Category: Nevin Manimala

J Med Microbiol. 2025 Dec;74(12). doi: 10.1099/jmm.0.002106.

ABSTRACT

Introduction. Fungal keratitis, particularly in tropical and subtropical regions, poses significant therapeutic challenges due to biofilm formation by fungal pathogens. These biofilms confer increased resistance to antifungal treatments and are associated with poorer clinical outcomes.Hypothesis/Gap Statement. Despite growing recognition of their impact, there remains a lack of comprehensive synthesis on the role of fungal biofilms in corneal ulcers.Aim. This study aims to determine the impact of and how biofilm formation influences the chronicity and treatment outcomes in fungal corneal ulcers.Methodology. A comprehensive literature search was performed across PubMed, ScienceDirect, Scopus and the Cochrane Library in April 2025. Only English articles were included, and animal studies were excluded. Eligible studies included clinical and in vitro investigations that assessed biofilm formation in fungal corneal ulcers and its impact on antifungal susceptibility and treatment outcomes. This systematic review and meta-analysis were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines and registered under PROSPERO (an international systematic review registry, ID:CRD420251017502). Independent data extraction was done by two reviewers. Data on MICs were synthesized using random-effects models, and heterogeneity was assessed with I² statistics and Cochran’s Q test. Clinical outcomes were analysed narratively due to reporting variability.Results. Seven studies were included, spanning Brazil, India, China and Mexico, and covering both in vitro and clinical designs. Meta-analysis showed significantly increased MIC values for biofilm-forming fungal isolates: amphotericin B [pooled log_₂ fold change=5.31; 95% confidence interval (CI): 2.92-7.70], voriconazole (6.06; 95% CI: 2.25-9.87) and natamycin (1.25; 95% CI: 0.48-2.02). High heterogeneity was noted for amphotericin B and voriconazole, while results for natamycin were consistent. Narrative synthesis of clinical data indicated that biofilm formation is associated with prolonged healing times, increased recurrence rates, reduced visual acuity and higher complication risks.Conclusion. Biofilm formation by fungal pathogens significantly reduces antifungal susceptibility and worsens clinical outcomes in fungal keratitis. Elevated MIC, delayed healing and increased rates of complications emphasize the need for targeted biofilm-disrupting therapies and standardized diagnostic protocols. Future research should focus on developing clinical strategies that integrate biofilm assessment to improve patient outcomes.

PMID:41411030 | DOI:10.1099/jmm.0.002106

Rehabil Psychol. 2025 Dec 18. doi: 10.1037/rep0000644. Online ahead of print.

ABSTRACT

OBJECTIVE: Examine the moderating effect of preinjury attention-deficit hyperactivity disorder (ADHD) and secondary ADHD on response to a family-based problem solving (FBPS) intervention following pediatric traumatic brain injury.

METHOD: Analyses included 233 participants (114 FBPS and 119 internet resource comparison group), aged 11-18 who had been hospitalized for a moderate-severe traumatic brain injury within the previous 18 months. Parents completed measures of child functioning and their own functioning at time of enrollment, 6-, 12-, and 18-month follow-ups. Linear mixed models examined the moderating effect of ADHD status on the effect of treatment over time.

RESULTS: Main effect of ADHD status was significant for executive functioning, F(2, 429) = 55.15, p < .0001; social competence, F(2, 421) = 22.94, p < .0001; parental depression, F(2, 420) = 4.83, p = .0085; and parental distress, F(2, 413) = 6.35, p = .0019. Consistently, those with ADHD demonstrated worse outcomes than those without ADHD. ADHD status moderated the effect of FBPS on functional impairment, F(6, 430) = 5.16, p < .0001. Among those who received FBPS, those without ADHD demonstrated the expected improvement in functional outcomes over time. The secondary ADHD group had a delayed improvement in outcomes, not present until the 18-month follow-up. The preinjury attention-deficit hyperactivity disorder group showed no change in outcomes over time.

CONCLUSIONS/IMPLICATIONS: ADHD status had a significant effect on adolescent and parent outcomes and moderated the effect of FBPS on functional outcomes. Findings highlight the importance of identifying children with preinjury ADHD as well as new onset ADHD symptoms after injury to guide intervention delivery. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:41411026 | DOI:10.1037/rep0000644

J Neuropathol Exp Neurol. 2025 Dec 18:nlaf127. doi: 10.1093/jnen/nlaf127. Online ahead of print.

ABSTRACT

Theiler’s murine encephalomyelitis virus (TMEV) infection in mice has been used to study diverse neurological diseases, including multiple sclerosis and epilepsy. In this investigation, 5 strains of collaborative cross (CC) mice were infected with TMEV and examined clinically and histologically at days 4, 14, and 90 post-infection (dpi). All CC strains tested exhibited lumbar spinal cord and/or ventral peripheral nerve lesions by 14 dpi; CC027, CC023, and CC078 strains exhibited lesions at 4 dpi. At 90 dpi, lesions were remnants of the inflammatory responses associated with earlier infection; there was skeletal muscle atrophy in the CC023 strain. Increased microglial/macrophage reactivity was observed in all strains at 4 and 14 dpi, but not at 90 dpi. TMEV mRNA expression was greatest in the CC023 and CC078 strains at the acute timepoints; TMEV was completely cleared in all mice at 90 dpi. The neuropathological and clinical profiles in CC023 mice, mainly at 14 dpi, share some clinical and histologic features with those in amyotrophic lateral sclerosis patients. This work demonstrates how viral infection might interact with the genetic background of a susceptible individual to contribute to the onset, clinical presentation and persistence of lesions despite viral clearance.

PMID:41411011 | DOI:10.1093/jnen/nlaf127

Int J Tuberc Lung Dis. 2025 Sep 26;29(10):441-446. doi: 10.5588/ijtld.25.0104.

ABSTRACT

<sec><title>BACKGROUND</title>Safety-net health systems and public health have a unique opportunity to collaborate and address Mycobacterium tuberculosis (MTB) in persons experiencing homelessness (PEH) in the United States (US).</sec><sec><title>METHODS</title>At a large academic safety-net health system in the US, from July 2013 to July 2015, we implemented a novel electronic health record (EHR) alert for physicians to identify, counsel, and order interferon-γ release assay screening tests for PEH potentially exposed to MTB in homeless shelters. Retrospectively, we collected socio-demographic, clinical, and genotyping data for all patients diagnosed with MTB disease from 2008 to 2017 and performed data analysis.</sec><sec><title>RESULTS</title>The EHR alert flagged 2,118 of 8,649 (24.5%) individuals; 1,117 (52.7%) were screened for MTB, and 313 (28%) tested positive. MTB disease was diagnosed in 531 patients from 2008 to 2017, of which 37 were among the potentially exposed 8,649 PEH. Housing instability was identified in 135 (25.4%) TB patients. Three genotypes were predominant: G10508 (56, 14.2%), G01521 (23, 5.8%), and G10509 (19, 4.8%).</sec><sec><title>CONCLUSION</title>A novel EHR alert was useful in identifying and increasing testing among potentially TB-exposed PEH. Housing instability and genotypic clustering were prominent among patients with MTB diagnosis.</sec>.

PMID:41410994 | DOI:10.5588/ijtld.25.0104

Int J Tuberc Lung Dis. 2025 Sep 26;29(10):473-475. doi: 10.5588/ijtld.25.0225.

NO ABSTRACT

PMID:41410991 | DOI:10.5588/ijtld.25.0225

Eur J Trauma Emerg Surg. 2025 Dec 18;51(1):358. doi: 10.1007/s00068-025-03044-w.

ABSTRACT

BACKGROUND: Suturing techniques play a crucial role in wound healing and the overall outcome of surgical procedures. The debate between the effectiveness of interrupted versus continuous suturing techniques remains unresolved. This study aims to compare the outcomes of these two suturing methods in terms of Burst Abdomen in patients undergoing emergency exploratory laparotomy, with a focus on personalized surgical strategies.

METHODS: This randomized controlled trial was conducted in the Department of General Surgery BPS GMC Khanpur. Ninety patients requiring emergency midline laparotomy were randomized into two groups: Group A (Interrupted Closure) and Group B (Continuous Closure). The rectus sheath was closed using No. 1 Prolene suture, either interrupted or continuous. The primary outcome was the incidence of wound dehiscence, with secondary outcomes including closure time and patient demographics.

RESULTS: The overall incidence of burst abdomen was higher in the continuous group (14.4%) compared to the interrupted group (6.7%), though this was not statistically significant (p = 0.071). The time taken for rectus closure was significantly longer in the interrupted group (mean 28.36 min) compared to the continuous group (mean 17.31 min, p < 0.0001). Subgroup analysis revealed a significantly lower incidence of burst abdomen in patients with tubercular perforation peritonitis in the interrupted group (7.7%) compared to the continuous group (57.1%, p = 0.01).

CONCLUSION: The Study showed that interrupted closure technique showed a lower incidence of burst abdomen and preferred in tubercular perforation peritonitis although it requires more time for closure.

PMID:41410943 | DOI:10.1007/s00068-025-03044-w

Eur J Trauma Emerg Surg. 2025 Dec 18;51(1):360. doi: 10.1007/s00068-025-03035-x.

ABSTRACT

PURPOSE: The purpose of this study was to compare the accuracy, precision and the rate of correct screw size selection of the ADEPTH^® automatic sensor to that of a manual depth gauge (DG) when measuring drill hole depths on human cadaveric bones.

METHODS: The depths of holes, drilled in the femur, tibia and bilateral radii of a Thiel embalmed human cadaver, were measured with both the ADEPTH and a DG. Depths measured on a high resolution computed tomography (CT) scan served as a reference for the ADEPTH and the DG measurements. Errors and variances of the errors of the ADEPTH and DG measurements, compared to the CT measurements, were analyzed to assess the accuracy and precision, respectively. Additionally, the proportion of correct screw size selection of both the DG and ADEPTH system were established based on the agreement with the CT measurements.

RESULTS: The ADEPTH showed a smaller mean absolute error (0.72 mm [0.62, 0.83]) compared to the DG measurements (0.88 mm [0.75, 1.02]), yet the difference was not statistically significant (p = 0.098). The ADEPTH showed higher precision compared to the DG measurements. The ADEPTH measurements showed a significantly higher agreement with the CT (68%) as compared to the DG measurements (52%) (p = 0.03).

CONCLUSION: The ADEPTH automatic sensor system has a comparable accuracy and higher precision than the conventional depth gauge (DG), translating into a higher rate of accurately selected screw sizes. Further clinical studies should be performed to investigate the employability and benefit of the ADEPTH in a clinical setting.

PMID:41410936 | DOI:10.1007/s00068-025-03035-x

Eur J Trauma Emerg Surg. 2025 Dec 18;51(1):361. doi: 10.1007/s00068-025-03034-y.

ABSTRACT

BACKGROUND: In trauma research, the complexity of patient presentations, variability across clinical environments, and diversity in outcomes often introduce substantial uncertainty into the interpretation of findings. Sensitivity analysis (SA) is a vital methodological tool for examining the stability and reliability of research conclusions by testing how they respond to changes in analytical methods, model structures, unmeasured confounding, and foundational assumptions.

METHODS: A literature review was conducted to provide an overview of current knowledge and updates on the application of sensitivity analysis in trauma research. A search was performed in PubMed and Google Scholar for studies conducted in humans and published in English between May 2000 and May 2025.

RESULTS: This review explored the crucial role that SA plays in trauma studies, outlining key techniques, including addressing missing data through multiple or single imputation, evaluating protocol noncompliance, adjusting for baseline imbalances, validating statistical assumptions, and conducting subgroup analyses. These strategies are particularly relevant in trauma research, where data fragmentation, wide population variability, and ethical challenges are common. Drawing on landmark trauma studies including PROMPTT, PROPPR, PATCH-Trauma, PAMPer, and recent neural network applications, we demonstrated how SA can be utilized to evaluate model accuracy, determine variable importance, and assess the consistency of treatment effects.

CONCLUSION: Although the implementation of SA in trauma research remains uneven across the field, establishing SA as a standard element of study design and reporting is vital. Doing so not only bolsters the transparency and trustworthiness of analytical results but also enhances the reproducibility and applicability of findings, ultimately supporting more robust and clinically meaningful advancements in trauma care.

PMID:41410935 | DOI:10.1007/s00068-025-03034-y

JAMA Otolaryngol Head Neck Surg. 2025 Dec 18. doi: 10.1001/jamaoto.2025.4573. Online ahead of print.

ABSTRACT

IMPORTANCE: Numerous phase 2 trials have evaluated the efficacy of neoadjuvant immune checkpoint inhibition (ICI) for mucosal head and neck squamous cell carcinoma (HNSCC), using some degree of pathologic treatment response as a primary or secondary end point. However, whether pathologic treatment response is a meaningful surrogate end point for survival has yet to be determined.

OBJECTIVE: To systematically assess the association between pathologic treatment response and overall survival (OS) and disease-free survival (DFS) after neoadjuvant ICI.

DATA SOURCES: A systematic search of the PubMed, OVID Medline, Embase, CINAHL, and Cochrane databases was performed from January 1, 2000, through May 31, 2025.

STUDY SELECTION: Peer-reviewed studies investigating neoadjuvant ICI for the treatment of mucosal HNSCC in patients 18 years and older were identified. Full-length English-language articles that presented pathologic treatment response and survival data (OS and/or DFS) and any association between the 2 were included.

DATA EXTRACTION AND SYNTHESIS: Three blinded reviewers independently extracted study characteristics, pathologic treatment response data, and survival data, including hazard ratios (HRs) and CIs when available, according to PRISMA guideline. Data were compiled for statistical analysis to calculate DFS, OS, and HRs using a random-effects model. The I2 index was used to report data heterogeneity.

MAIN OUTCOMES AND MEASURES: HRs for the association of pathologic treatment response with DFS and OS.

RESULTS: Eleven trials involving 451 patients met inclusion criteria, with 368 patients included in this meta-analysis. Nine nonrandomized and 2 randomized studies were included, including 7 cohort studies, 2 randomized clinical trials, and 2 retrospective cohort studies, each with a different neoadjuvant ICI regimen. Pooled analysis demonstrated that overall (primary tumor plus lymph node) partial pathologic response (PPR; ≤50% residual viable tumor; HR, 0.53; 95% CI, 0.28-0.97; I2 = 2.1%) and major pathologic response (MPR; ≤10% residual viable tumor; HR, 0.34; 95% CI, 0.12-0.93; I2 = 0.0%) were both associated with improved DFS up to 2 years. PPR and MPR were not associated with improved OS. Nine of 11 studies were at low risk of bias.

CONCLUSIONS AND RELEVANCE: Study findings suggest that overall PPR and MPR are associated with improved DFS. These data provide additional support for the potential use of pathologic treatment response as a surrogate for DFS after neoadjuvant ICI in resectable mucosal HNSCC.

PMID:41410931 | DOI:10.1001/jamaoto.2025.4573

JAMA Oncol. 2025 Dec 18. doi: 10.1001/jamaoncol.2025.5376. Online ahead of print.

ABSTRACT

IMPORTANCE: Molecular analyses of biospecimens collected from study participants are essential for identifying biomarkers that can tailor treatments to specific subsets of patients who are most likely to benefit. Sharing of data and biospecimens from clinical trials enables personalized, patient-centric use of cancer therapies and accelerates the development of new treatments.

OBJECTIVE: To describe obstacles to sharing data and biospecimens and to propose strategies to enhance access and collaboration.

EVIDENCE REVIEW: This is a Special Communication authored by 53 academic investigators and patient representatives from the breast cancer community with extensive experience in conducting clinical and translational research. The article also evaluates the impact of biomarker research on specifying responsive subpopulations in the 29 registrational clinical trials that have led to approval of a new drug for treatment of breast cancer between 2017 and 2024.

FINDINGS: Clinical trial participants are increasingly asked to provide tissue and/or body fluid biospecimens for biomarker research that is typically controlled by the sponsoring pharmaceutical company, but published biomarker studies are rare. Among 29 breast cancer registrational studies reported in the past 8 years, none resulted in biomarker research that restricted a drug’s approved indication. Herein, strategies to maximize the value of clinical data and biospecimens contributed by participants are proposed, thereby supporting the shared goals of the pharmaceutical industry and academia to improve patient care. These strategies include (1) establishing coleadership structures involving academia and patients in clinical trial design and conduct, (2) ensuring that informed consent forms state that data and biospecimens will be shared with academia for future research, (3) requiring the sharing of clinical data as a condition for regulatory approval, and (4) enabling access to biospecimens and translational research data for independent studies on biomarkers that may indicate drug efficacy and toxicity.

CONCLUSIONS AND RELEVANCE: Data and biospecimen sharing from registrational trials has been suboptimal. Improving clinical data, biospecimens, and biospecimens’ related data sharing requires concrete actions and a multidimensional stakeholder approach to accelerate the impact of clinical cancer research on the quality of patient care.

PMID:41410930 | DOI:10.1001/jamaoncol.2025.5376