Faculty Bibliography

OBJECTIVES/OBJECTIVE:Anemia is common in critically ill patients. In prior trials, a restrictive transfusion strategy was at least as effective as, and possibly superior to, a liberal strategy in critically ill adult patients. However, the Transfusion Requirements in Critical Care (TRICC) trial suggested that a restrictive strategy might be harmful in critically ill patients with ischemic heart disease. Our objective was to compare outcomes for restrictive and liberal transfusion strategies in critically ill and noncritically ill patients with acute myocardial infarction (AMI) and anemia. DESIGN/METHODS:Subgroup analysis of a parallel, two-arm randomized, controlled trial. SETTING/METHODS:One hundred forty-four sites in the United States, Canada, France, Brazil, New Zealand, and Australia. PATIENTS/METHODS:Adult patients with AMI and anemia enrolled in the Myocardial Ischemia and Transfusion (MINT) trial. Patients being treated in an ICU at randomization were considered critically ill. INTERVENTIONS/METHODS:Patients were randomly assigned to a restrictive (transfuse when hemoglobin < 7-8 g/dL) or liberal (transfuse when hemoglobin < 10 g/dL) transfusion strategy. MEASUREMENTS AND MAIN RESULTS/RESULTS:We determined the effect of transfusion strategy on death and the composite of death/myocardial infarction (MI) at 30 days among critically ill and noncritically ill patients. Of 3504 patients enrolled in MINT, 1679 (47.9%) were critically ill. At 30 days, death (11.9% vs. 6.5%) and death/MI (18.9% vs. 12.7%) occurred more frequently in critically ill patients compared with noncritically ill patients. A restrictive, compared with a liberal, transfusion strategy resulted in a nonsignificant increase in the risk of death by 9% (risk ratio [RR], 1.09; 95% CI, 0.77-1.54) and death/MI by 9% (RR, 1.09; 95% CI, 0.85-1.38) in noncritically ill patients and a nonsignificant increase in the risk of death by 24% (RR, 1.24; 95% CI, 0.95-1.61; interaction p = 0.55) and death/MI by 21% (RR, 1.21; 95% CI, 0.99-1.47; interaction p = 0.52) in critically ill patients. CONCLUSIONS:There is no evidence that the overall MINT trial results, which generally favor a liberal transfusion strategy in AMI patients, apply differently to noncritically ill and critically ill patients.

BACKGROUND:Despite the frequent late-stage diagnosis of gastric cancer (GC), the U.S. lacks a routine gastric cancer screening program. Liquid biopsy (LB), specifically blood-based tests, has emerged as a potential screening approach, but it is unclear whether such a strategy is cost-effective. We therefore evaluated the cost-effectiveness of liquid biopsy screening for GC in the U.S. METHODS:A Markov model was developed to compare no screening (current standard-of-care) and two liquid biopsy screening strategies. The study used a simulated cohort of 45-year-old individuals with average risk of gastric cancer. Primary model outcomes included life expectancy, quality-adjusted life-years (QALYs), total cost, and incremental cost-effectiveness ratios (ICERs). A strategy was considered cost-effective if the incremental cost-effectiveness ratio was less than the U.S. willingness-to-pay threshold of $100,000 per quality-adjusted-life-year gained. RESULTS:In the base-case analysis, LB screening strategies were not cost-effective, with an incremental cost-effectiveness ratio of $917,826 per QALY gained. Screening became cost-effective for high-risk subpopulations or when the per-test cost was approximately $89. CONCLUSIONS:This economic evaluation of LB for GC screening found that while LB strategies are effective in reducing cancer incidence and mortality, they are not cost-effective due to high test costs. Our findings could help inform the potential planning of future clinical validation studies for LB tests used for GC screening.

INTRODUCTION/BACKGROUND:We describe bleeding and cramping patterns during the first 90 days after intrauterine device (IUD) placement. METHODS:This was a planned sub-analysis of a prospective cohort study of IUD users in the United States who initiated the copper T380A (Cu-IUD) or the levonorgestrel 52 mg intrauterine device (LNG IUD) at any time in the menstrual cycle. Participants rated bleeding and cramping from 1 (no bleeding or cramping) to 4 (heavy bleeding or severe cramping). We included participants providing ≥ 60 days of continuous responses and described overall bleeding/cramping. RESULTS:Of 230 participants enrolled, 137 (60%) met inclusion criteria (Cu-IUD n = 69, 50% and LNG IUD n = 68, 50%). Cu-IUD users reported fewer days with any bleeding (26 days, IQR 18-31) compared with LNG IUD users (38 days, IQR 27-55, p < 0.001). LNG IUD users reported more spotting days (median 31 [IQR 17-41] vs. 13 [IQR 10-20], p < 0.01). Total bleeding/spotting days were similar for each IUD type regardless of placement timing or prior contraceptive method. Median reported cramping days were similar for both IUDs (Cu-IUD 18, IQR 7-29 and LNG IUD 18, IQR 10-38, p = 0.18). Cramping was most common in the week following placement for both IUD types, decreased over the 90-day period, and did not vary by IUD type. CONCLUSION/CONCLUSIONS:LNG IUD users reported more days with any bleeding in the first 90 days after placement overall compared with Cu-IUD users, largely driven by more than twice the number of spotting days. Cramping was most common in the first week following IUD placement and decreased over time. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.Gov Identifier: NCT01730911.

BACKGROUND/UNASSIGNED:Early-onset colorectal cancer (EOCRC), diagnosed in adults under the age of 50 years, is a significant public health challenge in the United States (US). While traditional colorectal cancer (CRC) incidence in older populations has declined due to screening, rates among younger adults are rising, likely driven by shifting birth cohort exposures to modifiable risk factors. This study aims to quantify the longitudinal burden of EOCRC and evaluates the contribution of dietary and metabolic risks from 1990 to 2023. METHODS/UNASSIGNED:Using data from the Global Burden of Disease (GBD) 2023 study, we analyzed age-specific incidence, mortality, prevalence, and disability-adjusted life years (DALYs) for EOCRC. Trends were evaluated using joinpoint regression to calculate annual percent changes (APCs). Risk factor attribution was performed for dietary, metabolic, and behavioral exposures. Future burdens were projected to 2050 using mixed-effects and autoregressive integrated moving average (ARIMA) models. RESULTS/UNASSIGNED:Between 1990 and 2023, the age-specific incidence rate (ASIR) of EOCRC increased by 47.1%, rising from 8.01 to 11.79 per 100,000. Age-specific mortality rose from 2.48 to 3.00, and DALYs increased from 125.41 to 150.82. Males consistently carried a higher burden, with widening sex disparities in incidence by 2023 (13.10 in males versus 10.44 in females). By 2023, diet high in processed meat (18.4%) surpassed diet low in whole grains (17.6%) as the leading modifiable contributor to EOCRC mortality, followed by high body-mass index and smoking. Under a risk-reduction scenario, projected mortality could decline by more than 50% by 2050 (1.14 per 100,000) compared to the reference trend (2.42 per 100,000). CONCLUSIONS/UNASSIGNED:The EOCRC burden in the US has intensified over three decades. The shifting dominance toward processed meat and metabolic dysfunction highlights a critical need for targeted primary prevention. Achieving significant mortality reductions by 2050 will require population-level interventions addressing dietary quality and metabolic health early in life.

How can theory and mathematical modeling help accelerate research in psychiatry? Here we highlight the promise of computational approaches via three recent trends: multi-scale models of working memory which link receptors and cell-types to brain-wide activity and behavior; the extension of mechanistic computational models from working memory to other cognitive functions including conscious perception, attention and planning; and cross-species comparative models of cognition that give rise to translational computational neuroscience. These developments demonstrate the feasibility of achieving understanding across spatial and biological scales in psychiatry research. Crucially, computational findings now can give rise to specific and testable mechanistic hypotheses for a wider range of symptoms associated with mental disorders. Finally, computational tools have emerged to guide translational neuroscience towards the experiments that are most likely to translate to treatment of human brain disease. We provide primer coding notebooks for several models to accompany the article.

PURPOSE/OBJECTIVE:Knobloch syndrome is a rare autosomal recessive condition characterized by lack of functional collagen type XVIII (COL18A1), occipital defects, high myopia, and vitreoretinal degeneration. Clinical features, retinal detachment (RD) rates, and role of prophylactic treatment are not well established. The purpose is to 1) report clinical/systemic features, 2) RD rates and 3) the role of prophylactic treatment in a U.S.-based genetically confirmed cohort. DESIGN/METHODS:Retrospective, nonrandomized multi-center case cohort SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Genetically confirmed Knobloch patients from 12 US -based pediatric retina tertiary referral centers MAIN OUTCOMES MEASURES: Baseline characteristics, RD rates, risk of RD with or without a history of prophylactic treatment RESULTS: 72 eyes (36 patients) were included. Mean follow up was 5.2 years. 14 patients (38.9%) were female. Most common systemic features included 1) occipital defects (n=17 (47.2%)), 2) intracranial abnormalities (n=10 (27.8%); polymicrogyria, plagiocephaly, cortical dysplasia, encephalomalacia, periventricular heterotopia), and 3) skin (n=5 (13.9%)); hemangioma, eczema). Mean +/-SE refractive error was - 9.85 (range -20.12 - +7.50). 18 eyes (25.0%) had cataracts, 16 (20.0%) iris defects (transillumination defects, absent crypts, pupillary membrane), 40 (57.1%) optically empty/vitreous condensations, and 64/70 eyes (91.4%) had macular abnormalities ranging from tessellated fundus to generalized macular atrophy.Of 72 eyes, 23 (31.9 %) experienced an RD, 12 (52.2%) at baseline. Two eyes (8.7%) had a concurrent macular hole. Mean age at RD was 6.24 years and time to RD was 18.6 months (0 - 86). 20 eyes (87.0%) underwent RD surgery (laser, SB, PPV, or PPV/SB). Single and final anatomic success was 60% and 85%. 21/72 eyes (29.2%) received laser or scleral buckle prophylaxis - only two of which (9.0%) developed an RD. Age-adjusted GEE logistic model demonstrated lower odds of RD in eyes that received prophylaxis than not (OR 0.20, P = 0.022). 4/19 fellow eyes (21%) developed an RD (n=1 with previous RD prophylaxis). There was a nonsignificant lower odds of RD in fellow eyes that received RD prophylaxis versus no prophylaxis (OR = 0.42, p = 0.41). CONCLUSION/CONCLUSIONS:In genetically confirmed Knobloch, RD rates are high, and RD prophylaxis appeared to reduce risk of RD. Early diagnosis and prophylaxis should be considered in this population.

PURPOSE/OBJECTIVE:To evaluate the effectiveness of Smart Crutch Tips™ in promoting adherence to prescribed early partial weight-bearing (PWB) protocols and to assess patient experience with real-time weight-bearing feedback during home rehabilitation. METHODS:Twenty patients with lower extremity fractures prescribed partial weight-bearing (PWB) were randomized into two groups utilizing real-time feedback crutch tips (RFC). The Intervention group (n = 10) used Smart Crutch Tips™ (ComeBack Mobility Inc., Kiev, Ukraine), which provided real-time feedback on weight-bearing compliance. The Control group (n = 10) also used crutches equipped with Smart Crutch Tips™, but notifications were disabled, allowing passive data collection without patient feedback. Weight-bearing compliance was defined as the percentage of steps within ± 10% of the prescribed target. Secondary outcomes included patient satisfaction and device usability assessed using the System Usability Scale (SUS) throughout the home rehabilitation period. RESULTS:The Intervention group demonstrated significantly greater PWB compliance compared with the Control group (73.6% vs. 21.1%, p < 0.01). The Intervention group reported a mean SUS score of 84.25, indicating excellent usability. No device-related complications or adverse events were observed. Patient satisfaction, assessed through video interviews, was high, with participants in the Intervention group expressing a strong willingness to recommend the device to others with similar injuries and rating it 10 out of 10. CONCLUSION/CONCLUSIONS:Smart Crutch Tips™ significantly improved adherence to prescribed partial weight-bearing protocols following lower extremity fracture surgery. The RFC device demonstrated high usability, excellent patient satisfaction, and no device-related complications during home rehabilitation throughout the study period.

Traumatic abdominal flank hernias are rare and challenging but more common than previously recognized. There is no consensus on the management of traumatic flank hernias. The majority of studies have been conducted in the setting of blunt trauma; however, there is a paucity of literature on penetrating trauma. We present the case of a man in his thirties with a persistent left flank hernia after sustaining penetrating abdominal wall trauma from a tree branch two years earlier and undergoing multiple subsequent reconstructive surgeries, including both open and minimally invasive approaches. Flank hernia repair is most commonly performed with mesh and can be accomplished using either an open or minimally invasive approach, either at the time of trauma or in a delayed fashion. In selected patients, definitive repair of traumatic abdominal wall defects may be delayed until acute injuries and contamination have resolved. In this patient, intra-abdominal injuries required immediate operative management, whereas definitive reconstruction of the subsequent symptomatic flank hernia was performed in a delayed fashion.

BACKGROUND AND OBJECTIVES/UNASSIGNED:Patients with neurologic disease have a variety of unmet palliative care needs. Both the Accreditation Council for Graduate Medical Education and Academy of Neurology have emphasized the need for neuropalliative care education in recent years. Neurology training programs have widely variable practices in teaching neuropalliative care. This study aims to characterize current practices in providing neuropalliative care education across graduate neurology training and to identify barriers to its delivery. METHODS/UNASSIGNED:We surveyed program directors (PDs) of neurology residency and fellowship training programs in the United States regarding their current methods of teaching neuropalliative care topics, perceived importance of these topics, relevant subspecialty resources, and perceived barriers to providing neuropalliative care education. RESULTS/UNASSIGNED:Our survey was emailed to 777 PDs and fellowship directors. In total, 118 responses were included in the analytic sample (response rate 15.2%). Program directors generally perceived neuropalliative care education as important, with a median rank of 7 of 10. 91% of adult neurology residency programs and 66% of fellowship programs included palliative care topics in their didactics curricula. Topics emphasized varied depending on the training program's subspecialty. Respondents highlighted barriers to implementing neuropalliative care training, including inadequate trainee and faculty time and lack of adequate teaching faculty. DISCUSSION/UNASSIGNED:Neurology training programs continue to exhibit considerable variability in palliative care education curricula. Although most programs reported a presence of palliative care in their institutions, variability exists in the amount of palliative care education taught, the topics emphasized, and the teaching methods. Notably, there is an opportunity for fellowship programs to increase the amount of neuropalliative care topics taught in their curricula. Neurology residency and fellowship directors may benefit from using existing neuropalliative care curricula to enhance this area of education, partnering with local non-neurology faculty to teach palliative topics, and integrating palliative care topics into subspecialty training.

BACKGROUND:Idiopathic clubfoot is a complex congenital foot and ankle anomaly commonly treated with the Ponseti method. While gross motor function and activity level are similar in children with clubfoot treated with this method compared with children without clubfoot, data are lacking on sports participation following this treatment. This study aimed to describe the prevalence of sports participation among children with idiopathic clubfoot treated with the Ponseti method. METHODS:This was a multicenter retrospective cross-sectional study. Patients aged 5 to 17 years were included if they had been diagnosed with idiopathic clubfoot and treated with the Ponseti method during infancy. Parents of subjects were asked to complete a 1-time REDCap survey that included basic demographic questions, 2 validated activity scores (PROMIS Physical Activity Short Form and PACE+), and questions relating to sports participation. The comparison group consisted of the siblings of patients with clubfoot. RESULTS:One hundred fifty-one patients with clubfoot and 45 siblings without clubfoot were included from 4 institutions. In the clubfoot group, 72.2% of participants were male compared with 60% in the sibling group ( P =0.12). Median PROMIS-PA t-scores were 53.3 [interquartile range (IQR) 8.6] and 56.3 (IQR 13.2) in the clubfoot and sibling groups, respectively ( P =0.016). The median PACE+ scores were 4 (IQR 3.5) in the clubfoot group and 4.75 (IQR 2.75) ( P =0.261) in the sibling group. Sports participation was reported in 120 (79.5%) patients with clubfoot and 43 siblings (95.6%) ( P =0.006). Soccer, baseball, basketball, football, and swimming were the most commonly played sports in both groups. CONCLUSIONS:Children treated for idiopathic clubfoot with the Ponseti method remain active and participate in sports similar to their siblings. Further prospective studies examining sports participation and injury prevalence are needed to better understand long-term clinical and functional outcomes in patients treated with the Ponseti method for idiopathic clubfoot. STUDY DESIGN/METHODS:Retrospective. LEVEL OF EVIDENCE/METHODS:Level IV.