Risk assessment for hypocalcemia in therapeutic apheresis for kidney transplantation.

INTRODUCTION: The increase in the number of kidney transplants performed in the United States has been paralleled with an increase in the utilization of therapeutic apheresis (TA) for kidney transplant indications. Hypocalcemia remains a significant contributor to the adverse event in TA. The magnitude of hypocalcemia and its risk factors are scarcely discussed in literature. METHODS: This is a retrospective cohort review of adults from 18 years and above who received TA for kidney transplant-related indications from January 1, 2017 to December 31, 2022. Data extracted included basic demographics, indication for apheresis, procedure characteristics, serum ionized calcium at the mid and end of procedure and serum creatinine at the beginning of apheresis, and so forth. RESULTS: Data from 131 patients and 860 sessions of TA were analyzed. Antibody-mediated rejection (69%) and recurrent FSGS (15%) were the leading indications for TA. There were 60 (7%) TA sessions complicated by hypocalcemia. Of these, 53 (88%) occurred in the first session, 5 (8%) occurred in second session while 2 (4%) occurred in the third and subsequent sessions. Female sex, elevated serum creatinine and use of fresh frozen plasma- are the risk factors for hypocalcemia with odd's ratio of 2.34, 7.42, and 5.01, respectively. Binary logistic regression showed that elevated serum creatinine at the commencement of therapy is an independent predictor of hypocalcemia (adjusted odd's ratio = 3.31, p = 0.001). CONCLUSION: Hypocalcemia is prevalent in this study. Clinical vigilance and tailored procedure will avert adverse consequences.

Therapeutic apheresis in kidney transplantation: Emerging trends.

INTRODUCTION: The use of therapeutic apheresis (TA) either as stand-alone or adjunctive treatment in kidney transplantation has increased over the years to become a leading indication. This study shows recent trends in indications for TA related to kidney transplantation, adverse events, and patient outcome in this cohort. METHODS: This is a retrospective cohort review of adults who received TA for kidney transplant-related indications from January 1, 2017, to December 31, 2022, at the University of Virginia Medical Centre, Charlottesville, VA, USA. Data extracted include basic demographics, indication for apheresis, number of procedures, procedure characteristics, procedure-related adverse events (complications), and serum ionized calcium and serum creatinine. Data were analyzed using statistical package for social sciences (SPSS 2022 IBM Inc). RESULTS: Data from a total of 131 patients who received 860 TA procedures were analyzed. Indications for TA were antibody-mediated rejection (65.5%), recurrent focal segmental glomerulosclerosis (15%), thrombotic microangiopathy (5%), desensitization for ABO incompatibility (4.5%) and for HLA-incompatibility (4.5%), and recurrent IgA nephropathy (1%). Some adverse events were encountered in 16.7% of the procedures and include hypocalcemia (7%), vascular access malfunction (0.7%), hypotension (1.2%), arrhythmia (0.6%), and depletion coagulopathy (0.6%). The overall case mortality rate was 8.4% over the 6-year period. There was one death recorded on machine during TA resulting in a procedure-mortality rate of 0.12%. CONCLUSION: Antibody-mediated rejection was the most common indication for TA related to kidney transplantation. Adverse events were minor and patient survival over the time was within usual limits.

Modelling of electrohydrodynamic drying kinetics for carrot at varying electrode distance.

This study was conducted to analyze the drying kinetics of carrot slices in electrohydrodynamic (EHD) dryer at different electrode distances. Higher drying rate was observed up to about 70% (w.b.) moisture content, which has been noted as first falling rate period. The time taken to dry the carrot slices to the safe moisture content of 2.5% (wb) was about 9, 8.5 and 6.8 h at a distance of 7, 5 and 3 cm respectively. Five empirical models, Page Model, Newton model, Henderson and Pabis model, logarithmic model and two term model, were tested for the best fit. The drying rate constant (k) increased in all the empirical models as the distance between the electrode decreased. For 7 cm electrode distance, the Page model fitted best whereas the Logarithmic model was found to be the best fit for 5 and 3 cm electrode distance. There is no significant difference found in shrinkage of dried carrot slices at different electrode distance. Rehydration ratio increased as the distance between electrodes decreased. Moisture diffusivity increased as the distance between the electrode decreased. No significant difference in colour, ß-carotene and sensory attributes were found between fresh and EHD dried carrot slices at 3 cm electrode distance. Specific energy consumption was significantly influenced by the electrode distance.

Nonsteroidal Mineralocorticoid Receptor Antagonist (Finerenone) in Cardiorenal Disease.

Nonsteroidal mineralocorticoid receptor antagonists (MRAs) present a promising therapeutic option in cardiorenal diseases, mitigating the limitations of steroidal MRAs. Finerenone, a third-generation nonsteroidal MRA, has demonstrated beneficial effects in heart failure (HF) and chronic kidney disease (CKD). Clinical trials, including FIDELIO-DKD and FIGARO-DKD, revealed finerenone's efficacy in improving kidney and cardiovascular (CV) outcomes. Patients with CKD and type 2 diabetes (T2DM) on finerenone experienced reduced rates of cardiovascular events, including hospitalization for HF. However, these trials excluded symptomatic HF patients, focusing on asymptomatic or early-stage HF. The ongoing FINEARTS-HF trial evaluates finerenone in HF with preserved ejection fraction (HFpEF). Additionally, studies exploring finerenone and sodium-glucose cotransporter 2 (SGLT2) inhibitors' (Empagliflozin) combination effects in CKD and T2DM (CONFIDENCE) and the selective MR modulator AZD9977 with another SGLT2 inhibitor (dapagliflozin) in HF and CKD (MIRACLE) aim to expand treatment options. While SGLT-2 inhibitors were shown to reduce hyperkalemia risk in FIDELIO-DKD and potentially lower new-onset HF incidence in FIGARO-DKD, further research is essential. So far, the evidence for the beneficial effect of finerenone in the spectrum of cardiorenal diseases is based only on the results of studies conducted in patients with T2DM, and clinical trials of finerenone in patients with nondiabetic kidney disease are ongoing. Nonsteroidal MRAs hold significant potential as pivotal treatment targets across the cardiorenal disease spectrum. This review will focus on the effects of finerenone on cardiorenal disease.

Treatment of membranous nephropathy: Perspectives on current and future therapies.

Primary membranous nephropathy remains one of the most frequent causes of nephrotic syndrome in adults. It is an autoimmune disorder in which auto-antibodies target antigens at the podocytes cell membrane-basement membrane interface. Our understanding of membranous nephropathy has expanded dramatically as of late. After the initial discovery of the phospholipase A2 receptor auto-antibody in 2009, eight more antigens have been discovered. These discoveries have led to refinement in our understanding of the pathogenesis, diagnosis, and natural history of primary membranous nephropathy. Now, many experts advocate for redefining primary membranous nephropathy based on antigen, potentially shedding the primary and secondary nomenclature. Recently, therapies for primary membranous have also expanded. Immunosuppressive therapies like cyclophosphamide and rituximab, which primarily target B-cells, remain the cornerstone of therapy. However, there is still significant room for improvement, as many as 30-40% do not respond to this therapy according to recent trials. Additionally, drugs targeting complement, and other novel therapies are also under investigation. In this review we will discuss the available therapies for primary membranous nephropathy in light of recent clinic trials like GEMRITUX, MENTOR, RI-CYCLO, and STARMEN, as well as management strategies. While the last 10 years have seen a boom in our mechanistic understanding of this ever-diversifying disease, we are likely to see a similar boom in the therapeutic options in the years to come.

Pathways to improve nephrologist comfort in managing patients on in-center or home self-care dialysis.

In end-stage kidney disease (ESKD), patient engagement and empowerment are associated with improved survival and complications. However, patients lack education and confidence to participate in self-care. The development of in center self-care hemodialysis can enable motivated patients to allocate autonomy, increase satisfaction and engagement, reduce human resource intensiveness, and cultivate a curiosity about home dialysis. In this review, we emphasize the role of education to overcome barriers to home dialysis, strategies of improving home dialysis utilization in the COVID 19 era, the significance of in-center self-care dialysis (e.g., cost containment and empowering patients), and implementation of an in-center self-care dialysis as a bridge to home hemodialysis (HHD).

COVID-19 Related Predisposition to Diabetic Ketoacidosis.

Background and aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exacerbate hyperglycemia and can cause life-threatening diabetic ketoacidosis (DKA) in patients with diabetes mellitus (DM). The objective of this study is to compare the characteristics of diabetic COVID-19 patients with and without DKA and to determine the predictors of mortality in the setting of COVID-19 and DKA. Methods This is a retrospective single-center cohort study including patients admitted to our hospital with COVID-19 and DM from March 2020 to June 2020. Patients with DKA were filtered as per the diagnostic criteria set by the American Diabetes Association (ADA). Patients with hyperosmolar hyperglycemic state (HHS) were excluded. A retrospective analysis was performed, which included those who developed DKA and those with neither DKA nor HHS. The primary outcome measurement was mortality rate and predictors of mortality for DKA. Results Out of 301 patients with COVID-19 and DM, 30 (10%) had DKA and five (1.7%) had HHS. Mortality was significantly higher in the DKA group compared to the non-DKA/HHS group (36.6% vs 19.5%; OR: 2.38; p=0.03). After adjusting for parameters used for multivariate logistic model for mortality, DKA was no longer associated with mortality (OR: 2.08, p=0.35). The independent predictors for mortality were age, platelet count, serum creatinine, C-reactive protein, hypoxic respiratory failure, need for intubation, and need for vasopressors. Conclusion Our study demonstrates higher mortality rate in diabetic COVID-19 patients with DKA. Though direct and independent statistical association of mortality with DKA could not be proven in our multivariate logistic model, physicians must be vigilant in risk-stratifying and managing these patients in a timely manner.

Treatment of Lethal Caffeine Overdose with Haemodialysis: A Case Report and Review.

Caffeine, chemically 1,3,7-trimethylxanthine, is the most widely consumed central nervous system stimulant in the world with pleiotropic effects on the cardiovascular, pulmonary, and renal systems. The advent of over the counter (OTC) caffeine formulations has opened the window for potential toxicity, either by inadvertent or intentional overdosing. We present the case of a patient who attempted suicide by caffeine overdose treated with emergent haemodialysis and a review of the literature.

Life-Threatening Retroperitoneal Hematoma in a Patient with COVID-19.

COVID-19 is a respiratory illness that affects the human body in many different ways. The disease carries both thrombotic and hemorrhagic complications, especially in those patients who are anticoagulated to prevent the thromboembolic manifestations. In this report, we discuss a case of retroperitoneal hemorrhage in a patient treated with therapeutic anticoagulation which ultimately led to the patient's death. The literature highlights the importance of anticoagulation because it reduces mortality in patients hospitalized with COVID-19. Although, more recent studies suggest that patients treated with therapeutic anticoagulation are at a higher risk of hemorrhage and increased mortality. Therefore, our case stresses the importance of active monitoring of these patients to detect any suspected case of hemorrhage early to reduce mortality. Overall, more research should be conducted to determine the optimal dosing of anticoagulation that balances safety and efficacy.

Mucormycosis and COVID-19: An epidemic within a pandemic in India.

IMPORTANCE: Coronavirus disease (COVID-19) causes an immunosuppressed state and increases risk of secondary infections like mucormycosis. We evaluated clinical features, predisposing factors, diagnosis and outcomes for mucormycosis among patients with COVID-19 infection. METHODS: This prospective, observational, multi-centre study included 47 consecutive patients with mucormycosis, diagnosed during their course of COVID-19 illness, between January 3 and March 27, 2021. Data regarding demography, underlying medical conditions, COVID-19 illness and treatment were collected. Clinical presentations of mucormycosis, imaging and biochemical characteristics and outcome were recorded. RESULTS: Of the 2567 COVID-19 patients admitted to 3 tertiary centres, 47 (1.8%) were diagnosed with mucormycosis. Mean age was 55 ± 12.8years, and majority suffered from diabetes mellitus (n = 36, 76.6%). Most were not COVID-19 vaccinated (n = 31, 66.0%) and majority (n = 43, 91.5%) had developed moderate-to-severe pneumonia, while 20 (42.6%) required invasive ventilation. All patients had received corticosteroids and broad-spectrum antibiotics while most (n = 37, 78.7%) received at least one anti-viral medication. Mean time elapsed from COVID-19 diagnosis to mucormycosis was 12.1 ± 4.6days. Eleven (23.4%) subjects succumbed to their disease, mostly (n = 8, 72.7%) within 7 days of diagnosis. Among the patients who died, 10 (90.9%) had pre-existing diabetes mellitus, only 2 (18.2%) had received just one vaccine dose and all developed moderate-to-severe pneumonia, requiring oxygen supplementation and mechanical ventilation. CONCLUSIONS: Mucormycosis can occur among COVID-19 patients, especially with poor glycaemic control, widespread and injudicious use of corticosteroids and broad-spectrum antibiotics, and invasive ventilation. Owing to the high mortality, high index of suspicion is required to ensure timely diagnosis and appropriate treatment in high-risk populations.

Shigellosis Presenting as Meningism.

Shigella is a common cause of gastroenteritis and can also lead to serious complications such as dehydration, seizures, hemolytic uremic syndrome, and neurological complications. In this paper, we describe a case of a 39-year-old man who was admitted septic, with altered mental status and gastrointestinal symptoms. During the evaluation, he was found to have positive meningeal signs, non-anion gap metabolic acidosis, enteric panel positive for Shigella flexneri, positive IgG for Strongyloides, and pancolitis on computed tomography (CT) of the abdomen and pelvis. He was treated for infectious colitis and initially treated empirically for meningitis, but antibiotics were later discontinued due to rapid improvement of meningeal signs. To reduce the risk of disseminated infection, the patient was also treated for Strongyloides.

Characterization of first-time hospitalizations in patients with newly diagnosed pulmonary arterial hypertension in the REVEAL registry.

BACKGROUND: Hospitalization is an important outcome in pulmonary arterial hypertension (PAH), shown previously to correlate with survival. Using the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry), we sought to characterize first-time hospitalizations and their effect on subsequent hospitalization and survival in patients with newly diagnosed disease. METHODS: Patients with newly diagnosed PAH (n = 862, World Health Organization group 1) were evaluated for first-time hospitalization. The hospitalizations were categorized as PAH related or PAH unrelated based on the case report form. Categories for PAH-related and PAH-unrelated hospitalization were defined before independent review. Patient demographics and disease characteristics are described as well as freedom from hospitalization and survival. RESULTS: Of 862 patients, 490 (56.8%) had one or more hospitalizations postenrollment: 257 (52.4%) PAH related, 214 (43.7%) PAH unrelated, and 19 (3.9%) of undetermined causes. The most common causes of PAH-related hospitalization were congestive heart failure and placement/removal of a central venous catheter. Patients with PAH-related hospitalizations were more likely to receive parenteral therapy, be in functional class III/IV, and have higher risk scores before hospitalization at enrollment. Following discharge, 25.4% ± 3.2% and 31.0% ± 4.0% of patients with PAH-related and PAH-unrelated first hospitalization, respectively, remained hospitalization-free for 3 years (P = .11). Survival estimates at 3 years postdischarge were 56.8% ± 3.5% and 67.8% ± 3.6% (P = .037) for patients with PAH-related and PAH-unrelated hospitalization, respectively. CONCLUSIONS: In the REVEAL Registry, PAH-related hospitalization was associated with relatively more rehospitalizations and worse survival at 3 years. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.