Nevin Manimala

JAMA Neurol. 2025 Aug 11. doi: 10.1001/jamaneurol.2025.2236. Online ahead of print.

ABSTRACT

IMPORTANCE: Sex differences may contribute to disparities in dementia outcomes.

OBJECTIVE: To understand the association between sex and mortality and health care services use after dementia diagnosis.

DESIGN, SETTING, AND PARTICIPANTS: This nationwide cohort study used Medicare enrollment data and took place from 2014 to 2021 with up to 8 years of follow-up. Analysis was performed from April 2024 to April 2025. This study included 5 721 711 patients 65 years or older with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for dementia with at least 1 year of prior fee-for-service Medicare enrollment.

EXPOSURES: Sex, determined from Medicare enrollment data, derived from Social Security Administration records.

MAIN OUTCOMES AND MEASURES: The primary outcome was hazard of all-cause mortality, estimated with Cox proportional hazard regression. Secondary outcomes included hazards of use of common health care services, such as all-cause hospitalizations, skilled nursing facility stays, receipt of neuroimaging services, and physical/occupational therapy.

RESULTS: A total of 5 721 711 patients (3 302 579 female and 2 419 132 male) with incident dementia between 2014 and 2021 were included in the study. Female patients had lower crude 1-year mortality rates (21.8% vs 27.2% for male patients; P < .001) and lower rates of all-cause hospitalizations (46.9% vs 50.5%; P < .001). The unadjusted hazard of death associated with male sex was 1.30 (95% CI, 1.29-1.31; P < .001). After adjustment for age, race and ethnicity, Medicaid dual eligibility, medical comorbidity burden, and access to health care resources, the association was modestly attenuated (adjusted hazard ratio, 1.24; 95% CI, 1.23-1.26; P < .001). Similarly, the unadjusted hazard ratio of all-cause hospitalization associated with male sex was 1.13 (95% CI, 1.12-1.14; P < .001); the adjusted hazard ratio was 1.08 (95% CI, 1.08-1.09; P < .001). Male patients also had increased hazards of hospice stay, neuroimaging services, and hospitalization for neurodegenerative disease diagnosis or behavioral disturbance.

CONCLUSIONS AND RELEVANCE: In this study, male patients with dementia had higher mortality rates and higher use of many health care services, especially hospital stays, than comparable female patients. Strategies to slow mortality and decrease health care use among male patients with dementia may be particularly impactful in limiting the burden of dementia. Given higher incidence of dementia among women, a focus on efforts to prevent dementia is necessary to achieve population-level health equity in dementia-attributable mortality by sex.

PMID:40788638 | DOI:10.1001/jamaneurol.2025.2236

JAMA Intern Med. 2025 Aug 11. doi: 10.1001/jamainternmed.2025.3904. Online ahead of print.

NO ABSTRACT

PMID:40788627 | DOI:10.1001/jamainternmed.2025.3904

Eur J Heart Fail. 2025 Aug 11. doi: 10.1002/ejhf.3801. Online ahead of print.

ABSTRACT

AIMS: Balanced dual V1a/ V2 vasopressin receptor antagonism may offer potential advantages as an adjunctive and/or a replacement therapy to loop diuretic therapy.

METHODS AND RESULTS: AVANTI was a double-blind, randomized trial in patients hospitalized with heart failure and residual congestion. In Part A, patients received pecavaptan or placebo as adjunctive therapy to standard of care for 30 days. In Part B, patients were randomized to continuation of furosemide or replacement by pecavaptan, as single diuretic therapies for 30 days. Co-primary endpoints were for Part A changes in weight and serum creatinine and for Part B, changes in weight and blood urea nitrogen/creatinine ratio. Among 483 patients randomized into Part A, there was no difference in weight reduction between pecavaptan and placebo (between-group difference: -0.27 kg, upper one-sided 95% confidence interval [CI] -0.29, p = 0.21) and no effect on serum creatinine (between-group difference: 0.05 mg/dl, upper one-sided 95% CI 0.12, p = 0.87). Subsequently, 286 patients were randomized into Part B. The difference in weight change between the pecavaptan and furosemide monotherapy groups over 30 days was 0.69 kg (upper one-sided 80% CI 0.95, p = 0.16), satisfying non-inferiority criteria of 1 kg. The between-group difference in log-transformed change in blood urea nitrogen/creatinine ratio was -0.22 (upper one-sided 80% CI -0.19, p < 0.0001) favouring pecavaptan. Adverse events and serious adverse events related to congestion including heart failure hospitalizations were numerically higher in the pecavaptan groups in both parts of the trial.

CONCLUSIONS: Adjunctive pecavaptan for 30 days in patients with residual congestion had no impact on weight loss nor on renal function. Post-discharge pecavaptan monotherapy was non-inferior to furosemide monotherapy for weight change over 30 days, but was associated with improved renal function. The increase in congestion events suggests that future trials will need optimized background diuretic dosing.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03901729.

PMID:40788619 | DOI:10.1002/ejhf.3801

Appl Biochem Biotechnol. 2025 Aug 11. doi: 10.1007/s12010-025-05343-9. Online ahead of print.

ABSTRACT

Environmental pollution from synthetic dyes is a serious conflict that threatens both aquatic ecosystems and human health. This review explores how indigenous microorganisms help in breaking down these azo dyes and highlights their potential as affordable and eco-friendly solutions in tackling problems caused by the discharge of untreated effluents. Synthetic dyes are widely used in industries like textiles, paper, and food, but their discharge into the environment has led to notable ecological problems. Traditional wastewater methods lack in effectively removing these harmful substances, which is also quite costly. As a result, there is a growing interest in using biological methods that involve bacteria, fungi, and algae to handle this problem. This review is based on how azo dyes are degraded by the microorganisms, especially by azo-reductases, and how various environmental factors like temperature, pH, and nutrient levels can affect the activity of these microbes. In addition to this, the modern computational tools and statistical methods, such as response surface methodology and artificial neural networks, aiding in optimising the dye degradation process, are discussed. Even though the biological method holds promising potential, there are still some challenges, which include scaling up the processes to handle larger volumes of wastewater, meeting various regulatory requirements, and increasing public awareness about the importance of this issue. In future perspectives, research must focus on enhancing bioremediation techniques by involving genetic engineering and fostering collaboration across different fields of study. So as a result, the development of more sustainable solutions for treating wastewater arises, which ultimately helps to decrease the environmental impact of industries that depend largely on dyes.

PMID:40788615 | DOI:10.1007/s12010-025-05343-9

Am J Gastroenterol. 2025 Aug 1. doi: 10.14309/ajg.0000000000003697. Online ahead of print.

ABSTRACT

INTRODUCTION: Hydrogen and methane breath testing (HMBT) is used to diagnose small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO). There are limited data on whether symptoms and medical history can predict outcomes on lactulose HMBT.

METHODS: A large survey-based study was conducted in 731 subjects who completed lactulose HMBT at a single tertiary centre in the UK. The 32-item survey included questions relating to symptoms and medical history. Survey items were statistically interrogated to determine associations with SIBO, IMO or breath gas production using fisher’s exact tests and regression models. SIBO was determined by a rise of ≥20 ppm in breath hydrogen from baseline within 90-minutes and IMO by the presence of ≥10 ppm methane in any breath sample. .

RESULTS: Abdominal pain (p = 0.022), excessive belching (p = 0.041) and regurgitation (p = 0.034) were associated with SIBO, as well as daily abdominal pain with diarrhoea (P = 0.035), and abdominal pain or discomfort immediately after eating (OR 2.20 [95% CI: 1.29, 3.79]). Patients reporting at least one skin condition were more likely to test positive for SIBO, with a trend towards significance for eczema (p = 0.051) and rosacea (p = 0.067). IMO was associated with constipation (p < 0.001) and with fatty/greasy stools that tend to float (p < 0.001). .

DISCUSSION: This large questionnaire study demonstrated that IBS-like symptoms, refractory gastroesophageal reflux symptoms, and skin conditions are associated with outcomes on HMBT. These findings support the use of HMBT in accordance with current clinical guidelines.

PMID:40788605 | DOI:10.14309/ajg.0000000000003697

JAMA Neurol. 2025 Aug 11. doi: 10.1001/jamaneurol.2025.2610. Online ahead of print.

ABSTRACT

IMPORTANCE: For patients with acute ischemic stroke due to anterior circulation large vessel occlusion and presenting directly to endovascular treatment (EVT)-capable centers, intravenous thrombolysis (IVT) before EVT raises concerns about intracranial hemorrhage (ICH), but details are not well understood.

OBJECTIVE: To determine the frequency and subtypes of ICH in patients treated with IVT plus EVT vs EVT alone and to determine the association between various ICH subtypes and patient functional outcomes.

DATA SOURCES: PubMed and MEDLINE were searched from database inception through March 9, 2023.

STUDY SELECTION: Randomized clinical trials comparing EVT alone with IVT plus EVT for anterior circulation large vessel occlusion stroke were included.

DATA EXTRACTION AND SYNTHESIS: Individual participant data were extracted following the Preferred Reporting Items for Systematic Review and Meta-Analyses of independent participant data (PRISMA-IPD) reporting guidelines. Data were pooled using a random-effects model. Data were analyzed between April 2024 and February 2025.

MAIN OUTCOMES AND MEASURES: The primary outcomes were ICH and its subtypes according to the Heidelberg Bleeding Classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], parenchymal hematoma type 2 [PH2], and others; symptomatic or asymptomatic ICH), which were evaluated using a mixed-model approach with multinomial or binary regression.

RESULTS: The analysis involved 2313 participants (1160 allocated to the IVT plus EVT group vs 1153 to EVT alone; median [IQR] age, 71 [62-78] years; 1025 female participants [44%]) from 6 studies. Any ICH occurred in 768 of 2261 participants (34%). IVT was associated with an increased rate of any ICH (411 of 1133 [36%] vs 357 of 1128 [32%]; adjusted odds ratio [OR], 1.23; 95% CI, 1.02-1.49; P = .03) and a higher rate of any parenchymal hematoma (PH1 or PH2) (82 of 1133 [7%] vs 61 of 1128 [5%]; adjusted OR, 1.54; 95% CI, 1.02-2.34; P = .04). Compared with participants without ICH, asymptomatic ICH (adjusted common OR, 0.55; 95% CI, 0.46-0.65) and symptomatic ICH (adjusted common OR, 0.08; 95% CI, 0.05-0.13) were both associated with worse functional outcomes, and there was a graded association of ICH radiologic patterns and patient outcomes.

CONCLUSIONS AND RELEVANCE: In this individual participant data meta-analysis, compared with EVT alone, IVT plus EVT modestly increased the risk of ICH, notably any parenchymal hematoma. Although ICH was associated with worse functional outcomes, this effect may be offset by IVT’s benefit in final successful reperfusion and early reperfusion.

PMID:40788598 | DOI:10.1001/jamaneurol.2025.2610

Abdom Radiol (NY). 2025 Aug 11. doi: 10.1007/s00261-025-05153-x. Online ahead of print.

ABSTRACT

PURPOSE: To explore the relationship between tumor-associated macrophages (TAMs) in gastric cancer and dual-energy computed tomography (DECT) parameters.

METHODS: This retrospective study was conducted with patients who underwent both DECT examination and gastric cancer resection. 89 patients (mean age ± standard deviations, 64.36 ± 9.37) were finally enrolled and analyzed. DECT parameters included iodine concentration (IC), normalized IC (NIC), effective atomic number (Z_eff), the slope of the Hounsfield unit curve (λ_Hu), and CT value in the late arterial phase (LAP) and venous phase (VP). CD206+ TAM infiltration density was detected by immunohistochemistry. The relationships between DECT parameters and TAM were analyzed with the Spearman rank correlation test. DECT parameters in different TAM infiltration density groups were compared with the Mann-Whitney U test.

RESULTS: CD206+ TAM infiltration density demonstrated statistically significant weak correlations with several DECT parameters in LAP (r = 0.236-0.258, all P < 0.05) rather than in VP in all 89 patients. In 48 tubular adenocarcinoma (TAC) patients, correlations in LAP were weak-to-moderate and involved more parameters (r = 0.287-0.358, all P < 0.05), while no significant correlations existed in poorly cohesive carcinoma (PCC). Z_eff-LAP, and λ_Hu-LAP significantly differed between low and high CD206+ TAM infiltration groups in TAC (P < 0.05), rather than in PCC.

CONCLUSION: DECT parameters in LAP showed weak to moderate correlations with TAM infiltration density in gastric adenocarcinoma. These correlations were statistically significant in TAC but absent in PCC. DECT has the potential to assess TAM infiltration density in an exploratory and adjuvant manner, though its assessment efficacy is affected by different WHO subtypes and heterogeneity of gastric cancer.

PMID:40788577 | DOI:10.1007/s00261-025-05153-x

Abdom Radiol (NY). 2025 Aug 11. doi: 10.1007/s00261-025-05145-x. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the diagnostic value of the delayed excretory phase in computed tomography urography (CTU) for detecting renal and urinary tract abnormalities and its impact on readers’ confidence in patients with hematuria, given concerns about radiation exposure, cost, and limited added benefit.

METHODS: This IRB-approved, HIPAA-compliant retrospective cross-sectional study included 489 CTU exams performed at a quaternary center between 2012 and 2023. Each scan included non-contrast, nephrographic, and delayed phases. Six radiologists with varying experience independently reviewed exams in two sessions: Session 1 (without delayed phase) and Session 2 (with delayed phase), separated by a minimum three-week washout period. Abnormalities were assessed using standardized criteria; diagnostic confidence was rated (0-100%). Analyses included McNemar’s test, mixed-effects logistic regressions, and Wilcoxon signed-rank tests; p < 0.05 was statistically significant.

RESULTS: No significant differences were found in detecting most abnormalities between sessions. Cystic renal masses were more often detected in Session 1 (p = 0.05, OR = 1.40, 95% CI: 0.99-1.98). Detection increased in Session 2 for renal (p = 0.002, OR = 0.35) and ureteral congenital anomalies (p = 0.004, OR = 0.30). Intermediate-experience readers had lower odds of detecting renal (OR = 0.09) and cystic masses (OR = 0.08); experienced readers missed more ureteral anomalies (OR = 0.21). Delayed imaging did not improve overall detection or reader performance. Diagnostic confidence was lower in Session 2 (p < 0.001), particularly among less experienced readers.

CONCLUSION: The delayed excretory phase in CTU modestly improved detection of congenital anomalies but did not enhance identification of ureteral or bladder lesions or diagnostic confidence. Selective use may reduce radiation exposure without compromising diagnostic performance.

PMID:40788575 | DOI:10.1007/s00261-025-05145-x

J Neurooncol. 2025 Aug 11. doi: 10.1007/s11060-025-05199-3. Online ahead of print.

ABSTRACT

PURPOSE: The implications of intratumoural cystic change on management and treatment outcomes in vestibular schwannoma (VS) remain uncertain. This retrospective analysis aims to compare the treatment outcomes of solid and cystic tumours treated with linear accelerator (LINAC)-based stereotactic radiosurgery (SRS).

METHODS: Sixty-eight patients were analysed including 22 with cystic tumours. All received a marginal dose of 12 Gy to the 80% isodose line (range: 70-90%) delivered in a single fraction. Local progression was defined as a maximum linear dimension (MLD) enlargement of > 2 mm persisting for over 2 years, pseudoprogression as an MLD enlargement of > 2 mm within the first 2 years followed by stability or reduction.

RESULTS: With an average follow-up of 92.2 months, crude tumour control rates were similar: 95.5% for cystic and 93.5% for solid tumours. Pseudoprogression occurred in 7 patients (10.3%), 2 with solid (4.3%) and 5 with cystic VS (22.7%). The mean MLD reduction was 4.2 mm for solid tumours and 5.0 mm for cystic tumours (p = 0.51). Only pretreatment size correlated with the percentage reduction in tumour diameter (p = 0.025). Although a higher proportion of cystic tumours demonstrated at least a 10%, 20%, and 30% size reduction compared to solid tumours, none of these differences were statistically significant.

CONCLUSION: LINAC-based SRS achieves similar tumour control for both cystic and solid VS. Despite cystic tumours being typically of higher Koos grade, they may demonstrate numerically greater reduction after SRS. Future studies should aim to standardise the criteria for classifying cystic tumours.

PMID:40788563 | DOI:10.1007/s11060-025-05199-3

Calcif Tissue Int. 2025 Aug 11;116(1):106. doi: 10.1007/s00223-025-01416-3.

ABSTRACT

Heterotopic ossification (HO) frequently occurs after procedures such as hip replacements, acetabular fractures, and elbow fractures. While radiotherapy (RT) has been a longstanding preventive measure against HO, its efficacy remains controversial, with some studies questioning its effectiveness and noting potential side effects. Previous research has predominantly focused on total hip arthroplasty (THA), leading to a gap in comprehensive evaluation of RT’s efficacy and safety across other conditions. This systematic review and meta-analysis were conducted strictly adhering to PRISMA guidelines, utilizing the PICO framework to critically assess randomized clinical trials. A thorough literature search was executed across PubMed, Embase, Cochrane Library, and Web of Science). Methodological integrity was ensured through structured data extraction and quality assessment using validated criteria. The protocol was prospectively registered with INPLASY, ensuring full methodological transparency. A total of seven studies with 933 patients were included in the analysis, comprising 594 patients receiving RT and 339 patients in the control condition. Subgroup analyses included 784 patients undergoing THA and 149 patients receiving other surgical interventions. Overall findings supported RT’s efficacy in significantly reducing severe HO formation. Notably, subgroup analysis of patients who underwent non-THA procedures indicated no statistically meaningful reduction in the incidence of mild-to-moderate HO (Brooker I-II) after RT treatment compared to controls. Conversely, an increased risk of nonunion was specifically noted among patients receiving elbow RT. Our meta-analysis strongly supports the preventive effect of RT on HO, especially for high-risk patients and in cases that other treatments, like NSAIDs, are contraindicated or avoided. However, the risk of nonunion in elbow treatments warrants caution. Further prospective randomized controlled trials, particularly focusing on non-hip joints, are necessary to validate these findings.

PMID:40788554 | DOI:10.1007/s00223-025-01416-3