Tag: nevin manimala

Neurology. 2026 Jul 14;107(1):e218198. doi: 10.1212/WNL.0000000000218198. Epub 2026 Jun 18.

ABSTRACT

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF)-associated ischemic stroke is often managed as a single clinical entity; however, prognosis may vary depending on whether AF was detected after the stroke or whether the stroke occurred despite prior oral anticoagulant (OAC) use. We aimed to describe long-term outcomes after ischemic stroke across 3 distinct AF phenotypes: AF complicated by ischemic stroke despite prior anticoagulation (AFIDA), AF complicated by ischemic stroke without prior anticoagulation (OAC-naive AF), and AF detected after stroke (AFDAS).

METHODS: This nationwide cohort study used the DeSC-IQVIA database, an administrative claims database covering approximately 16 million individuals in Japan. Adult stroke survivors with AF discharged with OAC prescriptions between April 2014 and January 2025 were included. Three mutually exclusive AF phenotypes defined by AF detection timing and prior anticoagulation status: AFIDA, OAC-naive AF, and AFDAS (diagnosed during the index hospitalization). The primary outcomes were hospitalization for recurrent ischemic stroke or systemic embolism (SE). The secondary outcomes included major bleeding, heart failure (HF) hospitalization, and all-cause mortality. Cumulative incidence was estimated using the Aalen-Johansen method, accounting for the competing risk of death. Adjusted subdistribution hazard ratios (aSHRs) were estimated using Fine-Gray models.

RESULTS: Among 21,586 patients (median age, 83 years [interquartile range (IQR), 78-88 years]; 10,604 [49.1%] female), 6,604 (30.6%) were classified as having AFIDA, 11,875 (55.0%) as having OAC-naive AF, and 3,107 (14.4%) as having AFDAS. During the 38,593 person-years of follow-up, 2,028 patients experienced stroke/SE. The 5-year cumulative incidence of stroke/SE was highest in AFIDA (18.6% [95% CI 17.0%-20.2%]), followed by OAC-naive AF (13.0% [95% CI 12.0%-13.9%]) and AFDAS (10.5% [95% CI 9.0%-12.1%]). Compared with OAC-naive AF, AFIDA was associated with a higher risk of recurrent stroke/SE (aSHR, 1.38; 95% CI 1.25-1.52), whereas AFDAS was associated with a lower risk (aSHR, 0.87; 95% CI 0.75-1.00). Among secondary outcomes, AFIDA showed an increased risk of HF hospitalization (aSHR, 1.15; 95% CI 1.02-1.31).

DISCUSSION: Long-term prognosis after AF-associated stroke is heterogeneous across AF phenotypes, with AFIDA representing a high-risk group and AFDAS representing a low-risk group. These findings highlight the need to treat these clinically identifiable phenotypes as distinct target populations for secondary prevention strategies and future clinical trials.

PMID:42314108 | DOI:10.1212/WNL.0000000000218198

Neurology. 2026 Jul 14;107(1):e218179. doi: 10.1212/WNL.0000000000218179. Epub 2026 Jun 18.

ABSTRACT

BACKGROUND AND OBJECTIVES: Recent randomized trials reported no overall functional benefit of endovascular treatment (EVT) for distal medium-vessel occlusion (DMVO) and did not identify consistent effect modifiers to guide patient selection. Consequently, the role of EVT-particularly for M2 occlusions-remains controversial. We investigated whether baseline clinical severity modifies the association between successful recanalization and 90-day outcome in patients with M2 occlusion.

METHODS: Multicenter retrospective cohort study at 2 tertiary stroke centers including consecutive adults with acute ischemic stroke due to M2 occlusion (January 2015-January 2023) triaged by multimodal CT and treated with EVT. The primary end point was functional independence (modified Rankin Scale [mRS] ≤ 2) at 90 days. Secondary end points included symptomatic intracerebral hemorrhage (sICH), mRS 0-1, and penumbra salvage volume (PSV). The primary analysis used multivariable logistic regression with baseline National Institutes of Health Stroke Scale (NIHSS) modeled linearly and an NIHSS×recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2b) interaction term. Johnson-Neyman probing and inverse probability weighting (IPW) were applied; a supplementary restricted cubic spline analysis was performed to explore potential nonlinearity.

RESULTS: Among 147 patients, 85 (58%) achieved successful recanalization. The mean age was 74 years (SD 13), and 47% were female. Higher baseline NIHSS (adjusted odds ratio [aOR] 0.83 per point, 95% CI 0.73-0.94) and older age (aOR 0.96 per year, 95% CI 0.94-0.99) were associated with lower odds of functional independence. NIHSS significantly modified the association between recanalization and outcome (interaction p = 0.03). The magnitude of the association between successful recanalization and functional independence was larger at higher NIHSS. Model-based estimates suggested a descriptive crossover around NIHSS 10, whereas statistical evidence of benefit emerged only at higher NIHSS values. Successful recanalization was associated with greater PSV (+33 mL, p = 0.01). In the PSV interaction model, onset-to-imaging time differed by recanalization status (p < 0.01): time was positively associated with PSV in the mTICI ≤2a group, but near zero in mTICI ≥2b. IPW analyses were concordant. sICH occurred in 8.2% vs 4.8% (p = 0.42).

DISCUSSION: In M2 occlusions, the magnitude of the association between successful recanalization and functional independence was larger at higher NIHSS and not reliably demonstrable at lower NIHSS. These findings support a severity-informed, individualized EVT approach while remaining hypothesis-generating rather than prescriptive for specific NIHSS thresholds. Major limitations include the retrospective observational design and potential residual confounding.

PMID:42314098 | DOI:10.1212/WNL.0000000000218179

JCO Oncol Pract. 2026 Jun 18:OP2501191. doi: 10.1200/OP-25-01191. Online ahead of print.

ABSTRACT

PURPOSE: Given the importance of timely comprehensive genomic profiling (CGP) for the treatment of cancer, this study aimed to provide generalizable estimates of turnaround time (TAT) for tissue-based CGP. Secondary aims were to identify TAT trends over time and explain variation based on clinical, demographic, and administrative factors.

METHODS: Data for solid tumor samples profiled from 2018 through 2024 from a commercial laboratory were analyzed. Descriptive statistics were used to summarize and compare TAT between sites. Linear regression was used to assess for yearly trends and to measure associations between clinical, demographic, and administrative variables and TAT.

RESULTS: A total of 271,574 solid tumor malignancies originating from 5,497 clinical sites were included in the analysis. The overall TAT (specimen collection to CGP results reporting) decreased from a median of 43 days (IQR, 31-72) to 32 days (IQR, 22-51) from 2018 to 2024. When comparing overall TAT for 2024 by clinical site, the shortest and longest overall TAT quintiles were 23.1 days (IQR, 20.6-24.6) and 46.5 days (IQR, 42.7-50.8), respectively (P < .001). There was variability in timeliness of ordering between sites with a median time from biopsy to CGP ordering of 10.0 days (IQR, 8.0-12.0) versus 30.8 days (IQR, 26.6-35.0) for the shortest and longest quintiles, respectively. Factors associated with shorter ordering and overall TAT included, but were not limited to, higher clinical site ordering volumes, cancer type, and ordering method.

CONCLUSION: Delay in the time from biopsy to CGP ordering was the largest contributor to protracted TAT and varied between clinical sites. Increasingly, the appropriate treatment of cancer is dependent on biomarker testing and delays in testing likely contribute to suboptimal patient care.

PMID:42314086 | DOI:10.1200/OP-25-01191

Arthroscopy. 2026 Jun 18. doi: 10.1002/arj.70370. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the impact of preoperative glucagon-like peptide-1 receptor agonist (GLP-1 RA) use on medical complications, emergency department use, and orthopaedic complications in obese patients undergoing arthroscopic rotator cuff repair.

METHODS: Obese patients (defined by relevant ICD-10 codes and confirmed by body mass index measurements) undergoing primary arthroscopic rotator cuff repair before June 2023 with at least 2-year follow-up were found in the TriNetX database and stratified according to GLP-1 RA use before surgery. Patients prescribed GLP-1 RAs were propensity-matched 1:1 to non-GLP-1 RAs controls by age, sex, ethnicity, and comorbidities. Outcomes assessed included emergency department use at 30 and 90 days, medical complications assessed at 90 days, and orthopaedic complications (including revision, retear, and conversion to arthroplasty rates, defined by ICD-10 codes) assessed at 1 and 2 years postoperatively. Statistical analysis was performed using TriNetX’s built-in statistical platform.

RESULTS: Following matching, both cohorts consisted of 1183 patients and had no baseline differences. At 90 days, there were no significant differences in medical complications, including acute kidney injury, pneumonia, venous thromboembolism, urinary tract infection, or cardiac events. At 1 and 2 years, GLP-1 RA use was associated with significantly lower revision rates after left-sided repairs (2.3% vs 7.2%, OR 0.3, P < .001; 4.0% vs 8.2%, OR 0.5, P = .010, respectively). In subgroup analyses, women undergoing left-sided repairs showed significantly lower retear rates at both 1 and 2 years (19.1% vs 30.9%, OR 0.5, P = .009; 20.2% vs 33.5%, OR 0.5, P = .004).

CONCLUSIONS: GLP-1 RAs appear to be generally safe for preoperative use in obese patients undergoing arthroscopic rotator cuff repair and were associated with decreased rates of revision and retear in certain subgroups.

LEVEL OF EVIDENCE: Level III, retrospective comparative case series.

PMID:42314072 | DOI:10.1002/arj.70370

Integr Comp Biol. 2026 Jun 18:icag092. doi: 10.1093/icb/icag092. Online ahead of print.

ABSTRACT

The study of endocrinology provides insights into the upstream drivers of behavior and physiology of wild and captive populations to both natural and anthropogenic stressors. Most studies of wildlife endocrinology rely on single samples from multiple individuals to understand differences between different demographic states or populations. However, neither stressors nor hormone secretion are static, fluctuating over time within and between individuals. The use of non-traditional sample types that accumulate hormone concentrations through time, or repeated sampling of individuals through time can elucidate natural hormone fluctuations and the influence of stressors over time. With studies containing a temporal component come numerous challenges when interpreting and analyzing the data due to the inherent correlation between data points. Time series analysis is a group of statistical methods that were developed to analyze data collected with a temporal component. Here we present a review of classic time series analysis methods, describing how they can be used with endocrinology data while providing worked examples and R code. By integrating time series analysis into endocrinology studies, researchers can get a better understanding of the temporal and individual variation in specific hormones. Through highlighting these tools and how they can be applied, we hope that they can be more readily available to all members of the endocrinology field to further understand wildlife endocrinology.

PMID:42314067 | DOI:10.1093/icb/icag092

Adv Sci (Weinh). 2026 Jun 18:e76142. doi: 10.1002/advs.76142. Online ahead of print.

ABSTRACT

Spatial transcriptomics (ST) enables the study of tissue architecture by resolving gene expression in space, but current ST platforms are constrained by limited sequencing depth and indirect single-cell identification. Existing deconvolution methods that integrate single-cell RNA sequencing (scRNA-seq) data with ST often overlook the biological principle that cells in communication with each other tend to be closer spatially. Here we introduce SPADE, a deep learning framework that aligns scRNA-seq data to spatial locations by jointly modeling expression similarity between scRNA-seq and ST data and concordance between the spot distance and cell-cell communication (CCC) patterns. SPADE also enables quantitative characterization of CCC across spots and regions. Evaluations on 55 simulated and real datasets show that SPADE achieves strong performance in recovering region-specific cell-type patterns and enhancing spatial gene expression profiles compared with existing methods. In the breast cancer datasets, SPADE demonstrates a unique advantage in identifying tumor-infiltrating immune cells and tertiary lymphoid structures. In the colorectal cancer liver metastasis dataset, SPADE distinguishes tumor heterogeneity with region-specific CCC events and describes the general CCC landscape in the tissue. Overall, SPADE highlights the key role of spatially constrained CCC in shaping tissue organization and enables biological interpretation of spatial transcriptomics data.

PMID:42314058 | DOI:10.1002/advs.76142

JMIR Form Res. 2026 Jun 18;10:e82923. doi: 10.2196/82923.

ABSTRACT

BACKGROUND: The clinical diagnosis rate of adenoid hypertrophy (AH) in children has increased in recent years, drawing growing attention from parents. Short-video platforms such as Bilibili, TikTok, and Xiaohongshu host a large volume of educational content on this condition. However, the quality and reliability of this information remain unclear.

OBJECTIVE: This study aimed to evaluate the completeness, understandability, actionability, reliability, and overall quality of short videos on AH across Bilibili, TikTok, and Xiaohongshu and to explore factors associated with these quality metrics, including uploader characteristics and engagement indicators.

METHODS: We collected 220 videos (Bilibili: n=90, 40.9%; TikTok: n=63, 28.6%; and Xiaohongshu: n=67, 30.5%) using newly registered accounts. Two independent reviewers evaluated video quality using a 6-item content completeness scale (score range 0-12), the Patient Education Materials Assessment Tool for Audiovisual Materials, the modified DISCERN instrument, and the Global Quality Scale (GQS). Interrater reliability was high (Cohen κ=0.77-0.993). Completeness assessed essential informational components of AH. As data were nonnormally distributed, results are presented as median (IQR). Cross-platform comparisons were conducted using the Kruskal-Wallis H test with post hoc Mann-Whitney U tests (with Bonferroni correction). Spearman correlation was used to explore associations between video characteristics (ie, duration and engagement metrics) and quality outcomes. Stepwise linear regression identified independent predictors of overall quality (GQS).

RESULTS: Video duration differed significantly across platforms (Bilibili: median 113.5, IQR 66.5-271.5 seconds; TikTok: median 73, IQR 44-100 seconds; and Xiaohongshu: median 63, IQR 41-127.5 seconds; P<.001). Bilibili videos demonstrated higher completeness than videos on the other 2 platforms (Bilibili: median 2, IQR 1.5-4.0; TikTok: median 1.5, IQR 0.5-2.0; and Xiaohongshu: median 1.5, IQR 0.5-2.8; P<.001); overall differences were observed for understandability and reliability, but pairwise comparisons did not reach statistical significance after Bonferroni correction. Xiaohongshu videos showed greater actionability than TikTok videos (P=.011). Medical professionals (n=158, 71.8%) had higher understandability than nonprofessionals (n=158, 81.8% vs n=62, 66.7%; P=.001). Video duration positively correlated with completeness (ρ=0.64, 95% CI 0.56-0.71; P<.001). Shares showed weak positive correlations with completeness and actionability. Stepwise regression identified understandability (using the Patient Education Materials Assessment Tool-Understandability) as the strongest independent predictor of overall quality (GQS), followed by actionability, video duration, and uploader type; engagement metrics and platform did not enter the final model.

CONCLUSIONS: The quality of AH-related videos on Chinese short-video platforms is generally suboptimal. Bilibili offers higher completeness, while Xiaohongshu excels in actionability and interactivity. Understandability is the strongest predictor of overall quality, surpassing uploader type and engagement metrics. To improve online health information, platforms should move beyond engagement-based algorithms, and health care professionals should prioritize clear, actionable content.

PMID:42314031 | DOI:10.2196/82923

Prostate. 2026 Jun 18. doi: 10.1002/pros.70210. Online ahead of print.

ABSTRACT

BACKGROUND: PI-RADS 3 lesions represent a diagnostic “gray zone” in which biopsy decision-making is particularly challenging, with reported clinically significant prostate cancer (csPCa) detection rates ranging from 13% to 50%. This study evaluated the predictive value of the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR)-alone and in combination with PSA density (PSAD) and PI-RADS score-for the detection of prostate cancer (PCa) and csPCa, with a specific focus on the PI-RADS 3 subgroup.

METHODS: In this two-center retrospective observational study, 982 patients who underwent prostate biopsy between 2020 and 2025 were included. csPCa was defined as ISUP Grade Group ≥ 2. Univariable and multivariable logistic regression analyzes were performed to identify independent predictors of PCa and csPCa. In the PI-RADS 3 subgroup (n = 251), two predictive models were compared using receiver operating characteristic analysis and the DeLong test: Model 1 (age, free/total PSA ratio, PSAD) and Model 2 (Model 1 + SII + NLR).

RESULTS: Of the 982 patients, 188 (19.1%) were diagnosed with PCa and 150 (15.3%) with csPCa. In the overall cohort, NLR ≥ 2.11 was independently associated with csPCa (OR, 15.924; 95% CI, 2.472-102.567; p = 0.004), whereas SII did not retain independent significance. PLR showed an inverse association with PCa, possibly reflecting tumor-related platelet dynamics. In the PI-RADS 3 subgroup, SII ≥ 661.37 (OR, 2.317; p = 0.039) remained an independent predictor of PCa alongside age, free/total PSA ratio, and PSAD ≥ 0.20 (OR, 6.111; p = 0.013), while NLR showed borderline significance. The addition of SII and NLR to the clinical model increased the AUC from 0.795 to 0.816 in the PI-RADS 3 subgroup, although this improvement did not reach statistical significance (p = 0.134).

CONCLUSIONS: Systemic inflammatory markers-particularly SII and NLR-provide complementary predictive information in the pre-biopsy risk stratification of prostate cancer. SII emerged as an independent predictor of PCa specifically within the PI-RADS 3 gray zone, while NLR independently predicted csPCa in the overall cohort. These routinely available, low-cost parameters may serve as practical adjuncts to PSA derivatives and mpMRI in the individualization of biopsy decisions, particularly for PI-RADS 3 patients.

PMID:42314010 | DOI:10.1002/pros.70210

JMIR Res Protoc. 2026 Jun 18;15:e99833. doi: 10.2196/99833.

ABSTRACT

BACKGROUND: Chronic pain affects over 30% of the global population and remains a major public health issue due to limited treatment efficacy and the need for mechanism-based, personalized approaches. Motor behavior is theorized to play a role in pain persistence through altered movement patterns, muscle recruitment, and proprioception. While motor behavior is linked to chronic pain, empirical evidence on underlying mechanisms, particularly cortical dynamics, remains scarce.

OBJECTIVE: This study aimed to investigate longitudinal changes in cortical sensorimotor excitability and their relationship with maladaptive motor behaviors.

METHODS: This prospective longitudinal study will follow 150 healthy participants, aged 18-65 years, recruited from the community, experiencing experimentally induced muscle pain across 4 visits (day 0, day +2, day +4, and 5 days after pain resolution). Pain will be induced using intramuscular injections of nerve growth factor into the extensor carpi radialis brevis muscle. The primary outcome is motor variability assessed during multidimensional wrist movement tasks, and quantified using root-mean-square deviation and muscle synergies (derived from electromyographic recordings of 4 forearm muscles). Secondary outcomes include cortical mechanisms (electroencephalographic peak alpha frequency, transcranial magnetic stimulation mapping, short-interval intracortical inhibition, and intracortical facilitation), sensorimotor integration (evoked potential), cognitive control (multisource interference task), and endogenous pain modulation (conditioned pain modulation). Self-report questionnaires will assess pain intensity and disability (Patient-Rated Tennis Elbow Evaluation, McGill Pain Questionnaire-Short Form, and Likert Muscle Soreness Scale) as well as psychological factors such as fear of movement, pain-related beliefs, and coping strategies (Tampa Scale for Kinesiophobia, Pain Beliefs Questionnaire, and Coping Strategies Questionnaire-Revised). This sample size provides 80% power at 5% significance to detect a medium effect size across 23 predictor variables, with Bonferroni correction and 10% loss-to-follow-up allowance. Data will be analyzed using 2-level growth curve modeling to characterize interindividual differences in motor behavior, cortical dynamics, and pain processing trajectories.

RESULTS: All study procedures have been approved by the Western University Health Science Research Ethics Board (review reference 2025-125757-103291). Funding was provided by the Canadian Institutes of Health Research under grant number 517783 for the period 2024-2029. Recruitment for the study began in April 2025, and all data collection is expected to be completed by 2028. As of April 2026, we have enrolled 26 participants. Results are expected to be published at the end of 2028.

CONCLUSIONS: The findings will advance understanding of motor behavior in pain and lay the foundation for personalized therapies, moving beyond current generic treatments that offer limited benefits.

PMID:42313885 | DOI:10.2196/99833

Clin Transl Allergy. 2026 Jun;16(6):e70176. doi: 10.1002/clt2.70176.

ABSTRACT

BACKGROUND: Multiple routes of allergen immunotherapy (AIT) are approved for several IgE-mediated allergic diseases; however, the use of AIT in eosinophilic esophagitis (EoE) remains controversial and is supported by limited evidence. This review, conducted within the frame of an EAACI Task Force, aims to systematically evaluate the use of AIT as a potential treatment for EoE.

METHODS: The protocol was registered and prepared in accordance with PRISMA guidelines. The literature search was conducted across three online databases (PubMed, Embase, and Scopus) and included studies published through January 31^st, 2025. Risk of Bias was assessed for each eligible study.

RESULTS: Four articles met the inclusion criteria. Three articles evaluated EPIT for milk-induced EoE in pediatric patients, all from the SMILEE (Study of Efficacy and Safety of Viaskin Milk for milk-induced EoE) trial and its extensions. These included a randomized, placebo-controlled trial, its open-label extension, and a pilot immunological study. The SMILEE trial found no statistically significant difference in tissue eosinophilia between the active (EPIT) and control (placebo) arms in the intention-to-treat population, while 47% of treated EoE patients tolerated milk without recurrence of esophageal eosinophilia. This finding was further supported by a subsequent open-label study with a 2-year follow-up. In the third publication, the researchers found that EPIT was associated with decreased Th2-related transcripts and increased regulatory T-cell-associated transcripts. Only one eligible study evaluated the use of SCIT for treating EoE. It was a retrospective case-control study reporting that SCIT had a neutral effect and yielded inconclusive findings regarding the course of EoE.

CONCLUSION: There is insufficient high-quality evidence to support the effectiveness of alternative routes of AIT for the treatment of EoE, either as an add-on or a standalone treatment.

PMID:42313883 | DOI:10.1002/clt2.70176