Citations

ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.

Abstract Atrial fibrillation (AF) is increasingly diagnosed early, close to its first occurrence due to: (i) increased public awareness with self-screening; (ii) health care initiatives including population screening and opportunistic case finding; and (iii) increased use and surveillance of implantable cardiac devices. At its onset, AF is often low burden, and cardiovascular co-morbidities may be absent or at an early stage. Thus, the management of recent-onset AF has become an issue of growing importance. Professional guidelines have traditionally focused on anticoagulant thromboprophylaxis, generally recommending a cautious approach to rhythm control, and priority has been given to rate control to alleviate symptoms. In recent guidelines, the importance of managing lifestyle and co-morbidities has increased. The AF-SCREEN collaboration proposes that a vigorous approach to active management of recent-onset AF may be warranted. This includes addressing co-morbidities and promoting healthy lifestyles to prevent the emergence or progression of AF and associated cardiovascular disease, as well as the initiation of active rhythm control ± anticoagulation to prevent AF-related morbidity and mortality, including stroke and heart failure (HF). Intuitively, intervention early after AF onset would be beneficial since lifestyle and co-morbidity management, plus rhythm control and anticoagulation, are important contributors to improved outcomes in patients with established AF, but robust evidence is lacking for recent-onset AF. There is a delicate balance between achieving favourable outcomes such as preventing strokes, HF and AF progression vs the complications and potential adverse effects of interventions. Given the serious long-term consequences, innovative approaches are necessary to determine the value and risks of initiating active therapy very early in the course of AF. More data are needed to guide the best management of recent-onset AF, bearing AF burden in mind. Long-term studies using large national databases linked to electronic medical records and rhythm monitoring devices offer excellent opportunities. Shorter-term studies focusing on reducing AF burden to slow AF progression and studies focusing on outcomes such as HF could be used in both randomized clinical trials and observational cohort studies.

Recent guidelines on biliary cannulation are lacking. This guideline is an initiative of the World Endoscopy Organization (WEO) with the involvement of a panel of experts from Asia, Europe, and America. Relevant clinical questions on four areas (post‐endoscopic retrograde cholangiopancreatography [ERCP] pancreatitis [PEP] prophylaxis, biliary cannulation techniques, sphincterotomy/papillary balloon dilation, and biliary cannulation in special circumstances) were developed and answered after systematic reviews of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Successful biliary cannulation and sphincterotomy are cornerstones of ERCP and are indispensable for almost all therapeutic and advanced diagnostic procedures. However, adverse events, particularly PEP, may commonly occur and impair patients' outcomes. A high cannulation rate and a low rate of PEP are quality indicators for ERCP and should be the goal of all endoscopists. With this guideline we aimed to provide clinical practice advice applicable worldwide, regardless of resources and expertise availability. The main recommendations focus on specific aspects of ERCP, including pre‐, intra‐, and postprocedural measures to reduce the risk of PEP, the technique for an initial biliary cannulation attempt, options for cannulation in cases of difficult biliary access, alternatives to ERCP in case of failure (percutaneous‐ and endoscopic ultrasound‐guided), and biliary access in altered anatomy (periampullary diverticulum and postsurgical anatomy) and in the presence of duodenal stenosis.

Abstract Breast image-guided procedures play a critical role in the diagnosis and management of breast cancer, serving as the gold standard for tissue sampling and preoperative localization. These minimally invasive procedures carry a very low risk of complications, with postprocedural infections occurring in fewer than 0.2% of cases. However, given the high volume of breast interventions performed annually, the potential impact of infections remains significant. Despite this, published guidelines addressing procedural cleanliness techniques in breast imaging are sparse and often provide conflicting recommendations, leading to variability in clinical practice and resource utilization. The lack of clear and specific guidance creates challenges for radiologists navigating institutional policies and best practice implementation. This review synthesizes existing standards and guidelines, evaluating the supporting evidence to propose an evidence-based best practice approach for maintaining clean techniques in breast image-guided procedures. By standardizing cleanliness protocols, we aim to enhance patient care, optimize procedural success, and promote consistency across breast imaging practices.

ABSTRACT Background Advancements in organ transplant technology are pushing global transplant capabilities to new heights. However, challenges persist in pediatric surgical and medical transplant fellowship training, primarily due to a limited number of adequate training programs and gaps in education. Addressing these gaps is essential for improving patient outcomes and advancing the field of pediatric transplantation. Methods An international survey was distributed to 416 pediatric transplant fellows via multiple global transplant associations. The 29‐question survey, available in English and Spanish, assessed current clinical knowledge, training satisfaction, and preferred learning formats. The survey received responses from 237 pediatric transplant fellows. Results One of the key findings was that respondents felt most confident in their pre‐transplantation clinical knowledge. About 75.5% of fellows reported being extremely or very aware of pre‐transplant workups and assessments. However, significant gaps were identified in other areas of training. Notably, 24% of respondents felt extremely knowledgeable about the side effects of immunosuppression, and only 22.8% were very confident in managing acute rejection. Fellows expressed strong interest in dynamic educational formats, particularly clinical case discussions (88.8%). Preferred methods to enhance training included continuing medical education (64.6%), hands‐on workshops, and support for transition protocols and psychosocial counseling. Conclusion This global survey highlights critical educational gaps in pediatric transplant fellowship training and identifies preferred learning methods among fellows. Targeted improvements such as standardized curricula, case‐based learning, interdisciplinary collaboration, and accessible continuing education are essential to enhance training. These strategies will ensure that future transplant professionals are well‐equipped to deliver high‐quality care across diverse healthcare settings.

Abstract An individual participant data (IPD) meta-analysis can assess the predictive value of data on outcomes at the individual level, offering a potential tool for developing personalized pain management. Pretreatment quantitative sensory testing (QST) may stratify patient groups, which are then linked to treatment outcomes. Our objective was to determine if measures of QST at baseline are related to treatment outcomes (at any time point) for pain and disability in lower-limb osteoarthritis. We performed a systematic review with an IPD meta-analysis. Searches were conducted in 9 databases until May 5, 2023 for intervention studies that measured baseline QST and longitudinal measures of participant-reported pain and disability. We performed a 2-stage approach to analyse longitudinal data. Individual models were fitted to each study and combined using random effects multivariate meta-analytic models. Study quality was assessed using the Joanna Briggs Institute checklist, and certainty of the evidence was assessed using GRADE. We identified 3082 records and included 1 hip and 28 knee datasets consisting of 2522 participants from 40 studies. Local warm detection thresholds (P = 0.024) predicted knee osteoarthritis pain outcomes (very-low certainty). Local warm detection thresholds (P = 0.030), remote cold detection thresholds (P = 0.05), and remote pressure tolerance thresholds (P = 0.007) predicted knee osteoarthritis disability outcomes (very-low certainty). Other QST variables were associated with hip and knee osteoarthritis pain and disability levels (eg, pressure pain thresholds), but this relationship did not change over time. This review finds that mechanism-based, QST methodologies do not consistently predict pain or disability on an individual level in hip or knee osteoarthritis.

AbstractIntroductionActive learning engages learners in constructing knowledge through interactive strategies such as simulation, small‐group discussion, and peer instruction. Although recognized as a superior approach to traditional passive learning, its adoption has been inconsistent. Barriers include reliance on traditional lectures, lack of training, and limited time to develop materials. Simulation educators have a unique skill set that may inform and support active learning initiatives.MethodsFifteen emergency medicine simulation experts convened to define the unique skill set of simulation educators and identify transferable simulation‐based medical education (SBME) skills and concepts to promote effective active learning beyond the simulation lab. Workgroup members are simulation education directors who have undergone specialized training in SBME. During biweekly meetings over 6 months, workgroup members reviewed primary literature in SBME and active learning, along with relevant simulation educator training materials. Objectives were achieved through iterative review, group conceptualization, and expert consensus.Unique treatmentThe increasing prevalence of SBME in medical education, along with the growth of simulation fellowships, has produced a group of education experts with shared competencies. Simulation educators acquire expertise in psychological safety, facilitation, communication, and debriefing, through specialized training and extensive experience. These skills are critical for active learning environments where learners benefit from structured, engaging, and psychologically safe experiences.Implications for educatorsKey transferable SBME topics were identified for use in active learning environments outside of the simulation lab: (1) psychological safety, (2) facilitation strategies, and (3) communication techniques. Transferable tools and concepts were identified to promote efficacy and learner engagement during active learning in diverse environments. Simulation educators’ expertise is an underutilized resource for faculty development initiatives aimed at advancing active learning. This work advocates for leveraging simulation educators’ skills to close the active learning implementation gap, enhance learner outcomes, and meet the evolving needs of contemporary medical education.