Citations

Abstract Background Women remain underrepresented in alcohol use disorder (AUD) research despite sex- and gender-specific health disparities and barriers to treatment. Community-engaged approaches can identify opportunities for patient-centered comparative effectiveness research (CER) that reflect women’s lived experiences. The WomenWise project used community engaged, bi-directional, partnered learning sessions (PLS) to qualitatively explore women’s perspectives on alcohol misuse, treatment barriers, and priorities for future CER. Methods In 2025, we conducted five 90-minute PLSs via Zoom with attendees who were aged ≥ 18 years, self-identified as a woman, reported lived experience of alcohol misuse, were a family member/caregiver of a woman with AUD, and were affiliated with a WomenWise partner organization or a healthcare provider treating AUD. Moderated PLSs focused on bi-directional knowledge exchange and sharing of experiences. Audio transcripts, Zoom chat content, and one asynchronous online discussion thread were analyzed using reflexive thematic analysis. Suggested future CER topics generated during sessions were presented to the WomenWise community advisory board (CAB), which ranked priority topics by vote. Results In total, 51 attendees shared their experiences. The major themes centered on a sense of shame and stigma unique to women, with many attendees mentioning gendered norms, “mom culture,” “quiet drinking,” and caregiver role strain. Barriers to treatment included structural challenges, poor healthcare provider communication, the need for trauma-informed care, and concerns about privacy particularly in rural areas. Six future CER topics emerged, of which the CAB selected three priorities: (1) harm reduction/moderation versus abstinence-only approaches, (2) trauma-focused care versus standard AUD treatment, and (3) care access and engagement strategies. Conclusions These bidirectional, co-learning sessions identified patient-centered, community-informed priorities for future AUD research in women. The findings highlight the importance of addressing stigma, trauma, structural barriers, and provider communication when designing future women-centered treatment studies and care models.

Purpose To assess the reliability, predictability, and discriminative capacity of 3 anatomic measurements, tibial tubercle‐trochlear groove (TT‐TG), tibial tubercle‐posterior cruciate ligament, and patellar tendon‐lateral trochlear ridge (PT‐LTR), where PT‐LTR may offer a complementary approach to assessing recurrent patellofemoral instability (PFI) risk. Methods Patients diagnosed with PFI before primary patellofemoral stabilization surgery at a single institution between 2022 and 2024 were included. A control group without PFI was propensity matched 1:1 for age, sex, and laterality. Magnetic resonance images were evaluated to measure TT‐TG, tibial tubercle‐posterior cruciate ligament, and PT‐LTR. A priori power analysis determined the cohort size. Statistical analyses compared differences between the PFI and control groups with Student t‐tests, receiver operating characteristic analyses, and area under the curve with resultant sensitivity, specificity, and an optimal cutoff. Results Patients included 50 knees with PFI (28 women, 22 men; mean age 18 ± 5 years). The control group included 50 knees (27 women, 23 men; mean age 18 ± 4 years). Excellent inter‐ and intra‐rater reliability (intraclass correlation coefficient > 0.7) was shown for TT‐TG and PT‐LTR in the PFI and control groups. The distances for TT‐TG, tibial tubercle‐posterior cruciate ligament, and PT‐LTR were significant predictors ( P ≤ .025) of PFI. The average PT‐LTR distance difference for the PFI and control groups was 7.0 mm ( P < .001). PT‐LTR showed an area under the curve of 0.80 and, when ≥4.6 mm, was 66% sensitive and 92% specific for PFI. Conclusions The PT‐LTR distance is a reliable and discriminative metric for identifying PFI in both pediatric and adult populations. A PT‐LTR cutoff value of 4.6 mm showed diagnostic discrimination and substantially high specificity for recurrent PFI, indicating strong ability to identify patients with instability. Level of Evidence Level III, retrospective case control study.

Transcranial magnetic stimulation can provide noninvasive measures of cortical excitability and plasticity, but relationships between these measures and clinically observable features of autism are not fully characterized. Nineteen autistic participants aged 15 to 40 years were included in the analysis of a left primary motor cortex continuous theta-burst stimulation (cTBS) biomarker protocol. Motor evoked potentials were measured at baseline and at seven assessments from 5 to 60 min after stimulation. Linear mixed-effects models evaluated whether clinical measures moderated the post-stimulation motor evoked potential log-response ratio over time. Aberrant Behavior Checklist (ABC) and Attenuated Behavior Questionnaire (ABQ) analyses were restricted to the same 15 participants with caregiver-informant assessments. Catatonia severity, social impairment, ABQ Motor Total, ABQ Total, and cognitive ability did not significantly moderate the post-stimulation response. ABC Inappropriate Speech was associated with progressively greater post-stimulation facilitation (standardized Time-by-Inappropriate Speech interaction: beta = +0.688, SE = 0.210, 95% CI +0.276 to +1.099; Holm-adjusted P = .008 across eight informant-rated models). Two individual speech-related items ("Talks excessively" and "Talks to self loudly") survived false-discovery-rate correction. An exploratory eight-item ABC phenotype showed a large descriptive in-sample association (beta = +0.904, SE = 0.200, P less than .001) and directionally positive held-out performance. However, full-pipeline permutation tests were nonsignificant for both Pearson (r = .357, two-sided empirical P = .360) and Spearman correlations (rho = .446, two-sided empirical P = .261). Caregiver-rated inappropriate speech may be associated with altered post-cTBS motor cortical facilitation in autism. The candidate phenotype remains hypothesis-generating and requires independent validation.

Summary Background Clonal haematopoiesis (CH), the age-related expansion of mutated blood stem cells, is detectable in around 10% of people in their seventies, rises steeply with age, and is associated with several diseases. Its relationship with neurodegeneration remains contentious, with conflicting evidence for both protective and detrimental effects on Alzheimer’s disease (AD). Methods Here, we applied COMET, a mutation-agnostic, methylation-based predictor of clonal haematopoiesis burden that estimates predicted VAF (pVAF), to examine longitudinal associations between clonal burden and brain structure in the Lothian Birth Cohort 1936. In addition, to capture broader clonal burden, we developed CIMS, a novel methylation-based score derived from clonal haematopoiesis of indeterminate potential (CHIP) EWAS summary statistics, which reflects the epigenetic profile of both mutant and wild-type blood immune cells. Blood DNA methylation and structural MRI data were available at three timepoints spanning ages 73–79 years. The analytic dataset comprised 1,091 participants, of whom 808 (pVAF) and 836 (CIMS) contributed clonality data and 744 had brain MRI; 479–481 had complete baseline and longitudinal imaging measures with covariates. Trajectories were modelled with latent growth curve models fitted by full information maximum likelihood. Findings Longitudinal trajectories of clonality and grey matter volume were significantly associated over 6 years (Std. est. = −0.176, p adj = 0.030), revealing a progressive, left-lateralised cortical atrophy pattern affecting medial temporal and parietal regions. This pattern showed significant spatial correspondence with established AD signatures ( r = 0.357, p = 0.003), suggesting that clonality is linked to AD-related patterns of neurodegeneration. Subcortical analyses revealed nominal relative preservation of the caudate and did not detect a statistically significant association with hippocampal volume, suggesting potential divergence from the canonical AD subcortical profile. The CIMS confirmed global atrophy but revealed divergent tissue-type and regional patterns, suggesting the two measures may capture distinct aspects of CH biology. Interpretation Together, these findings suggest that CH burden may mark biological processes associated with structural brain atrophy in cognitively healthy older adults, with clonality showing a regional pattern that resembles the one reported in AD. CH burden may therefore be a candidate marker of adverse brain ageing; whether it tracks AD pathology in particular, rather than age-related neurodegeneration more broadly, remains to be tested.

Aims: To synthesise and critically appraise evidence on artificial intelligence (AI) and multimodal data approaches for diagnosis, prognosis, and treatment decision support in diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukaemia (AML), and to compare how disease biology shapes model design and clinical readiness. Study Design: Systematic review with narrative synthesis. Place and Duration of Study: PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, IEEE Xplore, and the Cochrane Library were searched from database inception to 29 July 2026. Methodology: English-language original studies involving human participants, clinical images, human-derived samples, or patient-derived datasets were eligible. Two reviewers independently screened records, assessed full texts, and extracted study characteristics, data modalities, analytical methods, validation approaches, and performance measures. PROBAST+AI domains were used to guide appraisal of eligible patient-level prediction models; exploratory multi-omics, molecular-subtyping, biomarker-discovery, and segmentation studies underwent structured descriptive appraisal. TRIPOD+AI informed assessment of reporting completeness. Owing to substantial clinical and methodological heterogeneity, findings were synthesised narratively. Results: Twenty-eight studies were included: 22 on DLBCL and six on AML. DLBCL research was dominated by PET/CT radiomics, deep imaging, digital pathology, and imaging-clinical-molecular fusion. Internally evaluated diagnostic models reported area under the curve values as high as 0.999, whereas externally validated prognostic models achieved values of 0.66-0.71 and showed inconsistent incremental improvement over the International Prognostic Index. AML studies mainly integrated genomic, transcriptomic, epigenomic, single-cell, proteomic, metabolic, and functional drug-response data. Prognostic models reported concordance indices of 0.72-0.81 and time-dependent area under the curve values of 0.795-0.899. The most frequent methodological concerns were retrospective sampling, high-dimensional modelling in modest cohorts, incomplete calibration reporting, and limited independent validation. Treatment-response models in both diseases remained retrospective or exploratory, and none demonstrated improved outcomes through AI-guided treatment allocation. Conclusion: AI and multimodal data approaches show greatest maturity for prognostic stratification, but diagnostic replacement and treatment selection remain unproven. Prospective, multicentre clinical-impact validation is the principal requirement for translation into routine care.

Abstract The management of diverticular disease has undergone a major evolution over the past two decades, shifting away from episode-count triggers for surgery toward individualized strategies informed by patient-reported outcomes, recurrence risk, and high-quality randomized clinical trials. Pivotal decision analyses and randomized trials have reshaped the surgical treatment landscape, while parallel trials of antibiotic therapy have transformed the nonoperative management of uncomplicated disease. In this study, we provide a comprehensive synthesis of historical perspectives and modern evidence regarding the surgical and nonoperative management of diverticulitis, summarize key randomized trials across the disease spectrum, describe the evolution of operative techniques, and translate these findings into actionable guidance, including a patient-centered decision aid. A structured narrative review of pivotal trials, major guidelines, and multicenter randomized studies were performed, encompassing trials of antibiotic therapy for uncomplicated diverticulitis, laparoscopic lavage for perforated disease, operative strategy for complicated disease, elective resection versus conservative therapy for recurrent or persistent symptoms, and the evolution of minimally invasive and robotic surgical techniques. Trial design, eligibility, interventions, outcomes, and limitations were extracted and synthesized. The traditional “two-episode rule” has been supplanted by individualized, symptom- and quality of life (QoL)-driven decision-making. Routine antibiotic therapy for uncomplicated diverticulitis is not supported by randomized evidence and is now reserved for select patients. Laparoscopic lavage, initially promising for perforated diverticulitis, demonstrates variable outcomes and is now reserved for selected patients with Hinchey III disease; when resection is required, primary anastomosis with diverting ileostomy is increasingly favored over Hartmann's procedure because of markedly higher stoma reversal rates. Randomized trials of elective sigmoid resection show reduced recurrence and improved QoL for patients with persistent symptoms, though not universally across all patient groups, and minimally invasive-particularly robotic-surgical techniques continue to reduce perioperative morbidity. Contemporary management of diverticulitis requires individualized evaluation anchored in patient-reported outcomes, disease phenotype, comorbidity, and shared decision-making. This study synthesizes the current evidence and provides clinic-ready decision aid for patient discussions.

Abstract Objectives To compare the efficacy and safety of pharmacologic therapies for spontaneous epistaxis in hereditary hemorrhagic telangiectasia (HHT). Data Sources PubMed, Scopus, Embase, Web of Science, and the Cochrane Library were systematically searched up to August 2025. Review Methods Eligible randomized controlled trials evaluating bevacizumab, doxycycline, tranexamic acid, or β‐blockers versus placebo or standard care were included. Outcomes included epistaxis frequency and duration, hemoglobin (Hb), epistaxis severity score (ESS), transfusion or emergent‐care requirements, quality of life (QOL), and adverse events. Results Tranexamic acid did not significantly reduce epistaxis duration or frequency or improve Hb, and it did not change transfusion or emergent‐care needs, but it increased diarrhea (odds ratio 3.8, 95% confidence interval [CI] [1.7; 8.5]). Bevacizumab produced a modest reduction in epistaxis frequency (standardized mean difference −0.25, 95% CI [−0.47; −0.02]), without significant effects on duration, ESS, Hb, or QOL. Doxycycline showed no significant benefit for duration or frequency. Topical or systemic β‐blockers did not significantly affect ESS, QOL, Hb, or overall adverse events. Across agents, between‐study heterogeneity was generally low to moderate and CIs were wide, reflecting limited sample sizes. Conclusion No pharmacologic agent demonstrated consistent, clinically robust superiority over placebo across primary endpoints. Bevacizumab may modestly reduce bleeding burden, whereas tranexamic acid increases gastrointestinal toxicity without clear efficacy. Pharmacologic control of HHT‐related epistaxis remains suboptimal, underscoring the need for adequately powered trials with standardized outcome measures and optimized dosing and delivery strategies.