Nevin Manimala

JAMA Ophthalmol. 2025 Feb 20. doi: 10.1001/jamaophthalmol.2024.6492. Online ahead of print.

ABSTRACT

IMPORTANCE: Primary selective laser trabeculoplasty (SLT) is a safe primary treatment for open-angle glaucoma (OAG) and ocular hypertension (OHT). However, there is limited evidence on its use as a secondary treatment, ie, after prior use of ocular hypotensive eye drops.

OBJECTIVE: To evaluate outcomes following SLT after using hypotensive eye drops for at least 3 years.

DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc exploratory analysis of data from a multicenter randomized clinical trial conducted within the UK National Health Service. Participants were patients with OAG or OHT who participated in the LiGHT trial. Data were analyzed from February 2021 to December 2024.

INTERVENTION: Participants were initially randomized to either primary SLT or primary hypotensive eye drops and remained on the allocated treatment pathway for 3 years. Participants using eye drops were then allowed to have secondary SLT as a treatment switch (to reduce their medication load) or as a treatment escalation (if more intense treatment was needed). Participants were treated and monitored according to a predefined protocol.

MAIN OUTCOMES AND MEASURES: The outcomes of interest were rates of incisional glaucoma surgery, medication use, and intraocular pressure.

RESULTS: In total, 633 participants entered the extension of the LiGHT trial, and 524 participants (82.8%) completed the extension (72 months). Of 320 participants receiving primary hypotensive eye drops, 112 (35.0%) received SLT: 70 participants switched to SLT, 29 participants had SLT as a treatment escalation, and 13 participants had SLT as a treatment escalation in 1 eye and as a treatment switch in the other eye. Switching to SLT was associated with a reduction in the number of medications (mean [SD], 1.38 [0.62] to 0.59 [0.92] active ingredients; mean difference, 0.79 [95% CI 0.66 to 0.93] active ingredients; P < .001). At 72 months, 69 eyes that switched to SLT (60.5%) needed no medical or surgical treatment, and 62 eyes receiving 1 drug before switching (83.8%) needed no medical treatment. Escalating to SLT was associated with a mean intraocular pressure reduction of 4.6 mm Hg (21.8%), and 30 eyes (62.5%) reached target intraocular pressure at 72 months without the need for surgery; 9 eyes (18.7%) needed a trabeculectomy.

CONCLUSIONS AND RELEVANCE: This secondary analysis of a randomized clinical trial found that secondary SLT was associated with a reduction in the medication load for stable, medically treated eyes. For medically uncontrolled eyes, there is evidence that SLT could provide additional intraocular pressure control, but the need for trabeculectomy was not eliminated.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN32038223.

PMID:39976961 | DOI:10.1001/jamaophthalmol.2024.6492

JAMA Otolaryngol Head Neck Surg. 2025 Feb 20. doi: 10.1001/jamaoto.2024.5392. Online ahead of print.

ABSTRACT

IMPORTANCE: Cigarette smoking is a strong risk factor for mortality in patients diagnosed with head and neck squamous cell carcinoma (HNSCC). However, little evidence supports which smoking metric best models the association between smoking and survival in HNSCC.

OBJECTIVE: To determine which smoking metric best models a linear association between smoking exposure and overall survival (OS) in patients with HNSCC.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter cohort study of 6 clinical epidemiological studies was performed. Five were part of the Human Papillomavirus, Oral and Oropharyngeal Cancer Genomic Research (VOYAGER) consortium. Participants included patients 18 years and older with pathologically confirmed HNSCC. Data were collected from January 2002 to December 2019, and data were analyzed between January 2022 to November 2024.

MAIN OUTCOMES AND MEASURES: The primary outcome was OS. The performance of 8 smoking metrics, including pack-years, duration, and log cig-years (calculated as log10[cigarettes smoked per day + 1] × number of years smoked) for modeling OS were compared. Metric performance was measured by the strength of association in Cox proportional hazard models, linearity based on P for linear trend, Akaike information criterion (AIC; lower value indicates better model fit), and visual assessment of spline curves. Secondary outcomes included modeling OS in clinicodemographic subgroups and HNSCC anatomic subsites. Exploratory outcomes included cancer-specific survival and noncancer survival.

RESULTS: In total, 8875 patients with HNSCC (2114 [24%] female; median [IQR] age, 61 [54-69] years) were included. Of 8 smoking metrics evaluated, smoking duration (adjusted hazard ratio [aHR], 1.11 [95% CI, 1.03-1.19]) and log cig-years (aHR, 1.11 [95% CI, 1.04-1.18]) had the highest aHRs; both had a statistically significant linear association with OS. Log cig-years had the lowest AIC linear value and the most visually linear spline curve when modeling OS. Duration and log cig-years outperformed pack-years for modeling OS regardless of age, smoking status, and cancer stage. Both performed well in lip and oral cavity, laryngeal (only duration was significant), and human papillomavirus-negative oropharyngeal subsites. In an exploratory analysis, duration had the highest aHR (1.15 [95% CI, 1.02-1.29]), and log cig-years had the lowest AIC linear value when modeling noncancer survival.

CONCLUSIONS AND RELEVANCE: In this cohort study, smoking duration and log cig-years best modeled a linear relationship with OS for patients with HNSCC. Both metrics maintained robust performance within specific clinicodemographic subgroups and anatomic subsites. Although most HNSCC survival models control for smoking exposure using smoking status or pack-years, duration and log cig-years may be superior metrics to account for the effects of smoking on survival.

PMID:39976935 | DOI:10.1001/jamaoto.2024.5392

Cell Mol Biol (Noisy-le-grand). 2025 Feb 20;71(2):67-73. doi: 10.14715/cmb/2025.71.2.10.

ABSTRACT

Interferon-gamma (IFN-γ) plays a crucial role in resistance to mycobacterial infections, as it is a regulatory cytokine that acts as a pro-inflammatory mediator. Consequently, variants in the gene encoding this cytokine may be associated with a high risk of contracting pulmonary tuberculosis. The present study aimed to investigate the genetic susceptibility of polymorphisms in the gene coding for IFN-γ to infection by Mycobacterium tuberculosis in Burkina Faso. This cross-sectional study was conducted from May 2023 to January 2024. Venous blood was collected from suspected cases. Tuberculosis was confirmed by GeneXpert (CEPHEID). Human genomic DNA was extracted using the salting-out extraction technique, followed by the amplification and genotyping of IFN-γ gene polymorphisms,through the conventional PCR. Statistical analyses were performed using the SPSS and Epi info software. A total of 168 participants were included in the study, with an average age of 38.58 ±14.88, the majority of whom were men (76.19%). In our study population, 73.2% (123/168) were confirmed positive for tuberculosis. Some 46.4% (78/168) of the previous cases were contacts. Of these contact cases, 82.05% (64/78) were GeneXpert positive. The genotypic frequencies of the IFN-γ gene were distributed as follows: 73.3% (AA), 21.8% (AT) and 4.9% (TT), with a frequency of 84.2% for the A allele versus 15.8% for the mutated T allele. No statistically significant association was found between IFN-γ gene polymorphisms and M. tuberculosis infection in Burkina Faso. IFN-γ gene polymorphisms (IFN +874T/A) do not appear to be associated with M. tuberculosis infection in Burkina Faso.

PMID:39976911 | DOI:10.14715/cmb/2025.71.2.10

Pharmacoeconomics. 2025 Feb 20. doi: 10.1007/s40273-025-01469-0. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to assess the cost effectiveness of nirsevimab, a recently authorized monoclonal antibody (mAb) for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV), in comparison with the standard practice involving palivizumab for high-risk infants during their first RSV season in the Netherlands.

METHODS: A static cost-effectiveness model was populated for the Netherlands to evaluate different immunization strategies for nirsevimab over a single RSV season from a societal perspective. The model considered the most recently published RSV incidence data (average incidence from 2006 to2018), costs (adjusted to the 2023 price year), and associated health effects. Extensive scenario analyses were conducted to explore various strategies, and sensitivity analysis was performed to assess the model’s robustness.

RESULTS: In the base-case scenario, all-infant protection-a strategy of in-season with catch-up immunization for all infants-nirsevimab has the potential to prevent numerous RSV-related cases, including 2333 hospitalizations and 150 intensive-care admissions, in the overall population compared with the standard of care. Nirsevimab appears to be cost effective under this strategy with an economically justifiable acquisition price for nirsevimab of €220 at a willingness-to-pay threshold of €50,000 per quality-adjusted life-year. Sensitivity analyses indicate a 52% probability that nirsevimab is cost effective at this threshold. Comparison of different vaccination strategies revealed that the all-infant protection approach was the one that prevented the higher number of cases.

CONCLUSIONS: This study indicates that universal infant immunization with nirsevimab has the potential to be cost effective and significantly reduces the burden of RSV among Dutch infants. These findings underscore the importance of implementing effective protective measures against RSV-LRTD, reducing the pressure on the healthcare system during the RSV season.

PMID:39976899 | DOI:10.1007/s40273-025-01469-0

Discov Oncol. 2025 Feb 20;16(1):213. doi: 10.1007/s12672-025-01977-7.

ABSTRACT

This study analyzes the research landscape of nanomaterials in treating hepatocellular carcinoma (HCC) and examines publication trends in this field by conducting a comprehensive bibliometric analysis within the Web of Science Core Collection (WoSCC) database. Articles published from 2000 to September 16, 2024 were retrieved using a structured search formula targeting studies on nanomaterials in HCC, including nanoparticles, nanodots, nanorods, nanosheets, and nanomedicine. Only English full-text articles and reviews relevant to nanomaterial applications in HCC were considered, excluding conference abstracts and non-research items. The analysis encompasses annual publication trends, country-wise publication distribution, prominent institutions, and key journals in the field. Statistical and graphical analyses were performed using GraphPad Prism (v8.0.2) to illustrate publication trends. CiteSpace (6.2.4R) and VOSviewer (1.6.18) software were used to visualize co-citation and keyword networks, highlighting scientific knowledge structures and research hotspots. Notable advancements have emerged as a promising strategy, enabling hepatocyte-specific drug delivery to enhance therapeutic precision and minimize off-target effects. This analysis provides a comprehensive understanding of the evolution of HCC nanomaterials research, key contributing countries, major research institutions, and frequently cited keywords. The findings offer valuable insights into the field’s knowledge base, emerging trends, and future directions in HCC treatment with nanomaterials.

PMID:39976894 | DOI:10.1007/s12672-025-01977-7

Biochem Genet. 2025 Feb 20. doi: 10.1007/s10528-025-11051-0. Online ahead of print.

ABSTRACT

Breast cancer is one of the most prevalent cancers globally and remains a significant cause of cancer-related mortality among women despite advancements in early detection and treatment. The heterogeneity of breast cancer arises from a complex interplay of genetic and environmental factors. Early-stage breast cancer is often asymptomatic, with initial signs including subtle changes in breast morphology and localized swelling, emphasizing the need for reliable diagnostic tools for early detection. Recent research has highlighted the potential of molecular biomarkers, particularly non-coding RNAs such as circular RNAs (circRNAs), in cancer diagnosis. CircRNAs, a unique subset of non-coding RNAs, are characterized by their covalently closed-loop structure, which confers exceptional stability and resistance to exonuclease degradation. They are present in various body fluids and have demonstrated regulatory roles in transcription, translation, and as microRNA sponges, making them promising candidates for cancer diagnostics and prognostics. This study focuses on evaluating the diagnostic potential of two circRNAs, hsa_circ_0001666 and hsa_circ_0003227, by examining their expression in normal, tumor, and metastatic breast cancer cell lines. Breast cancer cell lines representing normal (MCF-10A), tumor (MCF-7), and metastatic (BT-20) stages were cultured for analysis. Total RNA was extracted using a column-based RNA extraction kit, and RNA quality was assessed through NanoDrop spectrophotometry and agarose gel electrophoresis. Complementary DNA (cDNA) synthesis was performed using random hexamers, and the expression levels of hsa_circ_0001666 and hsa_circ_0003227 were quantified using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR), with beta-actin serving as the internal control. Statistical analyses were conducted using SPSS software to evaluate differences in expression levels across cell lines. A significant downregulation of hsa_circ_0001666 and hsa_circ_0003227 was observed in tumor and metastatic cell lines compared to normal breast cell lines (P < 0.05). These results suggest that the expression of these circRNAs correlates with the progression of breast cancer, with decreased levels observed as cells transition from normal to tumorigenic and metastatic stages. The findings of this study indicate that hsa_circ_0001666 and hsa_circ_0003227 have potential utility as diagnostic biomarkers for breast cancer. Their significant expression changes across different stages of breast cancer highlight their relevance in early detection and disease monitoring. This study reinforces the potential of RNA-based biomarkers, particularly circRNAs, in cancer diagnosis and treatment. However, in vitro findings require validation in clinical samples and larger cohorts. Future research should explore their roles in breast cancer progression and integration into non-invasive diagnostics.

PMID:39976889 | DOI:10.1007/s10528-025-11051-0

J Robot Surg. 2025 Feb 20;19(1):76. doi: 10.1007/s11701-025-02237-0.

ABSTRACT

This meta-analysis examines and compares the perioperative results (such as complications, recovery, and other surgical outcomes) in obese patients who undergo either robotic-assisted partial nephrectomy (RPN) or open partial nephrectomy (OPN). Essentially, the study is looking at how these two types of surgeries perform in obese patients, specifically focusing on outcomes related to the surgery process itself. We conducted a comprehensive search of major databases, including PubMed, Cochrane Library, and Web of Science, focusing on English studies, up to November 2024. Review articles, research protocols without published data, conference abstracts, and irrelevant studies were excluded. We performed data analysis using the Cochran-Mantel-Haenszel method and random-effects models, followed by mean differences, inverse variance, and 95% confidence intervals (CIs). The results were presented as odds ratios (ORs) and 95% CIs, and data with p values less than 0.05 were identified. This meta-analysis included three cohort studies with a total of 604 patients. Compared to OPN, RPN was associated with significantly shorter hospital stays (WMD – 2.27, 95% CI – 3.67 to – 0.87; p = 0.002), lower overall complication rates (OR 0.50, 95% CI 0.34-0.73; p = 0.0004), and reduced estimated blood loss (WMD – 125.12, 95% CI – 198.02 to – 52.22; p = 0.0008). No significant differences were found between the two groups in transfusion rates, major complications, renal ischemia times, or operative times. RPN offers a safe and feasible option for obese patients compared to OPN, with advantages such as shorter hospital stays, reduced blood loss, and fewer overall complications.

PMID:39976852 | DOI:10.1007/s11701-025-02237-0

Community Ment Health J. 2025 Feb 20. doi: 10.1007/s10597-024-01417-w. Online ahead of print.

ABSTRACT

People living with psychosis live up to 20 years less compared to the general population. Cardiometabolic ill-health and barriers to health-related behaviour are significant contributors. This is a cross-sectional descriptive study of cardiometabolic health and health behaviours of consumers attending a public community mental health service in an Australian city. One hundred and fourteen consumers currently living with psychosis participated. Standard measures of cardiometabolic health, quality of life and, health-related behaviours were utilised. Data were analysed using descriptive statistics. The cohort reported higher fruit intake and physical activity, and lower excess alcohol use compared to previous studies. Health-related behaviours including smoking and vegetable intake were poorer than previously reported. Participants had low levels of cardiometabolic health (e.g. abnormal lipids). Physical and mental quality of life was also lower than for general populations. Improved efforts to address physical health for people with mental health conditions are urgently needed.

PMID:39976847 | DOI:10.1007/s10597-024-01417-w

Endocr Metab Immune Disord Drug Targets. 2025 Feb 19. doi: 10.2174/0118715303329277250120104421. Online ahead of print.

ABSTRACT

BACKGROUND: Chlorpyrifos (CPF) is an organophosphate insecticide that is mostly used in agriculture for pest control.

AIM: This investigation aimed to evaluate the possible protective role of chrysin nanocrystals on thyroid gland hormones and histology in male rats after exposure to a high dose of chlorpyrifos.

METHOD: Rats were randomly divided into 6 groups (6 rats in each group): 1. healthy control group, 2. treated with chrysin nanocrystal (5 mg/kg), 3. treated with chrysin nanocrystal (10 mg/kg), 4. treated with chrysin nanocrystal (5 mg/kg) + chlorpyrifos, 5. treated with chrysin nanocrystal (10 mg/kg) + chlorpyrifos, and 6. treated with chlorpyrifos (30 mg/kg). After 15 days of intervention, rats were anesthetized, and blood samples were taken from the heart to measure thyroid hormones. Then, the thyroid gland was isolated and stored in 10% formalin for histopathological studies. Thyroid samples were also stored at -80 ° C for measuring oxidative stress parameters.

RESULT: A significant reduction was observed in the serum concentrations of T3 and T4 in all treated groups compared with the control group (p < 0.01). In addition, hormone level examination revealed no statistically significant (p ˃ 0.05) changes in plasma TSH concentration in any of the groups. The treatment with CPF and chrysin nanocrystal did not affect the levels of oxidative biomarkers (MDA, GSH, and NO) in thyroid glands. Photomicrographs of a histological section of the thyroid gland showed vacuolar degenerated follicle epithelium and missing colloids in the histological section of the thyroid gland of all groups.

CONCLUSION: Our findings demonstrated that the oral administration of chrysin nanocrystals could not inhibit the toxic effect of a high dose of CPF on the thyroid gland in the rats.

PMID:39976093 | DOI:10.2174/0118715303329277250120104421

Curr Med Chem. 2025 Feb 18. doi: 10.2174/0109298673359149250212073143. Online ahead of print.

ABSTRACT

BACKGROUND: The precise function of DDX59 Antisense RNA 1 (DDX59- AS1) in lung adenocarcinoma (LUAD) has yet to be fully elucidated.

OBJECTIVE: This study uses bioinformatics analysis and experimental validation to investigate the association between DDX59-AS1 and LUAD.

METHODS: This study uses statistical analysis and database interrogation to investigate the potential association between DDX59-AS1 expression and various clinical characteristics, prognostic factors, regulatory networks, and immune infiltration in LUAD. The quantification of DDX59-AS1 expression in LUAD cell lines is conducted through the use of quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS: DDX59-AS1 showed significantly elevated levels of expression in patients with LUAD. High levels of DDX59-AS1 expression were found to be significantly associated with poorer overall survival (OS) in patients with LUAD (p = 0.024). Furthermore, an independent correlation was observed between high DDX59-AS1 expression (p = 0.037) and OS in LUAD patients. DDX59-AS1 was found to be involved in various pathways, including glutathione metabolism, proteasome function, and the cytosolic DNA sensing pathway, among others. A significant correlation was observed between the expression levels of DDX59-AS1 and immune cell infiltration in the context of LUAD. Notably, elevated expression of DDX59-AS1 was observed in LUAD cell lines compared to the non-cancerous Beas-2B cell line.

CONCLUSION: A significant correlation was observed between elevated DDX59-AS1 expression in patients with LUAD and adverse prognosis, alongside increased immune infiltration. These results indicate that DDX59-AS1 may function as a prognostic marker for LUAD and a potential predictor of immunotherapy response.

PMID:39976021 | DOI:10.2174/0109298673359149250212073143