Citations

Rationale Immunoglobulin A (IgA) deficiency, a rare, highly heritable trait, is associated with frequent pulmonary infections, emphysema, airway changes and low lung function; however, it is unclear if reduced IgA levels may affect lung structure and function. Methods Serum IgA, IgA1 and galactose-deficient IgA1 (Gd-IgA1) levels were measured in the population-based Multi-Ethnic Study on Atherosclerosis (MESA). The MESA Lung Study measured percent emphysema on cardiac CT and airway dimensions on chest CT, and performed spirometry. Regression models were evaluated after adjustment for demographic and CT factors. Mendelian randomisation (MR) analyses were conducted using genetic variants from the Trans-Omics for Precision Medicine (TOPMed) programme. A replication analysis was performed in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). Measurements and main results Among 5497 participants, lower log-normalised serum IgA levels were associated with greater percent emphysema (β=−0.084; 95% CI −0.14 to –0.026; p=0.005), which was confirmed on MR (β=−0.79; 95% CI −1.4 to –0.18; p=0.011). Greater log-normalised serum Gd-IgA1 levels were associated with airway wall thickness (β=0.0079; 95% CI 0.0017 to 0.014; p=0.012; n=2580) and decline in the forced expiratory volume in one second (FEV1) (β=−0.012; 95% CI −0.021 to –0.0036; p=0.0055; n=2778) and FEV1/forced vital capacity (FVC) ratio (β=−0.0028; 95% CI −0.0048 to –0.00084; p=0.0054; n=2778). Conclusion Lower serum IgA levels were associated with greater percent emphysema. Additionally, higher Gd-IgA1 levels were associated with airway wall thickness and lung function decline. These findings support a protective role of IgA in emphysema pathogenesis and possible deleterious role of Gd-IgA1 in airway diseases.

Inflammatory bowel disease (IBD) is associated with significant impacts on patients’ health and quality of life. Chronic inflammation is linked to an increased risk of malignancies, venous thromboembolisms and infections. Chronic diseases are also associated with an increased risk for psychiatric comorbidities, such as anxiety and depression. Consequently, IBD can greatly impact health-related quality of life. While endoscopic healing is a target of therapeutic efficacy in the management of IBD, patients prioritise achieving clinical remission, with symptom control being a primary motivator for IBD management. With the ever-evolving therapeutic landscape in IBD, the need for effective communication and shared decision-making (SDM) is crucial when relaying risks and benefits of treatment options: no treatment, complementary and alternative medicine, surgical resection and medical management. Various visual decision aids, patient-specific activities and predictive tools enhance patients’ understanding of the risks and benefits associated with certain treatments and enable patients to make informed decisions aligned with their personal values. Through SDM, the patient–provider relationship is strengthened, patient satisfaction is enhanced, patient quality of life is improved and better outcomes are achieved.

Background and objectives Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. Methods We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. Results Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). Discussion In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.

Abstract Objective Sleeper stretching (SS) and cross‐body stretching (CS) are common nonsurgical interventions for the management of glenohumeral internal rotation deficit (GIRD) in overhead athletes such as baseball and volleyball players. However, the effectiveness of these stretching interventions in enhancing the range of motion (ROM) of shoulder internal rotation (IR) in overhead athletes with GIRD remains a subject of uncertainty. This systematic review and meta‐analysis aim to critically assess the efficacy of SS and CS in the ROM of the IR among overhead athletes with GIRD, thereby providing evidence‐based recommendations for their use. Literature Survey A comprehensive search of MEDLINE, Embase, and Scopus databases up to November 2024 was conducted to identify randomized controlled trials investigating the influence of SS and CS on the ROM of shoulder IR in overhead athletes with GIRD. Methodology Data including study characteristics and outcomes were extracted. Risk of bias assessment and random‐effects model meta‐analysis were performed. Synthesis Six eligible studies involving 255 athletes with GIRD were included. The meta‐analysis demonstrated statistically significant differences between stretching and control groups in terms of enhancing the ROM of IR (mean difference [MD], 7°; 95% confidence interval [CI], 1°–13°; p = .02) and horizontal adduction (HAD) ([MD], 6°; [CI], 1°–11°; p = .03). Conclusion SS or combination of SS and CS interventions significantly enhanced the ROM of IR compared to the control group in overhead athletes diagnosed with GIRD. Furthermore, the review confirmed that SS alone also markedly enhances the ROM of HAD. These findings highlight the potential benefits of SS and CS in managing GIRD and suggest a need for further research to optimize these interventions for broader application in overhead athletes.

Abstract Artificial intelligence (AI) is poised to transform healthcare through the lens of 6P medicine: personalized, predictive, preventive, participatory, precision, and public health. This review explores how AI technologies contribute to these six crucial dimensions, offering powerful solutions for enhanced early disease detection, tailored treatment protocols, proactive preventive health measures, and significantly improved patient engagement in their care journey.Our findings highlight AI's immense potential in revolutionizing diagnostics by enabling more accurate and rapid analyses, as well as strengthening public health surveillance capabilities. However, successful and responsible implementation hinges on rigorously addressing crucial cross-cutting challenges such as ensuring data quality, safeguarding patient privacy, navigating complex ethical considerations, seamless system integration, and fostering model interpretability. Aligning AI applications with evolving regulatory frameworks, such as the European Health Data Space (EHDS) and the AI Act, is absolutely essential to accelerate the ethical and effective adoption of 6P medicine. Ultimately, interdisciplinary collaboration among clinicians, technologists, and policymakers is key to unlocking AI's full power to improve patient outcomes and overall healthcare operational efficiency.

Abstract Objective: Electronic Health Record (EHR) data are critical for advancing translational research and AI technologies. The ENACT network offers access to structured EHR data across 57 CTSA hubs. However, substantial information is contained in clinical narratives, requiring natural language processing (NLP) for research. The ENACT NLP Working Group was formed to make NLP-derived clinical information accessible and queryable across the network. Methods: We established the ENACT NLP Working Group with 13 sites selected based on criteria including clinical notes access, IT infrastructure, NLP expertise, and institutional support. We divided sites into five focus groups targeting clinical tasks within disease contexts. Each focus group consisted of two development sites and two validation sites. We extended the ENACT ontology to standardize NLP-derived data and conducted multisite evaluations using the Open Health Natural Language Processing (OHNLP) Toolkit. Results: The working group achieved 100% site retention and deployed NLP infrastructure across all sites. We developed and validated NLP algorithms for rare disease phenotyping, social determinants of health, opioid use disorder, sleep phenotyping, and delirium phenotyping. Performance varied across sites (F1 scores 0.53–0.96), highlighting data heterogeneity impacts. We extended the ENACT common data model and ontology to incorporate NLP-derived data while maintaining Shared Health Research Informatics NEtwork (SHRINE) compatibility. Conclusion: This demonstrates feasibility of deploying NLP infrastructure across large, federated networks. The focus group approach proved more practical than general-purpose approaches. Key lessons include the challenge of data heterogeneity and importance of collaborative governance. This work also provides a foundation that other networks can build on to implement NLP capabilities for translational research.

Abstract Background Compared to Parkinson's disease, atypical parkinsonian disorders (APD) are characterized by a more rapidly progressive course, often leading to profound disability. Effective communication between clinicians, patients, and care partners is essential to support patient‐centered care and shared decision‐making. However, most neurologists lack formal training in serious illness conversations (SIC). Objective To develop a practical SIC guide tailored to the needs of individuals with APD. Methods Members of the CurePSP Centers of Care Palliative Care Working Group, in collaboration with a SIC education expert (TC), developed a SIC guide for APD. A literature review was conducted, followed by online consensus‐building rounds. Results Applying core communication principles—such as active listening, pausing, naming and validating emotions, assessing understanding, and reframing—can foster alignment between clinicians, patients, and their care partners. Navigating the balance between maintaining hope and providing realistic, anticipatory guidance remains challenging but best achieved by honest, compassionate dialogue. Four practical guides were developed, addressing common and often challenging scenarios: delivering an APD diagnosis, eliciting patient goals in the context of changing clinical status, addressing safety concerns, and discussing quality of life and end‐of‐life considerations. Conclusions Patients and their care partners living with APD benefit greatly from individualized guidance, and honest, empathic communication is a vital part of patient‐centered care. While existing SIC frameworks offer valuable foundations, further research is needed to optimize their adaptation for APD—identifying best timing, specific frameworks, relevant outcome measures, and education strategies to build team‐wide competency.

ABSTRACT Background To explore the prevalence of serious adverse events ( SAEs ) associated with retinal viral gene therapy and to examine trends influencing SAE occurrences in human gene therapy surgeries and pre‐clinical animal trials. Methods Literature review was performed to identify peer‐reviewed human and animal studies relevant to viral gene therapy, subretinal injections, and intravitreal injections. For clinical trials and post‐approval LUXTURNA studies, only those that examined SAEs were included. Results Of included clinical trial studies ( n = 31), SAEs were recorded in 51 out of 438 eyes (11.6%) that received subretinal injections and in 11 out of 348 eyes (3.2%) that received intravitreal injections. There were fewer intravitreal‐related SAEs and less vision loss compared to subretinal gene therapy. Inflammation was the predominant SAE following intravitreal injections, whereas unexplained vision loss was the most common for subretinal injections. Clinical trials utilising subretinal injections met primary or secondary efficacy endpoints more than intravitreal trials. Eighteen studies (429 eyes) of post‐approval LUXTURNA were reviewed, and SAEs were reported in 24.7% of eyes, retinal degeneration being most common (20.7%). For 58 animal studies, SAEs were recorded in 17.3% of eyes that received subretinal injections and 8.7% of eyes that received intravitreal injections. Conclusions Subretinal injections show higher efficacy than intravitreal injections but are associated with more serious adverse events. Consistent adverse event patterns in humans and large animals highlight their predictive value for safety. There is a need for optimised delivery methods, refined dosing protocols, and improved post‐treatment monitoring to improve safety and effectiveness in gene therapy.