Faculty Bibliography

Pathogens infecting humans continue to emerge or reemerge to cause outbreaks and widespread disease. The National Institute of Allergy and Infectious Diseases has funded Vaccine Treatment and Evaluation Units (VTEUs) for more than 50 years. VTEUs perform clinical studies to assess the safety and immunogenicity of candidate vaccines and other interventions to mitigate the impact of emerging and ongoing infectious diseases. Here, we review clinical studies conducted in the VTEUs since 2000 that have addressed emerging pathogens and other infectious agents with pandemic potential or of bioterrorism concern. The studies conducted range from phase 1 to phase 3 clinical trials, and they have included vaccines, therapeutics, and epidemiological studies. The results of the trials have guided national and often international recommendations for treatment and prevention of many of the evaluated pathogens, culminating in coronavirus disease 2019 studies that began within three months of severe acute respiratory syndrome coronavirus 2 identification. The VTEU network continues to be a critical public health resource for addressing emerging pathogens and expediting the development of safe and effective vaccines and treatments to protect at-risk populations.

BACKGROUND:The "July Effect" refers to the potential increase in adverse outcomes associated with the annual turnover of medical trainees, though its impact on surgical fields remains uncertain. Additionally, few studies have examined whether the operative day of the week and subsequent flap monitoring during the weekend affect time to reoperation or flap salvage. This study investigated whether academic quarter and operative day influence reoperation rates, flap salvage, or flap failure in microvascular free flap procedures. METHODS:A retrospective review was conducted on 769 free flaps performed between June 2011 and November 2023. Multivariate analyses adjusted for patient demographics, comorbidities, flap type, and recipient region. Flaps were categorized by academic quarter and operative day, excluding weekends due to limited sample size. Primary outcomes included reoperation rates for vascular compromise, time to reoperation, and flap salvage. RESULTS:No significant differences in reoperation rates for vascular compromise were observed across academic quarters. While procedure duration trended longer in the first three quarters compared to the fourth, these differences were not statistically significant. Additionally, operative day did not impact reoperation rates, flap salvage, or time to reoperation. Flaps were predominantly indicated for head and neck reconstruction (74.4%) and had an overall flap loss rate of 3.0%. CONCLUSION/CONCLUSIONS:We found no evidence of a "July Effect" in microvascular surgery or that operative day affects free flap outcomes. Institutional factors, such as structured flap monitoring, attending oversight, and advanced practice provider support, likely mitigate risks associated with trainee turnover and shift-based staffing fluctuations.

PURPOSE/OBJECTIVE:The purpose of this study was to evaluate the effect that associated glenohumeral dislocations have on outcomes following surgical treatment of proximal humerus fractures. METHODS:This IRB-approved study reports on 301 patients, who underwent operative treatment for proximal humerus fractures at an academic medical center from January 2006 to January 2023. Fractures were classified according to the Neer system. Patients were separated into two cohorts based on whether a glenohumeral dislocation was present at the time of initial injury. Outcomes measured included the Disabilities of the Arm, Shoulder, and Hand (DASH) score, shoulder range of motion (forward elevation, external rotation, internal rotation), readmission rates, complications, hardware removal, and need for revision surgery. Independent samples t-tests and chi-squared analysis were used for continuous and categorical variables, respectively. A binary logistic regression was performed to analyze the influence of these factors on complication rate. RESULTS:230 patients sustained an isolated fracture (PHF) and 71 sustained a fracture-dislocation (FD). Significant differences were observed between the FD and PHF groups in all measured outcomes. The FD group had a poorer DASH score (24.38 ± 19.09 vs 10.54 ± 13.67; P < 0.001) and reduced range of shoulder motion in forward elevation (114° ± 40° vs 162° ± 19°; P < 0.001), external rotation (40° ± 19° vs 66° ± 19°; P < 0.001), and internal rotation (57° ± 26° vs 82° ± 21°; P < 0.001). Readmission rates were higher in the FD group (0.28 ± 0.85 vs 0.05 ± 0.28; P < 0.001). The FD cohort also had a higher rate of complications (25.35% vs 6.52%; P < 0.001), need for removal of hardware (14.08% vs 3.04%; P = 0.002), and overall revision surgery (11.27% vs 1.30%; P < 0.001). The FD cohort demonstrated a greater incidence of AVN (12.68% vs 4.35%; P = 0.012). No significant difference was observed regarding rates of fracture healing and recurrent dislocation. Multivariate analysis in the form of binary logistic regression indicated that fracture-dislocation significantly increased the complication risk (OR = 3.310, 95% CI = 1.42-7.70; P = 0.005). CONCLUSION/CONCLUSIONS:Proximal humerus fracture-dislocations are associated with worse functional outcomes and higher complication rates compared to those without dislocations. These findings highlight the potential need for specialized treatment strategies to mitigate the impact of dislocation on recovery.

Labetalol and nifedipine are first-line antihypertensives for hypertensive disorders of pregnancy. However, there is limited research comparing their effectiveness based on hemodynamic profiles seen in preeclampsia, such as high cardiac output (CO) and high systemic vascular resistance (SVR). This study assesses whether concordance of antihypertensive treatment with the hemodynamic status on echocardiogram reduces time to achieve target postpartum blood pressure (BP) before discharge.This retrospective cohort study included patients with preeclampsia with severe features who received a postpartum echocardiography, excluding patients with cardiac etiology. Antihypertensive choices were provider-dependent. The CO and SVR were calculated retrospectively from the echocardiogram in collaboration with cardiology. Concordance was defined as patients with high CO (>6 L/min) started on labetalol and high SVR (>1,200 dynes·sec·cm⁵) started on nifedipine; opposite pairings were discordant. The primary outcome was time to achieve target BP, defined as the period from the start of antihypertensive therapy to when no titration was needed to sustain BPs of less than 140/90 mm Hg. Chi-square and Fisher's tests were used for categorical variables, and Mann-Whitney U test for continuous variables.Of 298 patients, 155 (52%) received concordant therapy and 143 (48%) discordant. Of the cohort, 229 (76.8%) had high SVR and 69 (23.2%) had high CO. Median time to target BP was not significantly different (concordant: 32 hours [interquartile range, IQR: 0-61], discordant: 41 hours [IQR: 4-75], p = 0.13). The concordant group needed fewer titrations to achieve target BP (1 [IQR: 0-2] vs. 2 [IQR: 1-3]; p = 0.008) and were less likely to be discharged home on multiple antihypertensive medications compared with the discordant group (28.9 vs. 42.7%, p = 0.014). Maternal demographics were similar between groups.While time to target BP did not differ, concordance of antihypertensive therapy to postpartum hemodynamics in patients with severe preeclampsia reduced medication adjustments and increased the likelihood of discharge on a single-agent regimen. · Echocardiography can be used to assess maternal hemodynamics.. · Aligning BP meds to hemodynamics cuts the need for a second agent.. · Aligning BP meds to hemodynamics reduces dose adjustments..

BACKGROUND:Porcine genome editing has revolutionized xenotransplantation, recently enabling the first pig-to-human heart xenotransplants. However, the xeno-immune response in heart xenografts remains largely unexplored. This study aimed to precisely characterize the xeno-immune response and injury in two heart xenografts, transplanted from 10-gene-edited pigs into brain-dead human recipients. METHODS:We analyzed xenograft biopsies at 66-hour post-reperfusion using a multimodal phenotyping approach combining: morphological evaluation, immunophenotyping, ultrastructural assessment, automated quantification of multiplex immunofluorescence staining and gene expression profiling. Xenografts before implantation and wild-type pig hearts with and without ischemia reperfusion injury and brain death were used as controls. RESULTS:Both xenografts showed evidence of endothelial activation and mild microvascular inflammation without capillary C4d deposition. Immune infiltrates were mainly composed of CD15+ and CD68+ innate immune cells. Ultrastructural assessment showed endothelial swelling with occasional intravascular leucocytes. Deep-learning based automated multiplex immunofluorescence analysis confirmed that microvascular inflammation was primarily associated with CD15+ and CD68+ innate immune cells. Both xenografts showed increased expression of genes and pathways associated with monocyte/macrophage activation, neutrophil activation, interferon-gamma response, natural killer cell burden, endothelial activation, apoptosis and injury repair. This phenotype was absent in all control pig hearts, independently from ischemia reperfusion injury and brain death. CONCLUSIONS:Multimodal phenotyping of pig-to-human heart xenografts revealed early signs of xeno-immune response, characterized by mild innate microvascular inflammation, endothelial activation, and molecular signature characteristic of antibody-mediated rejection. Developing such precision diagnostic system could improve graft monitoring in future clinical settings.

BACKGROUND:Drug-coated balloons (DCBs) represent a novel treatment option for coronary in-stent restenosis (ISR). The AGENT DCB (Boston Scientific, Marlborough, MA) demonstrated superior efficacy in treating ISR compared to uncoated balloons in randomized controlled trials. However, real-world data on AGENT DCB safety remains limited. AIMS/OBJECTIVE:This study sought out to evaluate post-marketing adverse event reports related to the AGENT DCB. METHODS:This study analyzed post-marketing adverse event reports submitted to the FDA Manufacturer and User Facility Device Experience (MAUDE) database between March 1, 2024, and March 1, 2025, specifically focusing on coronary interventions utilizing the AGENT DCB. Reports were independently reviewed and categorized by device-related complications, patient injuries, and device failures. Data were summarized descriptively, and limitations inherent to the MAUDE database were considered. RESULTS:After screening and excluding duplicates, 155 reports on the AGENT DCB were included. Among all reports, device malfunctions without injury were most common (56.77%), followed by patient injury (30.97%) and death (12.26%). Of the total reported device problems, balloon rupture (33.55%) and shaft breakage (10.32%) were predominant. Injuries reported included angina (32.84%), acute myocardial infarction (29.85%), and coronary perforation (8.95%). Notably, 30 MAUDE reports described off-label treatment of de novo lesions; these off-label cases exhibited similar injury rates compared to ISR-treated lesions (53.33% vs. 57.89%). CONCLUSION/CONCLUSIONS:Real-world analysis of FDA MAUDE reports revealed frequent device malfunctions, mainly balloon rupture and shaft breakage, and patient complications such as angina, myocardial infarction, and coronary perforation. The off-label use for de novo lesions highlights the need for caution and further clinical investigation.

Trauma during pregnancy presents a clinical challenge because the health and survival of both the mother and fetus are key clinical concerns. Given the prevalence of trauma in pregnancy, affecting an estimated 5%-7% of pregnancies, knowledge of the appropriate treatment of such patients is crucial for emergency and general radiologists. Although US is the default imaging modality during pregnancy, urgent and accurate diagnosis frequently requires the use of CT, despite the potential risk of exposure to ionizing radiation and contrast media. As such, the radiologist must be familiar with both obstetric-specific injuries and how pregnancy may complicate otherwise familiar traumatic presentations. The authors discuss the general treatment of the pregnant trauma patient, with an emphasis on radiologic evaluation. They provide an overview of various imaging modalities available for evaluation of pregnant patients with traumatic injuries, emphasizing their potential risks, benefits, and limitations. The relative role of imaging assessment versus electronic fetal monitoring in a patient with suspected placental abruption is discussed. Proposed grading methods and management pathways for placental abruption, with respect to fetal age and maternal stability, are reviewed. Relevant cases are presented, demonstrating key obstetric abnormalities that may be seen in patients with pregnancy-related trauma. ^©RSNA, 2025 Supplemental material is available for this article. See the invited commentary by Mellnick and Raptis in this issue.

BACKGROUND AND AIMS/OBJECTIVE:PredictSURE IBD is a prognostic blood test that classifies newly diagnosed, treatment-naïve Inflammatory Bowel Disease (IBD) patients into 'IBDhi' (high-risk) or 'IBDlo' (low-risk) groups (risk of future aggressive disease). We evaluated this assay in a multinational cohort and explored the effect of concomitant corticosteroids on its discrimination. METHODS:One hundred thirty-six (71 Ulcerative colitis [UC], 65 Crohn's Disease [CD]) and 41 (15 UC, 26 CD) patients with active IBD were 'unexposed' and 'exposed', respectively, to corticosteroids at baseline blood sampling. The number of treatment escalations, time to first escalation, and need for repeated escalations were compared between the biomarker subgroups. Another 20 patients (13 UC, 7 CD) were longitudinally sampled over 6 weeks after commencing corticosteroids. RESULTS:In corticosteroids-naïve UC and CD patients, all bowel surgeries (n = 6) and multiple therapy escalations (n = 10) occurred in IBDhi patients. IBDhi UC patients required significantly more treatment escalations, had a shorter time to first escalation, and a greater need for multiple escalations than IBDlo patients. No statistically significant differences were observed among CD patients. In corticosteroid-exposed patients, 66.6% of 'misclassifications' were IBDlo patients who required escalations. Among corticosteroid-treated patients with longitudinal sampling, 81.3% of those classified as IBDhi before steroids switched to IBDlo during therapy. CONCLUSIONS:No significant differences in treatment escalations were observed between biomarker-defined subgroups in CD. However, IBDhi UC patients required significantly earlier and more frequent therapy escalations, highlighting the need to further investigate PredictSURE IBD in UC. Notably, the discrimination ability of the biomarker was unreliable in patients receiving corticosteroid therapy.