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AbstractBackgroundVasomotor symptoms (VMS), such as hot flashes and night sweats, are highly prevalent and burdensome for women experiencing menopausal transition. Fezolinetant, a selective neurokinin 3 receptor (NK3R) antagonist, is a potential therapeutic option for mitigating VMS.ObjectivesOur aim is to assess the efficacy and evaluate the safety profile of fezolinetant compared with placebo in post‐menopausal women suffering from VMS, by pooling all the relevant data and reflecting the most current evidence.Search Strategy/Selection CriteriaAn extensive literature search was performed in the PubMed, Medline and Cochrane Library databases from inception until June 2023 to identify relevant trials.Data Collection and AnalysisMean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous outcomes. Risk ratios (RRs) were calculated for dichotomous outcomes. All statistical analyses were performed using R Statistical Software.Main ResultsA total of six randomized controlled trials were added. For the frequency of daily VMS, the combined pooled result favored the fezolinetant group over placebo (MD –2.38, 95% CI –2.64 to −2.12; P < 0.001, I2 = 0%). For the severity of daily VMS, fezolinetant was again found to be superior to the placebo group (MD –0.40, 95% CI –0.51 to −0.29; P < 0.001, I2 = 70%). Fezolinetant (120 mg) consistently demonstrated a significant reduction in the severity of daily moderate/severe VMS compared with other doses at both 4 and 12 weeks. Patient‐reported outcomes (PROs) of Greene Climacteric Scale (GCS), PROMIS the Sleep Disturbance Short Form 8b and Menopause‐Specific Quality of Life (MENQoL) scores indicated significant improvement with fezolinetant. No significant difference in efficacy of fezolinetant at 4 and 12 weeks were observed in any outcome. As for safety, no significant differences in the treatment emergent adverse events at 12 weeks were found between fezolinetant and placebo.ConclusionsOur study significantly favors fezolinetant over placebo regarding the primary efficacy outcomes of daily moderate to severe VMS frequency and severity, including PROs, while both the groups are comparable in terms of treatment emergent adverse events. Further studies are needed to confirm these findings.

Background and aims: Increased use of digital devices in the modern era has led to the development of digital eye strain (DES) or computer vision syndrome in their users. This can result in the development of various ocular and visual symptoms among them. In this study, the authors aimed to view the prevalence of digital eye strain among radiology physicians in Pakistan and their associated risk factors. Materials and methods: A cross-sectional study was conducted to evaluate occupational DES among radiology physicians in Pakistan. The data collection was done using the convenience sampling technique, and the data were analyzed using IBM SPSS for Windows, Version 25.0. Results: Out of the 247 respondents, 33.6% were males and 66.4% were females. 41.7% of them were between 30 and 40 years of age and 51.8% of them were radiology residents. 52.2% of the participants had a refractive error and were using a corrective lens. The majority of the radiologists in our study (84.2%) preferred picture archiving and communication system (PACS) over films and 82.2% of them reported having breaks of less than 15 min. Major symptoms reported by the participants were tired or heavy eyes (69.6%) and headache (69.3%). The proportion of developing DES was higher in females [P=0.001, adjusted odds ratio (aOR)=2.94], radiology residents (P=0.031, aOR=3.29), and working hours of more than 4 h per day (P<0.001, aOR=0.04). Conclusion: With recent advances in the field of radiology in Pakistan, the frequency of developing DES among radiologists is increasing. Being a female, having long working hours, and having noticeable flickers on the digital screens were among the significant factors in developing DES among radiologists.

Rationale: Dengue fever is a widespread mosquito-borne viral disease, most prevalent in the tropical and subtropical areas of the world. There has been a significant rise in the incidence and number of outbreaks of dengue in recent years, which has made it a matter of global concern. It may be associated with a number of renal complications, ranging from hematuria, proteinuria, glomerulonephritis, and acute tubular necrosis. However, renal cortical necrosis (RCN) is a rare renal complication of this disease. Patients concerns: We report the case of a young gentleman who presented with fever, vomiting, and anuria. On workup, he was found to be having complicated Dengue fever with RCN resulting in acute renal failure. Diagnosis: To the best of our knowledge, RCN is not a reported renal complication of dengue fever. Interventions and outcomes: Our report highlights the importance of early consideration of renal cortical necrosis in patients with dengue fever and persistent anuria. Lesson: This would allow for better disease prognostication while enabling physicians to develop more effective treatment strategies.

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.