Category: Nevin Manimala

Gastric Cancer. 2025 Oct 4. doi: 10.1007/s10120-025-01660-4. Online ahead of print.

ABSTRACT

BACKGROUND: Several programmed cell death protein-1 inhibitors are approved for the first-line treatment of advanced gastric/gastroesophageal junction cancer, including pembrolizumab, nivolumab and, more recently, tislelizumab. Since direct comparisons between these agents are lacking, advanced statistical modeling can be utilized to evaluate the relative efficacy and safety of tislelizumab compared with other first-line immunotherapy regimens in this indication.

METHODS: A systematic literature review was performed to identify and summarize published randomized controlled trials investigating first-line treatments in adult patients with unresectable, locally advanced, or metastatic human epidermal growth factor receptor 2-negative gastric/gastroesophageal junction cancer. Relevant trials were synthesized using a Bayesian network meta-analysis; fixed-effect models were conducted for all analyses. The network meta-analysis base case used the intent-to-treat populations for tislelizumab + chemotherapy and placebo + chemotherapy from RATIONALE-305.

RESULTS: Key comparators included nivolumab + chemotherapy (ATTRACTION-4, CheckMate 649), and pembrolizumab + chemotherapy (KEYNOTE-062, KEYNOTE-859). Tislelizumab + chemotherapy demonstrated similar efficacy compared with nivolumab + chemotherapy and pembrolizumab + chemotherapy for both overall survival and progression-free survival. Tislelizumab + chemotherapy was associated with significantly lower odds of grade ≥ 3 treatment-related adverse events compared with nivolumab + chemotherapy, and there were no statistically significant differences between tislelizumab + chemotherapy compared with pembrolizumab + chemotherapy.

CONCLUSION: Overall, these analyses suggest that tislelizumab + chemotherapy is similarly efficacious to pembrolizumab + chemotherapy and nivolumab + chemotherapy, and is associated with a similar or lower incidence of grade ≥ 3 treatment-related adverse events in the first-line treatment of gastric/gastroesophageal junction cancer.

PMID:41045401 | DOI:10.1007/s10120-025-01660-4

Genes Genomics. 2025 Oct 4. doi: 10.1007/s13258-025-01688-x. Online ahead of print.

ABSTRACT

BACKGROUND: Predictive models using microbiome data often suffer from covariate imbalance and class imbalance, biasing results. Propensity Score Matching (PSM) balances covariates but reduces sample size, while borderline synthetic minority oversampling technique (borderline-SMOTE) oversamples minority classes but can generate uninformative examples.

OBJECTIVE: To develop and evaluate PSM-SMOTE, a novel hybrid sampling method that integrates PSM and borderline-SMOTE to handle both covariate and class imbalance in microbiome data.

METHODS: We developed PSM-SMOTE, a three-step hybrid sampling algorithm for microbiome data: (1) PSM at four caliper levels to balance covariates, (2) selection of at least ten robust differential markers via seven statistical tests with false discovery rate correction, and (3) application of borderline-SMOTE on the marker-based distance matrix to oversample minority classes. We evaluated PSM-SMOTE on three publicly available microbiome case-control datasets: pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and obesity, using logistic regression (LR), random forest (RF), and support vector machine (SVM) classifiers. Performance was assessed via area under the ROC curve (AUC).

RESULTS: PSM-SMOTE improved test AUCs in multiple model-dataset combinations compared with using PSM alone. Notably, for the RF model, PSM-SMOTE consistently enhanced AUC across nearly all oversampling settings in the PDAC and obesity cohorts. For the SVM model, PSM-SMOTE also achieved a significant AUC increase in the CRC cohort. For the LR model, PSM-SMOTE showed modest improvement under strict matching.

CONCLUSION: PSM-SMOTE effectively addresses dual imbalance in microbiome data and consistently enhances performance, providing a practical solution for imbalanced data analyses.

PMID:41045399 | DOI:10.1007/s13258-025-01688-x

World J Urol. 2025 Oct 4;43(1):596. doi: 10.1007/s00345-025-05979-6.

ABSTRACT

PURPOSE: To validate the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) Best Practice Policy Statement (BPPS) risk factors (RFs) for predicting urinary-tract infection (UTI) after urodynamic study (UDS) and to identify possible RFs that could better guide antibiotic prophylaxis.

METHODS: A retrospective cohort study included all adults undergoing UDS at a single institution. Patients with asymptomatic bacteriuria received a 3-day antibiotic course, while those without bacteriuria received no prophylaxis. The primary endpoint was a culture-confirmed UTI within 7 days. Regression analysis was performed to check SUFU BPPS RFs as predictors for post-UDS UTI.

RESULTS: Among 1666 patients (median age 68 years; 42% female), UTI occurred in 31 (1.9%). Abnormal GU anatomy was found as a predictor for post-UDS UTI (OR = 3.26, p = 0.033). Other examined RFs were not found to predict post-UDS UTI. More concise variables were identified as statistically significant predictors: hydronephrosis (OR = 4.98, p = 0.004), elevated post-void residual (PVR) (OR = 2.80, p = 0.011), and NLUTD due to neurologic disease (OR = 2.27, p = 0.042). In multivariate analysis, elevated PVR and NLUTD caused by neurologic disease remained independent predictors.

CONCLUSION: The current SUFU BPPS criteria exhibit limited accuracy for predicting post-UDS UTI. Our study emphasizes hydronephrosis, NLUTD caused by neurologic disease, and elevated PVR as predictors of post-UDS UTI. Updating prophylactic guidelines to incorporate these findings could enhance patient safety and antimicrobial stewardship without compromising infection control.

PMID:41045391 | DOI:10.1007/s00345-025-05979-6

J Robot Surg. 2025 Oct 4;19(1):661. doi: 10.1007/s11701-025-02820-5.

ABSTRACT

Hysterectomy could be performed through a vaginal approach, laparotomy, or laparoscopy. Robotic surgery is a technique that can be defined as a particular type of laparoscopy, often used in interventions where microsurgery can help improve radicality and effectiveness. In choosing patients for the robotic technique, many characteristics could be studied to tailor the surgical choice. Our aim is to describe the anthropomorphic and radiological parameters linked to worse surgical outcomes for the potential stratification of patients in the preoperative decision about the type of surgery. In our center, the AOU Maggiore della Carità Hospital in Novara (Italy), 104 patients diagnosed with endometrial cancer and candidated for total hysterectomy, with various degrees of radicality, underwent robotic surgery. Patients’ anthropomorphic parameters, such as body mass index, and radiological imaging such as uterine size and pelvis diameter, were compared with the surgical outcomes such as operating times, complications as blood loss, subsequent emergency room visits, and the possible need for laparotomy conversion. Our ratios between pelvic depth and uterine anteroposterior diameter (PD/UAP) and between uterine volume and pelvic volume index (UV/PCI) showed statistically significant correlations with surgical time.

PMID:41045388 | DOI:10.1007/s11701-025-02820-5

Environ Geochem Health. 2025 Oct 4;47(11):476. doi: 10.1007/s10653-025-02771-8.

ABSTRACT

Groundwater is increasingly vital under growing demand and climate pressures, making its effective management essential for sustainable use. A thorough understanding of hydrogeochemical processes is therefore critical to secure water quality and guide resource development. This study develops a conceptual model of a granitic aquifer in Daejeon, Korea, representing a typical weathered-fractured system under mixed urban and green land-use conditions. An integrated approach was applied, combining conventional geochemical analysis, multivariate statistics, geochemical modeling, and strontium isotope tracing. The results highlight silicate weathering as the dominant control on groundwater chemistry, validated by ⁸⁷Sr/⁸⁶Sr ratios (~ 0.716). Mineral-water interactions explain nearly half of the observed variance, mainly through the weathering of silicate minerals to secondary clays, which promote ion exchange processes. Anthropogenic activities, particularly agriculture and land use, account for ~ 15% of the variation, indicating localized contamination risks in the lowland areas. The conceptual model, supported by natural tracers, demonstrates that groundwater evolves from a Ca-HCO₃ type in recharge zones to mixed types, such as Ca(Na)-HCO₃ and Ca-Cl, along downgradient flow paths. This hydrogeochemical evolution reflects the combined effects of progressive mineral weathering and superimposed anthropogenic influences.By capturing both natural processes and human impacts, this study advances the understanding of hydrogeochemical dynamics in granite-based aquifers. The proposed conceptual framework provides a basis for predicting groundwater evolution and emphasizes the urgent need for sustainable management of these vulnerable resources in rapidly urbanizing regions.

PMID:41045384 | DOI:10.1007/s10653-025-02771-8

Support Care Cancer. 2025 Oct 4;33(10):907. doi: 10.1007/s00520-025-09993-7.

ABSTRACT

PURPOSE: The treatment landscape in gastric cancer has changed drastically over the last 15 years with surgical advancements and the introduction of new therapeutic agents and combinations. Despite the potential for improved survival, these new interventions can impact health-related quality of life (HRQoL). Our objective was to identify and synthesize health utility data for gastric cancer patients as part of the Health Utility Book (HUB) project.

METHODS: We searched MEDLINE, EMBASE, EconLit, and CINAHL from inception to March 2023 for original studies that reported health utility data for gastric cancer. Records were screened independently and in duplicate by two reviewers. Data on study design, patient characteristics, and health utilities were extracted using a standardized form. A random effects meta-analysis was conducted to synthesize health utilities by cancer stage. Heterogeneity was evaluated using the I² statistic.

RESULTS: 600 health utilities from 3,405 respondents were identified across 19 studies. All studies were published between 2018 and 2022 and most were conducted in Asia (n = 12, 63.2%). The EQ-5D was the most common method of preference elicitation (n = 17, 89.5%), and health utilities ranged from 0.298 (SD 0.088) to 0.920 (SD 0.130). Mean health utilities from random effects models were 0.82 (95% Confidence Interval [CI] 0.76-0.88), 0.76 (95% CI 0.68-0.85), and 0.67 (95% CI 0.46-0.87) for early stage, advanced stage, and metastatic gastric cancer, respectively.

CONCLUSION: This systematic review provides a reference set of health utilities for gastric cancer, which can help understand HRQoL and facilitate the retrieval and selection of health utilities for economic evaluations.

PMID:41045334 | DOI:10.1007/s00520-025-09993-7

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