The Use of Aspirin for Venous Thromboembolism Prophylaxis in Patients Who Have Morbid Obesity Undergoing Primary and Revision Total Joint Arthroplasty.

INTRODUCTION: Venous thromboembolism (VTE) poses a major clinical concern due to its life-threatening nature, and obese and morbidly obese patients are thought to be at an increased risk for VTE. The aims of this study were twofold; first, to explore VTE rates in patients who have a body mass index > 40 undergoing primary and revision total joint arthroplasty (TJA), and second, to investigate aspirin (ASA) efficacy and safety. METHODS: We identified all patients (n = 4,672) who had a BMI > 40 who underwent primary and revision TJA from 2016 to 2022 at a single academic tertiary care center. Patients were stratified by BMI groups: 40 to 44.9 (n = 3,462), 45 to 49.9 (n = 935), and 50+ (n = 275). The primary outcome was any venous thromboembolism (VTE) event within 90 days postoperatively. The secondary outcome consisted of wound complications within 90 days postoperatively. RESULTS: The total VTE rate was 0.4% (n = 21) and did not differ statistically between the BMI groups (0.4 versus 0.4 versus 0.7%, P = 0.669). The VTEs consisted of six deep venous thromboses (DVT), fourteen pulmonary embolisms (PE), and one concomitant DVT and PE. The VTE rates were not statistically different between patients who received aspirin 325 mg 0.5% (n = 9), aspirin 81 mg 0.2% (n = 1), aspirin + anticoagulant 0.5% (n = 6), and anticoagulant alone 0.4% (n = 5) (P = 0.954). In addition, wound complications did not differ significantly between patients who received ASA 325 mg, ASA 81mg, ASA + anticoagulant, or anticoagulant alone (1.6 versus 1.0 versus 1.8 versus 1.1%, P = 0.351). CONCLUSION: The use of aspirin 325 mg and 81 mg was found to have similar VTE rates as aspirin + anticoagulants and anticoagulants alone, with no significant increase in wound complications. In patients who have a BMI > 40, the use of aspirin is a safe option for VTE prophylaxis and should be prescribed in the context of the patient who has other risk factors for VTE.

Metastatic merkel cell carcinoma to the thyroid gland: Case report and review of the literature.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive and rare neuroendocrine tumor, accounting for less than 1% of skin cancers. Metastasis primarily manifests in the cervical lymph nodes but rarely affect the thyroid. METHODS: We report a case of primary head and neck cutaneous MCC with metastasis to the thyroid gland. A review of the literature of MCC with thyroid metastasis was conducted. RESULTS: We identified five cases of MCC with thyroid metastasis. Primary sites included the distal upper and lower extremities, axilla, buttock, and groin. Treatment courses varied including thyroidectomy, immunotherapy, and expectant palliative measures. Time from initial diagnosis to thyroid metastasis ranged from four months to four years. Tissue diagnosis was achieved in 5 of 6 cases. CONCLUSIONS: MCC with thyroid metastasis is rare and likely represents aggressive disease. Despite advances in treatment and surveillance, outcomes for MCC remain poor. Ongoing research may establish predictors for treatment response.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BACKGROUND: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. METHODS: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. RESULTS: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. CONCLUSIONS: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. LEVEL OF EVIDENCE: III.

Sensitive MRD Detection from Lymphatic Fluid after Surgery in HPV-Associated Oropharyngeal Cancer.

PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification. EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS). RESULTS: Postoperative lymph was enriched with cf-HPV compared with plasma (P < 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P < 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P < 0.0001). CONCLUSIONS: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223.

Short Term Outcomes (Average Follow-Up of 2.4 Years) of a Constrained Acetabular Liner in Primary and Revision Total Hip Arthroplasty.

BACKGROUND: As instability continues to be a burden post-total hip arthroplasty (THA), there has been a controversial discussion on the ideal implant choice. We report the outcomes of a modern constrained acetabular liner (CAL) system in primary and revision THA at an average follow-up of 2.4 years. METHODS: We performed a retrospective study of all patients undergoing primary and revision hip arthroplasty and being implanted with the modern CAL system from 2013 to 2021. We identified 31 hips, of which 13 underwent primary THA and the remaining 18 underwent revision THA for instability. RESULTS: Of those implanted with CAL primarily, 3 had concomitant abductor tear repair and gluteus maximus transfer, 5 had Parkinson's disease, 2 had inclusion body myositis, 1 had amyotrophic lateral sclerosis, and the remaining two were over 94 years of age. All patients implanted with the CAL had active instability post-primary THA and underwent only liner and head exchange without revision of the acetabular or femoral components. At an average follow-up of 2.4 years (ranging from 9 months to 5 years and 4 months), we had 1 case (3.2%) of dislocation post-CAL implantation. None of the patients undergoing surgery with CAL for active instability had a redislocation. CONCLUSION: In conclusion, a CAL provides excellent stability in both primary THA in high-risk individuals and revision THA in cases of active instability. There were no dislocations when using a CAL to treat active instability post-THA.

Integrative genomic analysis reveals low T-cell infiltration as the primary feature of tobacco use in HPV-positive oropharyngeal cancer.

Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T > C substitutions and a lower proportion of expected mutational signatures, but not with increases in mutational burden or recurrent oncogenic mutations. Our findings suggest that rather than increased mutational burden, tobacco's primary and clinically relevant association in HPV(+) OPSCC is immunosuppression of the tumor immune microenvironment. Quantitative assays of T cell infiltration merit further study as prognostic markers in HPV(+) OPSCC.

Commercial ctDNA Assays for Minimal Residual Disease Detection of Solid Tumors.

The detection of circulating tumor DNA via liquid biopsy has become an important diagnostic test for patients with cancer. While certain commercial liquid biopsy platforms designed to detect circulating tumor DNA have been approved to guide clinical decisions in advanced solid tumors, the clinical utility of these assays for detecting minimal residual disease after curative-intent treatment of nonmetastatic disease is currently limited. Predicting disease response and relapse has considerable potential for increasing the effective implementation of neoadjuvant and adjuvant therapies. As a result, many companies are rapidly investing in the development of liquid biopsy platforms to detect circulating tumor DNA in the minimal residual disease setting. In this review, we discuss the development and clinical implementation of commercial liquid biopsy platforms for circulating tumor DNA minimal residual disease detection of solid tumors. Here, we aim to highlight the technological features that enable highly sensitive detection of tumor-derived genomic alterations, the factors that differentiate these commercial platforms, and the ongoing trials that seek to increase clinical implementation of liquid biopsies using circulating tumor DNA-based minimal residual disease detection.

Survival of Young Versus Old Patients With Oral Cavity Squamous Cell Carcinoma: A Meta-Analysis.

OBJECTIVE/HYPOTHESIS: To assess whether young patients with oral cavity squamous cell carcinoma (OCSCC) demonstrate worse oncologic outcomes than older patients after definitive therapy. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A medical librarian composed a search strategy to identify relevant studies in Medline, Embase, Scopus, and other major databases (Prospero registration number CRD42019127974). Inclusion criteria were adults with histologically diagnosed OCSCC that underwent treatment, comparator groups with an age cutoff of 40 years old, and reported survival outcomes. Articles were excluded if they contained patients with oropharyngeal squamous cell carcinoma or patients treated for palliative intent. Overall survival hazard ratios were analyzed with a meta-analysis. RESULTS: There were 23,382 patients with OCSCC that were treated with definitive therapy from 22 included studies. The pooled cohort contained 2,238 (10%) patients ≤40 years of age. Oral tongue was the most common subsite in both the younger (n = 1,961, 91%) and older (n = 18,047, 88%) cohorts. The majority of OCSCCs were either T1 or T2, representing 859 (80%) malignancies in younger patients and 8,126 (77%) malignancies in older patients. A meta-analysis of nine studies demonstrated that younger patients did not experience worse survival outcomes than older patients (hazard ratio = 0.97, 95% confidence interval = 0.66-1.41). CONCLUSIONS: Young adults with OCSCC experienced similar oncologic outcomes as older patients with OCSCC after definitive treatment. Until compelling evidence demonstrates clinically relevant differences between these two cohorts, their approach to management should be similar. Future studies should consider comorbidities and using age 40 as a standard age cutoff to provide more uniform data moving forward. Laryngoscope, 131:1310-1319, 2021.

Head and Neck Cancer Survival Disparities by Race and Rural-Urban Context.

BACKGROUND: This study aims to examine the relationship between race and rural-urban context in head and neck cancer (HNC) survival and determine factors that potentially drive this disparity. METHODS: Using the National Cancer Database from 2004 to 2015, we identified a retrospective cohort of 146,256 patients with HNC. Kaplan-Meier survival curves and the Cox proportional hazards regression were used to calculate adjusted HRs. RESULTS: Median survival by patient subgroup was as follows: White urban [67 months; 95% confidence interval (CI), 66.0-67.9], White rural (59.1 months; 95% CI, 57.2-60), Black urban (43.1 months; 95% CI, 41.1-44.5), and Black rural (35.1 months; 95% CI, 31.9-39.0). The difference in 5-year survival, stratified by rural-urban context, was greater among Black patients [Δ restricted mean survival time (ΔRMST) 0.18; 95% CI, 0.10-0.27] than White patients (ΔRMST 0.08; 95% CI, 0.06-0.11). In the univariate Cox proportional hazards analysis with White urban patients as reference group, Black rural patients had the worst survival (HR, 1.45; 95% CI, 1.43-1.48; P < 0.001), followed by Black urban patients (HR, 1.29; 95% CI, 1.28-1.30; P < 0.001), and White rural patients (HR, 1.08; 95% CI, 1.07-1.09; P < 0.001). This disparity persisted when controlling for demographic, socioeconomic, and clinical factors. CONCLUSIONS: Black patients with HNC, specifically those living in rural areas, have decreased survival. Survival differences by rural-urban status are greater among Black patients than White patients. IMPACT: We have shown that race and rural-urban status impact HNC survival outcomes. Our findings will help future researchers to better frame approaches to address this disparity.

Tranexamic Acid Update in Trauma.

Following results from the CRASH-2 trial, tranexamic acid (TXA) gained considerable interest for the treatment of hemorrhage in trauma patients. Although TXA is effective at reducing mortality in patients presenting within 3 hours of injury, optimal dosing, timing of administration, mechanism, and pharmacokinetics require further elucidation. The concept of fibrinolysis shutdown in hemorrhagic trauma patients has prompted discussion of real-time viscoelastic testing and its potential role for appropriate patient selection. The results of ongoing clinical trials will help establish high-quality evidence for optimal incorporation of TXA in mature trauma networks in the United States and abroad.