Category: Nevin Manimala

Eur J Surg Oncol. 2026 Mar 3;52(4):111511. doi: 10.1016/j.ejso.2026.111511. Online ahead of print.

ABSTRACT

BACKGROUND: As the liver is the most common site of metastasis in colorectal cancer (CRC), and metastatic recurrence frequently occurs after resection of colorectal liver metastases (CRLM), hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment approach. This study investigates the feasibility, safety, and efficacy of postoperative HAIC with oxaliplatin following curative-intent resection of CRLM.

METHODS: A retrospective analysis was conducted on all patients with resected CRLM who received postoperative HAIC with oxaliplatin between 2008 and 2022 at a tertiary cancer center. The primary study endpoint were disease-free-survival (DFS) and overall survival (OS).

RESULTS: Overall, 119 patients (median age, 56 years; synchronous metastatic disease, 82%) received postoperative HAIC with oxaliplatin after complete resection of their CRLM (median number of metastases resected, 7). They received a median number of 6 HAIC cycles (range, 1-12), mostly combined with intravenous chemotherapy with 5-fluorouracil/leucovorin (n = 118, 99%) and irinotecan (n = 41, 34%). The median DFS was 10.2 months (95% CI 9-12.4) and the median intrahepatic DFS was 18.4 months (95% CI 12.4-29.7,12 months DFS rate, 60%). The median OS reached 55.5 months (95% CI, 50.0-86.6; 5-year OS rate, 46%). Grade 3-4 toxicities occurred in 45% of patients (neutropenia, 38%; peripheral neuropathy, 9%); 54% of patients experienced pain (mostly mild to moderate) during oxaliplatin infusion. HAI catheter-related complications included extrahepatic perfusion (30%) and catheter occlusion (11%).

CONCLUSIONS: HAIC with oxaliplatin is an effective, safe and feasible treatment option after resection/ablation of CRLM. These findings support the therapeutic relevance of postoperative HAIC in liver-limited metastatic CRC.

PMID:41795432 | DOI:10.1016/j.ejso.2026.111511

Eur J Surg Oncol. 2026 Feb 4;52(4):111425. doi: 10.1016/j.ejso.2026.111425. Online ahead of print.

ABSTRACT

BACKGROUND: HPV-negative cervical cancer (3-8% of cases) presents distinct clinical challenges and poorer prognosis compared to HPV-positive disease. We aimed to conduct an exploratory study to characterize its unique tumor immune microenvironment (TIME) and molecular drivers to inform immunotherapy development.

METHODS: We analyzed 70 cervical cancer patients (50 HPV-positive/HPV-A, 20 HPV-negative/HPV-I) using targeted next-generation sequencing and multiplex immunofluorescence. Clinical features, mutational profiles, immune cell infiltrates, and prognostic factors were compared between groups. Strict FDR correction and effect size analysis (Cliff’s Delta) were applied to statistical comparisons.

RESULTS: HPV-I tumors showed significant association with gastric-type adenocarcinoma (p < 0.001) and higher CA125 levels (p = 0.011). Molecularly, HPV-I tumors were substantially enriched for TP53 mutations (46.2% vs 2.2%, OR = 0.030, p < 0.001), while PIK3CA mutations predominated in HPV-A tumors (41.3% vs 7.7%, OR = 7.78, p = 0.047), suggesting notable mutual exclusivity. Immunologically, HPV-A tumors showed substantially higher stromal M2 macrophage density (Cliff’s Delta = -0.51, Large Effect), while HPV-I tumors displayed significantly higher stromal immune cell ratios: M1/M2 (5.34 vs 0.87, p = 0.003), CD8+/M2 (13.65 vs 2.66, p = 0.004), and NK/M2 (8.43 vs 0.59, p = 0.012), revealing the paradox of favorable immune balance coexisting with immune exclusion. In HPV-I subgroup analysis, high CD8+/M2 ratio was associated with superior progression-free survival (16.7% vs 71.4% event rates, p = 0.014).

CONCLUSIONS: HPV-negative and HPV-positive cervical cancers represent distinct entities with unique molecular and immunological profiles. Our exploratory findings suggest that HPV-I tumors exhibit the paradox of favorable stromal immune cell ratios coexisting with immune-excluded phenotype, while HPV-A tumors show higher M2 macrophage infiltration. The prognostic significance of CD8+/M2 ratio in HPV-I patients may provide a valuable biomarker and suggest specific therapeutic strategies targeting immune exclusion and macrophage polarization based on HPV status.

PMID:41795431 | DOI:10.1016/j.ejso.2026.111425

Soc Sci Med. 2026 Mar 4;397:119150. doi: 10.1016/j.socscimed.2026.119150. Online ahead of print.

ABSTRACT

Intersectionality offers a critical framework for understanding how multiple axes of social identity shape health outcomes. Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) has emerged as a popular method for operationalizing intersectionality in social epidemiology. By structuring individuals into intersecting social categories (strata), and modeling both within- and between-stratum variation, MAIHDA offers a way to quantify stratum-level heterogeneity while mitigating issues of sparse data through partial pooling. In this paper, we argue that the statistical structure of MAIHDA, and its subsequent interpretation, carries epistemic commitments that are rarely made explicit. First, shrinkage in MAIHDA induces an implicit reweighting of intersectional strata toward a population of equally sized groups. As a result, estimated between-stratum variation reflects a hypothetical target population rather than the empirical population distribution, raising questions about the interpretation of stratum-level effects. Second, we argue that the variance partition coefficient and proportional change in variance are the most informative metrics specifically with regards to intersectionality, and careful interpretation of these is required. In addition, observed heterogeneity is underdetermined by any single social theory, meaning that MAIHDA findings may be consistent with multiple explanatory frameworks beyond identity-based mechanisms, such as intersectionality. We conclude that MAIHDA is best understood as a descriptive tool that identifies stratified heterogeneity. This may provide empirical guidance for when intersectional explanations are relevant, but should remain open to alternative theoretical interpretations. This perspective encourages careful epistemic reflection on the assumptions and inferences made when applying MAIHDA to intersectionality-motivated research questions.

PMID:41795407 | DOI:10.1016/j.socscimed.2026.119150

Maturitas. 2026 Mar 4;208:108900. doi: 10.1016/j.maturitas.2026.108900. Online ahead of print.

ABSTRACT

BACKGROUND: Population aging has intensified interest in identifying physiological determinants of biological age beyond chronological age. Muscle loss and bone deterioration are key features of age-related decline, yet their individual, joint, and sex-specific contributions to biological age acceleration remain insufficiently characterized in Asian populations.

METHODS: A total of 29,437 adults aged 20-80 years from the China National Health Survey conducted in 2023-2024 were included. Appendicular skeletal muscle mass was assessed by bioelectrical impedance analysis, handgrip strength by dynamometer, and bone mineral density by quantitative ultrasound. Biological age acceleration was estimated using the Klemera-Doubal method based on sex-specific biomarker panels. Logistic regression models evaluated associations of low muscle mass, low muscle strength, and sarcopenia with elevated biological age acceleration. Additive and multiplicative interactions between muscle indicators and bone mineral density were examined. Population-attributable fractions were calculated to quantify the contributions of muscle- and bone-related deficits.

RESULTS: Lower muscle mass and lower muscle strength were strongly and inversely associated with biological age acceleration in both sexes (all P < 0.0001). Individuals with low muscle mass, low muscle strength, or sarcopenia had approximately 30% to 80% higher odds of accelerated aging. Bone mineral density showed modest and sex-dependent associations, with a weak inverse relationship observed in men but no clear association in women. Joint effects of low bone mineral density and muscle deficits were observed in men and in postmenopausal women with osteoporosis defined as a T-score below -2.5. Population-attributable fraction analysis indicated that muscle-related deficits contributed substantially more to the risk of accelerated aging than low bone mineral density.

CONCLUSIONS: Muscle-related indicators are strongly associated with biological age acceleration, whereas the influence of bone mineral density is weaker. Clear combined effects were observed in men and in postmenopausal women with osteoporosis. Muscle-related deficits accounted for a substantially greater proportion of the risk of accelerated aging than low bone mineral density in both sexes.

PMID:41795347 | DOI:10.1016/j.maturitas.2026.108900

J Mech Behav Biomed Mater. 2026 Feb 28;178:107385. doi: 10.1016/j.jmbbm.2026.107385. Online ahead of print.

ABSTRACT

PLGA/HA is a promising material for 3D printed bioresorbable bone scaffolds, but the effects of fused filament fabrication parameters on monotonic and cyclic mechanical performance of resulting structures are unknown. Furthermore, the evolution of mechanical properties and dimensional stability under prolonged exposure to temperature and cell culture immersion conditions is also poorly investigated. This study first applied a Taguchi L9 orthogonal array to evaluate the effects of layer height, nozzle temperature, print speed, and cooling fan speed on the flexural properties of 90:10 wt% PLGA/HA scaffolds. Statistical analysis revealed that flexural strength, modulus, and deflection at failure were significantly influenced by specific printing parameters, while energy absorption showed no significant dependence (p > 0.05). At 50% print porosity, flexural strength and modulus increased by 20% and 50%, respectively, under the optimal settings (0.12 mm layer height and 205 °C nozzle temperature), reaching 45.0 MPa and 1807.80 MPa. Differential scanning calorimetry revealed significant effects on second-cycle glass transition (p = 0.0029), first-cycle cold crystallization (p = 0.0086), second-cycle cold crystallization (p = 0.0177), and first-cycle crystallinity (p = 0.0177), with favorable transitions aligning with mechanical maxima. Fatigue samples were printed using parameters that provided maximum flexural strength, and tests in PBS at 37 °C showed an endurance limit of 1.2 MPa at 10⁶ cycles. In-vitro degradation over 60 days caused swelling of the scaffold by more than 20%, while the strength and the modulus decreased by 76% and 65% respectively, still above lower levels for trabecular bone. Consequently, optimization of 3D print parameters resulted in attaining improved mechanical properties of PLGA/HA, making scaffolds printed under these conditions viable for partial load bearing bone tissue regeneration applications.

PMID:41795333 | DOI:10.1016/j.jmbbm.2026.107385

Transplant Rev (Orlando). 2026 Mar 3;40(3):101008. doi: 10.1016/j.trre.2026.101008. Online ahead of print.

ABSTRACT

BACKGROUND: Graft rejection following liver transplantation remains a major complication affecting long-term survival. Current monitoring strategies, which rely on liver function tests and invasive biopsies, have inherent limitations, creating a need for non-invasive biomarkers. Donor-derived cell-free DNA (dd-cfDNA) has shown promise for monitoring rejection in solid organ transplantation, but its diagnostic accuracy in liver transplantation requires systematic evaluation.

OBJECTIVE: To comprehensively assess the diagnostic accuracy of dd-cfDNA for rejection after liver transplantation via a systematic review and meta-analysis.

METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library for studies published up to November 26, 2025. Studies were selected based on predefined inclusion and exclusion criteria. Data were extracted, and study quality was assessed. Pooled sensitivity, specificity, and other diagnostic measures were calculated. A summary receiver operating characteristic curve (SROC) was constructed, and heterogeneity along with subgroup analyses were performed.

RESULTS: Eleven studies were included. The meta-analysis demonstrated that dd-cfDNA achieved a pooled sensitivity of 0.90 (95% CI 0.76-0.96) and a pooled specificity of 0.90 (95% CI 0.82-0.94) for diagnosing acute rejection, with an area under the SROC curve of 0.95.

CONCLUSIONS: Dd-cfDNA demonstrates promising diagnostic value as a complementary noninvasive biomarker for rejection after liver transplantation. However, significant heterogeneity in diagnostic thresholds exists across studies. Large-scale, multicenter studies are required in the future to validate its clinical utility.

PMID:41795313 | DOI:10.1016/j.trre.2026.101008

J Pediatr Nurs. 2026 Mar 6;88:327-336. doi: 10.1016/j.pedn.2026.02.037. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to develop and evaluate the feasibility of a theory-driven, web-based discharge education program designed to enhance self-management among caregivers of children with epilepsy.

METHODS: Following the Analyze, Design, Develop, Implement, and Evaluate (ADDIE) model, educational needs were assessed through an integrative literature review and focus group interviews with caregivers and pediatric nurses. The program was structured using the Include, Discuss, Educate, Assess, and Listen (IDEAL) discharge planning framework, and individual and family self-management theory.

RESULTS: The key features included self-assessment tools, pre-discharge questions, multimedia materials, health diaries, and Q&A boards. Content validity was reviewed by experts, usability tested with caregivers and professionals, and clinical feasibility examined using a one-group pretest-posttest design involving 13 caregivers. Participants reported high satisfaction with the clarity and accessibility of the content, with strongest engagement in the self-assessment and pre-discharge sections. Although changes in discharge readiness and self-management scores were not statistically significant, moderate-to-large effect sizes suggested an increasing trend in practical improvement. Caregivers also reported improved confidence, medications awareness, and follow-up adherence. Feedback supported mobile-based delivery and highlighted the need for interactive and personalized features.

CONCLUSIONS: The program is a feasible and accepted intervention that incorporates self-assessment into discharge education and leverages web-based delivery to support family centered care.

PRACTICE IMPLICATIONS: The program addresses existing gaps in pediatric epilepsy education and shows potential for broader implementation. Integrating self-assessment and digital platforms into discharge education may enhance caregivers’ preparedness and support sustainable self-management.

PMID:41795271 | DOI:10.1016/j.pedn.2026.02.037

Environ Toxicol. 2026 Mar 7. doi: 10.1002/tox.70074. Online ahead of print.

ABSTRACT

Anthropogenic activities generate a significant amount of pollutants that are released into the environment, causing physiological and ecological disturbances. Among the xenobiotics present in aquatic ecosystems, numerous chemical and organic compounds have oxidative potential or are metabolized through oxidative processes, which may amplify the damage caused by reactive oxygen species to biological systems. The quantification of cellular damage and antioxidant defenses can be used as biomarkers for early aquatic contamination. The aim of this research was to use the shrimp Macrobrachium amazonicum as a bioindicator species to assess oxidative damage caused by xenobiotics in an Environmental Protection Area in the Brazilian Amazon. The analyses evaluated physicochemical parameters, Iron, Copper, Total Solids, pH, and Temperature, as well as non-enzymatic and enzymatic oxidative stress biomarkers: Thiobarbituric Acid Reactive Substances, glutathione (GSH), and catalase (CAT) in hepatopancreas homogenates. Among the analyzed metals, only copper (Cu) showed a statistically significant influence on GSH and CAT activities, whereas the other parameters did not exhibit significant effects. Oxidative stress parameters can be important tools in biomonitoring work, helping to understand the effects of contamination on aquatic organisms and providing important information on cellular defense modulations.

PMID:41795211 | DOI:10.1002/tox.70074

Clin Exp Allergy. 2026 Mar 7. doi: 10.1111/cea.70272. Online ahead of print.

ABSTRACT

BACKGROUND: Allergy is the most common and earliest onset non-communicable disease in children. The early identification of children who are at risk of allergy would allow early intervention to prevent the onset of the disease or reduce its impact. The origins of allergy are hypothesized to be derived from early developmental events which include prenatal events and early childhood exposures. We have previously identified that many placental glucocorticoid-regulated genes were also associated with child allergy.

OBJECTIVE: We have questioned if it is possible to predict which children are at risk of allergy based on their placental glucocorticoid-regulated mRNA profile.

METHODS: Placentae from two different populations located in South Australia (n = 105) and Victoria, Australia (n = 261) were included in the study. Glucocorticoid regulated genes were measured by qPCR. Statistical modelling was executed in R (version 4.4.1).

RESULTS: Evaluation of the importance of each gene in the model identified AFF1, ARID5B, IER3, ATF4 and SLC19A2 as the top five ranking genes. The best-performing random forest model achieved an AUC of 0.664, indicating moderate ability to distinguish between positive and negative allergic susceptibility. While our models demonstrate both measurable specificity and sensitivity, the glucocorticoid genes particularly excel at identifying children who will not develop an allergy.

CONCLUSION: This study demonstrates that placental glucocorticoid-regulated genes possess significant predictive power, especially in identifying individuals unlikely to develop allergies. It offers further evidence that the placentae of nonallergic children and allergic children are transcriptionally distinct.

PMID:41795204 | DOI:10.1111/cea.70272

Aust J Rural Health. 2026 Apr;34(2):e70158. doi: 10.1111/ajr.70158.

ABSTRACT

OBJECTIVE: Australians living in rural areas have a higher prevalence of dental caries and higher potentially preventable hospital admissions for oral health conditions compared to metropolitan-dwelling Australians. Despite high burdens of dental disease and a lack of systems supporting oral health, including water fluoridation and access to dental services, rural Australians have been given limited opportunities to participate in oral health research, resulting in gaps in our understanding. The objective of this study was to explore rural health consumer experiences of using and accessing oral health care services.

DESIGN: Cross-sectional online survey.

SETTING: Rural and remote Australia (MM2-MM7).

PARTICIPANTS: Members of the Rural Health Consumer Panel aged over 18 years.

RESULTS: One hundred and thirty-nine Rural Health Consumer Panel members responded to the survey. Key sociodemographic characteristics included a median age of 61 years, predominantly female (74.5%) and highly educated (73% holding tertiary qualifications). The majority of those visiting an oral health professional in the past 12 months reported visiting a dentist (47.5%). Over a third (38%) of respondents did not visit any oral health professional in the past 12 months. Private health insurance coverage was associated with more regular dental and oral health check-ups. Key challenges in accessing oral health care included cost, wait times for an appointment, and distance travelled to receive care.

CONCLUSION: Rural people in this study face barriers in accessing oral health care, contributing to low rates of preventative dental and oral health visits. The difficulty in accessing oral health services and lower rates of private health insurance in rural areas further exacerbate these inequities. Further research is required to gain a deeper understanding of the experiences of rural people in relation to accessing oral health services and involving rural people in developing place-based solutions across communities.

PMID:41795184 | DOI:10.1111/ajr.70158