Tag: nevin manimala

Otolaryngol Head Neck Surg. 2026 Mar 10. doi: 10.1002/ohn.70159. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the completeness, consistency, and transparency of adverse event (AE) reporting in clinical trials of inflammatory sinonasal diseases by comparing data from ClinicalTrials.gov and corresponding peer-reviewed publications.

DATA SOURCES: ClinicalTrials.gov registry and MEDLINE-indexed journal articles reporting results of interventional trials focused on inflammatory sinonasal disease.

REVIEW METHODS: We identified trials with posted results between 2014 and 2024 and matched registry records with corresponding publications. Data extraction included structured and narrative AE fields. Outcomes assessed were serious adverse events (SAEs), other adverse events (OAEs), mortality, and AE-related discontinuations. Reporting concordance was analyzed using descriptive statistics, Bland-Altman plots, funnel plots, and linear regression to evaluate temporal trends and reporting predictors. Only direct numerical matches were accepted; we made no inferences from narrative text.

RESULTS: Among 108 included trials, 57 (52.8%) met criteria for likely applicable clinical trials (ACTs). AE reporting was more complete on ClinicalTrials.gov than in publications. For example, 94.7% of ACTs reported SAEs in the registry compared to 80.7% in corresponding publications, and death reporting increased from 38% to 100% in registry data following the 2017 Final Rule. However, publication reporting did not show corresponding improvement. Funnel plots revealed dispersion in AE rates among smaller trials, while linear regression showed modest gains in registry reporting over time.

CONCLUSION: Despite regulatory improvements, publication-based AE reporting remains incomplete and inconsistent. Clinical trial registries remain an essential, yet underutilized, resource for harm-related evidence in sinonasal disease research.

PMID:41806298 | DOI:10.1002/ohn.70159

Environ Sci Pollut Res Int. 2026 Mar 10. doi: 10.1007/s11356-026-37607-0. Online ahead of print.

ABSTRACT

Globally, land use land cover (LULC) changes are recognized as a key factor contributing to environmental changes. Understanding the LULC changes in river basin areas is essential for river basin management. The present study aims to analyze LULC changes from 1994 to 2024 in the lower part of the Mahananda River basin and predict future LULC scenarios for 2034. The study cast off Landsat imagery and random forest (RF) classification technique for past LULC classification, while the Cellular Automata Markov Chain (CA-MA) model was employed for future LULC prediction. Furthermore, a statistical technique, Receiver Operating Characteristics (ROC), was utilized for CA-MC model validation. Results highlight a substantial reduction of vegetation cover of 2249.7 km² and barren land by 1774.08 km², while cultivated lands, settlement, and water body increased by 3389.75 km², 831.81 km², and 440.8 km², respectively, over the last three decades, revealing the influences of both natural disturbance and anthropogenic activities. The LULC classification’s accuracy was assessed using Kappa coefficient and these values are above 80%, indicating that the LULC classifications in this study are highly reliable. The prediction results reveal a further decrease of vegetation cover at 503.53 km², a continuous increase of cultivation land at 4725.29 km², and a settlement area of 919.85 km² over the future decades. The ROC value of 0.71 suggests that the CA-MC model performs reliably in predicting future LULC scenarios, demonstrating acceptable model accuracy. These comprehensive assessments aid in the creation of suitable land management plans and policies to accomplish or uphold sustainable development in the Mahananda River basin.

PMID:41806296 | DOI:10.1007/s11356-026-37607-0

Transfus Med. 2026 Mar 10. doi: 10.1111/tme.70070. Online ahead of print.

ABSTRACT

BACKGROUND: Perioperative patient blood management (PBM) is a crucial, multidisciplinary, evidence-based approach aimed at optimising patient outcomes by reducing unnecessary erythrocyte transfusions. This study assessed the knowledge and attitudes of healthcare professionals in two key surgical specialties toward PBM.

METHODS: This cross-sectional questionnaire-based survey involved personnel from the Department of Anaesthesiology and the Department of Orthopaedic Surgery at a university hospital. The questionnaire assessed knowledge (scored out of 100) and attitudes (specifically self-reported adherence, scored out of 100). The correct responses were based on the PBM guidelines and institutional protocols. Multivariable logistic regression was used to identify predictors of adherence.

RESULTS: The overall response rate was 86.2% (n = 250) from 163 Anaesthesiology and 87 Orthopaedic Surgery. The Orthopaedic Surgery group scored significantly lower on knowledge assessments than the Anaesthesiology group (median score 48 vs. 58, p < 0.001). However, the attitude scores were statistically similar (median score 77 vs. 76, p = 0.237), revealing a knowledge-attitude paradox. Multivariable logistic regression identified hierarchical position as the only significant independent predictor: staff physicians were 7.1 times more likely to report adherence compared to residents (adjusted odds ratios 7.1, 95% confidence interval 3.1-16.2, p < 0.001). Individual knowledge level was not a significant predictor.

CONCLUSIONS: Our study demonstrates that hierarchical mandate, not individual knowledge or department affiliation, is the primary driver of PBM adherence. Implementation efforts must therefore leverage staff physician leadership to mandate PBM as the institutional standard of care, ensuring that positive attitudes translate into consistent practice.

PMID:41806290 | DOI:10.1111/tme.70070

J Comput Neurosci. 2026 Mar 10. doi: 10.1007/s10827-026-00924-x. Online ahead of print.

NO ABSTRACT

PMID:41806289 | DOI:10.1007/s10827-026-00924-x

Am J Clin Dermatol. 2026 Mar 10. doi: 10.1007/s40257-026-01013-6. Online ahead of print.

ABSTRACT

BACKGROUND: Involvement of the head-and-neck area in atopic dermatitis (AD) is common, associated with reduced quality of life, and suggested as an independent criterion for moderate-to-severe AD. The effectiveness of systemic therapies for AD specifically in the head-and-neck area remains underexplored.

OBJECTIVE: The objective was to evaluate the effectiveness of approved anti-inflammatory systemic therapies for AD in the head-and-neck area through a systematic review and meta-analysis.

METHODS: We conducted a systematic literature search in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) indentifying studies reporting response to systemic anti-inflammatory therapies for AD in the head-and-neck region. Searches were conducted in the databases PubMed, EMBASE, and Web of Science from inception through June 2025. The primary outcomes were mean percentage change of Eczema Area and Severity Index (EASI) for the head-and-neck region (EASI-HN), and proportion of patients achieving 75% improvement of EASI for the head-and-neck region (EASI75-HN). Meta-analyses were performed where data permitted.

RESULTS: In total, 22 publications, encompassing 32 unique studies and 11,372 patients in total, met the inclusion criteria. Of the 22 included publications, eight were post hoc analyses of randomized controlled trials (RCTs), and 14 were observational real-world studies. Across studies, the mean reductions of EASI-HN after 16 weeks of treatment ranged from 59% (dupilumab 300 mg every 2 weeks (Q2W) without topical therapy) and 67% (lebrikizumab 250 mg Q2W without topical therapy) to 80% (upadacitinib 30 mg once daily (QD) without topical therapy) and 85% (dupilumab 300 mg Q2W with concomitant topical therapy). EASI75-HN after 16 weeks of treatment ranged from 20% (baricitinib 2 and 4 mg QD) to 66% (upadacitinib 30 mg QD). Evidence for the conventional systemic therapies, cyclosporine and methotrexate, was limited and not readily comparable to the other treatments.

CONCLUSIONS: In this systematic review, biologics and Janus kinase inhibitors (JAKis) were effective in treating AD in the head-and-neck region, achieving treatment responses comparable to those observed in other body regions. Further research providing direct comparison between therapies are warranted.

PMID:41806270 | DOI:10.1007/s40257-026-01013-6

J Autism Dev Disord. 2026 Mar 10. doi: 10.1007/s10803-026-07245-z. Online ahead of print.

ABSTRACT

PURPOSE: Prenatal maternal immune activation (MIA) and preterm birth (PTB) have each been linked to increased risk for neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, MIA definitions varied across studies and few investigations have examined their combined effects. This study assessed the relationship between MIA and NDDs using two MIA definitions: binary (fever and/or placental inflammation) and a four-level subtype (fever only, inflammation only, both, or neither); and examined the joint associations of MIA and PTB with NDDs.

METHODS: This report includes 2,975 mother-child dyads. Adjusted logistic regressions estimated associations between MIA and NDDs. Additive interactions between MIA and PTB were assessed using the Relative Excess Risk due to Interaction (RERI). Mediation-moderation analyses examined the extent to which the association between MIA and ADHD was statistically explained by PTB.

RESULTS: Binary MIA was associated with elevated odds of NDD (adjusted odds ratio [aOR] = 1.33, 1.08-1.64) and ADHD (aOR = 1.71, 1.30-2.25). Using the four-level definition, the highest risk was among children exposed to both maternal fever and placental inflammation (NDD: aOR = 3.25, 1.87-5.66; ADHD: aOR = 3.16, 1.50-6.65). Co-occurrence of binary MIA and PTB yielded a RERI of 0.88 (0.28-1.48) for ADHD, while both (Fever + IUI) MIA subtype and PTB yielded RERI of 2.14 (0.66-3.62), indicating greater-than-additive joint associations. In mediation analyses, we found that the positive associations of MIA with NDD and ADHD were partly explained by PTB.

CONCLUSION: Placental inflammation, more so than fever, is associated with NDDs and ADHD risk, supporting the value of MIA subtype measure. MIA and PTB are jointly associated with increased ADHD risk beyond additivity, and PTB partially mediated the association between MIA and ADHD.

PMID:41806249 | DOI:10.1007/s10803-026-07245-z

Int Urol Nephrol. 2026 Mar 10. doi: 10.1007/s11255-026-05092-6. Online ahead of print.

ABSTRACT

PURPOSE: Retinoic acid is essential for spermatogonial differentiation and meiotic initiation, providing a biologically plausible rationale for exploring retinoid-based therapies in the context of male infertility. Isotretinoin is widely prescribed for acne. However, it has historically raised concerns about potential sexual adverse effects. We aim to synthesize contemporary available clinical evidence on isotretinoin and clarify whether it poses reproductive risks or may hold any potential therapeutic relevance in men across both dermatologic and infertility settings.

METHODS: Following PRISMA guidelines, we systematically searched MEDLINE/PubMed, Scopus, and Web of Science from inception to November 2025 for original articles investigating the effects of isotretinoin on semen parameters, reproductive hormones, sexual function, or fertility outcomes. A narrative synthesis was conducted in conjunction with a random-effects meta-analysis for semen parameters when means and standard deviations were available.

RESULTS: Six clinical studies involving 225 men were included: three dermatologic cohorts (n = 167) with normal baseline fertility, treated with standard isotretinoin regimens for acne, and three infertility cohorts (n = 58), receiving low-dose isotretinoin for oligoasthenozoospermia, cryptozoospermia, or non-obstructive azoospermia. In dermatologic populations, random-effects meta-analysis showed small but statistically significant increases in sperm concentration (Mean Difference [MD] + 1.77 million/mL, p = 0.028) and vitality (MD + 3.74%, p = 0.009), with non-significant positive trends for progressive motility (MD + 4.12%) and normal morphology (MD + 1.13%). In infertility settings, sperm concentration increased by approximately + 1.3 million/mL, progressive motility improved by + 3%, and normal morphology remained stable in oligoasthenozoospermic men. In comparison, de novo sperm appeared in 37-44% of azoospermic or cryptozoospermic men, enabling pregnancies across three studies (both spontaneous and with assisted reproductive technology). No study reported impaired fertility or treatment-emergent sexual dysfunction. Overall, the certainty of evidence was low to moderate.

CONCLUSION: Current clinical data do not support reproductive harm from isotretinoin. Instead, isotretinoin may enhance semen quality in healthy men and promote clinically meaningful spermatogenic recovery in selected infertility contexts. Controlled trials are needed to define therapeutic efficacy, identify responders, and clarify its role in male infertility management.

PMID:41806242 | DOI:10.1007/s11255-026-05092-6

Clin Transl Oncol. 2026 Mar 10. doi: 10.1007/s12094-026-04301-z. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to construct and validate a dedicated prognostic model for patients with RAS-mutant metastatic colorectal cancer (mCRC) using real-world data from two centers and explore the differences in the efficacy of first-line standard chemotherapy regimens in this population to provide an evidence-based foundation for individualized prognostic assessment and the selection of first-line treatment strategies.

METHODS: Clinical, pathological, and follow-up data from 275 patients with RAS-mutant mCRC treated in two hospitals from January 2016 to December 2023 were retrospectively collected. Prognosis-related candidate variables were screened by univariate Cox regression and LASSO regression, and a prognostic model was constructed using a stepwise multivariate Cox proportional hazards model. For variables violating the proportional hazards assumption, a time-dependent Cox model was further used for correction. Model performance was evaluated by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Leave-one-out cross-validation (LOOCV) was used to test its stability, and the tercile method was adopted for stratified validation to assess the stratification efficiency. In addition, 129 patients receiving first-line standard chemotherapy were selected from the total cohort to form an efficacy analysis cohort. The Kaplan-Meier method and the Cox proportional hazards regression model combined with multivariate adjustment were used to explore the differences in efficacy of different chemotherapy regimens with or without bevacizumab.

RESULTS: The final prognostic model included four independent prognostic factors: lesion resection status, number of metastatic organs, CA19-9 level, and serum ALB concentration. The C-index of the model was 0.730 (95% CI: 0.689-0.771), and the pooled C-index verified by LOOCV was 0.705 (95% CI: 0.662-0.747). Time-dependent ROC analysis at 1, 2, and 3 years revealed that the AUC values of the model were 0.806, 0.781, and 0.772, respectively. The calibration curve had a good fit, and DCA confirmed that the model had clinical net benefit over a wide threshold range. There were significant differences in survival among patients in the high-, medium-, and low-risk groups (P < 0.001), indicating good stratification efficiency of the model. Exploratory efficacy analysis revealed that compared with single two-drug chemotherapy, two-drug chemotherapy combined with bevacizumab significantly prolonged the median progression-free survival (mPFS) of patients (9.61 vs. 6.74 months, P = 0.025), and this benefit remained stable after multivariate adjustment (HR = 0.437; 95% CI: 0.241-0.791; P = 0.006), but there was no significant difference in overall survival (OS) between the two groups. No statistically significant differences were observed in the objective response rate (ORR), PFS, or OS between patients receiving oxaliplatin-based or irinotecan-based two-drug chemotherapy combined with bevacizumab.

CONCLUSION: The prognostic model and the corresponding nomogram constructed in this study can be used to conveniently evaluate the 1- to 3-year survival probability of patients with RAS-mutant mCRC. Exploratory analysis using real-world data revealed that two-drug chemotherapy combined with bevacizumab can significantly prolong the PFS of this population, providing a reference for the selection of first-line treatment regimens for this group. Both oxaliplatin- and irinotecan-based two-drug regimens combined with bevacizumab can be used as options for first-line treatment, and clinical selection can be made comprehensively on the basis of the individual conditions of patients. This study has several limitations, such as its retrospective design, unbalanced sample size in efficacy subgroups, and lack of external validation of the model, and the conclusions need to be further verified by large-sample prospective multicenter studies.

PMID:41806240 | DOI:10.1007/s12094-026-04301-z

Clin Transl Oncol. 2026 Mar 10. doi: 10.1007/s12094-026-04296-7. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Cervical carcinoma, exhibits distinctive hallmarks, including sustained proliferation and replicative immortality. Ki-67 is a well-established marker of cell proliferation, while the presence of telomerase, particularly its catalytic subunit human Telomerase Reverse Transcriptase (hTERT), is associated with the uncontrolled proliferation seen in many cancers.

METHOD: The expression of Ki-67 and the hTERT component of telomerase was investigated in various cervical lesions. Tissue microarray blocks were prepared from a total of 586 paraffin-embedded cervical tissue specimens received at Sultan Qaboos University Hospital and Royal Hospital between January 2010 and December 2018. Immunohistochemistry was performed to assess the expression of both markers.

RESULTS: The results showed that Ki-67 expression increased significantly with the severity of cervical lesions (p < 0.05), with SCC displaying high Ki-67 expression in more than 50% of tumor cells. However, statistical analysis revealed no significant correlation between Ki-67 expression and lesion prognosis. On the other hand, hTERT showed a significantly higher expression in low-grade LSIL (p < 0.05), whereas high-grade squamous intraepithelial lesions and SCC predominantly showed negative hTERT expression. hTERT staining was mainly localized to the nucleus across all cervical lesions, with some cytoplasmic and combined expressions, and it was generally of mild intensity; however, this correlation was not statistically significant. Additionally, the percentage of hTERT-positive cells was mostly below 10% in all lesion types, with no statistically significant differences observed.

CONCLUSION: Our findings suggest that the use of Ki-67 and hTERT component of telomerase combination might not be sufficient to predict the prognosis of cervical lesions. Nonetheless, the observed expression patterns of each biomarker indicate a potential role in early carcinogenesis.

PMID:41806237 | DOI:10.1007/s12094-026-04296-7

Eur J Pediatr. 2026 Mar 10;185(3):171. doi: 10.1007/s00431-026-06828-3.

ABSTRACT

To evaluate whether implementation of a multidisciplinary care pathway was associated with changes in unplanned emergency department (ED) visits in children with musculoskeletal infections, and to assess its impact on readmissions, reoperations, and key process measures. We conducted a single-centre quality-improvement study of children with septic arthritis (SA) or acute osteomyelitis (AO) treated at a tertiary paediatric hospital in Canada. A pathway introduced in September 2021 standardised C-reactive protein (CRP) monitoring, discharge documentation, and coordinated in-person and virtual follow-up. Consecutive post-pathway patients (September 2021-July 2022) were compared with a pre-pathway cohort (June 2018-August 2021). The primary outcome was unplanned ED visits within three months of discharge. Secondary outcomes included readmission, reoperation, and predefined process measures. Analyses used regression models and statistical process control (SPC) p-charts. A total of 122 children were included (77 pre-pathway, 45 post-pathway). Median age was similar between groups (4.0 vs 6.5 years, p = 0.25). Unplanned ED visits decreased from 28.6% to 17.8% (RR 0.62, 95% CI 0.30-1.28; p = 0.18). However, this difference was not statistically significant, and SPC analysis demonstrated common-cause variation. Pathway phase was not independently associated with ED visits after adjustment (OR 1.46, 95% CI 0.53-4.04; p = 0.47). Readmissions and reoperations were unchanged. Several process measures improved, including day-3 CRP measurement (61.0 vs 86.7%; p = 0.003), number of follow-up visits (median 3 vs 5; p < 0.001), and fewer missed appointments (median 1 vs 0; p < 0.001).

LEVEL OF EVIDENCE: Level III (Prospective comparative quality improvement study).

CONCLUSION: Implementation of a multidisciplinary care pathway was associated with improved process reliability and follow-up adherence. Although unplanned ED visits were lower in the post-pathway cohort, this difference did not reach statistical significance. These findings support coordinated, team-based approaches to optimise care processes for paediatric musculoskeletal infections.

WHAT IS KNOWN: • Children with septic arthritis and acute osteomyelitis frequently have unplanned emergency department visits after discharge, despite relatively low readmission and reoperation rates. • Care delivery often varies across the inpatient-outpatient continuum, with inconsistent inflammatory marker monitoring and limited multidisciplinary coordination.

WHAT IS NEW: • Implementation of a multidisciplinary care pathway was associated with improved CRP monitoring, follow-up adherence, and appointment reliability. • Although unplanned ED visits were numerically lower post-pathway, this difference did not reach statistical significance; however, process reliability and continuity of care improved without increases in readmissions or reoperations.

PMID:41806202 | DOI:10.1007/s00431-026-06828-3