Category: Nevin Manimala

Eur Urol. 2025 Dec 31:S0302-2838(25)04877-8. doi: 10.1016/j.eururo.2025.12.022. Online ahead of print.

ABSTRACT

Intravesical bacillus Calmette-Guérin (BCG) therapy remains the cornerstone for high-risk non-muscle-invasive bladder cancer (NMIBC), but up to 40% of patients experience disease recurrence or progression within 2 yr. We conducted a systematic review and meta-analysis of three phase 3 randomized trials POTOMAC, CREST, and ALBAN; n = 2590) in BCG-naïve high-risk NMIBC disease treated with a combination of BCG and an immune checkpoint inhibitor (ICI). Overall risk of bias was low for all studies. Combination therapy with BCG maintenance was associated with better event-free survival (EFS) in comparison to BCG alone (pooled hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.60-0.99; Q = 3.29, p = 0.2). Using the HR for high-grade recurrence from ALBAN, the pooled estimate was directionally consistent, but not statistically significant (HR 0.78, 95% CI 0.58-1.04; Q = 3.94, p = 0.1). Overall survival was comparable between groups (HR 0.92, 95% CI 0.67-1.26). Grade ≥3 treatment-related adverse events were more frequent with combination therapy (risk ratio [RR] 3.66, 95% CI 2.56-5.24 for BCG induction only; RR 3.97, 95% CI 2.54-6.21 for BCG induction + maintenance). There was a moderate decline in patient-reported quality of life in the ICI + BCG maintenance arms. These findings are supported by moderate-certainty evidence for EFS. BCG monotherapy remains the benchmark for BCG-naïve high-risk NMIBC. ICI addition improves EFS but increases high-grade toxicity, which should prompt cautious and individualized adoption pending mature survival data.

PMID:41478774 | DOI:10.1016/j.eururo.2025.12.022

Br J Oral Maxillofac Surg. 2025 Dec 9:S0266-4356(25)00903-9. doi: 10.1016/j.bjoms.2025.11.015. Online ahead of print.

ABSTRACT

This study aims to provide an overview of patient characteristics, treatment modalities, and associated complications following microvascular free flap reconstructions in maxillofacial surgery, based on data from a large national tertiary care centre. Adult patients who received a microvascular free flap between April 2017 and December 2024 were analysed in this descriptive retrospective single-centre study. Follow up was recorded until February 2025. Fibular (FFF), scapular (SFF), deep circumflex artery (DCIA), radial forearm (RFF), anterolateral thigh (ALT) and latissimus dorsi (LDF) free flaps were included. Variables were stratified by flap type and the N-1 χ²-test used to test for statistical significance of complication rates across years. A total of 1373 cases met the inclusion criteria. DCIA flaps suffered the highest rates of early flap loss (8.7%; x¯ = 3.6%) and wound infection (39.1%; x¯ = 13.5%). SFFs had the highest rate of anastomotic revision (25.0%; x¯ = 6.9%) and longest mean (SD) surgery duration: 715 ± 181 min. Donor site complications were most common among RFFs (36.0%) and FFFs (34.5%). Overall, wound infection rates were higher among bony rather than soft tissue flaps (23.0% vs. 7.8%). FFFs were associated with fewer recipient-site complications than SFFs and DCIA flaps, but donor site complications were higher. Among soft tissue flaps, complication rates did not differ significantly. Overall, complications at the recipient site were more frequent among bony compared to soft tissue flaps.

PMID:41478764 | DOI:10.1016/j.bjoms.2025.11.015

Mol Biol (Mosk). 2025 Nov-Dec;59(6):1002-1021. doi: 10.7868/S3034555325060104.

ABSTRACT

The emergence of new data on the association between the composition of the intestinal microbiota and various human diseases has generated increasing interest in microbiome research. In this context, selection of the DNA extraction method represents a critical stage in the design of the experiment, significantly affecting the reliability and reproducibility of results. This study presents a comparative analysis of 12 DNA extraction methods, including nine commercial kits and three laboratory protocols. We evaluated the taxonomic representation, including Gram-positive (Lactobacillaceae, Coprococcus spp., Streptococcus sp., Clostridium leptum) and Gram-negative bacteria (Enterobacteriaceae, Akkermansia muciniphila, Fusobacterium nucleatum, Bacteroides fragilis). The extraction efficiency was assessed by the DNA yield, expressed in GE/pL of eluate or in GE/-µL of feces, as well as by the frequency of low-abundance taxa loss. Clustering of the methods according to the type of lysis was demonstrated: mechanical lysis provided stable and high DNA yields, particularly for Gram-positive bacteria, while chemical and enzymatic methods showed lower efficiency. We determined that the lysis type and pre-processing of intact fecal samples are the key factors affecting the DNA extraction efficiency and preservation of the native taxonomic profile. The best results were demonstrated by the QIAamp® PowerFecal® Pro DNA Kit (Qiagen) and the combination of AmpliTest UniProb + AmpliTest RIBO-prep kits (Center for Strategic Planning, Federal Medical-Biological Agency, Russia), both of which outperformed other methods in terms of DNA yield. The QIAamp® Fast DNA Stool Mini Kit (Qiagen) showed minimal losses of low-abundance taxa. These findings can be used for the standardization of gut microbiota DNA extraction methodologies and the development of domestic protocols.

PMID:41477720 | DOI:10.7868/S3034555325060104

Mol Biol (Mosk). 2025 Nov-Dec;59(6):979-987. doi: 10.7868/S3034555325060086.

ABSTRACT

Ovarian cancer remains one of the most lethal malignancies with a five-year survival rate around 20% at III-IV stages, which determines the urgent need to develop new therapeutic approaches. Newcastle disease virus (NDV) has demonstrated considerable promise as an oncolytic agent, capable of selectively lysing tumor cells, suppressing the metastatic potential and stimulating anti-tumor immunity. Despite the established therapeutic potential, studies that investigate oncolytic properties of this virus within the context of ovarian cancer remain limited. In this work, we evaluated oncolytic activity of the NDV vaccine strain H in SC-OV-3, TOV-21G and OV-90 ovarian cancer cell lines. Such parameters as ability to support viral replication and cell viability after infection were investigated. As a result, all three lines were permissive to NDV-H infection. Therapeutic efficacy in vivo was assessed using a model of TOV-21G subcutaneous xenografts in BALB/c nude mice. Upon intravenous administration of the virus, a statistically significant reduction in tumor volume was observed compared to the control group. Based on these results, NDV-H strain can be considered as a potential oncolytic agent for the treatment of ovarian cancer.

PMID:41477718 | DOI:10.7868/S3034555325060086

Mol Biol (Mosk). 2025 Nov-Dec;59(6):971-978. doi: 10.7868/S3034555325060076.

ABSTRACT

Although the role of NADPH oxidase 2 (NOX2) in the development of Alzheimer’s disease (AD) is widely recognized, its contribution to the initial stages of amyloid-induced pathology remains unclear. Intraventricular administration of β-amyloid (Aβ) causes acute amyloid toxicity, leading to neurodegenerative changes similar to AD. The acute phase, lasting several days, is a critical time window for studying early pathological mechanisms. In this work, we assessed the level of oxidative stress in the brain of BALB/c mice at the early stages of amyloid toxicity and the role of NOX2 in these processes. Analysis of key markers of oxidative stress in various fractions of brain homogenate on day 4 after Aβ administration showed that individual parameters demonstrated only a tendency to change, without reaching statistical significance. However, principal component analysis (PCA) revealed a clear separation between the Aβ-treated and control groups, indicating the need for a comprehensive rather than isolated analysis of biochemical changes at early stages of pathology. It is noteworthy that the centroids of the groups in PCA were located along the same straight line, and the group receiving Aβ together with the NOX2 inhibitor occupied an intermediate position between the control and Aβ groups. This indicates partial suppression of oxidative stress through NOX2. At the same time, the NOX2 inhibitor completely prevented Aβ-induced microgliosis in the hippocampus, confirming that the concentration used was sufficient to suppress NOX2-dependent microglial activation. The in vivo data demonstrate that oxidative stress induced by Aβ administration may not be entirely mediated by NOX2, although this mechanism plays an important role in the initiation of the pathological process in AD.

PMID:41477717 | DOI:10.7868/S3034555325060076

Mol Biol (Mosk). 2025 Nov-Dec;59(6):928-937. doi: 10.7868/S3034555325060041.

ABSTRACT

Sertraline, a selective serotonin reuptake inhibitor, is widely used as a first-line drug for anxiety and depressive disorders. The clinical efficacy and adverse reactions observed with antidepressants are closely related to the concentration of this drug in the patient’s blood, but the vast majority of antidepressants demonstrate significant pharmacokinetic variability, leading to pronounced interindividual differences in the steady-state concentration of the drug in the blood and its efficacy even with the same dosing regimen. In this regard, it has become obvious that genetic markers alone are not enough to obtain the most complete profile of the efficacy and safety of a drug; a combination of genotyping methods with omics biomarkers is necessary. As a result of examination of patients, residents of the Republic of Bashkortostan, that had been diagnosed with mixed anxiety-depressive disorder (F41.2), it was found that polymorphic variants rs16947 (CYP2D6*2), rs389209 (CYP2D6*4), and rs1065852 (CYP2D6*10) of the CYP2D6 gene do not have a significant effect on the activity of CYP2D6. Genetically determined variations in the activity of the CYP2D6 isoenzyme lead to differences in the metabolism of sertraline and its active metabolite N-desmethylsertraline in different patients, which causes variability in their concentrations in the blood plasma. A statistically significant increase in the plasma concentrations of sertraline and N-desmethylsertraline was found in patients carrying the slow allelic variants rs3892097, rs1065852, and rs16947 of the CYP2D6 gene. A statistically significant moderate inverse correlation was found between the dose and the metabolic ratio C6-HO-THBC/CP. The results obtained are preliminary, which makes it necessary to continue this study with an expanded sample size.

PMID:41477714 | DOI:10.7868/S3034555325060041

Disabil Rehabil. 2026 Jan 1:1-23. doi: 10.1080/09638288.2025.2605172. Online ahead of print.

ABSTRACT

PURPOSE: This pilot aimed to (1) assess the feasibility of “Smooth Sailing After Scams (SSAS)”, a novel 10-session cyberscam psychosocial group intervention, (2) explore the sensitivity of outcome measures in detecting intervention response in people with ABI.

MATERIALS AND METHODS: Of 23 screened adults with ABI, 10 were enrolled (M_age = 59.5, SD = 13.0). A concurrent multiple-baselines single-case design with randomised baseline lengths (2, 4 or 6 weeks) and 2-month follow-up was conducted. SSAS addressed cybersafety, finances, emotions, relationships and lifestyle. Groups were delivered online (n = 2) and in-person (n = 2). Feasibility outcomes included recruitment, retention, attendance, satisfaction, adverse events, fidelity. Scam-related distress and coping were assessed thrice weekly (baseline), and weekly (intervention/follow-up). Secondary outcomes included cyberscam adjustment/engagement, cybersafety, mood, financial strategies, relationships, goal achievement. Data were analysed visually and statistically.

RESULTS: Eight participants completed SSAS, with no cancellations or adverse events; two remained on waitlist. Recruitment was lower than expected, but other feasibility indicators were strong. All avoided further scams and demonstrated meaningful progress in cyberscam adjustment between baseline and 2-month follow-up. Moderate effects were observed for reduced distress (4/8) and improved coping (3/8), maintained at follow-up.

CONCLUSIONS: SSAS was largely feasible and promising for supporting cyberscam adjustment. Findings will inform a future randomised-controlled trial.

PMID:41477699 | DOI:10.1080/09638288.2025.2605172

JMIR Med Educ. 2025 Dec 31. doi: 10.2196/77702. Online ahead of print.

ABSTRACT

BACKGROUND: Ultrasound is very important in medicine and teaching, but there are not many formal training programs. We also don’t know much about what students think. To be good at using ultrasound, you need to learn technical, thinking, and seeing skills. This is especially true in regional anesthesia (RA), where mistakes in reading images can cause problems. Training with simulations is a safe and good way to learn these skills. Some models are helpful for teaching how to do procedures with ultrasound.

OBJECTIVE: This study aimed to evaluate the effectiveness, localization time, and success rate of traditional versus a new simulation-based teaching method for regional anaesthesia designed by the investigators in undergraduate medical students.

METHODS: A prospective, randomized controlled trial was conducted at the University of Salamanca from April 2022 to January 2023. Thirty-four medical students in their 4th to 6th academic years were randomly allocated to either a simulation-based training group utilizing the Haptic US Probe (HUSP) or a traditional teaching group. The simulation approach employed a realistic probe replica and a software-based ultrasound environment, while the traditional method comprised a theoretical lecture and curated audiovisual materials. Two days post-training, participants underwent a blinded assessment requiring the identification of peripheral nerve plexuses using an ultrasound device. The primary outcome measured was the successful identification of nerves, and the secondary outcome was the time taken to complete each procedure. Data were analyzed using an intention-to-treat approach.

RESULTS: A total of 34 medical students (4th to 6th year) were recruited to compare traditional teaching with simulation-based training in ultrasound-guided nerve localization. No statistically significant differences were found in the success rates between the groups. For the interscalene approach, the traditional group achieved a 100% success rate compared to 82.3% in the simulation group (p=0.07). The time to task completion was similar across most procedures. In the sciatic nerve division, the traditional group was significantly faster, with a mean time of 74.67 s (p = 0.02). The regression models showed no significant interaction between the intervention type and academic year. Both teaching methods had positive educational impacts.

CONCLUSIONS: Simulation-based learning effectively supports competency acquisition in regional anaesthesia and offers a safe, scalable alternative to traditional methods. Its integration into medical curricula may standardize training, improve skill consistency, and enhance patient safety. Further multicentre studies with larger, diverse cohorts are needed to validate these benefits and guide implementation in medical education.

PMID:41477696 | DOI:10.2196/77702

Int J Pediatr. 2025 Dec 12;2025:1501028. doi: 10.1155/ijpe/1501028. eCollection 2025.

ABSTRACT

BACKGROUND/OBJECTIVE: Delayed umbilical cord clamping (DCC) for 30-60 s after birth is recommended for both term and preterm infants. The additional neonatal blood volume rich in stem cells and immunoglobulins may protect the neonate from infections. We aim to compare the effect of DCC in term newborns on hyperbilirubinemia and respiratory infection-related pediatric emergency department (PED) encounters and hospitalizations within the first 6 months of life.

METHODS: We conducted a chart review of term infants born between January 1, 2022 and December 31, 2022 and grouped them as either having DCC or not having delayed umbilical cord clamping (nDCC) for 30-60 s after birth. Maternal and newborn characteristics, hyperbilirubinemia, respiratory infection-related PED encounters, hospitalizations, and length of stay in the initial 6 months after birth were compared. Data were analyzed using R software, a p value of < 0.05 was considered statistically significant.

RESULTS: Of the 2136 charts reviewed, 659 (31%) were in the DCC group. There were significantly fewer respiratory infection-related PED encounters (p < 0.001), fewer hospitalizations (p = 0.04), and a 5% lower incidence of hyperbilirubinemia in the DCC group (95% CI: 0.86%-8.6%; p = 0.02). The length of stay of each hospitalization was not significantly different between the two groups, p = 0.07.

CONCLUSIONS: We observed fewer respiratory infection-related PED encounters and hospitalizations in the initial 6 months of life and a lower incidence of hyperbilirubinemia among the infants who had DCC. The increased blood volume and its components appear to be supportive of the neonate’s developing immune system as seen in the lower disease burden up to 6 months of age.

PMID:41477680 | PMC:PMC12752858 | DOI:10.1155/ijpe/1501028

J Nurs Manag. 2025 Dec 29;2025:3338222. doi: 10.1155/jonm/3338222. eCollection 2025.

ABSTRACT

INTRODUCTION: Nursing home staff turnover remains a concern in long-term care facilities, with implications for job performance, organisational morale and patient outcomes. This study explored the factors influencing intention to leave among nursing home care staff in Singapore and focused on the influence of demographic variables, work environment and job satisfaction.

METHODS: A cross-sectional survey was employed to collect data from 167 care staff working at two nursing homes in Singapore. Instruments included the Practice Environment Scale of the Nursing Work Index (PES-NWI), Job Satisfaction Survey (JSS) and Intention to Leave Scale (ILS). Data were analysed using descriptive and inferential statistics, including hierarchical multiple regression, to examine relationships between demographic characteristics, work environment, job satisfaction and intention to leave.

RESULTS: The study found a moderate overall intention to leave (mean ILS = 9.18, SD = 2.494). Female staff, mid-career professionals (aged 30-39) and nursing aides exhibited the highest turnover intentions. Job satisfaction, particularly in terms of managerial support and staffing adequacy, emerged as a significant predictor of intention to leave. Work environment factors, especially staffing and resource adequacy, are crucial in turnover intentions.

DISCUSSION: This study highlights key factors driving turnover intentions among nursing home care staff in Singapore. Interventions to mitigate turnover and improve staff retention are recommended to improve staffing levels, managerial support and career development pathways.

PMID:41477676 | PMC:PMC12748931 | DOI:10.1155/jonm/3338222