Citations

Individuals with congenital heart disease are living well into adulthood, resulting in a growing population at risk for neurocognitive and psychosocial challenges. Numerous studies have described these risks in childhood, but significant gaps remain in our understanding of how those challenges evolve across stages of adulthood and how to optimally integrate neurocognitive and psychosocial care for adults with congenital heart disease. A multidisciplinary group of experts and patient partners assembled in April 2024 in Atlanta, GA, forming 3 working groups: (1) Genetics and Brain Health, (2) Characterizing Neuropsychological and Psychological Outcomes, and (3) Neuropsychological and Psychosocial Interventions. Current knowledge was reviewed, knowledge gaps were identified, and recommendations to address these gaps were formulated. Five critical questions regarding the characterization of neuropsychological and psychological outcomes of adults with congenital heart disease were prioritized for discussion: which neurocognitive and psychosocial domains should be prioritized in research and clinical care, what are the trajectories of neurocognitive and psychosocial functioning over the lifespan, how should neurocognitive and psychosocial screening be deployed, what should neurocognitive and psychosocial assessments include, and how do we make comprehensive neurocognitive and psychosocial care a reality. Although many gaps in knowledge were identified, particularly around characterizing neurocognitive trajectories throughout adulthood, there is substantial evidence of increased risk for poor psychosocial outcomes among adults with with congenital heart disease. Clinical and research advances must progress in tandem to address these risks. Specific recommendations for advancing this field over the next decade are offered.

With improvement in medical and surgical care, the number of adults with congenital heart disease (CHD) is soaring. Adults with CHD commonly have impairments in brain health. However, significant gaps in knowledge remain regarding the relevant types and prevalence of neurologic and psychiatric risk and their associated risk factors. We sought to review current evidence, identify gaps in knowledge, and develop key next steps to improve scientific understanding and clinical care. Three working groups—Genetics and Brain Health, Characterizing Neuropsychological and Psychological Outcomes, and Neuropsychological and Psychosocial Interventions—were composed of multidisciplinary experts in relevant clinical and research domains, as well as adults with CHD. Each group identified 5 key knowledge gaps and associated next investigations needed to address those gaps. For Genetics and Brain Health, 5 key knowledge gaps were identified: lack of a standardized neuroimaging protocol for adults with CHD, need to understand neuroradiological–pathological–neuropsychological correlates, role of gene–environment interactions, what can be learned from brain health risk models from other groups, and how existing multimodal approaches influence risk and neuroresilience. Adults with CHD can benefit from routine assessment of brain health, as well as increased clinical and basic research into the underlying factors that contribute to risk and neuroresilience for neurologic and psychiatric sequalae. Multidisciplinary collaborative efforts that incorporate adults with CHD across the research cycle are essential for all key next steps.

ABSTRACT Intraocular lymphomas, including vitreoretinal and choroidal lymphoma, can simulate the clinical presentation of other benign and malignant ocular diseases resulting in diagnostic delays. Multimodal imaging features can raise early clinical suspicion to support appropriate subspecialty referrals and treatment for patients affected by these conditions. This review synthesises current evidence on the diagnostic and prognostic value of characteristic imaging features of these rare malignancies. Findings are reviewed based on imaging modality, including fundus photography, optical coherence tomography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, and ultrasound. We emphasise discriminative biomarkers that heighten suspicion for either vitreoretinal or choroidal lymphoma, as well as key findings to discriminate between lymphoma and alternative diagnoses. We further describe longitudinal changes in multimodal imaging features that can facilitate tracking disease progression or treatment response. By consolidating modality‐specific findings, this review aims to facilitate early referral and accurate diagnosis of these rare malignancies.

Background: Pyrocarbon metacarpophalangeal (MCP) arthroplasty is associated with high rates of recurrent deformity and reoperation in patients with rheumatoid arthritis (RA). We sought to determine the impact of preoperative hand grip strength (HGS) on implant survivorship in these patients. Methods: We included primary pyrocarbon MCP arthroplasties in patients with RA at our single institution from 2000 to 2022. Cox proportional hazard models with restricted cubic splines were used to model the continuous relationship between HGS and hazard for revision, all-cause reoperation, and development of any complication, accounting for multiple joints per patient and adjusting for sex. Kaplan-Meier estimates were used to report survivorship at 2, 5, and 10 years. Results: We included 75 joints in 27 patients with an average preoperative HGS of 8.6 kg (11.1 years of follow-up). There were 16 (21%) total revisions, most commonly for recurrent deformity, along with 8 nonrevision reoperations, most commonly for tendon/ligamentous repair. There was a significant, J-shaped relationship between HGS and hazard for revision ( P = .001) and all-cause reoperation ( P < .001). Patients with HGS below 5.5 and 5.3 kg had an increased risk for revision (hazard ratio [HR]: 13.5) and all-cause reoperation (HR: 9.8) compared with patients with sufficiently high HGS. The 10-year revision survival was 93% in patients with HGS >5.5 kg and 63% in patients ≤5.5 kg. Hand grip strength did not significantly affect hazard for developing a first complication. Conclusion: Very low preoperative HGS is associated with worsened implant survivorship following pyrocarbon MCP arthroplasty in patients with RA.

Key Points Data were collected from a cohort of 759 patients with autosomal dominant polycystic kidney disease that were followed for a median of 10.2 years. Prognostic models were developed to predict kidney failure using routinely obtained clinical information and externally validated. Risk predictions had good discrimination and calibration over a time horizon of 15 years. Background Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of kidney failure. Progression is highly variable, and accurate prognostic information is needed to guide early treatment decisions. The objective of this study was to develop a multivariable predictive model for progression to kidney failure. Methods We developed prognostic models using Cox regression for the outcome of kidney failure, defined as eGFR <15 ml/min per 1.73 m 2 , dialysis, or kidney transplantation. The development dataset consisted of participants in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) and Halt Progression of Polycystic Kidney Disease study A (HALT-A) studies. The validation dataset consisted of patients with ADPKD in the Mayo clinical registry aged 15–49 years, with eGFR ≥60 ml/min per 1.73 m 2 . Predictor variables in the base model were age, sex, creatinine or eGFR, ADPKD genotype, and Mayo Imaging Class. Clinical and laboratory data were evaluated in the full model. Results The development cohort included 759 patients with baseline eGFR of 91±29 ml/min per 1.73 m 2 (mean±SD), of whom 16% reached end point after median (interquartile range) follow-up of 10.2 (5.5–16.7) years. The validation cohort included 535 patients with baseline eGFR of 90±31 ml/min per 1.73 m 2 (mean±SD), of whom 11% reached end point after median (interquartile range) follow-up of 5.5 (1.5–13.7) years. The full model, including age, sex, serum creatinine, Mayo Imaging Class, total carbon dioxide, hemoglobin, diastolic BP, and body mass index, had a C-index of 0.81 (95% confidence interval, 0.72 to 0.90) in the validation cohort and 0.75 (95% confidence interval, 0.62 to 0.88) when ADPKD genotype was also included. Risk predictions from base and full models were well-calibrated out to 15 years. Conclusions In persons with early ADPKD and preserved eGFR, a model using routinely obtained clinical information quantified risk of kidney failure over 15 years.

Background: Airway stenting is a critical intervention to restore airway patency, yet complications such as stent migration, mucostasis, airway injury, and granulation tissue formation remain major concerns. Although various covering materials have been explored, the effectiveness of amniotic membrane (AM) as a stent cover has not been evaluated. This study is the first to assess airway-related complications of a novel AM-covered self-expandable metallic stent (SEMS) compared with a commercially available synthetic polymer-covered SEMS. To compare the incidence of stent-related complications between AM-covered SEMS and synthetic polymer-covered SEMS over a 90-day in vivo survival period. Methods: Eight adult Yucatan miniswine were implanted with either an AM-covered or control stent and monitored over 90 days with bronchoscopic evaluations at 4 timepoints. Histologic assessments were performed at termination. Results: Seven animals completed the study (4 AM stents, 3 controls). One control animal was terminated early due to stent expectoration. AM-covered stents were associated with reduced stent migration, mucostasis, and granulation tissue formation compared with controls. Histologic analysis revealed significantly less airway injury and evidence of re-epithelialization with cilia in the AM group; a feature absent in control stents. One animal was excluded at implantation and replaced due to a procedural complication unrelated to the stent. Conclusion: This is the first study to evaluate stent-related complications of AM-covered airway stents. The results demonstrate that AM-covered SEMS reduce airway injury and common complications associated with synthetic polymer-covered stents. These findings suggest that AM-coverings may enhance biocompatibility and integration while mitigating adverse airway responses. Larger studies and human clinical trials are needed to validate these results and explore clinical application.

Pediatric obesity is an increasingly prevalent, chronic, and multifactorial disease. Achieving successful and sustained weight reduction with current interventions remains challenging due to significant heterogeneity in treatment response. This review summarizes current evidence describing variability in outcomes across lifestyle, pharmacologic, and metabolic/bariatric surgery interventions in children and adolescents, and examines key biological, metabolic, behavioral, environmental, and psychosocial factors that influence response. In adults, recent findings on energy balance obesity phenotypes (characterized by abnormal satiation, abnormal postprandial satiety, abnormal hedonic eating, and reduced energy expenditure) have demonstrated promise in predicting weight loss outcomes and guiding tailored interventions. However, data on obesity phenotyping within children and adolescents remain limited. Addressing this gap is essential for advancing precision medicine approaches in pediatric obesity, with the potential to improve treatment selection, enhance effectiveness, and optimize long-term clinical outcomes.

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases.

Abstract Magnetic Particle Imaging (MPI) is an advanced imaging modality that enables high temporal resolution functional imaging with zero tissue background signal. The adaptation of MPI scanners from small-animal research platforms to human-scale clinical applications introduces significant engineering challenges, particularly in generating high-gradient and temporally stable selection fields necessary for spatial encoding. Previous selection coil designs utilizing low-temperature superconductors (LTS), such as NbTi, have achieved the required gradient strengths but are dependent on liquid helium bath cooling. This reliance results in substantial operational costs, increased system complexity, and mechanical vibrations caused by cryogen boil-off and suspended cryostat structures, which may compromise image stability and signal integrity in MPI. High-temperature superconductors (HTS) have been investigated in recent years for high-gradient field generation in MPI applications due to their high current density and elevated operating temperatures. These studies indicate that HTS technology has the potential to address key limitations of LTS-based systems. However, the implementation of HTS magnets in human-scale MPI remains limited by unresolved challenges, including quench protection, mechanical robustness under large Lorentz forces, and the absence of integrated system-level design approaches tailored to MPI-specific requirements such as vibration suppression and gradient stability. This study introduces a next-generation HTS selection coil architecture specifically designed for human-scale MPI. The system utilizes REBCO tapes in a fully conduction-cooled, or 'dry,' configuration, thereby eliminating the need for liquid cryogens and providing a mechanically rigid structure that suppresses vibration sources. A no-insulation winding strategy with stainless steel reinforcement enables inherent quench self-protection and thermal stability. A comprehensive multi-physics design framework, integrating electromagnetic, thermal, and structural analyses, demonstrates a peak selection-field gradient of 5.58 T/m while maintaining both thermal and mechanical integrity. These results establish a robust and clinically viable pathway for HTS-based human-scale MPI systems.

ABSTRACT Amidst the opioid crisis, understanding the genetic basis of opioid use disorder (OUD) is crucial for identifying biological mechanisms and intervention points. However, genome‐wide association studies (GWASs) have been hampered by inadequate sample sizes and often the use of control populations not assessed for prior opioid exposure. Because opioid exposure is a prerequisite for the development of OUD, consideration of exposure history in controls is important. Electronic health record data (EHR) paired with genomic information allow a broader sampling of patients with OUD and exposed controls. We leveraged data across two healthcare systems to evaluate the impact of using controls not screened for opioid exposure (‘generic’) versus minimally opioid‐exposed control (‘exposed’). First, at the phenotypic level, we conducted phenome‐wide association studies (PheWAS) to compare the medical comorbidity profiles of OUD cases when using generic versus exposed controls. While PheWAS results for OUD‐related comorbidities were more pronounced when using the generic group, 83% of the disease associations were overlapping and of similar effect sizes. Second, at the genetic level, we conducted GWAS (cases vs. generic; cases vs. exposed) and assessed differences in genetic correlations and degrees of phenotypic misclassification. Genetic results were concordant across control groups based on heritability (generic: 0.16 ± 0.07 vs. 0.10 ± 0.07), associations with the coding OPRM1 variant rs1799971 ( p generic = 8.83E‐03 vs. p exposed = 1.83E‐02) and genetic correlations with prior OUD GWAS ( r g‐generic = 0.83 ± 0.26 vs. r g‐exposed = 0.78 ± 0.27). Although GWASs were limited by sample size ( N generic = 6269, N exposed = 6365), compared to an independent OUD GWAS ( N = 425 944), the dilution value for the two GWAS was not different from 1, suggesting no major impact of phenotypic misclassification. This study represents the first effort to enhance OUD genetic research through optimization of control definitions using EHR data. Generic controls ascertained within the US health systems, where exposure to prescription opioids is high, offer a practical alternative for genetic studies of OUD.