Asghar, Muhammad S

Key Points Increased protein expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase was observed in old adults compared with young adults. In old adults, overexpressed proteins were enriched in mitochondrial processes while under expressed proteins enriched in RNA metabolism. Validated differentially expressed proteins were not significantly correlated with kidney pathology after adjusting for age. Background Kidney aging is characterized by a loss of glomeruli, predominantly in the superficial cortex, with a resultant decline in GFR and an increased risk of various kidney-related diseases. The early molecular alterations in glomeruli associated with the aging process are not well studied. Methods We combined laser capture microdissection and mass spectrometry–based unbiased proteomic analysis of nonsclerosed, nonischemic glomeruli in the superficial cortex from young and old adults who underwent a radical nephrectomy for a tumor to understand the age-related molecular changes in glomeruli. Twenty-four young and 30 old adults were used for the discovery dataset, and the significant differentially expressed proteins were further validated using an independent set comprising six young and eight old adults. Results Kidneys from old adults had lower eGFR, less kidney parenchyma on computed tomography imaging, and more glomerulosclerosis and arteriosclerosis on histology. Quantitative proteomic analysis of nonsclerosed, nonischemic glomeruli identified increased expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase in old adults that were further validated in an independent set. Pathway analysis indicated that proteins with increased expression in old adults were enriched in mitochondrial translational processes, aerobic respiration, and TCA cycle, whereas proteins with decreased expression in old adults were enriched in mRNA splicing, mRNA processing, and nonsense mediated decay. Furthermore, validated differentially expressed proteins did not show any significant correlation with the kidney pathology independent of age group. Conclusions Overall, this study identified proteins that are specifically associated with the aging process in otherwise normal-appearing glomeruli.

Background: Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker for AP prognosis. This study systematically reviews the literature on suPAR’s prognostic roles in assessing AP severity, organ failure, mortality, and other pathological markers. Methods: A comprehensive search of 5 databases up to March 19, 2023, was conducted, selecting cohort studies that examined suPAR’s relationship with AP outcomes. Outcome variables included AP severity, organ failure, mortality, hospital stay length, and suPAR’s association with other inflammatory markers. Our paper has been registered on Prospero (ID: CRD42023410628). Results: Nine prospective observational studies with 1033 AP patients were included. Seven of eight studies found suPAR significantly elevated in severe acute pancreatitis ( P < .05). Four studies showed suPAR effectively predicted organ failure risk, and 4 studies concluded suPAR significantly predicted mortality ( P < .05). The review had no high-risk studies, enhancing credibility. Conclusion: suPAR is a valuable prognostic marker in AP, significantly predicting severity, organ failure, hospital stay length, and mortality. Further large-scale studies are needed to explore suPAR’s role in other clinical outcomes related to AP disease course, to establish it as a mainstay of AP prognosis.

Abstract Introduction An unusual association between thyroid dysfunction and autoimmune encephalitis (AE) was noticed when patients presented with low free triiodothyronine (fT3) levels and antithyroid antibodies. We conducted a meta‐analysis to investigate whether thyroid dysfunction, that is, lower fT3 levels are associated with worsening clinical manifestations and prognosis in patients with AE. Methods Literature search of five electronic databases was performed till April 5, 2023. Inclusion criteria were as follows: Observational studies reporting patients with all subtypes of AE and assessing thyroid dysfunction categorized as low fT3 and non‐low fT3. Primary endpoints included modified Rankin scale (mRS) at admission, abnormal magnetic resonance imaging, length of stay, seizures, and consciousness declination. Results Comprehensive literature search resulted in 5127 studies. After duplicate removal and full‐text screening, six observational studies were included in this analysis. Patients with low fT3 were 2.95 times more likely to experience consciousness declination ( p = .0003), had higher mRS at admission ( p < .00001), had 3.14 times increased chances of having a tumor ( p = .003), were 3.88 times more likely to experience central hypoventilation, and were 2.36 times more likely to have positivity for antithyroid antibodies ( p = .009) as compared to patients with non‐low fT3. Conclusion The findings of our study suggest that low fT3 levels might be related to a more severe disease state, implying the significance of thyroid hormones in AE pathogenesis. This finding is crucial in not only improving the early diagnosis of severe AE but also in the efficient management of the disease.

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.

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.