School of Medicine

Purpose of ReviewTailoring treatment strategies to the biological features of invasive disease and the individual needs and preference of each patient has transformed the way we manage breast cancer. This article calls for a similar shift in the management paradigm of ductal carcinoma in situ (DCIS) from a uniform treatment model toward a risk-stratified stepwise approach that aligns with the heterogeneous nature of the disease to avoid overtreatment.Recent FindingsMost DCIS lesions are hormone receptor positive, and only a subset have a risk for progression to invasive cancer. Early results from observational and clinical studies indicate that active surveillance is a safe and feasible alternative to upfront surgical treatment for low-risk DCIS. Ongoing clinical trials like RECAST will further inform and refine strategies for optimal management of this condition.SummaryThe integration of risk-adapted management strategies, endocrine risk-reducing interventions, and advanced imaging modalities into active surveillance protocols hold significant potential to reduce overtreatment and personalize care for patients with DCIS. Early data from clinical trials support the notion that providing a period of active surveillance is safe and offers a critical assessment window during which DCIS treatment can be individualized. Strengthening the evidence base to support the adoption of active surveillance as an initial approach in the management of DCIS is an important clinical priority.

Objective To evaluate the Apple Vision Pro (AVP), a wearable spatial computing headset, as the primary intraoperative display for endoscopic dacryocystorhinostomy (DCR), assessing operative efficiency, ergonomics, cognitive workload, and cost. Design Consecutive, non-randomized comparative study at a single academic center, following institutional review board approval. Subjects and Controls Thirty-two consecutive endoscopic DCR procedures were analyzed: 16 with the AVP and 16 size-matched controls. Two fellows were the primary surgeons; three attending surgeons assisted. Methods Endoscopic DCR for primary unilateral nasolacrimal duct obstruction was performed using either the AVP or a traditional tower-mounted monitor for intraoperative visualization. Outcomes were operative time, functional success, intraoperative complications, surgeon-reported ergonomics, and perceived workload measured with the NASA Task Load Index (NASA-TLX). An exploratory cost analysis was also performed. Results Groups were comparable in age and sex. Operative time was shorter with the AVP (34.4 ± 8.6 vs 42.7 ± 8.5 minutes; reduction approximately 8.3 minutes, about 19%; p = 0.006). Functional success was 100% in both groups (16 of 16) with no complications; follow-up was 4 to 12 months. Overall workload was lower with the AVP (median 19.2 vs 40.0; one-sided p = 0.031; mean reduction 14.3 points, 95% CI 2.4 to 26.2; dz = 1.50); all five surgeons favored the AVP, with the largest reduction in physical demand, and subscale differences did not survive multiplicity correction. Surgeons reported improved comfort and a more neutral head and neck posture. The AVP occupied a small fraction of the cost and footprint of standard operating-room equipment. Conclusions In this preliminary, non-randomized series, use of the AVP as a wearable display for endoscopic DCR was associated with shorter operative times and lower surgeon-reported workload while occupying minimal space. As among the first prospective evaluations of the device for endoscopic lacrimal surgery, these findings suggest ergonomic and workflow advantages but require confirmation in larger, controlled studies.

Background Anastomotic leakage (AL) rates have been reported as high as 40% with associated mortality approaching 27%. Non-osmotic activation of vasopressin may result in hyponatremia. It has been suggested that perioperative sodium changes may function as an inexpensive and widely available biomarker for early identification of AL. Methods A systematic review and meta-analysis was performed, registered with PROSPERO (CRD42024522436). English language observational studies were eligible regardless of publication date. Methodological quality was evaluated using the QUADAS 2 tool. Quantitative synthesis was conducted using Meta Mar version 3.5.1. Results Among 121 screened records, five studies fulfilled the inclusion criteria. One study demonstrated a high risk of bias related to patient selection, while the remaining studies were assessed as low risk across all evaluated domains. The combined cohort included 2,034 patients, with AL occurring in 188 individuals (9%). Although all studies measured preoperative serum sodium, only three reported these values, and three studies assessed postoperative sodium levels. Pooled analysis showed no statistically significant differences in preoperative (SMD −0.45, p=0.33) or postoperative sodium (SMD −3.61, p=0.15) between patients with and without AL. In contrast, individual studies consistently demonstrated lower postoperative sodium levels among patients who developed AL that were statistically significant. Two studies identified postoperative hyponatremia or a postoperative decline in sodium as an independent predictor of AL. Reported sodium cutoffs ranging from 130 to 139.5 mEq/L yielded sensitivities between 23% and 70% and specificities between 72% and 93%. Conclusions Current evidence does not demonstrate a statistically significant association between perioperative serum sodium levels and anastomotic leakage. While individual studies have suggested a potential relationship, the substantial heterogeneity and methodological limitations limit the reliability of these findings. Further well-designed prospective studies are required before serum sodium can be considered a clinically useful biomarker.

HLA sensitization poses a major challenge to kidney transplantation for patients with end-stage kidney disease, especially for highly sensitized candidates. Attempts at antibody elimination (desensitization) have had inconsistent efficacy and have often failed to produce sustained reductions in anti-HLA antibodies in patients with the highest level of sensitization (calculated panel-reactive antibody score, ≥99.9%). We now report the results for the safety run-in cohort of a multicenter phase 1 clinical study evaluating the safety and efficacy of combined CD19-targeted and B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cells in eliminating the cellular sources of preformed anti-HLA antibodies (ClinicalTrials.gov number, NCT06056102). Kidney transplantation was performed in two highly sensitized candidates after desensitization with the use of dual CAR T-cell therapy.

The neural crest generates a broad spectrum of cell types that migrate across the body plan to populate multiple tissues1. However, the relationship between lineages of neural crest derivatives remains unclear, and the extent to which neural crest cells delaminated from the neural tube have specified fates remains debated. Here, leveraging CRISPR barcoding in mice and mosaic variant barcode analysis in humans, we demonstrate robust bilateral progenitor clonal spread of neural crest progenitors along the rostrocaudal axis but limited clonal overlap between sensory and sympathetic lineages. Computational modelling of mosaic variants suggests that most neural crest cells show strong fate restriction before delamination. Real-time imaging of quail embryos further shows a fibroblast-growth-factor-dependent rostrocaudal dispersion of neural crest cells across multiple axial levels. These findings support a model in which neural crest fate bias predominantly emerges within the neural tube, with only a minor subset of delaminated progenitors retaining multipotency to generate both sensory and sympathetic derivatives.

BACKGROUND: Military trauma/surgical critical care (T/SCC) surgeons perform both clinical "inside-the-tent" (ITT) and leadership/administrative "outside-the-tent" (OTT) responsibilities during forward deployments. Despite these demands, fellowship programs lack a standardized curriculum addressing the full spectrum of military-specific requirements. This study evaluates military T/SCC surgeons' perceptions of training quality, satisfaction, and confidence in managing deployment trauma situations, and readiness to assume leadership roles. METHODS: A survey was distributed to all current military T/SCC fellows and attendings to evaluate their perception of ITT and OTT skill training during fellowship. Respondents reported their satisfaction with fellowship training, as well as their confidence, satisfaction, and frequency with which they practiced on ITT and OTT skills. Attendings were additionally asked how often they utilized OTT skills and assumed key OTT leadership positions, such as unit commander or deputy commander, trauma director, or chief medical officer, during deployments. RESULTS: Ninety-four military T/SCC surgeons (80% attendings and 20% fellows) participated; 68% had deployed after fellowship. Confidence in core ITT skills, such as damage control surgery and resuscitation, was high (99% for both), but confidence was low for thoracic (58%) and complex liver trauma procedures (53%). Exposure to OTT domains-triage, systems, and tactical leadership-was limited; fewer than one-third of respondents reported frequent exposure or satisfaction with OTT training during fellowship. However, 84% of attendings frequently performed OTT functions during deployment. Previously deployed surgeons showed significantly greater confidence in disaster management (69% vs. 42%; p<0.05) and tactical decision-making (75% vs. 46%; p<0.05) OTT skills. CONCLUSIONS: While operative training was viewed favorably, many surgeons felt clinically confident but underprepared for deployment leadership roles. Greater OTT confidence among previously deployed surgeons suggests that operational experience-not fellowship training-currently drives proficiency. A military-specific curriculum is needed to prepare surgeons for leadership responsibilities in combat settings. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level IV.

Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality worldwide, with limited treatment options for patients with locally advanced disease. CD47 immune checkpoint inhibitors have been used to block the CD47/SIRPa interaction that inhibits antigen-presenting cell phagocytosis, thereby enhancing antigen presentation to cytotoxic T-cells, and have shown promise in combination with anti-PD1 immunotherapy in tumors, including recurrent/metastatic HNSCC. We found that CD47 expression is associated with poor prognosis in HNSCC and explored the anti-tumor activity of an anti-CD47 fusion protein in combination with anti-PD1 and lymphatic-sparing radiotherapy in a locally advanced HNSCC model. In the 4MOSC1 syngeneic HPV-negative HNSCC mouse model, ALX301 (an engineered CD47-blocking SIRPα fusion for murine models) induced complete tumor regression when combined with anti-PD-1, and produced a partial tumor response as a monotherapy. An anti-PD1 immune checkpoint inhibitor in a CD47-null tumor background led to complete tumor regression confirming a key role for CD47 in tumor immunity. ALX301 treated mice demonstrated increased MHC-II expression on dendritic cells within the tumor and upregulation of CD86 co-stimulatory molecule on dendritic cells within the tumor, sentinel lymph nodes, and contralateral lymph nodes. Combination ALX301 and anti-PD1 treatment in an anti-PD1 resistant 4MOSC2 model demonstrated significant tumor regression, enhanced survivability, improved response with neoadjuvant radiotherapy, and greater retention of CD8 + T-cells within the tumor microenvironment. Notably, T-cell receptor sequencing revealed increased shared clonality between the tumor and sentinel lymph nodes of ALX301 treated mice. These data demonstrate that a combination of CD47 blockade and anti-PD1 therapy enhances tumor antigen presentation and immune cell infiltration, while further improving anti-tumor responses in combination with tumor-targeted radiotherapy. This study provides support for the rational design of combinatorial immunoradiotherapy, using anti-CD47 inhibitors and anti-PD1 therapy, in a clinical trial targeting locally advanced HPV-negative HNSCC.

Background Prophylactic postoperative vasopressors (PPV) are used to induce hemodynamic augmentation to prevent spinal cord ischemia (SCI) in patients undergoing thoracic endovascular aortic repair (TEVAR). However, the scientific evidence on its effectiveness and safety is limited. This study aims to investigate the safety and effectiveness of PPV in patients undergoing TEVAR in a multi-institutional real-world setting. Methods All TEVAR patients in the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) database between March 1, 2012, and January 28, 2023, were identified. Univariable and multivariable analyses were performed to assess the association between the use of PPV and the rates of postoperative 30-day mortality, Major Adverse Cardiovascular Events (MACE, defined as new onset of postoperative myocardial infarction (MI), congestive heart failure (CHF), dysrhythmias, or stroke), SCI, and other adverse events for patients undergoing TEVAR. Results Out of 25,549 reviewed patients, 11,342 underwent TEVAR, matching the study criteria, and were analyzed. 2,420 patients (21.3%) received PPV. Patients who received PPV had significantly higher rates of 30-day mortality (9.3% vs 2.1%, p<0.001), MACE (18.2% vs 7.4%, p<0.001), postoperative SCI (2.6% vs 1.3%, p<0.001), and other adverse events. After adjusting for confounders, the use of PPV was associated with significantly increased odds of 30-day mortality (OR, 3.23, 95%CI: 2.58-4.04, p<0.001), MACE (OR, 2.18, 95%CI: 1.89-2.51, p<0.001), postoperative SCI (OR, 1.46, 95%CI: 1.05-2.01, p=0.022) and other adverse events. Conclusions PPV was associated with significantly higher odds of 30-day mortality, MACE, SCI, and other adverse outcomes. The role of PPV should be re-evaluated, and the decision for administration should be made on an individualized basis, considering patient comorbidities and risk factors. A prospective study is required to confirm these findings.

PURPOSE: Medical students feel inadequately prepared to cope with patient death. Simulation training may provide learners with the opportunity to experience death in a safe environment with a structured debriefing. METHODS: Nineteen fourth-year medical students who matched into surgical specialties participated in a 2-week surgical intern preparatory course. During an individual surgical decision-making simulation, 6 learners experienced unexpected patient death at the hands of a facilitator who deviated from the simulation script. Subjectively, these learners displayed high anxiety before the debriefing. Objectively, their self-reported anxiety after the structured debriefing was similar to the self-reported anxiety of learners who did not experience simulation death. RESULTS: We formalized a bi-directional debriefing instrument using the Gather Analyze Summarize (GAS) model as a framework. We recognized that learners who experienced simulation death need to debrief on 2 aspects of the simulation: 1) Simulation death and 2) Scientific content. CONCLUSION: Our unexpected experience with simulation death led to the development of a debriefing tool that can be used by other surgical educators. Learning how to process the ensuing emotional response to patient death in simulation may benefit trainees provided they undergo a structured debriefing.

BACKGROUND: Fenestrated/branched endovascular aortic repair (F/BEVAR) with commercially available devices require a paravisceral segment >20 mm. We compared commercial and physician-modified F/BEVAR outcomes in a narrowed flow lumen (NFL, <20 mm) to a standard flow lumen (SFL, ≥20 mm). METHODS: We conducted a retrospective review of F/BEVAR repairs between 2016 and 2024. Primary outcome was technical success, and secondary endpoints were target vessel stability, type 1/3 endoleaks requiring reintervention, and major adverse events (MAEs). RESULTS: A total of 136 patients underwent 138 repairs (75% male, 74 ± 10 years), 35 repairs (25%) were in NFL and 103 (75%) in SFL. Median visceral segment diameter was 24 mm (interquartile range [IQR] 19-29; 16 mm, IQR 15-18 in NFL; 28 mm, IQR 23-30 in SFL, P < 0.001). We observed 99% technical success. Mean fenestrations per repair was higher in NFL (3.1 vs. 1.5, P < 0.001), and mean branches was higher in SFL (2.1 vs. 0.7, P < 0.001). There were 24 (17%; 2 in NFL, 22 in SFL, P = 0.035) MAEs. There were nine branch vessel occlusions (three in NFL, six in SFL, P = 0.463) at a median follow-up of 516 days. Target vessel stability (86% in NFL vs. 84% in SFL, P = 0.757) and rate of reinterventions (2, 6% in NFL; 14, 14% in SFL, P = 0.209) did not differ significantly. CONCLUSION: Custom F/BEVAR offers equivalent outcomes in complex anatomy with narrowed paravisceral flow lumens compared to on-label branched and fenestrated repairs in SFLs. Early results demonstrate reasonable target vessel stability and freedom from reintervention, though additional follow-up is needed.