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Importance Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. Objective To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. Design, Setting, and Participants A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Interventions Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. Main outcomes and measures The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Results Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. Conclusion and relevance In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. Trial registration ClinicalTrials.gov Identifier: NCT04571840

OBJECTIVES: Many PICU admissions start with presentation in the emergency department (ED). However, we do not know whether there are any ED-related factors associated with the subsequent development of pediatric delirium (PD) within 24 hours of PICU admission. DESIGN: Retrospective cohort study. SETTING: Single-center ED and PICU serving a quaternary referral center in the United States. PATIENTS: Children younger than 18 years old presenting to the ED between January 2022 and December 2023 who required direct admission to the PICU, and who had at least one positive delirium screening within 24 hours of the admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of delirium in the PICU was defined as a Cornell Assessment of Pediatric Delirium (CAPD) score of 9 and higher. We identified 138 patients for the final analysis. Overall, 51 of 138 patients (37%) developed PD within 24 hours of admission. The majority of delirium cases were classified as hypoactive (53%, 27/51) and mixed (31%, 16/51) subtypes, while only 16% (8/51) were identified as hyperactive delirium. Factors associated with greater odds (95% CI) of delirium in the PICU in multivariable analysis were use of mechanical ventilation (odds ratio [OR], 3.42 [95% CI, 1.09–10.78]; p = 0.04) and intermittent urinary catheterization (OR, 3.7 [95% CI, 1.21–11.30]; p = 0.02). Initial CAPD score positively correlated with PICU length of stay (LOS; r = 0.32; p < 0.01), Pediatric Index of Mortality 3 (PIM 3) score ( r = 0.26; p < 0.01), and negatively correlated with emergency severity index (ESI) in the ED ( r = –0.35; p < 0.01). CONCLUSIONS: Mechanical ventilation and intermittent urinary catheterization in the ED are associated with greater odds of PD within 24 hours of PICU admission. CAPD at admission positively correlates with PICU LOS, PIM 3 scores, and negatively correlates with ESI in the ED.

ABSTRACTWe describe a case of a 56‐year‐old male who developed severe, refractory hypotension after an intentional ingestion of clozapine and who became hemodynamically stable after one session of therapeutic plasma exchange (TPE). The patient, who presented after an ingestion of clozapine, was found to have altered mental status and hypotension in the emergency department. Escalating catecholamine vasoactive agents were necessary to maintain adequate hemodynamics. Angiotensin II was added and rapidly up titrated in efforts to maintain adequate blood pressure. Due to persistent hemodynamic instability despite four vasoactive agents, TPE was attempted to enhance the elimination of the highly protein bound medication. Within 2 h of completing TPE, the catecholamines and vasopressin were stopped, and angiotensin II dosing was significantly decreased. This is the first report of utilizing TPE as a method of enhanced elimination of a toxic clozapine ingestion resulting in severe hemodynamic compromise. Further study is necessary to determine if TPE should be incorporated into the care of patients experiencing clozapine toxicity.

Abstract Background: Understanding of the diagnosis and treatment of adults with community-acquired pneumonia (CAP) has evolved thanks to new evidence, experience, and emerging technologies. This document updates evidence-based clinical practice guidelines on four key questions for the diagnosis and management of adult patients with CAP. Methods: A multidisciplinary panel integrated systematic reviews of comparative evidence with other relevant research and clinical experience, then applied Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology to produce recommendations using the Evidence to Decision Framework. Results: The panel formulated clinical recommendations that address questions related to CAP, including lung ultrasound for diagnosis, empiric antibacterial therapy if a test for a respiratory virus is positive, antibiotic duration, and the use of systemic corticosteroids. Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with CAP.

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (&lt;30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

ABSTRACTBackground and ObjectivesMedicaid reimbursement to physicians has been demonstrated to be lower than reimbursement from Medicare and private insurance. Studies on Medicaid reimbursement for orthopedic oncology procedures, however, are limited. This study compares Medicaid reimbursement rates to Medicare for 38 common musculoskeletal oncology procedures and assesses variability among states.MethodsWe collected 38 current procedural terminology (CPT) codes for commonly performed orthopedic oncology procedures. Medicare rates were obtained from the 2023 Centers for Medicare and Medicaid physician (CMS) fee schedule. Medicaid rates were collected from electronic state website fee schedules. Reimbursement for the two insurance types were compared with state and national averages. Dollar differences were adjusted for work relative value units (RVU) to ascertain procedural variability. The Medicare Wage Index, representing differences in wages across states, was used to adjust medicaid rates to compare more accurately to medicare. Coefficient of variation values, calculated by dividing the standard deviation by the mean, were calculated to assess variation among procedures.ResultsMedicaid reimbursed orthopedic oncologists 22.1% less than medicare on average, increasing to 33.0% when adjusting for wage differences. State Medicaid reimbursement ranged from 37% to 131% of Medicare, with 38 states reimbursing less than Medicare on average. The coefficient of variation for Medicaid procedures ranged from 0.24 to 0.46, indicating wide variability among states and procedures, while for Medicare, the coefficient of variation was low at 0.06 to 0.07.ConclusionsMedicaid reimbursement for common orthopedic oncology procedures is substantially lower and more variable than Medicare, despite the often urgent nature of these surgeries. Disparities in reimbursement may impact access to care for this population, highlighting the need for policy reform.

Background: Rheumatoid arthritis is a relatively common rheumatic disease that can present with inflammatory arthritis and subcutaneous nodules. Multicentric reticulohistiocytosis and fibroblastic rheumatism are rarer entities that also present with these features. Methods: Two cases, one of each of fibroblastic rheumatism and multicentric reticulohistiocytosis, are described highlighting characteristic clinical, radiographic, and histologic findings. A narrative review of the literature on these rarer conditions, compared with rheumatoid arthritis, is provided with a focus on articular and cutaneous findings, available information on disease presentations, and key contrasting features that can aid in diagnosis. Results: Radiographic erosion distribution and joint space narrowing, clinical nodule distribution and characteristics, and nodule histology can differ between these diseases. Conclusions: Multicentric reticulohistiocytosis and fibroblastic rheumatism should be considered in the evaluation of seronegative rheumatoid arthritis, especially in cases that do not respond predictably to standard therapies, and cutaneous nodule biopsy can aid in differentiating these three conditions.

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.

Objective To provide a comprehensive analysis of initial suicide attempts, covering incidence, risk factors, outcomes, and healthcare use in the month before and the month after the attempts. Design Comprehensive analysis of the Swedish population that included three designs: a retrospective cohort study to investigate incidence and healthcare use, a nested case-control study to investigate risk factors, and a matched cohort study to examine subsequent suicide attempts and mortality. Setting Comprehensive Swedish national registers that include patient diagnoses from hospitals and specialist outpatient care, and cause of death information updated to the end of 2019. Participants 3.7 million people born in Sweden in 1963-98 and followed from age 10 to 57 years. Main outcome measure First lifetime suicide attempt identified in patient and death registers using ICD (international classification of diseases) codes for intentional self-harm, any self-harm with lethal methods or requiring hospital admission, or any self-harm resulting in death. Results The lifetime risk of an initial suicide attempt in the study population was 4.6%, with greater risk in females and highest risk between ages 18 and 24. One in 10 families in Sweden had at least one family member who attempted suicide. Overdose and poisoning were the most common methods. Previous psychiatric disorders, general medical diseases, and adverse life events were associated with increased risk of initial suicide attempt, while higher socioeconomic status was associated with decreased risk. People with an initial suicide attempt were at substantially increased risk of subsequent attempts (hazard ratio 23.4), death by suicide (16.4), and all cause mortality (7.3). At least 60% of those who made an initial suicide attempt had a healthcare contact in the month before the attempt. Conclusions This study provides comprehensive data on the incidence, risk factors, outcomes, and healthcare use of initial suicide attempts in the Swedish population, highlighting the need for systematic prevention efforts for people who have attempted suicide for the first time.