Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer: OPTIMA II Phase 2 Open-Label Nonrandomized Clinical Trial.

Importance: Immune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role in curative human papillomavirus-positive oropharyngeal cancer (HPV+ OPC) remains undefined. Neoadjuvant nivolumab and chemotherapy followed by response-adaptive treatment in HPV+ OPC may increase efficacy while reducing toxicity. Objective: To determine the deep response rate and tolerability of the addition of neoadjuvant nivolumab to chemotherapy followed by response-adapted locoregional therapy (LRT) in patients with HPV+ OPC. Design, Setting, and Participants: This phase 2 nonrandomized clinical trial conducted at a single academic center enrolled 77 patients with locoregionally advanced HPV+ OPC from 2017 to 2020. Data analyses were performed from February 10, 2021, to January 9, 2023. Interventions: Addition of nivolumab to neoadjuvant nab-paclitaxel and carboplatin (studied in the first OPTIMA trial) followed by response-adapted LRT in patients with HPV+ OPC stages III to IV. Main Outcomes and Measures: Primary outcome was deep response rate to neoadjuvant nivolumab plus chemotherapy, defined as the proportion of tumors with 50% or greater shrinkage per the Response Evaluation Criteria in Solid Tumors 1.1. Secondary outcomes were progression-free survival (PFS) and overall survival (OS). Swallowing function, quality of life, and tissue- and blood-based biomarkers, including programmed death-ligand 1 (PD-L1) expression and circulating tumor HPV-DNA (ctHPV-DNA), were also evaluated. Results: The 73 eligible patients (median [range] age, 61 [37-82] years; 6 [8.2%] female; 67 [91.8%] male) started neoadjuvant nivolumab and chemotherapy. Deep responses were observed in 51 patients (70.8%; 95% CI, 0.59-0.81). Subsequent risk- and response-adaptive therapy was assigned as follows: group A, single-modality radiotherapy alone or transoral robotic surgery (28 patients); group B, intermediate-dose chemoradiotherapy of 45 to 50 Gray (34 patients); and group C, regular-dose chemoradiotherapy of 70 to 75 Gray (10 patients). Two-year PFS and OS were 90.0% (95% CI, 0.80-0.95) and 91.4% (95% CI, 0.82-0.96), respectively. By response-adapted group, 2-year PFS and OS for group A were 96.4% and 96.4%, and group B, 88.0% and 91.0%, respectively. Lower enteral feeding rates and changes in weight, as well as improved swallowing, were observed among patients who received response-adapted LRT. Pathologic complete response rate among patients who underwent transoral robotic surgery was 67.0%. PD-L1 expression was nonsignificantly higher for deeper responses and improved PFS, and ctHPV-DNA clearance was significantly associated with improved PFS. Conclusions and Relevance: This phase 2 nonrandomized clinical trial found that neoadjuvant nivolumab and chemotherapy followed by response-adapted LRT is feasible and has favorable tolerability, excellent OS, and improved functional outcomes in HPV+ OPC, including among patients with high-risk disease. Moreover, addition of nivolumab may benefit high PD-L1 expressors, and sensitive dynamic biomarkers (eg, ctHPV-DNA) are useful for patient selection. Trial Registration: ClinicalTrials.gov Identifier: NCT03107182.

Long-term outcomes of total arch replacement with bilateral antegrade cerebral perfusion using the "arch first" approach.

OBJECTIVE: To report outcomes of total arch replacement (TAR) with hypothermic circulatory arrest and bilateral antegrade cerebral perfusion (bACP) using an "arch first" approach for acute Type A aortic dissection (ATAAD). The "arch first" approach involved revascularization of the aortic arch branch vessels with uninterrupted ACP, before lower body circulatory arrest, while the patient was cooling. METHODS: This was an observational study of aortic surgeries from 2010 to 2021. All patients who underwent TAR with bACP for ATAAD were included. Short-term and long-term outcomes were reported utilizing descriptive statistics and Kaplan-Meier survival estimation. RESULTS: A total of 215 patients were identified who underwent TAR + bACP for ATAAD. Age was 59.0 [49.0-67.0] years and 35.3% were female. 73 patients (34.0%) underwent a concomitant aortic root replacement, 188 (87.4%) had aortic cannulation, circulatory arrest time was 37.0 [26.0-52.0] minutes, and nadir temperature was 20.8 [19.4-22.5] degrees Celsius. 35 patients (16.3%) had operative mortality (STS definition), 17 (7.9%) had a new stroke, 79 (36.7%) had prolonged mechanical ventilation (>24 h), 35 (16.3%) had acute renal failure (by RIFLE criteria), and 128 (59.5%) had blood product transfusions. One-year survival was 77.1%, while 5-years survival was 67.1%. During follow-up, there were 23 (10.7%) reinterventions involving the descending thoracic aorta - either thoracic endovascular aortic repair or open thoracoabdominal aortic replacement. CONCLUSIONS: Among patients with ATAAD, short-term postoperative outcomes after TAR + bACP using the "arch first" approach are acceptable. Moreover, this operative strategy may furnish long-term durability, with a reasonably low reintervention rate and satisfactory overall survival.

Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer.

The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient's tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.

Outcomes of Impella 5.0 and 5.5 for cardiogenic shock: A single-center 137 patient experience.

BACKGROUND: This study evaluated the outcomes of patients with cardiogenic shock (CS) supported with Impella 5.0 or 5.5 and identified risk factors for in-hospital mortality. METHODS: Adults with CS who were supported with Impella 5.0 or 5.5 at a single institution were included. Patients were stratified into three groups according to their CS etiology: (1) acute myocardial infarction (AMI), (2) acute decompensated heart failure (ADHF), and (3) postcardiotomy (PC). The primary outcome was survival, and secondary outcomes included adverse events during Impella support and length of stay. Multivariable logistic regression was performed to identify risk factors for in-hospital mortality. RESULTS: One hundred and thirty-seven patients with CS secondary to AMI (n = 47), ADHF (n = 86), and PC (n = 4) were included. The ADHF group had the highest survival rates at all time points. Acute kidney injury (AKI) was the most common complication during Impella support in all 3 groups. Increased rates of AKI and de novo renal replacement therapy were observed in the PC group, and the AMI group experienced a higher incidence of bleeding requiring transfusion. Multivariable analysis demonstrated diabetes mellitus, elevated pre-insertion serum lactate, and elevated pre-insertion serum creatinine were independent predictors of in-hospital mortality, but the etiology of CS did not impact mortality. CONCLUSIONS: This study demonstrates that Impella 5.0 and 5.5 provide effective mechanical support for patients with CS with favorable outcomes, with nearly two-thirds of patients alive at 180 days. Diabetes, elevated pre-insertion serum lactate, and elevated pre-insertion serum creatinine are strong risk factors for in-hospital mortality.

The genomic and evolutionary landscapes of anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

Evolutionary dynamics of tipifarnib in HRAS mutated head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent malignancy worldwide, with a significant proportion of patients developing recurrent and/or metastatic (R/M) disease. Despite recent advances in therapy, the prognosis for patients with advanced HNSCC remains poor. Here, we present the case of a patient with recurrent metastatic HNSCC harboring an HRAS G12S mutation who achieved a durable response to treatment with tipifarnib, a selective inhibitor of farnesyltransferase. The patient was a 48-year-old woman who had previously received multiple lines of therapy with no significant clinical response. However, treatment with tipifarnib resulted in a durable partial response that lasted 8 months. Serial genomic and transcriptomic analyses demonstrated upregulation of YAP1 and AXL in metastatic lesions compared with the primary tumor, the evolution of the tumor microenvironment from an immune-enriched to a fibrotic subtype with increased angiogenesis, and activation of the PI3K/AKT/mTOR pathway in tipifarnib treatment. Lastly, in HRAS-mutated PDXs and in the syngeneic HRAS model, we demonstrated that tipifarnib efficacy is limited by activation of the AKT pathway, and dual treatment with tipifarnib and the PI3K inhibitor, BYL719, resulted in enhanced anti-tumor efficacy. Our case study highlights the potential of targeting HRAS mutations with tipifarnib in R/M HNSCC and identifies potential mechanisms of acquired resistance to tipifarnib, along with immuno-, chemo-, and radiation therapy. Preclinical results provide a firm foundation for further investigation of drug combinations of HRAS-and PI3K -targeting therapeutics in R/M HRAS-driven HNSCC.

Cardiogenic shock etiology and exit strategy impact survival in patients with Impella 5.5.

BACKGROUND: Despite historical differences in cardiogenic shock (CS) outcomes by etiology, outcomes by CS etiology have yet to be described in patients supported by temporary mechanical circulatory support (MCS) with Impella 5.5. OBJECTIVES: This study aims to identify differences in survival and post-support destination for these patients in acute myocardial infarction (AMI) and acute decompensated heart failure (ADHF) CS at a high-volume, tertiary, transplant center. METHODS: A retrospective review of patients who received Impella 5.5 at our center from November 2020 to June 2022 was conducted. RESULTS: Sixty-seven patients underwent Impella 5.5 implantation for CS; 23 (34%) for AMI and 44 (66%) for ADHF. AMI patients presented with higher SCAI stage, pre-implant lactate, and rate of prior MCS devices, and fewer days from admission to implantation. Survival was lower for AMI patients at 30 days, 90 days, and discharge. No difference in time to all-cause mortality was found when excluding patients receiving transplant. There was no significant difference in complication rates between groups. CONCLUSIONS: ADHF-CS patients with Impella 5.5 support have a significantly higher rate of survival than patients with AMI-CS. ADHF patients were successfully bridged to heart transplant more often than AMI patients, contributing to increased survival.

An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma.

Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced by the hallmark histone mutation H3K27M, which results in aberrantly permissive activation of oncogenic signaling pathways. Previous studies of diffuse midline glioma with altered H3K27 (DMG-H3K27a) have shown that the RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), is critical for tumor growth. Further downstream effectors of ERK5 and their role in DMG-H3K27a metabolic reprogramming have not been explored. We establish that ERK5 is a critical regulator of cell proliferation and glycolysis in DMG-H3K27a. We demonstrate that ERK5 mediates glycolysis through activation of transcription factor MEF2A, which subsequently modulates expression of glycolytic enzyme PFKFB3. We show that in vitro and mouse models of DMG-H3K27a are sensitive to the loss of PFKFB3. Multi-targeted drug therapy against the ERK5-PFKFB3 axis, such as with small-molecule inhibitors, may represent a promising therapeutic approach in patients with pediatric diffuse midline glioma.

Heterotopic ossification in right popliteal fossa causing arterial insufficiency.

Heterotopic ossification (HO) is the abnormal formation of extra-skeletal bone in soft tissue, which can occur after trauma or surgery. HO in joints can cause pain, hinder mobility, and compress surrounding nerves and blood vessels. We present an unusual case of arterial insufficiency caused by HO in the right popliteal fossa.

Inflammatory Tongue Conditions and Risk of Oral Tongue Cancer Among the US Elderly Individuals.

PURPOSE: The incidence of oral tongue cancers has increased since the 1980s among US men and women for unknown reasons. We investigated associations of inflammatory tongue conditions with risk of cancers of the oral tongue, other oral cavity, and oropharynx among the US elderly individuals (age 65 years or older). METHODS: We conducted a case-control study (2,534 oral tongue cancers, 6,832 other oral cavity cancers, 9,373 oropharyngeal cancers, and 200,000 controls) within the SEER-Medicare data set (1992-2013). Medicare records were used to identify patients with clinically diagnosed inflammatory tongue conditions (glossitis, benign migratory glossitis, median rhomboid glossitis, atrophic glossitis, glossodynia, other specified conditions [eg, atrophy and hypertrophy], and other unspecified conditions) and oral precancer (leukoplakia/erythroplakia). Only conditions preceding cancer/control selection by >12 months were included. RESULTS: The prevalence of inflammatory tongue conditions was significantly higher in patients with tongue cancer than controls (6.0% v 0.6%; odds ratios [ORs], adjusted for age, sex, race, Medicare utilization, and precancer, 5.8 [95% CI, 4.7 to 7.2]). This overall association primarily arose from glossitis, 5.6 (95% CI, 4.4 to 7.2); other specified conditions, 9.1 (95% CI, 5.5 to 15.2); and other unspecified conditions, 13.7 (95% CI, 8.0 to 23.7). These associations remained strongly elevated >5 years preceding tongue cancer (arguing against reverse causation), for conditions diagnosed by a specialist (arguing against misclassification), and among patients who received an oral biopsy (arguing against missed cancer). During 2013, an estimated 1 in 11 patients with oral tongue cancer had a preceding diagnosis of inflammatory tongue conditions. Associations of inflammatory tongue conditions were relatively weak for other oral cavity cancers (ORs, 1.8 [95% CI, 1.5 to 2.3]) and oropharyngeal cancer (OR, 1.3 [95% CI, 1.0 to 1.6]) and were observed only closest to cancer diagnosis. CONCLUSION: Inflammatory tongue conditions were associated with strongly increased risks of oral tongue cancers and preceded cancer diagnosis by several years, underscoring the need for increased clinical surveillance among patients with such apparently benign diagnoses.

A comprehensive AI-driven analysis of large-scale omic datasets reveals novel dual-purpose targets for the treatment of cancer and aging.

As aging and tumorigenesis are tightly interconnected biological processes, targeting their common underlying driving pathways may induce dual-purpose anti-aging and anti-cancer effects. Our transcriptomic analyses of 16,740 healthy samples demonstrated tissue-specific age-associated gene expression, with most tumor suppressor genes downregulated during aging. Furthermore, a large-scale pan-cancer analysis of 11 solid tumor types (11,303 cases and 4431 control samples) revealed that many cellular processes, such as protein localization, DNA replication, DNA repair, cell cycle, and RNA metabolism, were upregulated in cancer but downregulated in healthy aging tissues, whereas pathways regulating cellular senescence were upregulated in both aging and cancer. Common cancer targets were identified by the AI-driven target discovery platform-PandaOmics. Age-associated cancer targets were selected and further classified into four groups based on their reported roles in lifespan. Among the 51 identified age-associated cancer targets with anti-aging experimental evidence, 22 were proposed as dual-purpose targets for anti-aging and anti-cancer treatment with the same therapeutic direction. Among age-associated cancer targets without known lifespan-regulating activity, 23 genes were selected based on predicted dual-purpose properties. Knockdown of histone demethylase KDM1A, one of these unexplored candidates, significantly extended lifespan in Caenorhabditis elegans. Given KDM1A's anti-cancer activities reported in both preclinical and clinical studies, our findings propose KDM1A as a promising dual-purpose target. This is the first study utilizing an innovative AI-driven approach to identify dual-purpose target candidates for anti-aging and anti-cancer treatment, supporting the value of AI-assisted target identification for drug discovery.

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring.

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.

Race, sex, and socioeconomic disparities affect the clinical stage of patients presenting for treatment of superficial venous disease.

OBJECTIVE: Superficial venous disease has a U.S. prevalence of nearly 30%, with advanced disease contributing to a significant healthcare burden. Although the risk factors for venous disease are well known, the correlation between race, sex, socioeconomic status, and disease severity on presentation is not well established. The area deprivation index (ADI) is a validated metric with respect to regional geography, social determinants of health, and degree of socioeconomic disadvantage. In the present study, we aimed to identify the disparities and the effect that the ADI, in addition to race and sex, has among patients associated with an advanced venous disease presentation. METHODS: A retrospective review between 2012 and 2022 was performed at four tertiary U.S. institutions to identify patients who underwent endovenous closure of their saphenous veins. Patient demographics, state ADI, comorbidities, CEAP (clinical, etiologic, anatomic, pathophysiologic) classification, and periprocedural outcomes were included. Pearson's correlation was performed between the CEAP classification and ADI. Poisson regression analysis was performed to identify factors predicting for an increasing CEAP classification at presentation. Variables with P < .05 were deemed significant. RESULTS: A total of 2346 patients underwent endovenous saphenous vein closure during the study period, of whom 7 were excluded because of a lack of follow-up data. The mean age was 60.4 ± 14.9 years, 65.9% were women, and 55.4% were White. Of the 2339 patients, 73.3% presented with an advanced CEAP class (≥3). The mean state ADI for the entire cohort was 4.9 ± 3.1. The percent change in the CEAP classification is an increase of 2% and 1% for every level increase in the state ADI for unadjusted (incidence rate ratio [IRR] = 1.02; P < .001) and adjusted (IRR = 1.01; P < .001) models, respectively. Black race has a 12% increased risk of a higher CEAP class on presentation compared with White race (IRR = 1.12; P = .005). Female sex had a 16% lower risk of a higher CEAP presentation compared with male sex (IRR = 0.84; P < .01). CONCLUSIONS: Low socioeconomic status, Black race, and male sex are predictive of an advanced CEAP classification on initial presentation. These findings highlight the opportunity for improved mechanisms for identification of venous disease and at-risk patients before advanced disease progression in known disadvantaged patient populations.

Type IV Hypersensitivity Reaction after Cyanoacrylate Venous Closure.

BACKGROUND: Nonthermal endovenous closure techniques are routinely utilized to treat superficial axial venous reflux. Cyanoacrylate closure is a safe and effective modality implemented for truncal closure. However, an adverse reaction of type IV hypersensitivity (T4H), unique to cyanoacrylate, is a known risk. This study aims to evaluate the real-world incidence of T4H and examine risk factors that may predispose its development. METHODS: A retrospective review between 2012- and 2022 was performed at four tertiary US institutions to examine patients who underwent cyanoacrylate vein closure of their saphenous veins. Patient demographics, comorbidities, CEAP (Clinical [C], Etiological [E], Anatomical [A], and Pathophysiological [P]) classification, and periprocedural outcomes were included. The primary endpoint was development of T4H post procedure. Logistic regression analysis for risk factors predictive of T4H was performed. Variables with a P-value of <0.05 were deemed significant. RESULTS: 595 patients underwent 881 cyanoacrylate venous closures. Mean age was 66.2 ± 14.9, and 66% of patients were female. There were 92 (10.4%) T4H events in 79 (13%) patients. Oral steroids were administered to 23% for persistent and/or severe symptoms. There were no systemic allergic reactions to cyanoacrylate. Multivariate analysis revealed younger age (P = 0.015), active smoking status (P = 0.033), and CEAP 3 (P < 0.001) and 4 (P = 0.005) classifications as independent risk factors associated with development of T4H. CONCLUSIONS: This real-world multicenter study shows the overall incidence of T4H to be 10%. CEAP 3 and 4 patients of younger age and smokers predicted a higher risk of T4H to cyanoacrylate.

Comparison of admission GCS score to admission GCS-P and FOUR scores for prediction of outcomes among patients with traumatic brain injury in the intensive care unit in India.

BACKGROUND: This study aimed to determine the predictive power of the Full Outline of Unresponsiveness (FOUR) score and the Glasgow Coma Scale Pupil (GCS-P) score in determining outcomes for traumatic brain injury (TBI) patients. The Glasgow Outcome Scale (GOS) was used to evaluate patients at 1 month and 6 months after the injury. METHODS: We conducted a 15-month prospective observational study. It included 50 TBI patients admitted to the ICU who met our inclusion criteria. We used Pearson's correlation coefficient to relate coma scales and outcome measures. The predictive value of these scales was determined using the receiver operating characteristic (ROC) curve, calculating the area under the curve with a 99% confidence interval. All hypotheses were two-tailed, and significance was defined as P<0.01. RESULTS: In the present study, the GCS-P and FOUR scores among all patients on admission as well as in the subset of patients who were mechanically ventilated were statistically significant and strongly correlated with patient outcomes. The correlation coefficient of the GCS score compared to GCS-P and FOUR scores was higher and statistically significant. The areas under the ROC curve for the GCS, GCS-P, and FOUR scores and the number of computed tomography abnormalities were 0.912, 0.905, 0.937, and 0.324, respectively. CONCLUSIONS: The GCS, GCS-P, and FOUR scores are all excellent predictors with a strong positive linear correlation with final outcome prediction. In particular, the GCS score has the best correlation with final outcome.

Vestibular Schwannoma Stereotactic Radiosurgery in Octogenarians: Case Series.

BACKGROUND AND OBJECTIVES: The management of octogenarians with vestibular schwannomas (VS) has received little attention. However, with the increase in octogenarian population, more effort is needed to clarify the value of stereotactic radiosurgery (SRS) in this population. The aim of this study was to evaluate the safety and efficacy of SRS in this patient age group. METHODS: A retrospective study of 62 patients aged 80 years or older who underwent single-session SRS for symptomatic VS during a 35-year interval was performed. The median patient age was 82 years, and 61.3% were male. SRS was performed as planned adjuvant management or for delayed progression after prior partial resection in 5 patients. RESULTS: SRS resulted in a 5-year tumor control rate of 95.6% with a 4.8% risk of adverse radiation effects (ARE). Tumor control was unrelated to patient age, tumor volume, Koos grade, sex, SRS margin dose, or prior surgical management. Four patients underwent additional management including 1 patient with symptomatic progression requiring surgical resection, 2 patients with symptomatic hydrocephalus requiring cerebrospinal fluid diversion, and 1 patient whose tumor-related cyst required delayed cyst aspiration. Three patients developed ARE, including 1 patient with permanent facial weakness (House-Brackmann grade II), 1 who developed trigeminal neuropathy, and 1 who had worsening gait disorder. Six patients had serviceable hearing preservation before SRS, and 2 maintained serviceable hearing preservation after 4 years. A total of 44 (71%) patients died at an interval ranging from 6 to 244 months after SRS. CONCLUSION: SRS resulted in tumor and symptom control in most octogenarian patients with VS.

Adductor canal syndrome after lesser trochanter avulsion fracture in a 19-year-old.

A rare cause of limb ischemia in young patients, adductor canal syndrome, can be debilitating and result in functional impairment. Diagnosis and treatment may be delayed due to this vascular disease's rarity in young people and because the presenting symptoms can overlap with other more common causes of leg pain in young athletes. Here, authors discuss a young athletic patient with a history of year-long claudication. The patient's reported symptoms, exam findings, and imaging results were consistent with a diagnosis of adductor canal syndrome. This case proved uniquely challenging, given the extent of disease and illustrates potential approach considerations.

Personalizing Surveillance in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) encompasses a spectrum of heterogeneous diseases originating in the oral cavity, pharynx, and larynx. Within the United States, head and neck cancer (HNC) accounts for 66,470 new cases, or 3% of all malignancies, annually.1 The incidence of HNC is rising, largely driven by increases in oropharyngeal cancer.2-4 Recent molecular and clinical advancements, particularly with regard to molecular and tumor biology, reflect the heterogeneity of the subsites contained within the head and neck. Despite this, existing guidelines for post-treatment surveillance remain broad without much consideration given to different anatomic subsites and etiologic factors (such as human papillomavirus [HPV] status or tobacco exposure).5 Surveillance incorporating the physical examination, imaging, and emerging molecular biomarkers is an essential part of care for patients treated for HNC and allows for the detection of locoregional recurrence, distant metastases, and second primary malignancies aiming for better functional and survival outcomes. Additionally, it allows for evaluation and management of post-treatment complications.

Microbial Changes Associated With Oral Cavity Cancer Progression.

OBJECTIVE: To examine the oral microbiome in the context of oral cavity squamous cell carcinoma. STUDY DESIGN: Basic science research. SETTING: Academic medical center. METHODS: Oral swabs were collected from patients presenting to the operating room for management of oral cavity squamous cell carcinoma and from age- and sex-matched control patients receiving surgery for unrelated benign conditions. 16S ribosomal RNA (rRNA) sequencing was performed on genetic material obtained from swabs. A bacterial rRNA gene library was created and sequence reads were sorted into taxonomic units. RESULTS: Thirty-one control patients (17 males) and 35 cancer patients (21 males) were enrolled. Ages ranged from 23 to 89 (median 63) for control patients and 35 to 86 (median 66) for cancer patients. Sixty-one percent of control patients and 63% of cancer patients were smokers. 16S analyses demonstrated a significant decrease in Streptococcus genera in oral cancer patients (34.11% vs 21.74% of the population, p = .04). Increases in Fusobacterium, Peptostreptococcus, Parvimonas, and Neisseria were also found. The abundance of these bacteria correlated with tumor T-stage. CONCLUSION: 16S rRNA sequencing demonstrated changes in bacterial populations in oral cavity cancer and its progression compared to noncancer controls. We found increases in bacteria genera that correspond with tumor stage-Fusobacteria, Peptostreptococcus, Parvimonas, Neisseria, and Treponema. These data suggest that oral cancer creates an environment to facilitate foreign bacterial growth, rather than implicating a specific bacterial species in carcinogenesis. These bacteria can be employed as a potential marker for tumor progression or interrogated to better characterize the tumor microenvironment.

Clinical Outcomes and Hospital Utilization Among Patients Undergoing Bariatric Surgery With Telemedicine Preoperative Care.

Importance: Bariatric surgery is the mainstay of treatment for medically refractory obesity; however, it is underutilized. Telemedicine affords patient cost and time savings and may increase availability and accessibility of bariatric surgery. Objective: To determine clinical outcomes and postoperative hospital utilization for patients undergoing bariatric surgery who receive fully remote vs in-person preoperative care. Design, Setting, and Participants: This cohort study comparing postoperative clinical outcomes and hospital utilization after telemedicine or in-person preoperative surgical evaluation included patients treated at a US academic hospital. Participants underwent laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy after telemedicine or in-person preoperative surgical evaluation between July 1, 2020, to December 22, 2021, or January 1, 2018, to December 31, 2019, respectively. Follow-up was 60 days from date of surgery. Exposures: Telemedicine-based preoperative care. Main Outcomes and Measures: Clinical outcomes, including operating room delay, procedure duration, length of hospital stay (LOS), and major adverse events (MAE), and postoperative hospital resource utilization, including emergency department (ED) visit or hospital readmission within 30 days of the surgical procedure. Results: A total of 1182 patients were included; patients in the telemedicine group were younger (mean [SD] age, 40.8 [12.5] years vs 43.0 [12.2] years; P = .01) and more likely to be female (230 of 257 [89.5%] vs 766 of 925 [82.8%]; P = .01) compared with the control group. The control group had a higher frequency of comorbidity (887 of 925 [95.9%] vs 208 of 257 [80.9%]; P < .001). The telemedicine group was found to be noninferior to the control group with respect to operating room delay (mean [SD] minutes, 7.8 [25.1]; 95% CI, 5.1-10.5 vs 4.2 [11.1]; 95% CI, 1.0-7.4; P = .002), procedure duration (mean [SD] minutes, 134.4 [52.8]; 95% CI, 130.9-137.8 vs 105.3 [41.5]; 95% CI, 100.2-110.4; P < .001), LOS (mean [SD] days, 1.9 [1.1]; 95% CI, 1.8-1.9 vs 2.1 [1.0]; 95% CI, 1.9-2.2; P < .001), MAE within 30 days (3.8%; 95% CI, 3.0%-5.7% vs 1.6%; 95% CI, 0.4%-3.9%; P = .001), MAE between 31 and 60 days (2.2%; 95% CI, 1.3%-3.3% vs 1.6%; 95% CI, 0.4%-3.9%; P < .001), frequency of ER visits (18.8%; 95% CI, 16.3%-21.4% vs 17.9%; 95% CI, 13.2%-22.6%; P = .03), and hospital readmission (10.1%; 95% CI, 8.1%-12.0% vs 6.6%; 95% CI, 3.9%-10.4%; P = .02). Conclusions and Relevance: In this cohort study, clinical outcomes in the telemedicine group were not inferior to the control group. This observation suggests that telemedicine can be used safely and effectively for bariatric surgical preoperative care.