Citations

ABSTRACT Chronic changes on kidney biopsy specimens include increasing amounts of arteriosclerosis, glomerulosclerosis, interstitial fibrosis and tubular atrophy, enlarged nephron size, and reduced nephron number. These chronic changes are difficult to accurately assess by visual inspection but are reasonably quantified using morphometry. This review describes the various patient populations that have undergone morphometric analysis of kidney biopsies. The common approaches to morphometric analysis are described. The chronic kidney disease outcomes associated with various chronic changes by morphometry are also summarized. Morphometry enriches the characterization of chronicity on a kidney biopsy and this can supplement the pathologist's diagnosis. Artificial intelligence image processing tools are needed to automate the annotations needed for practical morphometric analysis of kidney biopsy specimens in routine clinical care.

The coronavirus disease-2019 (COVID-19) infection has taken the world by storm within a few months. Evidence has suggested that patients with electrolyte imbalances at baseline may have a longer duration of hospital stay. We aimed to determine the factors associated with hyponatremia on admission in COVID-19 patients and its impact on the length of stay. We conducted a retrospective study including 521 patients who tested positive for COVID-19 and had their electrolytes checked on admission from June 2020 to October 2020. Patients with sodium <135 mmol/l were included in the hyponatremic group and were compared against normonatremic patients. The severity of COVID-19 was found to be more prevalent in the case group as compared to control (38.3% vs 29.2%; 21.1% vs 17.7%). Hyponatremic patients stayed more than 5 days in hospital (56.3% vs 46.5%), and stayed longer in special care (23.4% vs 20.0%) as compared to controls. Hyponatremic patients as compared to control were more likely to have diabetes (47.9% vs 30.0%), hypertension (49.0% vs 38.5%), ischemic heart disease (20.7% vs 15.4%), chronic liver disease (2.7% vs 1.2%), and chronic kidney disease (9.6% vs 3.8%). Upon matching on the age, the adjusted odds of hyponatremia in COVID-19-positive patients were 1.9 times among diabetic patients. Moreover, COVID-19-positive patients suffering from CKD had a higher risk of developing hyponatremia (OR = 2.3, 95% CI: 1.1–5.6). The risk of hyponatremia among COVID-19-positive patients is statistically higher in patients with 1 comorbidity (OR = 1.9, 95%CI: 1.3–3.4). Hyponatremia on admission can be used to forecast the length of hospital stay and the severity of illness in COVID-19 patients.

Background: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus, serves as a useful tool for ED physicians. Our study aims to analyze the efficacy of suPAR in predicting these prognostic markers in ED. Methods: We performed a comprehensive search on 6 databases from the inception to 30th November 2022, to select the following eligibility criteria; a) observation or triage trial studies investigating the role of suPAR levels in predicting: 30 day and 90-day mortality, 30-day readmission, early discharge (within 24hr), and LOS in patients coming to AMU. Results: A total of 13 studies were included, with a population size of 35,178, of which 52.9% were female with a mean age of 62.93 years. Increased risk of 30-day mortality (RR = 10.52; 95% CI = 4.82–22.95; I2 = 38%; P < .00001), and risk of 90-day mortality (RR = 5.76; 95% CI = 3.35–9.91; I2 = 36%; P < .00001) was observed in high suPAR patients. However, a slightly increased risk was observed for 30-day readmission (RR = 1.50; 95% CI = 1.16–1.94; I2 = 54%; P = .002). More people were discharged within 24hr in the low suPAR level group compared to high suPAR group (RR = 0.46; 95% CI = 0.40–0.53; I2 = 41%; P < .00001). LOS was thrice as long in high suPAR level patients than in patients with low suPAR (WMD = 3.20; 95% CI = 1.84–4.56; I2 = 99%; P < .00001). Conclusion: suPAR is proven to be a significant marker in predicting 30-day and 90-day mortality in ED patients.

The chimeric antigen receptor (CAR) design, first invented by Zelig Eshhar, paved the way for the use of genetically modified T-cells in targeted therapy against cancer cells. Since then, it has gone through many generations, especially with the integration of co-stimulation in the second and third-generation CARs. However, it also mounts a hyperactive immune response named as cytokine release syndrome with the release of several cytokines eventually resulting in multiple end-organ toxicities. The severity of cytokine release syndrome depends upon certain factors such as the tumor burden, choice of co-stimulation, and degree of lymphodepletion, and can manifest as pulmonary edema, vascular leak, renal dysfunction, cardiac problems, hepatic failure, and coagulopathy. Many grading criteria have been used to define these clinical manifestations but they lack harmonization. Neurotoxicity has also been significantly associated with CAR T-cell therapy but it has not been studied much in previous literature. This review aims to provide a comprehensive account of the clinical manifestations, diagnosis, management, and treatment of CAR T-cell associated neurotoxicity.

Coronavirus disease 2019 (COVID-19) vaccine side effects have an important role in the hesitancy of the general population toward vaccine administration. Another reason for vaccine hesitancy might be that healthcare professionals may not address their concerns regarding vaccines appropriately. Regardless, hesitancy in the form of delay, refusal, or acceptance with doubts about its usefulness can limit the downward trajectory of the COVID-19 pandemic. Therefore, the authors conducted a national cross-sectional study (n=306) to assess causes and concerns for vaccine hesitancy in caregivers in Pakistan toward getting their children vaccinated. The questions identified caregivers by socioeconomic demographics, perceived COVID-19 pandemic severity, and concerns toward the COVID-19 vaccine. The majority of the participants were 45–59 years of age (42.8%) with a mean age of 36.11 years (SD: 7.81). A total of 80% of these participants were willing to vaccinate their child with any COVID-19 vaccine. Present comorbidities had a frequency of 28.4% (n=87/306) and only 26.9% (n=66/245) participants were willing to vaccinate their child. Participants with high social standing were 15.4% (n=47/306) with the majority of them being willing to vaccinate their children (45/47). Socioeconomic status (OR:2.911 [0.999–8.483]), and the child’s vaccinations being up to date (OR:1.904 [1.078–3.365]) were found to be independent factors for caregivers to be willing to vaccinate their child. Around 62% (n=191/306) were not willing to vaccinate due to the concern for side effects, 67.6% (n=207/306) were not willing because they did not have ample information available, and 51% (n=156/306) were not willing as they were concerned about vaccine effectiveness. Further studies on vaccine safety in the pediatric population are required to improve caregivers’ perceptions.

Background and objectives: The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels. Methods: After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15 462 patients (n=8487 in the finerenone group; n=6975 in the control group) were included. Results: Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)]. Conclusion: Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.

Abstract Aim Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease‐modifying agents, such as anti‐CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease‐modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti‐CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes. Methods A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta‐analysis was performed using a random‐effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment. Results In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow‐up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti‐CD3 monoclonal antibody treatment significantly increased the C‐peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti‐CD3 monoclonal antibodies significantly reduced the patients' insulin intake across all timeframes (mean difference = −0.123, 95% CI: −0.151 to −0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed. Conclusion The findings of this review suggest that anti‐CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow‐up, to validate the generalizability of these findings further.