Nevin Manimala

Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct 4. doi: 10.1007/s00210-025-04555-4. Online ahead of print.

ABSTRACT

To evaluate the clinical efficacy and safety of Almonertinib in EGFR-mutant advanced NSCLC patients with different nutritional statuses. Clinical data from 56 patients with advanced EGFR-mutant NSCLC admitted to the First Affiliated Hospital of Anhui Medical University from April 2021 to April 2023 were retrospectively analyzed. Patients were stratified into two groups based on nutritional risk (nutritional risk group, n = 30; non-risk group, n = 26) and into two groups based on malnutrition status (malnutrition group, n = 35; regular nutrition group, n = 21). Kaplan-Meier methods were used to plot survival curves, the Chi-square test was employed to evaluate clinical efficacy, and Cox regression analysis was applied to identify factors associated with adverse reactions. Patients in the nutritional risk group had a median progression-free survival (mPFS) of 12.8 months (95% CI: 9.146-16.454), which was shorter than that of the non-risk group (mPFS: 19.7 months; 95% CI: 12.234-27.166), showing statistical significance (P = 0.049). However, there was no significant difference in median overall survival (mOS) between the two groups (P = 0.546). In the malnutrition group, patients had an mPFS of 12.6 months (95% CI: 9.648-15.552) and an mOS of 29.8 months (95% CI: 24.476-35.124), both significantly shorter than those of the regular nutrition group (mPFS: 19.7 months, 95% CI: 13.097-26.303; mOS: 32.1 months, 95% CI: 23.781-40.419) (P = 0.034 and P = 0.046, respectively). There was no significant difference in objective response rate (ORR) between groups (P > 0.05). Serum albumin levels were independently associated with the incidence of adverse reactions (P = 0.003; HR: 7.194, 95% CI: 1.925-26.886). Almonertinib demonstrates favorable efficacy and safety in treating advanced NSCLC patients with malnutrition or nutritional risk accompanying EGFR mutations. The shortened PFS observed in cachectic patients may reflect accelerated disease progression related to poor nutritional status rather than Almonertinib-specific resistance. Moreover, mild to moderate anxiety was observed in all patients receiving Almonertinib, underscoring the importance of incorporating psychological support in cancer care.

PMID:41045332 | DOI:10.1007/s00210-025-04555-4

Exp Brain Res. 2025 Oct 4;243(11):219. doi: 10.1007/s00221-025-07169-7.

ABSTRACT

A substantial body of literature has examined gait during cognitive dual-tasking in younger and older adults. However, it remains unclear how, and to what extent, different cognitive tasks uniquely influence gait. This meta-analysis quantified age-related differences in gait speed during dual-task walking. Importantly, we examined cognitive task as a potential moderator. We searched Web of Science for studies comparing young and older adults during single-task and dual-task walking conditions. Twenty-two studies met the inclusion criteria, representing 544 young adults (mean age range: 20-31 years) and 511 older adults (mean age range: 62-85 years). Studies employed primarily serial subtraction tasks (n = 12) and verbal fluency tasks (n = 8); however, one study used digit vigilance, and another used a texting paradigm during walking. Random-effects meta-analysis using standardized mean differences (Hedges’ g) revealed a significant overall effect (g = -0.2612, 95% CI [-0.4914, -0.0310], p = 0.0261), indicating greater dual-task costs in older adults compared to younger adults with a small to medium effect size. Substantial heterogeneity was observed across studies (I² = 66.53%, p < 0.0001). Subgroup analysis demonstrated that verbal fluency tasks produced a larger and statistically significant age-related difference (g = -0.4744, 95% CI [-0.8712, -0.0777], p = 0.0191), while serial subtraction tasks showed smaller, non-significant effects (g = -0.1412, p = 0.3474). These findings suggest that verbal fluency creates unique neural resource competition in older adults, involving prefrontal, cerebellar, and basal ganglia circuits that support both language production and gait control. The task-specific vulnerability to verbal fluency, and not serial subtraction, provides evidence for age-related changes in cognitive-motor integration. Rehabilitation strategies targeting executive functions may be effective for maintaining mobility in aging populations.

PMID:41045320 | DOI:10.1007/s00221-025-07169-7

Cell Tissue Bank. 2025 Oct 4;26(4):44. doi: 10.1007/s10561-025-10195-y.

ABSTRACT

Bone grafts and its substitutes are commonly used in periodontics to enhance bone formation and periodontal regeneration. Allografts, derived from human donors, support new bone growth and are biocompatible, with reduced disease transmission risk due to rigorous screening. Combining bone grafts with growth factors can further improve treatment outcomes. Platelet Rich Fibrin (PRF) releases growth factors that enhance regeneration. This study evaluates the effectiveness of combining processed fresh frozen bone allograft (FFBA) with PRF mambrane for treating periodontal bone defects. The FFBA was prepared from bone chips collected from systemically healthy patients in an aseptic environment during orthopedic surgeries, which was then processed and tested for microbiological and cytotoxicity concerns using Human Osteosarcoma (MG-63) and Normal Mouse Fibroblast (L929) cell lines. PRF was prepared by centrifuging blood collected from patients at 2300 rpm for 12 min. A case study comprising of ten patients with chronic periodontitis was conducted, Clinical and radiographic measurements, including plaque index (PI), gingival index (GI), probing depth (PD), and bone defect fill percentage using radiographs were recorded at baseline and nine months. Descriptive statistics (Mean ± SD), a 5% significance level, and 90% confidence intervals were used. Paired t-tests showed significant improvements in GI (p < 0.001), PI (p < 0.001), PPD (p < 0.001), and Bone defect fill (p < 0.001). The study concluded that using processed fresh frozen bone allograft with PRF positively affects the treatment of periodontal osseous defects.

PMID:41045316 | DOI:10.1007/s10561-025-10195-y

Virchows Arch. 2025 Oct 4. doi: 10.1007/s00428-025-04250-y. Online ahead of print.

ABSTRACT

While perivascular epithelioid cell tumor (PEComas) have been described in most organ systems, only a few bladder PEComas have been reported. Although most behave in an indolent fashion, a subset may develop metastasis. Herein, we describe the clinicopathologic and molecular characteristics of 21 bladder PEComas, including biomarker analysis and comprehensive sequencing. Patients included 13 females and 8 males, with age ranging from 17-81 years (mean = 47.6 years). Clinical follow-up data was available for 17 patients (ranging 5-60 months; mean = 19.4 months). The morphologic features significantly associated with metastatic disease included ≥ 2 mitoses/10 high-power fields (p = 0.0023), atypical mitoses (p = 0.0152), and necrosis (p = 0.0023); the presence of ≥ 70% atypical epithelioid cells and vascular invasion did not meet statistical significance. The Biomarker profile (p16, p53, TRIM63 ISH, ATRX, RB1) found no statistical significance with metastasis. TRIM63 ISH showed high sensitivity (86%) with poor specificity (11%) for TFE3 rearrangements. NGS revealed TFE3 fusions in 8/17 cases (47%): 7 with SFPQ::TFE3 fusions and 1 with NONO::TFE3 fusion). Overall, mTOR pathway mutations were detected in 9 cases (53%): TSC1/2 mutations in 6 (35%), MTOR mutation in 1 (6%), and co-mutations of TSC/MTOR in 2 (12%) cases. Additionally, co-mutations involving p53 were noted in 2 tumors (1 SFPQ::TFE3/p53; 1 MTOR/p53). Metastasis was identified in 5 TFE3-rearranged PEComas (OR = 8.7509) and 2 TSC/MTOR- mutated tumors (OR = 0.1143). TFE3-rearranged bladder PEComas show a higher propensity towards aggressive behavior compared to TSC/MTOR- mutated tumors. Awareness of the molecular signature may be important for prognostic stratification and targeted therapeutic approaches.

PMID:41045311 | DOI:10.1007/s00428-025-04250-y

Eur Radiol. 2025 Oct 4. doi: 10.1007/s00330-025-12039-5. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the impact of MRI-defined bladder wall invasion from uterine cervical cancer (CC) on disease recurrence and overall survival.

MATERIALS AND METHODS: IRB-approved multicenter retrospective study including women who underwent staging MRI for histologically confirmed CC (Jan 2015-Dec 2020). Image analysis was independently performed by two radiologists. Bladder wall invasion was diagnosed if ≥ 3 of the following criteria were met: loss of the cervix-bladder fat plane, bladder wall thickening, loss of bladder wall T2-hypointensity, and presence of endoluminal tumor growth. MRI findings were compared with endoscopy/cytology. The impact of MRI-defined bladder wall invasion on tumor recurrence and survival was assessed using logistic regression. Survival curves were compared using the log-rank test.

RESULTS: We included 214 women with a median age of 55 (IQR 47-65) years. MRI-defined bladder wall invasion was observed in 21.5% of patients. Cystoscopy revealed bladder mucosal infiltration in 7.0% of patients, all of whom demonstrated MRI-defined bladder wall invasion. No patients without MRI-defined bladder wall invasion showed mucosal infiltration on cystoscopy/cytology. The median follow-up was 32 months: 46.7% of patients had recurrence, and 23.4% had CC-related death. On logistic regression, MRI-defined bladder wall invasion was an independent risk factor for tumor recurrence (OR 2.24, p = 0.047) and mortality (OR 3.55, p = 0.006), whereas cystoscopy-defined bladder mucosa infiltration was not. The log-rank test demonstrated a significant difference in survival between patients with and without MRI-defined bladder wall invasion (χ² = 15.40, p = 0.0001).

CONCLUSIONS: MRI-defined bladder wall invasion represents an independent negative prognostic factor in patients with cervical cancer.

KEY POINTS: Question The prognostic significance of MRI-defined bladder wall invasion in patients with cervical cancer remains unclear with respect to disease recurrence and survival. Findings Bladder wall invasion identified on MRI is an independent predictor of tumor recurrence and tumor-specific mortality, whereas mucosal infiltration detected via cystoscopy is not. Clinical relevance MRI can safely replace cystoscopy in the preoperative staging of patients with uterine cervical cancer. This approach can reduce costs and expedite the staging process.

PMID:41045303 | DOI:10.1007/s00330-025-12039-5

Vet Med Sci. 2025 Nov;11(6):e70622. doi: 10.1002/vms3.70622.

ABSTRACT

BACKGROUND: Cattle have been domesticated by humans for thousands of years for various purposes, including their economic significance. Despite advancements in livestock farming technologies, challenges such as disease outbreaks continue to affect productivity and economic stability.

OBJECTIVES: The aim is to investigate the prevalence and factors associated with various diseases in cattle around the Madhumati River in Gopalganj, Bangladesh. The study also offers insights into the current disease landscape, focusing on animal health status, farmer knowledge and treatment and prevention strategies in Gopalganj.

METHOD: A standardized closed-ended questionnaire was administered using KoboToolBox (2021.2.4) for data collection. Statistical analyses included descriptive statistics, Fisher’s exact test, χ² test, and multivariate logistic regression models with 95% confidence intervals. R (4.4.0) and SPSS (27.0.1) were utilized to explore associations between variables influencing disease prevalence.

RESULT: The findings of the study indicate that Foot and Mouth Disease (17.39%) and Lumpy Skin Disease (13.04%) were the most prevalent diseases. A linear model (95% CI) predicted that poor husbandry practices, lack of knowledge, and inadequate treatment strategies contributed to disease occurrence in different regions of Gobra, Gopalganj.

CONCLUSION: This cross-sectional study investigated the major prevalence rate and causes of diseases in the Gobra region of Gopalganj, identifying FMD and LSD as significant diseases in cattle farming. From the study, we can suggest some strategies to mitigate disease prevalence, including seasonal preventive measures, routine vaccination, deworming protocols, and stringent sanitation practices.

PMID:41045291 | DOI:10.1002/vms3.70622

Clin Trials. 2025 Oct 4:17407745251378117. doi: 10.1177/17407745251378117. Online ahead of print.

ABSTRACT

BACKGROUND: Cluster randomized controlled trials are increasingly used to evaluate the effectiveness of interventions in clinical and public health research. However, missing data in cluster randomized controlled trials can lead to biased results and reduce statistical power if not handled appropriately. This study aimed to review, describe and summarize how missing primary outcome data are handled in reports of publicly funded cluster randomized controlled trials.

METHODS: This study reviewed the handling of missing data in cluster randomized controlled trials published in the UK National Institute for Health and Care Research Journals Library from 1 January 1997 to 31 December 2024. Data extraction focused on trial design, missing data mechanisms, handling methods in primary analyses and sensitivity analyses.

RESULTS: Among the 110 identified cluster randomized controlled trials, 45% (50/110) did not report or take any action on missing data in either primary analysis or sensitivity analysis. In total, 75% (82/110) of the identified cluster randomized controlled trials did not impute missing values in their primary analysis. Advanced methods like multiple imputation were applied in only 15% (16/110) of primary analyses and 28% (31/110) of sensitivity analyses. On the contrary, the review highlighted that missing data handling methods have evolved over time, with an increasing adoption of multiple imputation since 2017. Overall, the reporting of how missing data is handled in cluster randomized controlled trials has improved in recent years, but there are still a large proportion of cluster randomized controlled trials lack of transparency in reporting missing data, where essential information such as the assumed missing mechanism could not be extracted from the reports.

CONCLUSION: Despite progress in adopting multiple imputation, inconsistent reporting and reliance on simplistic methods (e.g. complete case analysis) undermine cluster randomized controlled trial credibility. Recommendations include stricter adherence to CONSORT guidelines, routine sensitivity analyses for different missing mechanisms and enhanced training in advanced imputation techniques. This review provides updated insights into how missing data are handled in cluster randomized controlled trials and highlight the urgency for methodological transparency to ensure robust evidence generation in clustered trial designs.

PMID:41045255 | DOI:10.1177/17407745251378117

Equine Vet J. 2025 Oct 4. doi: 10.1111/evj.70108. Online ahead of print.

ABSTRACT

BACKGROUND: The healthcare sector contributes significantly to global greenhouse gas (GHG) emissions, with anaesthetic gases being a notable contributor. Implementing sustainable practices in equine anaesthesia, such as low-flow anaesthesia, offers potential benefits.

OBJECTIVES: To audit oxygen and isoflurane usage in five equine hospitals, their associated GHG emissions, and the impact of anaesthesia training on mitigating these emissions.

STUDY DESIGN: Multi-centre clinical audit.

METHODS: This audit covered two periods: study period one (1 June-30 September 2022) and study period two (1 June-30 September 2023). After period one, an anaesthesia training programme introduced low-flow techniques. Data collected retrospectively included patient signalment, anaesthetic protocol, and 5-min recordings of fresh gas flow (FGF) and vapouriser settings. GHG emissions (in carbon dioxide equivalents) and costs (in £) were calculated. Statistical analysis used a linear mixed-effects model with a significance level of p-value <0.05.

RESULTS: A total of 414 general anaesthetics were audited. Between study period one and two, isoflurane and oxygen usage decreased by 9.6% and 17.9%, respectively, resulting in a 9.6% reduction in GHG emissions (from 14.6 to 13.2 tCO₂e). A linear mixed-effects model identified five significant predictors of GHG emissions per case: study period, oxygen usage, anaesthesia duration, average isoflurane vapouriser setting, and the interaction between oxygen usage and study period. Cases in study period two were associated with lower GHG emissions, producing on average 10.4 kgCO₂e less per case (p = 0.01), while each additional litre of oxygen consumed increased emissions by 0.12 kgCO₂e (p < 0.001).

MAIN LIMITATIONS: Missing data from FGF and/or vapouriser settings and the minimal variability between hospitals could be perceived as limitations.

CONCLUSIONS: This audit demonstrates that practising low-flow anaesthesia can effectively reduce the environmental impact of inhalant anaesthetic agents during equine anaesthesia. Wider adoption could improve sustainability, although further research and broader professional engagement are needed.

PMID:41045252 | DOI:10.1111/evj.70108

ESC Heart Fail. 2025 Oct 4. doi: 10.1002/ehf2.15417. Online ahead of print.

ABSTRACT

AIMS: Despite the potential of alginate hydrogel intramyocardial injections in the treatment of heart failure (HF), minimally invasive implantation techniques remain scarce. This study evaluated the safety and feasibility of percutaneous transcatheter endocardial alginate hydrogel injection (TEAi), facilitated by novel implants and a dedicated catheter-based device, in patients with HF with reduced ejection fraction (HFrEF).

METHODS AND RESULTS: This first-in-human study enrolled HFrEF patients [New York Heart Association (NYHA) Class III-IV and left ventricular ejection fraction (LVEF) ≤35%]. The primary endpoint was the incidence of procedure- or device-related serious adverse events (SADEs) at 30 days. Secondary endpoints included the device success rate, HF hospitalization at 6 months, and change from baseline to 6 months post-procedure in the following parameters: LVEF as assessed by MRI; NYHA functional class; 6 min walk test distance (6MWT); the quality of life assessed by the Kansas City Cardiomyopathy Heart Failure Questionnaire (KCCQ); and serum N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) level. Pre- and post-procedural biomechanical analysis was also evaluated. Ten patients successfully underwent TEAi with no SADEs at 30 days. There was one death and two HF hospitalizations at 6 months. At 6 months, LVEF improved from 17.7% ± 3.8% to 24.9% ± 11.2% (P = 0.021), end-systolic volume decreased from 297.5 ± 67.9 mL to 264.8 ± 101.4 mL (P = 0.029), and KCCQ scores increased from 49.7 ± 3.9 to 79.0 ± 8.07 (P = 0.008). No statistically significant changes were observed in end-diastolic volume, NT-proBNP and 6MWT at six months compared with the baseline. Biomechanical analysis revealed a reduction in peak left ventricular end-diastolic wall stress (6.5 ± 1.1 kPa vs. 5.9 ± 1.3 kPa, P = 0.043).

CONCLUSIONS: TEAi is feasible and safe for the treatment of HFrEF, warranting further randomized, efficacy clinical trials.

PMID:41045241 | DOI:10.1002/ehf2.15417

Waste Manag Res. 2025 Oct 4:734242X251374491. doi: 10.1177/0734242X251374491. Online ahead of print.

ABSTRACT

Of the carbon emissions that the National Health Service (NHS) directly produces, waste and water currently make up about 21%, only second to building energy. This study evaluated current knowledge, perception, attitude and behaviour on sustainable healthcare waste management (SHCWM) practices within selected NHS Trusts in Northwest England post-COVID-19 as part of wider research to develop a resilient assessment tool for SHCWM implementation within NHS Trusts in the United Kingdom. The study utilised a questionnaire survey of hospital staff across three NHS Trusts. A total of 58 respondents from clinical and non-clinical roles were analysed. The results showed lack of periodic training, reflected in generally low levels of knowledge on health/environmental risks of healthcare waste management (HCWM), SHCWM practices and legislation on HCWM in the United Kingdom and deficiencies in segregation practice. Statistical tests showed significant differences in attitude among age groups and roles. Those under the age of 35 demonstrated more positive attitude towards SHCWM, whereas clinical support staff demonstrated more positive attitude towards SHCWM compared to doctors and nurses. While the findings demonstrate a lack of periodic training on SHCWM, there appears to be a generally positive perception and attitude towards SHCWM practices. Where SHCWM initiatives are introduced, the findings suggest that staff would be willing to engage and participate. This paper gives those leading sustainability efforts at NHS Trusts a snapshot of current sentiment towards SHCWM and elevates the need to develop minimum mandatory periodic training to improve staff knowledge and practice on SHCWM as part of efforts towards a net zero future.

PMID:41045201 | DOI:10.1177/0734242X251374491