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Background: The Sequential Organ Failure Assessment (SOFA) score monitors organ failure and defines sepsis but may not fully capture factors influencing sepsis mortality. Socioeconomic and demographic impacts on sepsis outcomes have been highlighted recently., Objective: To evaluate the prognostic value of SOFA scores against demographic and social health determinants for predicting sepsis mortality in critically ill patients, and to assess if a combined model increases predictive accuracy., Methods: The study utilized retrospective data from the MIMIC-IV database and prospective external validation from the Penn State Health cohort. A Random Forest model incorporating SOFA scores, demographic/social data, and the Charlson Comorbidity Index was trained and validated., Findings: In the MIMIC-IV dataset of 32,970 sepsis patients, 6,824 (20.7%) died within 30 days. A model including demographic, socioeconomic, and comorbidity data with SOFA scores improved predictive accuracy beyond SOFA scores alone. Day 2 SOFA, age, weight, and comorbidities were significant predictors. External validation showed consistent performance, highlighting the importance of delta SOFA between days 1 and 3., Conclusion: Adding patient-specific demographic and socioeconomic information to clinical metrics significantly improves sepsis mortality prediction. This suggests a more comprehensive, multidimensional prognostic approach is needed for accurate sepsis outcome predictions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Persistent post-COVID conditions (PCCs) have become inevitable challenges for individuals who have survived COVID. The National Research Plan on Long COVID-19 underscores the priority of addressing post-COVID conditions (PCCs) within specific subgroups of the United States (US) population. This study aimed to investigate the prevalence and factors associated with PCCs among stroke survivors in the US., Method: In this retrospective cross-sectional study, we utilized the Behavioral Risk Factor Surveillance System (BRFSS) 2022 dataset. First, we identified respondents with a positive history of both COVID-19 and stroke. Subsequently, we categorized these respondents based on whether they experienced PCCs and conducted a comparative analysis of their characteristics. Additionally, our study included a comparison of our findings with those among individuals who have survived myocardial infarction (MI) and cancer., Results: A total of 3999 stroke, 5406 MI, and 10551 cancer survivors were included. The estimated prevalence of PCCs among stroke survivors was 30.6 %, compared to 22.4 %, 29.2 %, and 24.6 % among non-stroke (p < 0.001), MI, and cancer survivors, respectively. Fatigue, dyspnea, and taste/smell loss were the most common primary symptoms. In multivariate regression analysis, female sex (adjusted odds ratio (aOR):1.62, 95 %CI:[1.17-2.24]), stroke-belt residence (aOR:1.67, 95 %CI: [1.13-2.46]), pulmonary disease (aOR:2.12, 95 %CI:[1.53-2.92]), and depression (aOR:1.55, 95 %CI: [1.1-2.2]) were independent factors associated with higher odds of PCCs among stroke survivors. Additionally, age above 64 years was associated with lower odds of PCCs (aOR:0.6, 95 %CI: [0.41-0.86])., Conclusion: Our study highlights a considerable prevalence of PCCs among stroke survivors, particularly among younger women and individuals with other chronic conditions., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: The estimated glomerular filtration rate (eGFR) and kinetic estimated glomerular filtration rate (KeGFR) have not been compared, with urinary measured creatinine clearance (mCrCl) or serum cystatin C (CysC) eGFR, soon after kidney transplantation (KTx) with prompt primary function. This study aims to compare post-KTx, urinary mCrCl, and eGFR CysC with eGFR and KeGFR., Methods: Post-KTx, urine was collected every 12 hours from 25 of the 34 consenting subjects to calculate mCrCl and compare with Modification of Diet in Renal Disease (MDRD)-4, Jelliffe eGFR, Cockcroft-Gault creatinine clearance (CrCl), and KeGFR by Chen and Brater formulae. Serum CysC levels were also measured in the last 14 subjects to compare with creatinine, mCrCl, and eGFR CysC . RESULTS: At 12 to 96 hours post-KTx (n = 25), mCrCl was 55.8% to 13.6% higher than MDRD-4 eGFR. The mean CysC level (n = 14) was 58% to 14% lower than creatinine for up to 3.0 days post-KTx, with higher MDRD-4 eGFR CysC. Chen and Brater KeGFR were significantly lower than mCrCl and eGFR (Fig 1B, Table 1). Within 3 days post-KTx, a 50% decrease in creatinine provided ≥ 50 mL/min CrCl in 90% of cases (mean mCrCl 61.7 ± 22.8). This difference was greater when the initial creatinine was higher with the rapid decrease in creatinine., Conclusions: (1) Post-KTx eGFR/KeGFR formulae underestimated mCrCl. (2) Serum CysC levels were lower than creatinine, corresponding with higher eGFR CysC. (3) A 50% decrease from initial serum creatinine; mean mCrCl was 61.7 ± 22.8 mL/min, and 90% of them have mCrCl > 50 mL/min. Post-KTx, until creatinine is stabilized, recipients are often receiving subtherapeutic dosing of renally adjusted medications. More prospective studies are necessary, including radioisotope clearance., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: A significant proportion of COVID survivors experience lingering and debilitating symptoms following acute COVID-19 infection. According to the national research plan on long COVID, it is a national priority to identify the prevalence of post-COVID conditions and their associated factors., Method: We performed a cross-sectional analysis of the Prevention Behavioral Risk Factor Surveillance System (BRFSS) 2022, the largest continuously gathered health survey dataset worldwide by the Centers for Disease Control. After identifying individuals with a positive history of COVID-19, we grouped COVID-19 survivors based on whether they experienced long-term post-COVID conditions. Using survey-specific R packages, we compared the two groups' socio-demographics, comorbidities, and lifestyle-related factors. A logistic regression model was used to identify factors associated with post-COVID conditions., Results: The overall estimated prevalence of long-term post-COVID conditions among COVID survivors was 21.7%. Fatigue (5.7%), dyspnea (4.2%), and anosmia/ageusia (3.8%) were the most frequent symptoms. Based on multivariate logistic regression analysis, female sex, body mass index (BMI)≥25, lack of insurance, history of pulmonary disease, depression, and arthritis, being a former smoker, and sleep duration <7 h/d were associated with higher odds of post-COVID conditions. On the other hand, age >64 y/o, Black race, and annual household income ≥$100k were associated with lower odds of post-COVID conditions., Conclusion: Our findings indicate a notable prevalence of post-COVID conditions, particularly among middle-aged women and individuals with comorbidities or adverse lifestyles. This high-risk demographic may require long-term follow-up and support. Further investigations are essential to facilitate the development of specified healthcare and therapeutic strategies for those suffering from post-COVID conditions., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Significance Statement: We hypothesized that triple therapy with inhibitors of the renin-angiotensin system (RAS), sodium-glucose transporter (SGLT)-2, and the mineralocorticoid receptor (MR) would be superior to dual RAS/SGLT2 blockade in attenuating CKD progression in Col4a3 -deficient mice, a model of Alport syndrome. Late-onset ramipril monotherapy or dual ramipril/empagliflozin therapy attenuated CKD and prolonged overall survival by 2 weeks. Adding the nonsteroidal MR antagonist finerenone extended survival by 4 weeks. Pathomics and RNA sequencing revealed significant protective effects on the tubulointerstitium when adding finerenone to RAS/SGLT2 inhibition. Thus, triple RAS/SGLT2/MR blockade has synergistic effects and might attenuate CKD progression in patients with Alport syndrome and possibly other progressive chronic kidney disorders., Background: Dual inhibition of the renin-angiotensin system (RAS) plus sodium-glucose transporter (SGLT)-2 or the mineralocorticoid receptor (MR) demonstrated additive renoprotective effects in large clinical trials. We hypothesized that triple therapy with RAS/SGLT2/MR inhibitors would be superior to dual RAS/SGLT2 blockade in attenuating CKD progression., Methods: We performed a preclinical randomized controlled trial (PCTE0000266) in Col4a3 -deficient mice with established Alport nephropathy. Treatment was initiated late (age 6 weeks) in mice with elevated serum creatinine and albuminuria and with glomerulosclerosis, interstitial fibrosis, and tubular atrophy. We block-randomized 40 male and 40 female mice to either nil (vehicle) or late-onset food admixes of ramipril monotherapy (10 mg/kg), ramipril plus empagliflozin (30 mg/kg), or ramipril plus empagliflozin plus finerenone (10 mg/kg). Primary end point was mean survival., Results: Mean survival was 63.7±10.0 days (vehicle), 77.3±5.3 days (ramipril), 80.3±11.0 days (dual), and 103.1±20.3 days (triple). Sex did not affect outcome. Histopathology, pathomics, and RNA sequencing revealed that finerenone mainly suppressed the residual interstitial inflammation and fibrosis despite dual RAS/SGLT2 inhibition., Conclusion: Experiments in mice suggest that triple RAS/SGLT2/MR blockade may substantially improve renal outcomes in Alport syndrome and possibly other progressive CKDs because of synergistic effects on the glomerular and tubulointerstitial compartments., (Copyright © 2023 by the American Society of Nephrology.)

Pathology diagnostics relies on the assessment of morphology by trained experts, which remains subjective and qualitative. Here we developed a framework for large-scale histomorphometry (FLASH) performing deep learning-based semantic segmentation and subsequent large-scale extraction of interpretable, quantitative, morphometric features in non-tumour kidney histology. We use two internal and three external, multi-centre cohorts to analyse over 1000 kidney biopsies and nephrectomies. By associating morphometric features with clinical parameters, we confirm previous concepts and reveal unexpected relations. We show that the extracted features are independent predictors of long-term clinical outcomes in IgA-nephropathy. We introduce single-structure morphometric analysis by applying techniques from single-cell transcriptomics, identifying distinct glomerular populations and morphometric phenotypes along a trajectory of disease progression. Our study provides a concept for Next-generation Morphometry (NGM), enabling comprehensive quantitative pathology data mining, i.e., pathomics., (© 2023. The Author(s).)

Importance: Transient ischemic attack (TIA) often indicates a high risk of subsequent cerebral ischemic events. Timely preventive measures improve the outcome., Objective: To estimate and compare the risk of subsequent ischemic stroke among patients with TIA or minor ischemic stroke (mIS) by care setting., Data Sources: MEDLINE, Web of Science, Scopus, Embase, International Clinical Trials Registry Platform, ClinicalTrials.gov, Trip Medical Database, CINAHL, and all Evidence-Based Medicine review series were searched from the inception of each database until October 1, 2020., Study Selection: Studies evaluating the occurrence of ischemic stroke after TIA or mIS were included. Cohorts without data on evaluation time for reporting subsequent stroke, with retrospective diagnosis of the index event after stroke occurrence, and with a report of outcomes that were not limited to patients with TIA or mIS were excluded. Two authors independently screened the titles and abstracts and provided the list of candidate studies for full-text review; discrepancies and disagreements in all steps of the review were addressed by input from a third reviewer., Data Extraction and Synthesis: The study was prepared and reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, Meta-analysis of Observational Studies in Epidemiology, Methodological Expectations of Cochrane Intervention Reviews, and Enhancing the Quality and Transparency of Health Research guidelines. The Risk of Bias in Nonrandomized Studies-of Exposures (ROBINS-E) tool was used for critical appraisal of cohorts, and funnel plots, Begg-Mazumdar rank correlation, Kendall τ2, and the Egger bias test were used for evaluating the publication bias. All meta-analyses were conducted under random-effects models., Main Outcomes and Measures: Risk of subsequent ischemic stroke among patients with TIA or mIS who received care at rapid-access TIA or neurology clinics, inpatient units, emergency departments (EDs), and unspecified or multiple settings within 4 evaluation intervals (ie, 2, 7, 30, and 90 days)., Results: The analysis included 226 683 patients from 71 articles recruited between 1981 and 2018; 5636 patients received care at TIA clinics (mean [SD] age, 65.7 [3.9] years; 2291 of 4513 [50.8%] men), 130 139 as inpatients (mean [SD] age, 78.3 [4.0] years; 49 458 of 128 745 [38.4%] men), 3605 at EDs (mean [SD] age, 68.9 [3.9] years; 1596 of 3046 [52.4%] men), and 87 303 patients received care in an unspecified setting (mean [SD] age, 70.8 [3.8] years, 43 495 of 87 303 [49.8%] men). Among the patients who were treated at a TIA clinic, the risk of subsequent stroke following a TIA or mIS was 0.3% (95% CI, 0.0%-1.2%) within 2 days, 1.0% (95% CI, 0.3%-2.0%) within 7 days, 1.3% (95% CI, 0.4%-2.6%) within 30 days, and 2.1% (95% CI, 1.4%-2.8%) within 90 days. Among the patients who were treated as inpatients, the risk of subsequent stroke was to 0.5% (95% CI, 0.1%-1.1%) within 2 days, 1.2% (95% CI, 0.4%-2.2%) within 7 days, 1.6% (95% CI, 0.6%-3.1%) within 30 days, and 2.8% (95% CI, 2.1%-3.5%) within 90 days. The risk of stroke among patients treated at TIA clinics was not significantly different from those hospitalized. Compared with the inpatient cohort, TIA clinic patients were younger and had had lower ABCD2 (age, blood pressure, clinical features, duration of TIA, diabetes) scores (inpatients with ABCD2 score >3, 1101 of 1806 [61.0%]; TIA clinic patients with ABCD2 score >3, 1933 of 3703 [52.2%])., Conclusions and Relevance: In this systematic review and meta-analysis, the risk of subsequent stroke among patients who were evaluated in a TIA clinic was not higher than those hospitalized. Patients who received treatment in EDs without further follow-up had a higher risk of subsequent stroke. These findings suggest that TIA clinics can be an effective component of the TIA care component pathway.

Olfaction dysfunction is considered as a robust marker of prodromal Parkinson disease (PD). Measurement of olfaction function as a screening test is unsatisfactory due to long lead time interval and low specificity for detection of PD. Use of imaging markers might yield more accurate predictive values and provide bases for combined use of imaging and clinical markers for early PD. Diffusion MRI connectometry was conducted on 85 de novo PD patients in and 36 healthy controls to find: first, white matter tracts with significant difference in quantitative anisotropy between PD groups with various degrees of olfaction dysfunction and second, second fibers with correlation with University of Pennsylvania Smell Identification Test (UPSIT) score in each group using a multiple regression analysis considering age, sex, GDS and MoCA score. Local connectomes were determined in seven of all the possible comparisons, correcting for false discovery rate (FDR). PD patients with anosmia and normal olfaction had the highest number of fibers with decreased connectivity in left inferior longitudinal fasciculus, bilateral fornix, bilateral middle cerebellar peduncle (MCP), bilateral cingulum, bilateral corticospinal tract (CST) and body, genu and splenium of corpus callosum (CC) (FDR = 0.0013). In multiple regression analysis, connectivity in the body, genu and splenium of CC and bilateral fornix had significant negative correlation (FDR between 0.019 and 0.083), and bilateral cingulum and MCP had significant positive correlation (FDR between 0.022 and 0.092) with UPSIT score. White matter connectivity in healthy controls could not be predicted by UPSIT score using the same model. The results of this study provide compelling evidence that microstructural degenerative changes in these areas underlie the clinical phenotype of prodromal olfaction dysfunction in PD and that diffusion parameters of these areas might be able to serve as signature markers for early detection of PD. This is the first report that confirms a discriminative role for UPSIT score in identifying PD specific changes in white matter microstructure. Our results open a window to identify microstructural signatures of prodromal PD in white matter.