune-mediated kidney disease via the lens of direct and indirect immune-mediated mechanisms. In the direct immune-mediated disease, recently described antigens in anti-glomerular basement membrane (GBM) disease and membranous nephropathy are discussed, along with new therapeutic regimens in membranous nephropathy and focal segmental glomerulosclerosis. From an indirect immune-mediated disease standpoint, recent pivotal trials in antineutrophil cytoplasmic antibody vasculitis, lupus nephritis, and IgA nephropathy are examined from a real-world practice perspective. New molecular pathways in various disorders of alternate complement pathway are described, which in turn have led to development of various experimental therapies. In addition, pivotal and ongoing therapeutic trials in the aforementioned diseases are presented.