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Higher-risk medication use-including regimens with polypharmacy, drug-drug interactions (DDIs), and potentially inappropriate medications (PIMs)-has been linked to adverse outcomes in older adults. However, studies establishing associations between higher-risk medication use and mortality have lacked measures of organ function and considered types of higher-risk medication exposures in isolation, allowing potential confounding and overestimation of harm. We conducted a prospective cohort study of adults aged ≥ 65 years who took part in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016, with mortality follow-up through 2019. Our primary exposures were three types of higher-risk medication use: polypharmacy, DDIs, and PIMs. In primary analyses, these were defined, respectively, as follows: being on ≥ 5 prescription medications (polypharmacy); using two medications with ≥ 1 major DDI; and using ≥ 1 prescription PIM. Exposures were determined by medication review during the baseline survey. The primary outcome was all-cause mortality. Multivariable Cox regression models estimated mortality risk associated with each type of higher-risk medication use, sequentially adjusting for sociodemographic factors and comorbidities, organ function and health behaviors, and patterns of higher-risk medication use. Among 7828 eligible participants (representing 26.5 million adults), 54.3% experienced at least one type of higher-risk medication use: 40.0% had polypharmacy, 11.4% had a DDI, and 37.6% used a PIM. In fully adjusted models including all higher-risk medication exposures, only polypharmacy remained significantly associated with increased mortality (hazard ratio [HR] 1.38; 95% CI 1.26-1.51). Sensitivity and subgroup analyses by age and health status yielded generally consistent findings. When considering multiple types of higher-risk medication exposure, only polypharmacy was consistently and independently associated with increased mortality among older adults. These results highlight the harms of polypharmacy specifically and could help further target deprescribing interventions to the most high-risk patients.

Masculinizing gender-affirming chest surgery is the most frequently accessed gender-affirming procedure. The GENDER-Q Chest scales were developed to better assess patient-reported outcomes in masculinizing gender-affirming chest surgery, yet previous psychometric assessment of these scales is limited. The objective of this study was to assess the construct validity of the GENDER-Q Chest scales (Chest, Nipples & Areolas, and Scars). An international, cross-sectional study was performed to develop the GENDER-Q between February 2022 and March 2024. Individuals were included in this analysis if they had sought or received masculinizing gender-affirming chest surgery and completed the GENDER-Q Chest scale. Construct validity was assessed for each scale by testing a priori hypotheses. According to Consensus-based Standards for the Selection of Health Measurement Instruments guidelines, greater than 75% acceptance of hypotheses indicates sufficient evidence of construct validity. A total of 2,846 participants completed the GENDER-Q Chest scale. For the GENDER-Q Chest, Nipples & Areolas, and Scars scales, 95% (21/22), 79% (15/19), and 100% (12/12) of hypotheses were accepted for each scale, respectively. Patients who underwent surgery and do not currently need revisions reported the highest satisfaction, while patients who had not yet undergone surgery reported the lowest satisfaction. The GENDER-Q Chest scales evidenced construct validity to measure appearance of chest, nipples, and scars for individuals seeking or undergoing masculinizing gender-affirming chest surgery. The GENDER-Q Chest scales provide a robust, validated approach for assessing outcomes in this context and are well-suited for generating high-quality evidence on patient-reported outcomes. Masculinizing gender-affirming chest surgery is a common gender-affirming procedure for transgender and gender-diverse people who want their chest to better match their gender identity. The GENDER-Q Chest scales are questionnaires that measure satisfaction with chest appearance, nipples, and scars after this surgery. Before questionnaires like these can be used widely, they need to be tested to ensure they accurately measure what they intend to measure. This is called construct validity. In a study of 2,846 participants from multiple countries, the GENDER-Q Chest scales showed strong construct validity. This means that they are trustworthy tools that can produce high-quality evidence that can be used to improve surgical care for transgender and gender-diverse people undergoing these procedures.

Primary enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles, known as congenital cerebral ventriculomegaly (CCV), is a hallmark of congenital hydrocephalus. CCV is also enigmatically but frequently associated with autism and other neurodevelopmental disorders. To gain insight into the developmental genetic regulation of the human CSF-ventricular system, we conducted an integrated, multiomic study of about 2700 trio-based exomes from patients with primary CCV. We found that about 25% of cases were associated with rare, damaging de novo variants in mutation-intolerant genes, many of which are linked to other dominant Mendelian disorders. Thirty-five exome-wide significant CCV genes and dozens of other high-confidence CCV genes converged on pathways involved in ATP-dependent Brahma-related gene 1/Brahma-associated factor chromatin remodeling, histone H3 lysine 4 methylation, and phosphoinositide 3-kinase signaling. Knockout of selected CCV genes in mouse models supported that de novo variants in CCV genes caused ventriculomegaly by impairing both CSF dynamics and cortical cytoarchitecture through dysregulation of neuroprogenitor cell growth and maturation in the ventricular and subventricular zones. These findings indicated that genetic and epigenetic programs coordinate the "hand-in-glove" development of the CSF-ventricular system with that of the cerebral cortex and establish a genetic connection between CCV and neurodevelopmental disorders, potentially explaining why some patients with hydrocephalus continue to exhibit CCV and neurodevelopmental disorders despite CSF shunting. We suggest that combined brain imaging and whole-exome sequencing could enable early detection of, and intervention for, autism and other neurodevelopmental disorders.

Cardiovascular magnetic resonance (CMR) has evolved over the past two decades into a central component of modern cardiology diagnostics. Its particular strength lies in the unique combination of highly accurate functional assessment and non-invasive tissue characterization within a single examination. The indications for CMR in contemporary clinical practice are broad. In the evaluation of coronary artery disease, stress perfusion CMR enables reliable assessment of myocardial ischemia and complements this with simultaneous viability analysis using late gadolinium enhancement (LGE). In inflammatory myocardial diseases, CMR, based on the Lake Louise criteria, allows differentiation between acute and chronic injury and supports therapeutic decision-making. In the assessment of unexplained left ventricular hypertrophy, CMR provides decisive insights for differential diagnosis through mapping techniques and characteristic tissue patterns, for example in amyloidosis or hypertrophic cardiomyopathy. It also plays a key role in heart failure by contributing to etiological clarification and prognostic assessment. Additional important applications include genetic and arrhythmogenic cardiomyopathies, where CMR enables detailed evaluation of morphology, biventricular function, and fibrofatty myocardial remodeling, as well as valvular heart disease, where it allows precise quantification of regurgitant volumes, flow, and ventricular volumes, particularly when echocardiography is limited. Further indications include cardiac masses, congenital heart disease, and transplant cardiology. Overall, CMR provides an integrated, precise, and non-invasive diagnostic approach that reduces diagnostic uncertainty, improves risk stratification, and supports clinical decision-making. Future developments, particularly in quantitative imaging, standardization, and the generation of robust clinical evidence, are expected to further strengthen its role in clinical care. This article follows an indication-based approach and provides practical guidance on clinical scenarios in which CMR should be considered. Die kardiovaskuläre Magnetresonanztomographie (MRT) hat sich in den letzten zwei Jahrzehnten zu einem zentralen Bestandteil der kardiologischen Diagnostik entwickelt. Ihr besonderer Stellenwert ergibt sich aus der einzigartigen Kombination aus hochpräziser Funktionsanalysen und nichtinvasiver Gewebecharakterisierung in einer einzigen Untersuchung. Die Indikationen zum Einsatz der kardiovaskulären MRT in der modernen klinischen Routine sind vielfältig. In der Diagnostik der koronaren Herzkrankheit (KHK) ermöglicht die Stress-Perfusions-MRT eine zuverlässige Ischämiebeurteilung und ergänzt diese durch die simultane Vitalitätsanalyse mittels „late gadolinium enhancement“. Bei inflammatorischen myokardialen Erkrankungen erlaubt die MRT anhand der Lake-Louise-Kriterien die Unterscheidung zwischen akuter und chronischer Schädigung sowie die Steuerung therapeutischer Entscheidungen. In der Abklärung einer unklaren linksventrikulären Hypertrophie liefert die MRT durch Mapping-Techniken und Darstellung charakteristischer Gewebemuster entscheidende Hinweise zur Differenzialdiagnose, etwa bei Amyloidose oder hypertropher Kardiomyopathie. Auch in der Herzinsuffizienzdiagnostik trägt sie wesentlich zur Ursachenklärung und Prognoseabschätzung bei. Weitere wichtige Einsatzgebiete umfassen genetische und arrhythmogene Kardiomyopathien, bei denen die MRT Morphologie, biventrikuläre Funktion und fibrotisch-fettigen Umbau erfassen kann, sowie Klappenvitien, bei denen sie insbesondere bei eingeschränkter Echokardiographie eine präzise Quantifizierung von Regurgitationsvolumina, Flüssen und ventrikulären Volumina ermöglicht. Weitere Indikationen sind kardiale Raumforderungen, angeborene Herzfehler sowie die Transplantationsmedizin. Insgesamt ermöglicht die kardiovaskuläre MRT eine integrierte, präzise und nichtinvasive Diagnostik, die diagnostische Unsicherheiten reduziert, die Risikostratifizierung verbessert und therapeutische Entscheidungen unterstützt. Zukünftige Entwicklungen – insbesondere in der quantitativen Bildgebung, Standardisierung und Evidenzgenerierung – werden ihren klinischen Stellenwert weiter stärken. Dieser Beitrag verfolgt einen indikationsbasierten Ansatz und zeigt praxisnah auf, in welchen klinischen Situationen die kardiovaskuläre MRT gezielt eingesetzt werden sollte.

Functional imaging with fluorodeoxyglucose (FDG) PET has substantially advanced our understanding of the biological processes underlying a wide range of neurologic and systemic disorders. In particular, brain FDG PET enables the visualization of regional metabolic activity associated with different mental states and neuropsychiatric conditions. By assessing patterns of cerebral glucose metabolism, FDG PET can provide insight into an individual's current brain function, including age-related metabolic changes and early alterations suggestive of neurodegenerative disorders such as Alzheimer's disease. This article reviews potential indications for FDG PET scanning in integrative medicine practice and situates it within the broader landscape of functional imaging modalities.

Intraoperative navigation improves screw placement accuracy in pediatric occipitocervical fusion. All reports of navigated occipitocervical fusion using occipital plates in any age patient describe navigation placed at case onset to guide occipital and cervical fixation, or navigation placed at case onset to guide cervical screw placement alone before occipital fixation. We describe a novel technique for navigated occipitocervical fusion and analyze short-term outcomes in a pediatric case series. We describe a novel technique for occipitocervical fusion using intraoperative navigation with the reference array attached to the occipital plate after occipital plate fixation, before distal instrumentation. Navigation was used for subaxial fixation only, and not for occipital fixation. A retrospective review of cases treated with this technique was conducted to summarize patient and surgical variables. Three pediatric (median; 4 y) patients underwent occipitocervical fusion using the described technique. There were no intraoperative complications related to navigation, including the need for repeat spin, movement of the array, inaccurate navigation, or loss of navigation. There were no intraoperative complications related to occipital fixation, including dural leak, venous sinus penetration, or dislodgement of instrumentation. This technique is successful in obtaining occipitocervical fusion in complex patients, with no navigation-related or fixation-related complications in the intraoperative or postoperative period. This technique has the potential to reduce operative time and navigation-related complications, as well as improve patient safety and construct alignment. Level IV.

We present FOMO260K, a large-scale, heterogeneous dataset of 260,927 brain Magnetic Resonance Imaging (MRI) scans from 77,589 MRI sessions and 55,378 subjects, aggregated from 910 publicly available sources. The dataset includes both clinical- and research-grade images, multiple MRI sequences, and a wide range of anatomical and pathological variability, including scans with large brain anomalies. Minimal preprocessing was applied to preserve the original image characteristics while reducing entry barriers for new users. Companion code for self-supervised pretraining and finetuning is provided, along with pretrained models. FOMO260K is intended to support the development and benchmarking of self-supervised learning methods in medical imaging at scale.

Targeted perturbations of individual microbial taxa can propagate through complex ecological networks and generate ripple effects that reshape gut microbiota structure and function. Here, we discuss the need for predictive ecological and data-driven frameworks that enable precise and controllable microbiome engineering to minimize or leverage ripple effects.

This issue of NEJM Catalyst Innovations in Care Delivery includes articles, case studies, and research reports on hospital transfers, outpatient antibiotic therapy, pediatric care quality, pediatric cardiac care, musculoskeletal care costs, frontline clinician support, patient portals, an AI digital assistant, and home-based care.

PurposeTrust is a critical part of patient-provider relationships and has been shown to improve patient outcomes, including increased utilization of preventative services and greater adherence to medications. However, few studies have examined health care provider trust (HCPT) among older sexual minority men (SMM) and its association with healthcare avoidance.DesignCross-sectional secondary data analysis.Setting/Sample: Baseline data from the MACS/WIHS Combined Cohort Study's Stigma and Non-Communicable Disease Syndemic Sub-Study (N = 997).MethodsMultiple linear and multivariable logistic regression models were conducted to estimate associations between HCPT and past-year healthcare avoidance.ResultsParticipants had a mean age of 59 years (SD = 13.3); 64% were White, 30% Black, and 5% identified as other races. Fifty-six percent were living with HIV. HCPT was lower among Black SMM (b = -2.23; 95% CI = -4.46, 0.00) and was positively associated with multiple income groups and having 1 (b = 3.80; 95% CI = 1.49, 6.11), 2 (b = 2.96; 95% CI = 0.67, 5.25), and 3 (b = 3.03; 95% CI = 0.53, 5.53) chronic health conditions. Past-year healthcare avoidance was inversely associated with HCPT (aOR = 0.95; 95% CI = 0.94, 0.97) and age (age 26-45 years vs 65-75 years, aOR = 0.26; 95% CI = 0.11, 0.58).ConclusionThis work demonstrates various associations between healthcare provider trust and sociodemographic and health factors. Furthermore, lower HCPT was associated with a higher likelihood of avoiding medical care, indicating the importance of provider trust for accessing health services.

Neonatal Intensive Care Units (NICU) are often designed to primarily optimize the health of critically ill newborns. However, prolonged hospitalizations and stressors, in particular for diverse families can lead to alienation. In this Perspective, we explore how NICUs can be designed to center the diversity of families care for in the NICU including, but not limited to, racial and ethnic diversity, LGBTQ+ headed families, non-traditional families, families with disabled caregivers, families who prefer a language other than English, and those with low health literacy. Through thoughtful and inclusive designed spaces, we highlight how a NICU can become a place of healing for families and infants and foster a sense of inclusion and belonging.

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The short-term and long-term effects of genotoxic pre-transplant conditioning remain barriers to the broader application of haematopoietic stem/progenitor cell (HSPC) transplantation and gene therapies1-4. Although monoclonal antibodies targeting KIT have been proposed as alternatives to chemotherapy or radiotherapy5-7, their pharmacokinetics hinder clinical applications owing to the risk of depleting transplanted HSPCs. Here, to address this issue, we identified amino acid changes in the extracellular domain of KIT that disrupt the binding of two therapeutic monoclonal antibodies8,9, which impair stem cell factor (SCF)-mediated signalling without affecting KIT expression or functionality. We exploited adenine base editing10 or prime editing11 to efficiently introduce these mutations in HSPCs and combined them with the disruption of the BCL11A erythroid enhancer to promote expression of fetal haemoglobin (HbF)12,13, a therapeutic approach for several haemoglobinopathies. This strategy enables in vivo co-selection of gene-engineered cells to reach the threshold required to provide therapeutic benefit in patients affected by sickle cell disease and β-thalassaemia. We show progressive enrichment of KIT plus BCL11A multiplex-edited haematopoiesis under selective pressure with KIT monoclonal antibody, in vitro and in vivo. We report that extended treatment with anti-KIT regimens leads to superior in vivo enrichment while avoiding clonal selection, as assessed by a lentiviral barcoded library. Finally, by overcoming the limitations of monoclonal antibody pharmacokinetics, epitope editing enables novel haematopoietic replacement regimens that are not limited by on-target graft elimination, allowing prolonged immune-based conditioning that maximizes haematopoietic niche clearance without chemo-radiotherapy or monoclonal antibody wash-out.

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From disparities in the number of exhibiting artists to auction opportunities, there is evidence of women's under-representation in visual art. Here we explore the exhibition history and auction sales of 65,768 contemporary artists in 20,389 institutions, revealing gender differences in the artist population, exhibitions and auctions. We distinguish between two criteria for gender equity: gender-neutrality, when artists have gender-independent access to exhibition opportunities, and gender-balanced, that strives for gender parity in representation, finding that 58% of institutions are gender-neutral but only 24% are gender-balanced, and that the fraction of man-overrepresented institutions increases with institutional prestige. We define artist's co-exhibition gender to capture the gender inequality of the institutions that an artist exhibits. Finally, we use logistic regression to predict an artist's access to the auction market, finding that co-exhibition gender has a stronger correlation with success than the artist's gender. These results help unveil and quantify the institutional forces that relate to the persistent gender imbalance in the art world.

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Only preliminary investigations on the use of the 445 nm wavelength blue light laser (BLL) for various laryngeal pathologies have been described. Currently, no standard exists for reporting treatment technique and tissue effect with this modality. Here, we aim to establish and validate a classification system to describe laser-induced tissue effects. Retrospective video-based study for classification development and reliability validation. Video recordings from procedures performed with the BLL by multiple academic laryngologists were retrospectively reviewed. A preliminary six-point classification (BLL 1-6) was developed based on expert consensus. Thirteen additional procedural clips were independently rated utilizing the classification schema to assess perceived tissue effect and measure inter- and intra-rate reliability. The final five-point classification system (BLL 1-5) included angiolysis, blanching, tissue vaporization, ablation with mechanical tissue removal, and cutting. The consensus of the combined reviewers in rating all cases was 89% (58 of 65). Complete consensus was not achieved in 11% (7/65) of cases. Of those incorrect, 57% (4/7) were of clips illustrating the BLL-2 classification. Intra-rater reliability among the reviewers was 100%. The tissue effect of the 445 nm blue light laser can reliably be standardized with this proposed classification system. This rating system can be used to facilitate future systematic study of outcomes and effective communication between laryngologists and trainees.

The United States remains the only high-income nation without a national paid family leave (PFL) policy. It also has persistently high maternal and infant mortality rates. Understanding PFL impacts on perinatal health is critical. We determined the impact of state PFL policies on perinatal health, with additional focus on socioeconomic disparities. We analyzed live singleton births using 2016 to 2022 birth certificate data (N = 11 452 411). We conducted a quasi-experimental analysis using heterogeneity-robust differences in differences, comparing pre-post trends in a comprehensive set of perinatal outcomes in jurisdictions with (Connecticut; Washington, DC; Massachusetts; New York; and Washington) and non-South states without PFL. Analyses were additionally stratified by maternal race and ethnicity, education, insurance, and Special Supplemental Nutrition Program for Women, Infants, and Children participation and adjusted for individual- and state-level time-varying covariates. Hypertensive disorders of pregnancy risk decreased by 13% following PFL implementation, as did excess gestational weight gain. PFL implementation was associated with modest increases in small for gestational age (0.290 percentage points [pp]; 95% CI, -0.300 to -0.102), preterm birth (0.590 pp; 95% CI, 0.465-0.715), and lower mean birthweight (-5.205 g; 95% CI, -7.096 to -3.314). Socioeconomically disadvantaged subgroups saw higher risks of adverse birth outcomes but improved maternal outcomes. This study adds to prior research that found that PFL is associated with improvements in parental health and breastfeeding in the United States. Our findings suggest that state PFL policies had mixed impacts on perinatal health; further investigation of policy parameters and mechanisms is warranted.

The corporatization of medicine that sociologist Paul Starr predicted in his 1982 landmark work, The Social Transformation of American Medicine, has come to pass in many ways and is reshaping the delivery of American health care for both good and bad. Although the corporate focus on cost and efficiency is welcome at a time of constrained resources, the more pernicious impacts of corporatization must be managed to keep the health care industry focused on the health of our patients and our communities. The corporation is here to stay. The challenge is to make peace with that reality and work within it to reap its potential benefits while maintaining health care as a social good.