Faculty Bibliography

BACKGROUND:Fewer than 20% of donated lungs are transplanted. We examined the impacts of donor management and recovery at an in-hospital donor care unit (DCU) established in 2021 versus the donor hospital (DH). METHODS:(P/F ratio) were examined as a hypothesized effect modifier. We projected the national impact of improved utilization on lung transplant volume. RESULTS:After adjusting for donor differences, lung utilization was 88% higher (aRR: 1.88; 95% CI: 1.40, 2.53) in the DCU versus DH setting. Median P/F ratio increased from 275 to 348 mmHg (p<0.0001) in the DCU and explained approximately 38% of the improvement in lung utilization. Non-lung organ utilization was either improved or non-inferior in the DCU. Lung graft survival and pulmonary function were similar for recipients of DCU versus DH-managed donors. Nationally, an 88% improvement in lung utilization among donors not currently transferred to a DCU could theoretically result in ≥300 more lung transplants per year. CONCLUSIONS:Lung transplantation can be nearly doubled through lung-centric donor management in a DCU, without sacrificing recipient outcomes nor the utilization of other organs. Donor management practices to optimize lung utilization should be proliferated by establishing more DCUs and, where feasible, applying lung-centric protocols in donor hospitals.

BACKGROUND:Robotic surgery is increasingly used in emergency general surgery (EGS), but its adoption and outcomes after interhospital transfer remain unclear. We evaluated robotic adoption, hospital-level variation, predictors of use, and comparative outcomes among transferred EGS patients. STUDY DESIGN/METHODS:Using the Nationwide Readmissions Database (2016-2019), we identified adults transferred from acute-care hospitals who underwent EGS procedures. Mixed-effects models evaluated predictors and between-hospital variation in robotic use, summarized by intraclass correlation coefficients (ICC) and median odds ratios (MOR). Multivariable logistic and generalized linear models compared cost, length of stay (LOS), non-home discharge, complications, mortality, and 30-day readmission across robotic, laparoscopic, and open approaches. RESULTS:Robotics was used for ≥1 transferred patient in 8.5% of transfer-receiving hospital-years and 13.7% of robot-capable transfer-receiving hospital-years. Hospital-level variation was substantial for robotic vs laparoscopic selection (MOR 3.59; ICC 35.3%) but modest for robotic vs open selection (MOR 1.31; ICC 2.3%). Investor-owned hospitals and later years were associated with greater odds of robotic use, whereas extreme illness severity and rural residence were associated with lower odds. Compared with laparoscopy, robotics was associated with shorter LOS and higher cost, without statistically significant differences in adjusted clinical outcomes. Compared with open surgery, robotics was associated with shorter LOS, lower cost, and lower odds of non-home discharge and surgical complications. CONCLUSIONS:Robotic surgery after interhospital transfer was uncommon, with substantial hospital-level variation relative to laparoscopy despite similar adjusted clinical outcomes. These findings support defining selection criteria and evaluating equitable access to minimally invasive platforms.

BACKGROUND:Soft tissue sarcoma (STS) is a rare and heterogeneous malignancy with more than 100 histologic subtypes that can arise in virtually any part of the body. Although surgical resection is the standard of care, complete surgical resection is often limited by involvement of critical anatomy, and most subtypes are resistant to systemic therapies. Histotripsy uses microsecond length, high-pressure ultrasound (US) pulses delivered externally to generate cavitation inside the target tumor to mechanically liquefy tissue to acellular homogenate. This study tested the effect of histotripsy in a variety of soft tissue tumors (STTs) including benign tumors and sarcomas. METHODS:Histotripsy was delivered to 45 surgically excised ex vivo human samples with a custom 1 MHz 8-element US transducer guided by US imaging. RESULTS:Histotripsy was successful in creating an identifiable treatment effect across all subtypes including adipocytic tumors, benign myxoid and nerve sheath tumors, aggressive fibrous sarcomas, and high-grade sarcomas. Immediately after histotripsy, B-mode and shear-wave elastography US imaging was shown to effectively evaluate the treatment. Tissue structure heterogeneity among the tumor subtypes dictated the variation in histologic treatment effects. CONCLUSIONS:The data demonstrate effective US-guided histotripsy ablation on a robust cohort of ex vivo STTs. The variable treatment effects observed across tumor subtypes highlight the need for histotripsy parameter optimization, with support for its potential as a promising non-invasive treatment modality for sarcoma patients who currently have limited therapeutic options.

Type 2 diabetes is a risk factor for cardiac arrhythmias, but it is unknown how specific aberrations in glucose (e.g., episodes of high or low glucose) might contribute to the occurrence of heart rhythm abnormalities. The overarching goal of this study is to address research questions regarding how glucose patterns might contribute to the occurrence of arrhythmias, primarily atrial fibrillation, in adults with diabetes. To fulfill this goal, the Atherosclerosis Risk in Communities (ARIC) Gen2 study recruited 507 community-dwelling adults aged 50-80 years with type 2 diabetes to wear continuous glucose monitoring (CGM) and electrocardiogram (ECG) "patch" monitoring sensors simultaneously for up to 14 days. Gen2 study had high CGM and ECG completeness: the median wear time for sensors was 14 days and approximately 80% of participants wore both sensors for ≥10 days. By combining Gen2 and data from the original ongoing ARIC cohort (aged 80+), we have the capacity to conduct a comprehensive evaluation of the impact of CGM-defined glucose patterns on arrhythmias across a wide age spectrum from middle-aged to very old adults (aged 50-100) with type 2 diabetes. The findings from this study may help inform clinical strategies for the prevention and management of arrhythmias among adults with type 2 diabetes.

BACKGROUND:Abnormalities in Autonomic Nervous System activity are well described in psychosis but their peripheral versus CNS origins remains unresolved. However, the purely peripheral component of the sudomotor sweat reflex can be quantified using the Quantitative Sudomotor Axon Reflex Test (Q-SWEAT), in which local postganglionic fibers are stimulated by applying acetylcholine to the skin. METHOD/METHODS:This study assessed Q-SWEAT, psychiatric symptoms (PANSS; HAMD) and cognition (MATRICS) in 33 participants with psychosis, 17 with nonpsychotic affective disorders, and 23 healthy controls. Statistical analyses included ANOVA, GENLIN ordinal logistic regression, and Spearman correlations. RESULTS:(2)=9.75, p = 0.008). Specifically, the psychosis group was 5.37-fold more likely to have sudomotor dysfunction compared to healthy controls (95% CI 1.86, 15.45) and this remained significant when controlling for anticholinergic burden. The NP-affective group did not differ from those with psychosis or healthy controls. Across the overall sample, sudomotor dysfunction was significantly associated with greater cognitive impairment and increased psychiatric symptom severity. DISCUSSION/CONCLUSIONS:This first of its kind study shows abnormal sudomotor sweat reflexes in psychosis are independent of CNS input and not fully explained by anticholinergic medications but are associated with symptoms and cognition. We propose that muscarinic M3 acetylcholine receptors, which occur in eccrine sweat glands and in the CNS, may be relevant, although microvascular and inflammatory pathologies can impact the PNS and CNS. Sudomotor dysfunction could also underlie the abnormal thermoregulation in psychosis. More research is needed to confirm and extend these observations implicating a novel biomarker for psychosis.

STUDY DESIGN/METHODS:Retrospective analysis of a multicenter series of deformity patients undergoing thoracolumbar instrumentation to the pelvis. OBJECTIVE:Introduce the C2 coronal angle (C2C) as a novel metric, assess its association with quality-of-life and neck-specific outcomes, and compare the strength of this association with the traditional linear C7-CSVL offset. SUMMARY OF BACKGROUND DATA/BACKGROUND:While assessment of the sagittal plane incorporates vertebropelvic angles for surgical planning, angular coronal measurements have not been evaluated as predictors of patient-reported outcomes following adult spinal deformity (ASD) surgery. METHODS:Demographics, comorbidities, and radiographic parameters were collected preoperatively and at 2-year follow-up. Coronal angles were measured between CSVL and the center of the C2 body (C2C). Primary endpoints were patient‑reported outcomes at two years (SRS‑22, SF‑36, NDI) and whether patients achieved the minimal clinically important difference (MCID). Univariable and multivariable regression models examined the relationship between C2C and PROMs. An ROC analysis with Youden's Index identified optimal C2C thresholds for predicting NDI >20. RESULTS:Among 328 patients (mean age 64.0 years, 12.6 levels fused), postoperative absolute C2C was independently associated with PROMs. Each 1° increase in C2C was associated with decreased 2-yr SRS-Total (P=0.014) and activity (P=0.024), pain (P=0.033), and mental health (P=0.029) subdomains. Each 1° increase reduced odds of achieving NDI MCID by 34% (OR=0.66, P=0.022). ROC identified an optimal C2C threshold of 3.5°. Patients exceeding this had nearly twice the odds of neck disability (OR=1.90, P=0.049) and significantly lower SF-36 Physical Component (P=0.004) and Physical Functioning (P=0.011) scores. C2C was more strongly associated with SRS-Total than C7-CSVL (AIC=657 vs. 660; adj. R²=0.058 vs.0.048). CONCLUSIONS:Achieving postoperative C2C ≤3.5° is independently associated with reduced neck disability and optimized quality of life after ASD surgery. C2C was more strongly associated with SRS-Total than C7-CSVL and could be considered as a complementary measure of coronal alignment.

Cell motility, characterized by random walk and exploratory search movement, enables effector CD8+ T cells to search for sparse antigen-specific cancer targets within a tumor. This is of special relevance for treatment of solid cancers with adoptive T-cell receptor (TCR) T-cell therapy, where administered effector CD8+ T cells recognize specific MHC-I-presented antigens. Cell motility requires cytoskeleton remodeling to facilitate shape changes and movement. Herein, we show that increased mitochondrial Ca2+ levels are essential to reduce cytoskeleton stiffness of effector CD8+ T cells, leading to acquisition of a polarized shape and high motility. IL-21, but not IL-7 or IL-15, was able to raise mitochondrial Ca2+ levels in effector CD8+ T cells and increase their motility without affecting survival and proliferation. This increase in mitochondrial Ca2+ levels triggered by IL-21 was driven by sustaining mitochondrial membrane potential through mitochondrial STAT3, independently of its transcriptional activity. Enhanced motility of effector CD8+ T cells led to a superior killing efficacy of antigen-specific melanoma cells in vitro. Furthermore, enhanced mitochondrial Ca2+-mediated motility of adoptive TCR-specific effector CD8+ T cells resulted in a superior antitumor efficacy of this treatment against solid tumors in vivo. Thus, enhancing effector CD8+ T-cell motility is a promising strategy to boost efficacy of adoptive T-cell therapies against solid tumors.

Glucagonomas are a rare hormone-producing pancreatic neuroendocrine tumor (panNET), with an estimated incidence of 1 to 2 cases per million persons. They typically present at diagnosis as large, metastatic panNET and are characterized clinically by diabetes mellitus, weight loss, thromboembolic complications and necrolytic migratory erythema. The diagnosis of glucagonoma syndrome requires the presence of both elevated fasting plasma glucagon levels and glucagonoma symptoms. Staging relies on cross-sectional imaging with computed tomography (CT) or magnetic resonance imaging (MRI), complemented by somatostatin receptor positron emission tomography (PET) imaging. Initial management of glucagonoma includes supportive therapy with supplementation of amino acids, essential fatty acids, zinc, and other micronutrients as well as glycemic control and anticoagulation. Surgical resection is the only curative treatment. For unresectable or metastatic disease, palliative management parallels that of nonfunctioning panNET and includes somatostatin analogues, targeted therapies, peptide receptor radionuclide therapy with radiolabeled somatostatin analogues, and cytotoxic chemotherapy. Prognosis depends on tumor stage and grade, with reported 10-year survival rates approaching 100% for localized disease and approximately 50% for metastatic glucagonoma. A rare hereditary cause of hyperglucagonemia due to glucagon receptor mutations is glucagon cell hyperplasia and neoplasia, also termed Mahvash disease. These patients develop alpha cell hyperplasia and panNET but lack the classical glucagonoma symptoms. In conclusion, fasting glucagon levels should be measured in patients with typical features such as necrolytic migratory erythema, an advanced panNET associated with cachexia and new-onset or worsening diabetes mellitus or diffuse alpha cell hyperplasia.

OBJECTIVE:Interest in psychedelic medicine is increasing, yet psychiatry trainees report limited education in this area. The authors developed a standardized curriculum and evaluated its impact on trainee knowledge and attitudes toward psychedelic medicines. METHODS:A 6-h psychedelic medicine course was delivered across four psychiatry residency programs in the Northeast United States in 2025-2026. The curriculum included six modules covering foundational concepts and evidence, as well as clinical considerations. Anonymous pre- and post-course surveys assessed knowledge, interest, and confidence in counseling. Statistical comparisons were used to evaluate pre-post changes. RESULTS:Forty trainees participated across institutions; 34 completed a pre-course survey and 22 completed a post-course survey. Most trainees reported minimal prior didactic exposure to psychedelic medicine. Self-assessed knowledge as well as scores on a knowledge quiz improved significantly following the course. Self-rated understanding of both the rationale for psychedelic treatments and limitations of evidence increased. Most substantially, confidence in counseling patients about clinical research, harm reduction, and treatment risks improved across domains. Baseline interest in psychedelic medicine was high at the start of the course and did not change significantly following its completion. CONCLUSIONS:A multi-site curriculum in psychedelic medicine was associated with increased knowledge and counseling confidence in trainees. The curriculum did not significantly impact interest or plans to pursue opportunities in psychedelic medicine, suggesting the course did not overinflate enthusiasm for the field. Standardized curricula in residency education may help address gaps in psychiatric training as clinicians increasingly encounter questions about these emerging treatments.