Nevin Manimala

Ann Med. 2025 Dec;57(1):2534094. doi: 10.1080/07853890.2025.2534094. Epub 2025 Jul 25.

ABSTRACT

BACKGROUND: Interhospital transfer (IHT) for pulmonary embolism (PE) is increasingly performed to improve access to advanced reperfusion therapies, but it is unclear if IHT times influence overall outcomes. We studied the association between transfer times and outcomes of patients with acute PE requiring IHT.

METHODS: 139 patients with acute PE undergoing IHT to the Mount Sinai Health System between September 2021 and June 2023 were retrospectively studied. Primary outcomes were 30-day mortality and 30-day major bleeding. ‘Door to IHT’ time was defined as the time from diagnosis of acute PE to the time patient physically arrived in the receiving hospital. Patients were divided into groups based on quartiles of ‘door to IHT’ time; those within the first and fourth quartiles of ‘door to IHT’ time were compared using propensity score-weighted analyses. The propensity score was calculated from six variables: age, sex, BMI [Body Mass Index], PESI [PE Severity Index] score, ESC [European Society of Cardiology] risk class and presence of a central PE. Multivariable regression models were fitted within the propensity score-matched sample to assess the association of ‘door to IHT’ time with primary outcomes.

RESULTS: Median age of included patients was 61 years and 76 (54.7%) were women. Median PESI score was 88 points. Median ‘door to IHT’ time was 10.8 (IQR: 7.3-19.4) hours. Rates of 30-day mortality and 30-day major bleeding were 7.2% and 2.2%. Within propensity score-weighted analyses, no significant associations were found between ‘door to IHT’ time and any of the primary outcomes (30-day mortality or 30-day major bleeding).

CONCLUSION: In this retrospective study of patients with acute PE undergoing IHT, differences in ‘door to IHT’ time were not significantly associated with 30-day mortality or 30-day major bleeding. This suggests that delays in IHT do not adversely influence outcomes of patients with acute PE undergoing IHT.

PMID:40711763 | DOI:10.1080/07853890.2025.2534094

Strabismus. 2025 Jul 25:1-10. doi: 10.1080/09273972.2025.2537361. Online ahead of print.

ABSTRACT

Background: Amblyopia is a neurodevelopmental disorder of vision with various treatment modalities available for treatment. This study was conducted to compare visual outcomes and stereoacuity in sequential and simultaneous refractive correction and patching in treatment of amblyopia. Materials and methods: A prospective randomized interventional study was conducted in age group 3-14 years with unilateral mild-to-moderate amblyopia in two groups (total 70 patients, 35 each) over a period of 1 year. Group A patients underwent simultaneous treatment and Group B patients underwent sequential treatment. Follow-up data for distant and near best corrected visual acuity (BCVA) and stereopsis was taken at baseline, 1 week, 6 weeks, 9 weeks and 12 weeks. Results: At final follow-up, the mean distant BCVA in amblyopic eye was 0.35LogMAReq (SD – 0.14) and 0.33LogMAReq (SD – 0.15) in Group A and Group B, respectively, with no statistically significant difference between both groups (p = .58). At final follow-up, there was a significant improvement in mean near BCVA in amblyopic eye in both the groups (p, Group A < .01, Group B < .01) with no statistically significant difference between the two groups (p = .93). The mean stereoacuity at final follow-up was 512.3 arc secs and 165.74 arc secs in Group A and Group B, respectively. The median (IQR) stereoacuity at final follow-up was 200 (300) and 100 (137) for Group A and Group B, respectively. The difference between the two groups was statistically significant (p = .01) at 9 weeks and (p < .01) at 12 weeks. For intergroup comparison, while the difference in stereoacuity was not statistically different comparing anisometropia amblyopia subtype (p = .95), there was a statistically significant difference in stereoacuity at final follow-up for strabismic amblyopia (p = .04), with Group B having better stereoacuity. Conclusion: It is concluded that there is no significant difference between simultaneous and sequential group for BCVA, however sequential group yields better stereopsis as compared to simultaneous group.

PMID:40711760 | DOI:10.1080/09273972.2025.2537361

J Mater Chem B. 2025 Jul 25. doi: 10.1039/d5tb01157d. Online ahead of print.

ABSTRACT

Surgical precision in tumor resection critically relies on real-time intraoperative imaging, yet conventional probes face limitations in specificity and spatiotemporal control. Here, we present a tumor microenvironment (TME)-activated near-infrared (NIR) fluorescent nanoprobe (DNS-DYE/PEG-NI) that integrates dual responsiveness to hypoxia and glutathione (GSH) for submillimeter-level surgical navigation. The system comprises a GSH-activatable NIR fluorophore (λ_ex/em = 679/730 nm) quenched by 2,4-dinitrobenzenesulfonyl (DNS) moieties and hypoxia-sensitive amphiphilic PEG-NI micelles. Upon tumor accumulation via the enhanced permeability and retention (EPR) effect, a hypoxic TME triggers micelle disassembly through nitroimidazole (NI) reduction, releasing DNS-DYE. Subsequent GSH cleavage restores fluorescence via intramolecular charge transfer (ICT) recovery, achieving a 12.3-fold tumor-to-normal tissue signal ratio and >90% reduction in off-target activation compared to non-responsive controls. Systematic validation demonstrates: (1) dose-dependent fluorescence recovery (35-fold intensity increase at 10 mM GSH); (2) hypoxia-driven micelle destabilization (800% hydrodynamic diameter expansion); (3) sustained colloidal stability (12.9% size variation over 15 days); and (4) low cytotoxicity (cell viability >90% at 125 μg mL^-1). In vivo studies reveal precise tumor delineation within 12 h post-injection, enabling real-time resection of submillimeter lesions. By coupling TME-specific activation with prolonged tumor retention, this dual-responsive nanoprobe advances fluorescence-guided surgery toward precision oncology, reducing positive margin rates from 70% to <5% in preclinical models.

PMID:40711756 | DOI:10.1039/d5tb01157d

Ann Nucl Med. 2025 Jul 25. doi: 10.1007/s12149-025-02069-w. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the prognostic value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in patients with mucosal melanoma of the head and neck (MMHN) treated with carbon ion radiotherapy (CIRT).

METHODS: This single-center retrospective study included patients with MMHN who underwent CIRT and FDG-PET/CT. Correlations between pre-treatment FDG-PET/CT-derived parameters, including the maximum standardized uptake variable (SUVmax), metabolic tumor volume (MTV) with a 50% threshold, total lesion glycolysis (TLG), bone marrow/liver SUVmax and mean standardized uptake variable (SUVmean) ratios, and spleen/liver SUVmax and SUVmean ratios (SLRmax, SLRmean), with clinical parameters and prognosis were statistically analyzed.

RESULTS: A total of 32 patients with MMHN were enrolled (median age, 72.5 years). The tumor stages were distributed as follows: T3, 17 patients; T4a, 14 patients; T4b, one patient. The median total observation period was 22.6 months, the median overall survival (OS) was 21.6 months, and the median progression-free survival (PFS) was 11.5 months. Thirteen patients (40.6%) died, 10 (31.3%) experienced local recurrence, and 19 (59.4%) had distant metastases during the observation period. The 1 and 3-year survival rates were 78.1% and 62.5%, respectively. FDG-PET/CT showed pronounced positive uptake for all tumors (median SUVmax: 13.8, range 2.7-33.0). SLRmax was high in patients with negative programmed death-ligand 1 expression in the tumor (p = 0.05). PFS was shorter in patients with a high MTV (p = 0.018). In the multivariate analysis, MTV was an independent prognostic factor for PFS (hazard ratio, 2.60; 95% confidence interval, 1.065-6.345; p = 0.036). MTV and TLG were not predictive of OS in the univariate analysis.

CONCLUSIONS: FDG-PET/CT showed a strong positive uptake for MMHN. FDG-PET/CT-derived imaging parameters may be significant prognostic biomarkers for predicting tumor progression in patients with MMHN.

PMID:40711750 | DOI:10.1007/s12149-025-02069-w

Aging Clin Exp Res. 2025 Jul 25;37(1):232. doi: 10.1007/s40520-025-03138-w.

ABSTRACT

BACKGROUND: Some observational studies have indicated that osteoarthritis (OA) is a fall risk factor. However, the causal relationship between OA and falls remains unclear.

METHODS: We conducted a two-step Mendelian randomization (MR) to investigate the causal relationships between OA, paracetamol use, and the risk of falls and to estimate the mediating effect of paracetamol use. Publicly accessible data for hip OA, knee OA, paracetamol use, and falling risk were sourced from Genome-Wide Association Studies (GWAS).

RESULT: In the forward MR analysis, the Inverse Variance Weighted (IVW) method indicated that a genetic predisposition to hip OA was significantly associated with an increased risk of falls (OR: 1.053, 95% CI: 1.014 to 1.094, P = 0.007). Consistent directions of effect were observed across other MR analysis methods. The mediated proportion of paracetamol use on the relationship between hip OA and falling risk was 21.70% (β = 0.0113, 95% CI: 5.73-37.8%, P = 0.0078). No causal relationship was observed between knee OA and falling risk, nor between knee OA and the use of paracetamol. In the reversed MR analysis, the IVW method showed that a genetic predisposition to falls may not increase the risk of developing hip and knee OA.

CONCLUSION: These results provide genetic evidence for a causal effect of hip OA on fall risk, partially mediated by paracetamol, and underscore the importance of fall prevention education and cautious paracetamol use for patients with hip OA.

PMID:40711723 | DOI:10.1007/s40520-025-03138-w

Ophthalmol Ther. 2025 Jul 25. doi: 10.1007/s40123-025-01194-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Ocular redness is common, can affect quality of life, and can be relieved by short-term use of topical adrenergic receptor (AR) agonists. Brimonidine tartrate ophthalmic solution 0.025% (LUMIFY^® 0.025%) is the first α2-AR-selective agonist approved for ocular redness. The preservative benzalkonium chloride (BAK) maintains ophthalmic solution sterility, reducing the risk of ocular infections, but may cause symptoms of ocular surface disease (OSD) in some patients. A BAK-free formulation of LUMIFY 0.025% (BTOS-PF 0.025%) could offer a solution for BAK-sensitive patients.

METHODS: This randomized, active-controlled, multicenter study aimed to establish non-inferior efficacy of BTOS-PF 0.025% to LUMIFY 0.025% and compare safety. Randomized participants received either formulation instilled as a single drop four times daily, for 4 weeks. The primary endpoint was investigator-assessed ocular redness at 5, 15, 30, 60, 90, 120, 180, and 240 min post-instillation at visit 1 (day 1). Eight hierarchical secondary endpoints included additional post-instillation timepoints at visit 1 and visits 2 and 3 (days 14 and 28), and participant-assessed redness.

RESULTS: BTOS-PF 0.025% was statistically non-inferior to LUMIFY 0.025% for ocular redness reduction across the eight timepoints at visit 1. Efficacy for both formulations was seen as early as 1 min and up to 8 h post-instillation. BTOS-PF 0.025% performed similarly to LUMIFY 0.025% after 14 and 28 days, rebound redness rates were low and similar, and total clearance of ocular redness and participant-evaluated redness were similar. The safety profile of both formulations was similar, with no severe or serious ocular events.

CONCLUSIONS: BTOS-PF 0.025% was non-inferior to LUMIFY 0.025% in reducing ocular redness in adults, was well-tolerated, and offers an alternative topical solution, without loss of efficacy or compromised safety, for patients who prefer a preservative-free formulation or are at increased risk of OSD.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05360784. Date of registration: 29 April 2022.

PMID:40711722 | DOI:10.1007/s40123-025-01194-z

Pulm Ther. 2025 Jul 25. doi: 10.1007/s41030-025-00307-0. Online ahead of print.

ABSTRACT

INTRODUCTION: A common complication of interstitial lung disease (ILD) is pulmonary hypertension (PH), which is associated with increased morbidity and mortality and worsened quality of life. In ILD, evaluating for PH is recommended prior to lung transplantation. However, this is not standardized or routinely performed in earlier stages of ILD, and guidelines lack an evidence-based approach for PH screening in this population. Furthermore, right-heart catheterization (RHC) access can be limited in many settings. The objective of PHINDER (Pulmonary Hypertension Screening in Patients with Interstitial Lung Disease for Earlier Detection) is to prospectively develop screening strategies for PH in patients with ILD.

METHODS: PHINDER is a prospective, non-interventional study that will enroll approximately 200 patients with ILD treated in a variety of settings in the United States (community centers, academic institutions, etc.). Patients must be diagnosed with ILD by high-resolution computed tomography (HRCT) and must not have a previously reported mean pulmonary arterial pressure (mPAP) > 20 mmHg. To enrich the population for PH, patients must meet additional criteria on Pulmonary Function Tests, HRCT, signs/symptoms, 6-min walk test, or echocardiography. Patients will undergo a variety of routine ILD clinical assessments. Lastly, patients receive a RHC to assess for PH, defined as mPAP > 20 mmHg with pulmonary arterial wedge pressure ≤ 15 mmHg and a pulmonary vascular resistance > 2 Wood Units. All treatment decisions are at the discretion of the provider and not influenced by study participation.

PLANNED OUTCOMES: Following study completion, statistical tools will be used to derive a practical model for a screening algorithm using the variables identified in the study as most predictive of PH in patients with ILD.

CONCLUSIONS: Using a previously developed list of clinical assessments from PH and ILD experts, the PHINDER study aims to be the first prospectively enrolled study to evaluate prognostic screening strategies that can be used to develop an algorithm to predict the risk of PH in patients with ILD.

TRAIL REGISTRATION: NCT05776225.

PMID:40711711 | DOI:10.1007/s41030-025-00307-0

Health Justice. 2025 Jul 25;13(1):46. doi: 10.1186/s40352-025-00356-2.

ABSTRACT

BACKGROUND: As the opioid overdose crisis continues to produce excessive morbidity and mortality in the United States, government agencies have applied various approaches to prevent overdoses, including law-enforcement efforts (e.g., arresting people who use drugs, interrupting drug traffickers, etc.) and treatment-based approaches (e.g., naloxone, medications for opioid use disorder, etc.). Public perception and support of these approaches are relevant for informing policy, allocating resources, and effectively implementing community interventions to prevent drug-related harms.

METHODS: Using an embedded informational survey design, we experimentally assessed whether public support for strategies to prevent overdose in South Carolina is influenced by language from federal agencies describing treatment- or enforcement-based approaches. Respondents were randomly assigned to one of three groups: (1) enforcement -based approach, (2) treatment-based approach, or (3) the control condition. Those assigned to experimental groups were presented with statistics on drug overdose deaths, followed by an informational prompt with language about overdose prevention approaches from either DEA (enforcement) or NIH (treatment), while the control group received no informational prompt.

RESULTS: Findings from a sample of 4,675 respondents indicated that those assigned the DEA prompt were significantly more likely to support enforcement-based approaches in arresting drug traffickers and people who use drugs (AME = 0.060, p < 0.001). On the other hand, those assigned to the NIH prompt were significantly more likely to agree that both law enforcement (AME = 0.065, p < 0.0001) and clinicians (AME = 0.044, p < 0.05) are capable of preventing drug overdose deaths.

CONCLUSIONS: These findings shed light on public perceptions of approaches to addressing the opioid epidemic and limited modifiability when presented with language from federal agencies. This may inform future research, practice, and/or policy aiming to maintain public safety while also providing treatment options to people who use drugs in order to reduce overdose deaths.

PMID:40711698 | DOI:10.1186/s40352-025-00356-2

Pharmacoecon Open. 2025 Jul 25. doi: 10.1007/s41669-025-00595-x. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients surviving a non-ST-elevation myocardial infarction (NSTEMI) have an elevated risk of future major adverse cardiovascular events (MACE), which can be mitigated through long-term cardiac arrhythmia monitoring. The present study evaluated the cost-effectiveness of continuous remote arrhythmia monitoring using an insertable cardiac monitor (ICM) combined with standard of care (SoC) compared with SoC alone.

METHODS: A cost-effectiveness analysis using a lifetime partitioned survival model was developed for high-risk NSTEMI patients from a UK National Health Service (NHS) perspective. Survival analysis was used to determine the transition of patients from the pre-MACE health state (where patients could experience arrhythmia, major bleeding, or systemic embolism) to the MACE health state (worsening heart failure, stroke, and acute coronary syndrome events). The survival analysis and arrhythmia diagnosis rates were informed by the BIO|GUARD-MI trial. The model captured direct costs associated with each MACE and implantation and removal of the ICM device and treatment costs following arrhythmia detection. The model captured the health implications for an ICM with SoC, compared with SoC alone, in terms of the total quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were undertaken to explore the impact of parameter uncertainty on the model results.

RESULTS: The use of ICMs plus SoC for daily remote cardiac arrhythmia monitoring is cost effective, when compared with SoC alone, in high-risk NSTEMI patients over a lifetime horizon, with an incremental cost-effectiveness ratio of £7766 per QALY gained. The ICM was associated with an additional 0.184 QALYs per patient for an additional cost of £1430. The ICM remained cost effective during the deterministic and probabilistic sensitivity analyses.

CONCLUSION: The addition of an ICM to SoC in high-risk NSTEMI patients is cost effective from the perspective of the UK NHS and would, therefore, be a further option for the management of such patients in clinical practice.

PMID:40711697 | DOI:10.1007/s41669-025-00595-x

Ann Surg Oncol. 2025 Jul 25. doi: 10.1245/s10434-025-17840-6. Online ahead of print.

ABSTRACT

BACKGROUND: Extended pelvic lymph node dissection (ePLND) plays a critical role in the accurate staging of prostate cancer; however, it is associated with increased perioperative morbidity. Refinement of the indications for ePLND through the identification of predictive factors for contralateral lymph node involvement (LNI) may contribute to minimizing overtreatment and associated complications.

PATIENTS AND METHODS: In this retrospective study, we analyzed a cohort of 223 patients with clinically unilateral prostate cancer who underwent robot-assisted radical prostatectomy combined with bilateral ePLND. Tumor laterality was defined by biopsy and magnetic resonance imaging (MRI) findings. Associations between preoperative clinical factors and contralateral LNI were assessed using statistical tests.

RESULTS: Contralateral LNI was significantly associated with PSA ≥10 ng/mL (6.3% vs. 0.7%; p = 0.047) and ≥66% positive biopsy cores in the ipsilateral lobe (8.0% vs. 0%; p = 0.0037). A risk classification model combining these two factors identified a high-risk group with 13.2% incidence of contralateral LNI, compared with 0.5% in the low-risk group (p = 0.0003).

CONCLUSIONS: PSA level at diagnosis and the proportion of positive biopsy cores in the ipsilateral lobe are useful predictors of contralateral LNI in clinically unilateral prostate cancer. A preoperative risk model incorporating these variables may support a tailored approach to ePLND, minimizing surgical burden without compromising diagnostic accuracy.

PMID:40711688 | DOI:10.1245/s10434-025-17840-6