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AbstractDue to the anatomic complexity of the head and neck and variable proximity between laboratory and operating room (OR), effective communication during frozen section analysis (FSA) between surgeons and pathologists is challenging. This proof‐of‐concept study investigates an augmented reality (AR) protocol that allows pathologists to virtually join the OR from the laboratory. Head and neck cancer specimens were scanned ex vivo using a 3‐dimensional scanner and uploaded into an AR platform. Eight head and neck specimens were discussed by surgeons and pathologists in an AR environment. AR‐guided intraoperative consultation was used for specimen orientation and discussion of FSA margin sampling sites. One patient had positive initial margins on FSA and was re‐resected to negative final margins. AR‐guided FSA is possible and allows pathologists to join the operating from any location for intraoperative discussion.

Background The purpose of this study was to describe the correlates and outcomes in adults with unrepaired partial anomalous pulmonary venous return and intact atrial septum (PAPVR‐IAS). Methods and Results We identified adults with PAPVR‐IAS who received care at the Mayo Clinic, while those with unrepaired PAPVR‐IAS comprised the reference group. Clinical indices (New York Heart Association class, peak oxygen consumption, and NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]) and echo‐derived right heart indices (right atrial [RA] volume, RA reservoir strain, right ventricular [RV] free wall strain, RV end‐diastolic area, and RV systolic pressure) were assessed at baseline and 3‐year and 5‐year follow‐up. There were 80 patients and 38 patients with unrepaired versus repaired PAPVR‐IAS, respectively. The clinical predictors of surgical repair were the number of anomalous veins, RA volume, and RV end‐diastolic area. The PAPVR‐IAS risk score, derived from these clinical predictors, was associated with surgical repair (adjusted odds ratio, 1.37 [95% CI, 1.24–1.65] per unit increase in risk score; area under the curve, 0.742). Among patients with unrepaired PAPVR‐IAS with 3‐year (n=73) and 5‐year follow‐up (n=36), there was no temporal change in clinical indices (New York Heart Association class, predicted peak oxygen consumption, and NT‐proBNP) and right heart indices (RA volume index, RA reservoir strain, RV end‐diastolic area index, RV free wall strain, and RV systolic pressure). Conclusions The PAPVR‐IAS risk score can be used to assess the odds of requiring surgical repair. Furthermore, there was no temporal deterioration in clinical and right heart indices during follow‐up in adults with unrepaired PAPVR‐IAS.

ImportanceExposure to repetitive head impacts (RHI) is associated with increased risk for neurodegeneration. Accumulation of toxic proteins due to impaired brain clearance is suspected to play a role.ObjectiveTo investigate whether perivascular space (PVS) volume is associated with lifetime exposure to RHI in individuals at risk for RHI-associated neurodegeneration.Design, Setting, and ParticipantsThis cross-sectional study was part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project, a 7-year multicenter study consisting of 4 US study sites. Data were collected from September 2016 to February 2020 and analyses were performed between May 2021 and October 2023. After controlling for magnetic resonance image (MRI) and processing quality, former American football players and unexposed asymptomatic control participants were included in analyses.ExposurePrior exposure to RHI while participating in American football was estimated using the 3 cumulative head impact indices (CHII-G, linear acceleration; CHII-R, rotational acceleration; and CHII, number of head impacts).Main Outcomes and MeasuresIndividual PVS volume was calculated in the white matter of structural MRI. Cognitive impairment was based on neuropsychological assessment. Linear regression models were used to assess associations of PVS volume with neuropsychological assessments in former American football players. All analyses were adjusted for confounders associated with PVS volume.ResultsAnalyses included 224 participants (median [IQR] age, 57 [51-65] years), with 170 male former football players (114 former professional athletes, 56 former collegiate athletes) and 54 male unexposed control participants. Former football players had larger PVS volume compared with the unexposed group (mean difference, 0.28 [95% CI, 0.00-0.56]; P = .05). Within the football group, PVS volume was associated with higher CHII-R (β = 2.71 × 10−8 [95% CI, 0.50 × 10−8 to 4.93 × 10−8]; P = .03) and CHII-G (β = 2.24 × 10−6 [95% CI, 0.35 × 10−6 to 4.13 × 10−6]; P = .03). Larger PVS volume was also associated with worse performance on cognitive functioning in former American football players (β = −0.74 [95% CI, −1.35 to −0.13]; P = .04).Conclusions and RelevanceThese findings suggest that impaired perivascular brain clearance, as indicated by larger PVS volume, may contribute to the association observed between RHI exposure and neurodegeneration.

ABSTRACT In the past two decades, plastic surgeons have advanced to the forefront of spinal surgery, joining orthopedic and neurosurgeons in the multidisciplinary field of spino-plastics. As the global disease burden grows with an increased incidence of spinal pathologies, vascularized bone grafts (VBGs) define the current frontier of spino-plastic surgery. Vascularized bone grafting involves lifting segments of bone with the muscular attachments but without the inclusion of a named vessel. When compared to traditional nonvascular bone grafts and allografts, VBGs have come forward as a favored technique for complex spinal reconstruction due to the unique opportunity to capitalize on the relationship between the tendons and Sharpey's fibers which maintain blood flow to both the bone and muscular segments. This technique ensures robust autologous tissue rearrangement and also takes advantage of the osteoinductive properties of the bone segments, promoting adequate structural support and the perfusion necessary for efficient direct healing and fusion in intricate spine reconstructions. Another one of the many favorable qualities of VBGs is the diversity of sources available to surgeons. The review explores the role of VBGs in enhancing spinal fusion rates and minimizing morbidity compared to traditional approaches. Additionally, a detailed examination of six common VBG sources-the iliac crest, ribs, medial scapula, occiput, spinous processes, and clavicle is included, highlighting each graft's specific techniques and emphasizing the range of options available to spino-plastic surgeons. Highlights Vascularized Bone Grafts (VBGs) have emerged as a favored technique in complex spinal reconstruction.The field of spino-plastic surgery highlights the collaboration between plastic, orthopedic, and neurosurgery.The article outlines the reconstructive ladder for bony defects, with VBGs being a critical addition.Advantages of VBGs include enhanced fusion rates, lower risk of infection, and reduced operative time.Preserving the vascular supply during graft harvest is crucial.Preoperative planning is essential as VBG selection is made on a case-by-case basis.

Abstract Radial meniscal tears can be challenging to address and require advanced arthroscopic techniques for satisfactory repair. When radial tears occur in older patients, the surgeon often encounters suboptimal tissue integrity that presents its own challenges. Incorporating ripstop sutures in tie‐grip repair constructs for radial tears has been documented in the literature with favorable biomechanical properties. This Technical Note and accompanying video present a reproducible method for incorporating tie‐grip and mobile ripstop stitches to fortify traditional meniscal repair configurations for radial tears. This technique augments the biomechanical strength of repair and may prove useful in poor tissue quality and areas of small focal deficiency, especially in scenarios with repairable but degenerative meniscal tissue. This is particularly relevant considering many repairs fail due to pull‐through of sutures within the meniscal tissue. Technique Video video See video under supplementary data.

Abstract Purpose: Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSI) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood. Experimental Design: We applied targeted cell-free DNA (cfDNA) sequencing to 126 patients with mCRPC from three academic cancer centers and separately performed genome-wide cfDNA methylation sequencing on 43 plasma samples collected prior to the initiation of first-line ARSI treatment. To analyze the genome-wide sequencing data, we performed nucleosome positioning and differential methylated region analysis. We additionally analyzed single-cell and bulk RNA sequencing data from 14 and 80 patients with mCRPC, respectively, to develop and validate a stem-like signature, which we inferred from cfDNA. Results: Targeted cfDNA sequencing detected AR/enhancer alterations prior to first-line ARSIs that correlated with significantly worse progression-free survival (P = 0.01; HR = 2.12) and overall survival (P = 0.02; HR = 2.48). Plasma methylome analysis revealed that AR/enhancer lethal mCRPC patients have significantly higher promoter-level hypomethylation than AR/enhancer wild-type mCRPC patients (P < 0.0001). Moreover, gene ontology and CytoTRACE analysis of nucleosomally more accessible transcription factors in cfDNA revealed enrichment for stemness-associated transcription factors in patients with lethal mCRPC. The resulting stemness signature was then validated in a completely held-out cohort of 80 patients with mCRPC profiled by tumor RNA sequencing. Conclusions: We analyzed a total of 220 patients with mCRPC, validated the importance of cell-free AR/enhancer alterations as a prognostic biomarker in lethal mCRPC, and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness. See related commentary by Nawfal et al., p. 7

Abstract The Blood and Marrow Transplant (BMT) Clinical Trials Network conducted a phase 3 randomized trial comparing gilteritinib with placebo after allogeneic hematopoietic cell transplantation (HCT) for FLT3-ITD+ acute myeloid leukemia (AML). The primary analysis demonstrated no statistically significant difference in relapse-free survival (RFS); however, patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib. This analysis investigates the effect of post-HCT gilteritinib vs placebo on health-related quality of life (HRQOL). HRQOL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both arms. Despite higher treatment-emergent adverse effects with gilteritinib, response to the question of being “bothered by side effects of treatment” did not differ between groups. Subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms. For patients with FLT3-ITD+ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. This trial was registered at www.ClinicalTrials.gov as #NCT02997202.

Respiratory failure occurs more frequently after thoracic surgery than abdominal surgery. Although the etiology for this complication is frequently attributed to underlying lung disease present in patients undergoing thoracic surgery, this notion is often unfounded because many patients with normal preoperative pulmonary function often require prolonged oxygen supplementation even after minimal resection of lung tissue. Using a murine model of pulmonary resection and peripheral blood samples from patients undergoing resection of the lung or abdominal organs, we demonstrated that lung surgery initiates a proinflammatory loop that results in damage to the remaining lung tissue, noncardiogenic pulmonary edema, hypoxia, and even death. Specifically, we demonstrated that resection of murine lung tissue increased concentrations of the homeostatic cytokine interleukin-7, which led to local and systemic activation of type 2 innate lymphoid cells. This process activated lung-resident eosinophils and facilitated stress-induced eosinophil maturation in the bone marrow in a granulocyte-macrophage colony-stimulating factor–dependent manner, resulting in systemic eosinophilia in both mice and humans. Up-regulation of inducible nitric oxide synthase in lung-resident eosinophils led to tissue nitrosylation, pulmonary edema, hypoxia, and, at times, death. Disrupting this activation cascade at any stage ameliorated deleterious outcomes and improved survival after lung resection in the mouse model. Our data suggest that repurposing US Food and Drug Administration–approved eosinophil-targeting strategies may potentially offer a therapeutic intervention to improve outcomes for patients who require lung resection for benign or malignant etiology.