Faculty Bibliography

Deep venous drainage (DVD) is considered a negative prognostic factor in AVM surgery, yet its effect on postoperative functional decline remains incompletely defined. This study evaluates whether DVD predicts worsened functional status after surgical resection of Spetzler-Martin Grade II-III AVMs. This retrospective multicenter study analyzed 129 patients with Spetzler-Martin Grade II-III AVMs across nine centers in North America and Europe who underwent primary surgical resection. We excluded cases with prior endovascular or stereotactic interventions. The primary outcome measured was poor functional status, defined as modified Rankin Scale (mRS) score 3-6 at last follow up. Among 129 patients with Spetzler-Martin Grade II-III AVMs, 38 (29.5%) exhibited deep venous drainage (DVD). Poor functional outcome (mRS ≥ 3) at last follow-up occurred in 14 patients (10.9%). This occurred in 6 of 38 patients with DVD (15.8%) compared with 8 of 91 without DVD (8.8%; Fisher's exact p = 0.244). On univariate Firth-penalized logistic regression, DVD was not significantly associated with poor outcome (OR 1.96, 95% CI 0.65-5.89; p = 0.228). In the primary reduced Firth model adjusting for age and pre-existing functional disability, DVD was independently associated with poor outcome (OR 6.87, 95% CI 1.07-44.20; p = 0.042). Increasing age (OR 1.08 per year, 95% CI 1.02-1.13; p = 0.004) and pre-existing functional disability (OR 6.53, 95% CI 1.63-26.22; p = 0.008) were also independently associated with poor outcome. DVD is associated with functional decline following surgical resection of Spetzler-Martin Grade II-III AVMs after adjustment for age and pre-existing functional disability.

Almost five years after COVID-19 emerged, multiple scientific uncertainties remain about why some people experience ongoing symptoms long after being infected with SARS-CoV-2 (Long COVID). The pathophysiology underlying Long COVID and its potential to represent several endotypes are still under investigation. These scientific uncertainties around Long COVID have been cited as a reason to delay treatment trials until the disease is better understood. In this paper, a group of bioethicists, clinician-scientists and people with lived experience with Long COVID argue that it is ethically imperative to conduct trials of disease-modifying treatments for Long COVID now. Furthermore, we argue that although conducting such trials can pose ethical challenges, these challenges can be overcome through careful research priority-setting, rigorous trial design, fair participant selection, and ensuring that the risk-benefit profile is favorable.

OBJECTIVE:To examine the early experiences influencing research career intentions (RCI) among MD students from racial and ethnic backgrounds underrepresented in medicine (URiM). METHODS:We conducted semi-structured, in-depth interviews with 31 first-year URiM medical students from MD-granting programs across the US to examine student-reported experiences influencing RCI. RESULTS:Participants were first-year medical students (N = 31; mean age 24.8 ± 2.6 years; 64.5% female) identifying as Black (38.7%), Hispanic (32.3%), or Multiracial (29%). Four themes were identified: (1) structured premedical research exposure was described as pivotal to developing early research engagement and interest in research careers; (2) research orientations reflected a commitment to using research as a vehicle for social justice and community impact; (3) high-quality research mentorship was characterized by authentic relational investment, skill development, and the distinct value of racial and ethnic identity-concordant role models; and (4) the research arms race for residency placement was described as amplifying systemic inequities that constrained students' research engagement. Across themes, students described tensions between academic research culture and their personal values, including a desire to advance equity and contribute meaningfully to science. For some, this misalignment made research feel less purposeful or personally aligned. CONCLUSIONS:Medical training programs seeking to support URiM students' RCI should invest in structured premedical research programs and expand access to research mentorship that is both relationally invested and identity concordant. Efforts to cultivate sustained engagement should address publication pressures tied to residency competitiveness, which amplify structural barriers and misalign with students' motivations for pursuing research. Broadening definitions of scholarly contribution and fostering research environments that affirm students' values may be critical to building a robust physician-scientist workforce.

INTRODUCTION/BACKGROUND:Many children with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI) have meal-related symptoms. The aim of the current study was to determine if meal-related symptoms defined specific mutually exclusive subgroups (classes) and, if so, whether these relate to other pathophysiologic factors. METHODS:Between 2020 and 2022, 289 children with AP-DGBI completed questionnaires evaluating gastrointestinal symptoms, psychosocial variables (e.g., somatization), and health-related quality of life (HRQoL). Latent class analysis (LCA) evaluated symptom patterns using 10 gastrointestinal symptoms, while univariable latent class regression (LCR) analyzed associations with covariates. KEY RESULTS/RESULTS:Three latent classes emerged: Class 1 (characterized by low meal- and stool-related symptom burden, 35.0%), Class 2 (exhibiting meal-related symptoms, 32.2%), and Class 3 (manifesting meal- and stool-related symptoms, 32.8%). Compared to Class 1, odds of belonging to Class 2 were significantly associated with increasing age, female sex, and lower HRQoL in physical and school functioning. Compared to Class 1, odds of belonging to Class 3 were similarly associated with increasing age, female sex, somatization, and with reduced HRQoL in physical, social, and psychosocial domains. There were no group differences with respect to depression, social stress, or anxiety. CONCLUSIONS AND INFERENCES/CONCLUSIONS:In youth with AP-DGBI, three distinct phenotypic groups are identified. Two of these distinct groups experience meal-related symptoms: one with associated bowel symptoms and the other without. These two meal-related symptom groups are associated with increasing age, female sex, somatization, and reduced HRQoL (particularly physical). These findings underscore the distinctness and importance of identifying the drivers of meal-related symptoms in children with AP-DGBI.

Childhood is a period of peak developmental plasticity, involving drastic changes in the maturation of the neural circuitry underlying fear learning. Disruption and atypical development of fear learning are candidate mechanisms underlying child psychopathology. While there is a lack of understanding behind the maturation of fear learning systems in humans, rodent studies in this area delineate the normative development of fear learning systems early in life, and the effects of early threatening and fearful experiences on this developmental trajectory. Here, we review the rodent literature on developmental fear learning, as well as human studies that show translational convergence in typical development and children exposed to early life threat. We identify several gaps in research, including the role that caregivers play in regulating fear learning at different developmental stages and the intergenerational transmission of learned fear. Finally, we provide recommendations on how to address these gaps in a way that would improve our developmental frameworks of fear learning.

BACKGROUND:Timely transport of critically injured patients by Emergency Medical Services to verified trauma centers significantly reduces morbidity and mortality. Prior studies demonstrate that undertriage in the prehospital setting impacts outcomes, with rural communities facing additional geographic and systemic barriers to timely trauma care. The area deprivation index, a validated measure of neighborhood-level socioeconomic disadvantage, is associated with poorer health outcomes and may further influence access to trauma centers. Yet, the association between socioeconomic deprivation, rurality, and trauma center transport remains poorly defined. This study aimed to evaluate the extent of urban-rural inequities in Emergency Medical Services transport of critically injured patients to verified trauma centers across all regions of the United States and to assess the association between area deprivation index and likelihood of transport to a trauma center. METHODS:We identified all Emergency Medical Services transported critically injured patients meeting Centers for Disease Control and Prevention field triage criteria for trauma center transport in the National Emergency Medical Services Information System from 2018 to 2022 and mapped Zone Improvement Plan (ZIP) Codes containing verified trauma centers (Levels I-V) using data from the American College of Surgeons, the Trauma Center Association of America, and the American Trauma Society. The cohort was stratified by regions in the United States: Northeast, Midwest, South, and West. The incident scene area deprivation index was obtained from the Neighborhood Atlas at the census block group level. The total number and percentage of patients located in urban and rural Zone Improvement Plan (ZIP) codes transported either to a confirmed trauma center (via the National Emergency Medical Services Information System data) or to a Zone Improvement Plan (ZIP) code that contains a trauma center and the area deprivation index distribution in tertiles (low area deprivation index, moderate area deprivation index, and high area deprivation index) within regions in the United States were calculated with their statistical significance derived from t tests and analyses of variance with post hoc Tukey tests. RESULTS:A total of 36,897,269 critically injured patients met the inclusion criteria, of which 19,874,008 (53.86%) were brought to a trauma center. When stratified by rurality, 7,608,704 (54.01%) and 12,265,304 (53.77%) of critically injured patients within rural and urban areas, respectively, were transported to a trauma center. When comparing across regions, the Northeast region of the United States had the lowest percentage of critically injured patients being transported to a trauma center, whereas the Midwest region had the highest percentage (44.04% vs 67.40%; P < .001). When stratified by rurality, 35.33% vs 46.92% of critically injured patients within rural versus urban areas of the Northeast were transported to a trauma center, whereas 65.47% vs 68.57% of critically injured patients within rural versus urban areas of the Midwest were transported to a trauma center (P < .001). When evaluating area deprivation index, critically injured patients who were injured in more disadvantaged versus advantaged Zone Improvement Plan (ZIP) codes had a higher percentage of patients being transported to a trauma center even when controlling for rurality (56% vs 47%; P < .001). CONCLUSION/CONCLUSIONS:Substantial geographic inequities in the Emergency Medical Services transport of critically injured adult patients to verified trauma centers, varied by geographic region, rurality, and neighborhood-level socioeconomic disadvantage that exist. These findings highlight the complex and regionally variable landscape of trauma access in the United States and underscore the need for targeted, equity-focused strategies to optimize prehospital triage and ensure timely, trauma-informed care across diverse communities.

BACKGROUND:Brachial plexus injury (BPI) following shoulder trauma is an uncommon but potentially disabling complication that is often underrecognized, leading to delayed diagnosis. This study aimed to define the institutional incidence, nerve distribution, and recovery patterns of BPI after shoulder trauma and to identify factors associated with injury severity and recovery. METHODS:We performed a retrospective review of adult patients diagnosed with BPI following isolated shoulder trauma at a single academic center from January 2016 to July 2023. Patients with BPI were compared with a randomized cohort of shoulder trauma patients without BPI. Variables included demographics, mechanism of injury, injury pattern, nerve involvement, severity grading, management, and ≥1-year outcomes. BPI severity was categorized using a standardized clinical grading system. Logistic regression was used to evaluate factors associated with severity and predictors of recovery. RESULTS:Among 6,195 patients with shoulder trauma, 111 (1.8%) were diagnosed with BPI. Patients with BPI were younger than controls (51.5 vs. 58.8 years, p=0.004), and fracture-dislocations were more common (p<0.001). The axillary nerve was most frequently affected (67.1%), followed by radial (41.5%), median (36.6%), ulnar (32.9%), and musculocutaneous nerves (22.0%). Most patients (74.4%) achieved complete recovery within one year, and 85.4% were managed nonoperatively. Musculocutaneous nerve injury was associated with reduced odds of recovery (OR 0.17, p=0.002), whereas dislocation (OR 5.43, p=0.017) and fracture-dislocation (OR 5.60, p=0.020) were associated with improved recovery compared with isolated fracture. CONCLUSION/CONCLUSIONS:BPI occurred in 1.8% of shoulder trauma cases and was most associated with fracture-dislocations. Musculocutaneous nerve injury and female sex were independently associated with lower likelihood of recovery, whereas dislocation and fracture-dislocation patterns were associated with improved recovery compared with isolated fractures. These findings underscore the importance of early, nerve-specific evaluation and more refined prognostic stratification following shoulder trauma.

Management of critically ill patients with pulmonary hypertension (PH) presents significant clinical challenges. Regardless of the underlying etiology or chronicity of PH, superimposed acute illness can precipitate decompensated right ventricular failure (RVF) and death. Hospitalization, particularly in the intensive care unit (ICU), is associated with high mortality, with RVF serving as the direct or indirect cause in most cases. In this article we will focus on the management of acute decompensated RVF in patients with known pulmonary arterial hypertension (PAH). ICU management of the PAH patient with RVF centers on the recognition and treatment of potentially reversible precipitants for decompensation and supportive strategies to optimize right ventricular (RV) function. Key goals include maintaining adequate oxygenation and tissue perfusion, correcting electrolyte and other metabolic abnormalities, optimizing fluid balance and RV preload, enhancing RV contractility, and reducing RV afterload. Continuous monitoring of cardiac function is essential, as is identifying and treating potential complications, such as arrhythmias or acute kidney injury (AKI). When RVF persists despite maximal medical therapy, extracorporeal life support may be considered as a bridge to recovery or transplantation. In patients with advanced disease multidisciplinary discussions aligned with patient and family preferences should guide the goals of care. Integration of palliative care specialists to manage symptoms and support caregivers remains a critical component of comprehensive ICU management for patients with PAH.

BACKGROUND:Optimising the dosage of pharmacological treatments for ADHD is key to maximising their benefits, yet most clinical guidelines provide only limited information on this issue. Dose-effect relationships have not been comprehensively assessed across all ADHD medications and age groups, despite growing concerns about subtherapeutic prescribing. We aimed to estimate dose-effect curves for efficacy and tolerability of ADHD medications (stimulants and non-stimulants) across age groups. METHODS:We conducted a systematic review and dose-effect network meta-analysis of double-blind randomised controlled trials (RCTs) evaluating oral monotherapy (stimulants and non-stimulants) in individuals aged 5 years and older meeting standardised ADHD criteria. Studies involving genetic syndromes, treatment-resistant populations, or withdrawal-phase designs were excluded. We retrieved eligible studies from the MED-ADHD database, updated on Feb 17, 2025, without language restrictions. We included published and unpublished aggregated-level data. The primary outcome was efficacy (measured using validated clinical scales) and the secondary outcome was tolerability (discontinuation due to adverse events). Within-study bias was assessed with the Cochrane Risk of Bias Tool (version 2). We summarised dose-effect associations using a hierarchical Bayesian model with restricted cubic splines. Separate analyses were conducted for children or adolescents (aged <18 years) and adults (aged ≥18 years). The distribution of key effect modifiers was used to examine transitivity of the network. People with lived experience were involved in the conceptualisation and design of the study, and in the interpretation of the findings. The protocol was pre-registered on OSF. FINDINGS/RESULTS:Our 2017 search identified 9948 potential references for inclusion and our Feb 17, 2025 search identified 5148 references. Of these 15 096 references, 8467 were excluded after title and abstract screening, and a further 5862 references were excluded after a full-text read. Of the 767 remaining reports, 164 were included in the systematic review and 113 RCTs (45 in adults and 68 in children and adolescents) were included in the dose-effect network meta-analysis. The 68 RCTs on children and adolescents included 14 138 participants (9981 [70·6%] males and 4157 [29·4%] females) and the 45 RCTs on adults included 11 016 participants (5958 [54·0%] males and 5056 [46·0%] females). Data on ethnicity or race were inconsistently reported across RCTs. We found distinct dose-effect patterns by medication class and age group. In children and adolescents, methylphenidate, amphetamines, and guanfacine showed increasing median efficacy up to 45 mg/day, 25 mg/day and 4 mg/day, respectively, with no evidence of additional benefit at higher doses, although estimates at higher doses were characterised by wide credible intervals. In adults, amphetamines showed a plateau above approximatively 50 mg/day, whereas methylphenidate efficacy increased without evidence of a plateau, possibly due to sparse data. Dose-dependent increases in discontinuation probability due to adverse events were observed for amphetamines (above 25 mg/day for children and 50 mg/day for adults) and methylphenidate (above 50 mg/day for adults, with no clear dose-dependent risk for children). We found no evidence of dose-effect patterns for atomoxetine (in fixed-doses studies) and modafinil. Multiple sensitivity analyses confirmed the robustness of these findings. We found no evidence of intransitivity. INTERPRETATION/CONCLUSIONS:Our findings challenge both therapeutic inertia-accepting suboptimal response without further dose titration-and uncritical dose escalation beyond licensed limits, when potential harms outweigh expected benefits. Our findings can inform clinical guidelines and should support shared decision making regarding ADHD medication dosage. FUNDING/BACKGROUND:National Institute for Health and Care Research (NIHR303122).