Diagnostic Accuracy of Circulating Tumor HPV DNA Testing in Patients With a Lateral Neck Mass.

Importance: The most frequent presenting symptom for patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a lateral neck mass. Circulating tumor tissue-modified viral (TTMV)-HPV DNA is a unique biomarker produced by the fragmentation of HPV DNA during the degradation of HPV-associated tumors, and its detection and quantitation are currently being used as an adjunct to imaging in monitoring for disease recurrence and may have utility for diagnosis. Objective: To measure the diagnostic characteristics of TTMV-HPV DNA compared with gold standard tissue biopsy for diagnosing HPV-OPSCC in patients presenting with an indeterminate lateral neck mass. Design, Setting, and Participants: This prospective diagnostic test study enrolled patients 18 years or older who presented with a lateral neck mass to a large urban tertiary health care system from December 2021 to June 2023. Participants underwent standard-of-care testing to obtain a tissue diagnosis and a single TTMV-HPV DNA measurement. Main Outcomes and Measures: The primary outcome of interest was sensitivity, while specificity, positive predictive value, and negative predictive value were secondary end points. A subset analysis was performed comparing test performance metrics between TTMV-HPV DNA testing and fine-needle aspiration. Results: A total of 138 patients were included, of whom 80 (58.0%) were men, with median age of 57.5 years (IQR, 43.3-67.0 years). Of 138 patients, 87 (63.0%) had neck masses in level 2 and 47 (34.1%) had HPV-OPSCC. TTMV-HPV DNA testing exhibited a sensitivity of 95.7% (95% CI, 85.5%-99.5% [45 of 47 patients]), specificity of 97.8% (95% CI, 92.3%-99.7% [89 of 91 patients]), positive predictive value of 95.7% (95% CI, 85.5%-99.5% [45 of 47 patients]), and negative predictive value of 97.8% (95% CI, 92.3%-99.7% [89 of 91 patients]). Conclusions and Relevance: In this diagnostic study of patients presenting with a lateral neck mass, circulating TTMV-HPV DNA demonstrated excellent diagnostic test characteristics for the detection of HPV-OPSCC. Such testing may have particular utility for patients in whom obtaining adequate tissue is problematic, as is often the case with cystic neck masses and unknown primary tumors.

Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

Evaluating human papillomavirus testing, prevalence, and association with prognosis in head and neck squamous cell carcinoma by subsite: A national cancer database study.

PURPOSE: To compare human papillomavirus (HPV) testing, prevalence, and association with prognosis between head and neck squamous cell carcinoma (HNSCC) subsites. MATERIALS AND METHODS: This study utilized the National Cancer Database (NCDB) to identify patients diagnosed with HNSCC between 2010 and 2017. Rates of HPV testing, HPV-positivity, and changes in these rates over time were measured by subsite. The impact of HPV-positivity on overall survival across six head and neck subsites was assessed using multivariable-adjusted Cox proportional hazards analysis. RESULTS: A total of 121,550 patients were included. Of this cohort, 87,575 (72.1%) were tested for HPV, with the oropharynx (55,049/64,158; 85.8%) displaying the highest rates of testing and the sinonasal tract (1519/2853; 53.2%) displaying the lowest testing rates. Of the 86,136 with a definitive result, 46,878 (54.4%) were HPV-positive, with the oropharynx (40,313/54,205; 74.4%) displaying the highest rates of HPV-positivity and the oral cavity (1818/11,505; 15.8%) displaying the lowest. HPV-positive malignancy was associated with significantly improved adjusted overall survival in the oropharynx (HR = 0.42 [95% CI: 0.43-0.47]), oral cavity (HR = 0.86 [95% CI: 0.79-0.95]), sinonasal tract (HR = 0.63 [95% CI: 0.48-0.83]), larynx (HR = 0.78 [95% CI: 0.71-0.87]), and hypopharynx (HR = 0.56 [95% CI: 0.48-0.66]), but not the nasopharynx (HR = 0.93 [95% CI: 0.77-1.14]). CONCLUSION: HPV testing rates were significantly lower in non-oropharyngeal subsites. This is relevant as HPV-associated disease displayed significantly improved overall survival in both the oropharynx and four of five non-oropharyngeal subsites. While validation with prospective studies is necessary, these findings may warrant HPV testing in all HNSCC subsites.

Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus-Associated Oropharyngeal Cancer.

Importance: There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials. Objective: To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting. Design, Setting, and Participants: This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy. Main Outcomes and Measures: Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing. Results: Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days. Conclusions and Relevance: This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.

Neutrophil-to-lymphocyte ratio as a predictor of surgical outcomes in head and neck cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker of systemic inflammation that is associated with adverse oncologic and surgical outcomes. We investigated the use of NLR as a prognostic indicator of complications of head and neck cancer (HNC) surgeries. METHODS: We conducted a retrospective study of 11 187 Veterans who underwent HNC surgery between 2000 and 2020. We calculated preoperative NLR values and fit logistic regression models adjusting for potential confounding factors, comparing high-NLR patients to low-NLR patients. RESULTS: The cohort had a median age of 63 and was 98% men. High-NLR patients had increased odds of 30-day mortality (p < 0.001), having 1+ perioperative complications (p < 0.001), sepsis (p = 0.03), failure to wean from mechanical ventilation (p = 0.04), pneumonia (p < 0.001), and pulmonary embolism (p = 0.02) compared with low-NLR patients. CONCLUSION: NLR was a robust, independent predictor of 30-day mortality, having 1+ surgical complications, sepsis, failure to wean from mechanical ventilation, pneumonia, and pulmonary embolism.

Prophylactic feeding tube placement for squamous cell carcinoma of the head and neck.

BACKGROUND: Percutaneous endoscopic gastronomy (PEG) tubes are commonly used to administer enteral nutrition during head and neck cancer (HNC) treatment. However, the benefits of placing a prophylactic feeding tube (PFT; prior to radiotherapy [RT]) or reactive feeding tube (RFT, after RT initiation) are unclear. We sought to compare survival, body mass trends, and hospitalization rates between strategies. METHODS: We conducted a retrospective cohort study of 11,473 Veterans with stages III-IVC HNC treated with chemoradiotherapy. Patients with PEG tube placement within 30 days prior to treatment initiation (PFT) were compared to all other patients (non-PFT) or patients with PEG tube placement within 3 months after treatment initiation placement (RFT). We compared survival, longitudinal body mass changes, and hospitalization rates for PFT versus non-PFT or RFT patients in propensity score (PS)-matched Cox regression models. RESULTS: 3,186 (28 %) patients received PFT and 8,287 (72 %) were non-PFT, of which 1,874 (23 %) received RFT. After PS-matching, there were no significant differences in overall survival (HR 0.97, 95 % CI 0.92-1.02), HNC-specific survival (HR 0.98, 95 % CI 0.92-1.09), change in BMI (p = 0.24), or hospitalization rates between PFT and non-PFT groups. Significant differences in hospitalization rates between PFT and RFT groups persisted after PS-matching (-0.11 hospitalizations/month), but no differences were found for other outcomes. CONCLUSION: Timing of PEG tube placement in Veterans with HNC was not associated with any significant survival or body mass advantage. However, patients who received PFT had a lower hospitalization rate than those who received RFT.

The Sinai Robotic Surgery Trial in HPV-related oropharyngeal squamous cell carcinoma (SIRS 2.0 trial) - study protocol for a phase II non-randomized non-inferiority trial.

Background: Human papillomavirus associated oropharyngeal squamous cell carcinoma (HPVOPSCC) usually affects a younger patient population. As such, the risk for long term toxicity associated with therapy is an important consideration. Multiple trials focused on de-escalation of therapy to preserve survival outcomes while minimizing treatment toxicity are currently in progress, however the question of which patients are ideal candidates for de-escalation remains unanswered. Circulating tumor DNA (cfHPVDNA) has emerged as a means of monitoring disease in patients with HPVOPSCC. Undetectable postoperative cfHPVDNA levels portend a better prognosis and by extension, may identify ideal candidates for de-escalation therapy. We propose an overview and rationale for a new institutional clinical trial protocol focusing on the use of cfHPVDNA to risk stratify patients for adjuvant therapy. We hypothesize that many surgical patients currently receiving radiation therapy may be clinically observed without adjuvant therapy. Methods: Patients with measurable cfHPVDNA and clinically resectable HPVOPSCC will undergo TORS resection of tumors and neck dissection. Patients with undetectable cfHPVDNA at 3 weeks post-op will be allocated to low or high-risk treatment protocol groups. The low risk group consists of patients with <4 positive lymph nodes, ≤2 mm extranodal extension (ENE), and perineural invasion (PNI) or lymphovascular invasion (LVI) alone. The high-risk group is made up of patients with ≥4 positive lymph nodes, gross ENE, positive margins, N2c disease and/or the combination of both PNI and LVI. The low-risk group will be allocated to an observation arm, while the high-risk group will receive 46 Gy of adjuvant radiotherapy and weekly cisplatin therapy. The primary outcome of interest is 2-year disease recurrence with secondary outcomes of 2-year disease free survival, locoregional control, overall survival, and quality of life measures. A sample of 126 patients in the low-risk group and 73 patients in the high-risk group will be required to evaluate non-inferiority to the standard of care. Discussion: This study will provide much needed recurrence and survival data for patients that undergo primary TORS followed by observation or de-escalated adjuvant therapy. Additionally, it will help delineate the role of cfHPVDNA in the risk stratification of patients that undergo treatment de-intensification.

Sex-Related Differences in Outcomes for Oropharyngeal Squamous Cell Carcinoma by HPV Status.

Background: Overall survival for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) has differed by sex, but little is known regarding cancer-specific outcomes. We assessed the independent association of sex with cancer-specific survival in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods: We identified 14,183 patients from the Surveillance, Epidemiology, and End Results (SEER) program with OPSCC and tumor HPV status. We used Kaplan-Meier methods to compare overall survival (OS) and OPSCC-specific survival (HNCSS) by patient sex and by tumor HPV status. We then separately fit multivariable survival and competing risk models evaluating the association of sex on these outcomes by tumor HPV status and stratified by the use of guideline-concordant OPSCC treatment. Results: A total of 10,210 persons with HPV-positive tumors (72.0%) and 3,973 with HPV-negative tumors (28.0%) were identified. A larger proportion of women had HPV-negative tumors (24.0%) versus HPV-positive tumors (13.2%; p < 0.001). Women with HPV-positive tumors were less likely to receive guideline-concordant treatment compared to men. In unadjusted survival analyses, women did not differ in OS or HNCSS compared to men for HPV-positive tumors but had worse OS and HNCSS for HPV-negative tumors. After adjustment, men and women with HPV-positive OPSCC did not differ in OS or HNCSS. However, women with HPV-negative tumors faced worse overall survival (hazard ratio (HR) 1.15, 95% CI 1.02-1.29) that persisted even after stratifying for stage-appropriate treatment (HR 1.28, 95% CI 1.11-1.47). Conclusions: Women with HPV-positive OPSCC had similar survival outcomes compared to men, but those with HPV-negative tumors have worse overall and cancer-specific survival.

Impact of preoperative and intraoperative management on outcomes in osteoradionecrosis requiring free flap reconstruction.

BACKGROUND: Perioperative management of advanced osteoradionecrosis of the head and neck requiring free flap (FF) reconstruction varies. Our objectives included assessment of practice patterns and outcomes. METHODS: Multi-institutional, retrospective review of FF reconstruction for head and neck osteoradionecrosis (n = 260). RESULTS: Administration of preoperative antibiotics did not correlate with reduction in postoperative complications. Preoperative alcohol use correlated with higher rates of hardware exposure (p = 0.03) and 30-day readmission (p = 0.04). Patients with FF compromise had higher TSH (p = 0.04) and lower albumin levels (p = 0.005). Prealbumin levels were lower in patients who required neck washouts (p = 0.02) or a second FF (p = 0.03). TSH levels were higher in patients undergoing postoperative debridement (p = 0.03) or local flap procedures (p = 0.04). CONCLUSION: Malnutrition, hypothyroidism, and substance abuse correlated with a higher incidence of postoperative wound complications in patients undergoing FF reconstruction for advanced osteoradionecrosis. Preoperative antibiotics use did not correlate with a reduction in postoperative wound complications.

Neutrophil-to-lymphocyte ratio as a prognostic indicator for overall and cancer-specific survival in squamous cell carcinoma of the head and neck.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker that is correlated with systemic inflammation and poor prognosis in solid tumors. We investigated the value of NLR in predicting survival in a large population of head and neck cancer patients in the United States. METHODS: We performed a retrospective cohort study of Veterans Affairs patients with head and neck squamous cell carcinoma (HNSCC) diagnosed between January 2000 and December 2017. We compared 5-year overall survival and cancer-specific survival for different NLR tertiles using cox proportional hazards modeling with adjustment for covariates. RESULTS: The primary cohort consisted of 14 644 subjects of which 99% were male. Relative to patients with NLRs in the lower tertile, patients with NLRs in the top tertile had an 71% increased hazard of all-cause mortality (P < .001) and 44% increased hazard of cancer-specific mortality (P < .001) at 5 years. CONCLUSIONS: Elevated NLR in HNSCC confers a poor prognosis.

2-Octyl cyanoacrylate to prevent salivary fistula formation following oral cavity microvascular reconstruction: A prospective trial.

BACKGROUND: Salivary fistulas remain a significant problem in patients undergoing major head and neck reconstructive surgery. Surgical sealants have become increasingly used in cutaneous and non-cutaneous wound closure, providing a barrier to fluids/gases and promoting healing. The purpose of this study was to determine the efficacy of a common surgical sealant, 2-Octyl Cyanoacrylate (2-OCA, Dermabond®), in the prevention of salivary fistulas following free flap reconstruction of the oral cavity. METHODS: In this non-randomized, single arm prospective trial, patients undergoing free flap reconstruction of gravity-dependent oral cavity defects were recruited. Application of 2-OCA was performed along flap inset suture lines at the time of surgery. Prospectively collected trial data were propensity score matched to a control cohort to compare outcomes. Data collected include demographics, medical co-morbidities, previous treatments, primary tumor site, and subsites reconstructed. The primary outcome measure was rate of salivary fistula formation. Secondary outcomes were time to development of leak and percentage of patients tolerating oral feeding at one month post-operatively. RESULTS: In the 46 propensity score matched pairs, eight (17.4%) out of 46 patients in the 2-OCA prospective cohort and seven (15.2%) out of 46 patients in the control cohort developed postoperative salivary fistulas within the one-month study interval (p = 1.00). The average time to postoperative leak in the 2-OCA group was 12.5 days versus 7.1 days in the control cohort (p = 0.10). In the 2-OCA group, 30 (65.2%) patients were tolerating regular diet at one month post-operatively compared to 33 (71.7%) in the control cohort (p = 0.65). CONCLUSION: Salivary fistula rates after application of a 2-OCA surgical sealant were not improved compared to a control cohort in this single institutional trial. There are several surgical sealants available, each with varying elasticity and adhesiveness. Future studies are needed to identify surgical sealants that are able to provide sufficient strength and adhesion to seal closures and combat corrosive saliva, but elastic enough to handle motion related tension during swallowing and post-operative movements in the head and neck.

Infection Rates After Microlaryngeal and Open Phonosurgery: The Role of Postoperative Antibiotics.

OBJECTIVE: Although it is known that the airway has bacterial contamination that seeds the surgical site during microlaryngeal surgery, literature on the use of postoperative antibiotics is lacking. We performed a retrospective analysis of open phonosurgical and phonomicrosurgical cases at a single institution to assess whether use of postoperative antibiotics impacts the incidence of surgical site infections (SSI). METHODS: In this retrospective cohort study, we reviewed 228 phonomicrosurgery and 53 open phonosurgery cases performed for benign diseases. Surgeries were performed by two laryngologists between February 2016 and August 2018. The surgeons differ in their postoperative antibiotic regimens: no antibiotics versus a 5- to 7-day postoperative course. Data collected include demographics, medical comorbidities, type of benign laryngeal disease, and surgical procedure. The primary outcome measure was postoperative infection, defined as the patient requiring a new prescription for antibiotics, an extended course of antibiotics, or any mention of infection at follow-up/emergency visits within the first month postoperatively. RESULTS: The overall rate of SSI was 3.1% and 0% for phonomicrosurgery and open phonosurgery cases, respectively. For phonomicrosurgery, there was no difference in the rate of SSI for patients who received or did not receive antibiotics perioperatively: 2.9% versus 3.2% (P = 0.99). Similarly, there was no difference in the infection rate for open phonosurgical cases. CONCLUSION: Infection rates after endoscopic and open phonosurgery are low. In this study, we found no evidence to suggest a protective effect associated with postoperative use of antibiotics. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1128-1131, 2020.

Are Otolaryngology Milestones Predictive of Otolaryngology Training Examination Scores?

IMPORTANCE:: Otolaryngology residents take the otolaryngology training examination (OTE) yearly to assess their fund of knowledge. The Accreditation Council for Graduate Medical Education (ACGME) milestone evaluations are also conducted semiannually. Accurate prediction of training examination performance allows identification of residents who are performing well and those who need targeted remediation. Prior studies in other specialties have attempted to use milestone evaluations to help predict in-training examination scores. OBJECTIVE:: In this study, we aim to identify whether ACGME milestone evaluation scores predict OTE performance. DESIGN:: Milestone ratings and OTE scores for residents at 2 US otolaryngology residency programs were collected. Multivariate analysis was achieved using linear mixed modeling. We considered a 2-tailed P value of ≤ .05 as statistically significant. SETTING:: Two US otolaryngology residency programs. PARTICIPANTS:: Forty-eight otolaryngology residents postgraduate years 2 to 5. RESULTS:: Otolaryngology training examination scores and ACGME milestone evaluations were collected from 48 residents from postgraduate year 2 to 5 between the years 2014 and 2017. One hundred eight OTE scores were available. Linear mixed-effect models were constructed, and after adjusting for level of training and OTE year, the total milestone rating made a negligible impact in estimating OTE percentage correct (ß = -.01, P = .9). Similarly, total milestone rating demonstrated a minimal contribution in approximating OTE national stanine score after adjusting for the level of training (ß = -.003, P = .9). CONCLUSIONS AND RELEVANCE:: In our study, ACGME milestone evaluations are not predictive of residents' OTE performance. What these milestone evaluation data mean and how they should be used continues to be an unanswered question. We should aim to identify the most effective applications of the milestone data collected yearly by otolaryngology programs.

Behavioral analysis of HPV+ oropharyngeal cancer: Do you know your patients?

OBJECTIVE: Evaluate the epidemiologic makeup of a population of HPV+ OPSCC patients treated at one institution over approximately a decade. STUDY DESIGN: Prospective survey study of HPV+ OPSCC treated between 2007 and 2016. SETTING: Mount Sinai Health System SUBJECTS AND METHODS: Patients aged 18+ who underwent treatment for HPV+ OPSCC. 223 patients were asked to complete a health survey including substance use and sexual history in order to specifically characterize the social behaviors of patients with HPV + OPSCC. RESULTS: Eighty-two patients responded, 70 male (85.4%) and 12 female (14.6%). While half of patients were nonsmokers, 18.3% had a smoking history of <15 pack years, and 32.9% had a 15+ pack-year smoking history. Nearly 25% reported significant drinking history (3+ drinks/day). Males had an average of 18 lifetime sexual partners, and females had 7 partners. Eight patients reported >100 sexual partners. CONCLUSIONS: HPV+ OPSCC was more prevalent in white males with a high number of lifetime sexual partners, as expected. Careful evaluation revealed other findings of significance that are not generally associated with this population. Half of our patients had significant historical tobacco and alcohol consumption. One quarter of patients had a history of another malignancy. These findings highlight the importance of taking a comprehensive history when determining appropriate treatment or designing future de-escalation trials in HPV+ OPSCC.

Machine Learning Accurately Predicts Short-Term Outcomes Following Open Reduction and Internal Fixation of Ankle Fractures.

Ankle fractures are common orthopedic injuries with favorable outcomes when managed with open reduction and internal fixation (ORIF). Several patient-related risk factors may contribute to poor short-term outcomes, and machine learning may be a valuable tool for predicting outcomes. The objective of this study was to evaluate machine-learning algorithms for accurately predicting short-term outcomes after ORIF for ankle fractures. The Nationwide Inpatient Sample and Nationwide Readmissions Database were queried for adult patients ≥18 years old who underwent ORIF of an ankle fracture during 2013 or 2014. Morbidity and mortality, length of stay >3 days, and 30-day all-cause readmission were the outcomes of interest. Two machine-learning models were created to identify patient and hospital characteristics associated with the 3 outcomes. The machine learning models were evaluated using confusion matrices and receiver operating characteristic area under the curve values. A total of 16,501 cases were drawn from the Nationwide Inpatient Sample and used to assess morbidity and mortality and length of stay >3 days, and 33,504 cases were drawn from the Nationwide Readmissions Database to assess 30-day readmission. Older age, Medicaid, Medicare, deficiency anemia, congestive heart failure, chronic lung disease, diabetes, hypertension, and renal failure were the variables associated with a statistically significant increased risk of developing all 3 adverse events. Logistic regression and gradient boosting had similar area under the curve values for each outcome, but gradient boosting was more accurate and more specific for predicting each outcome. Our results suggest that several comorbidities may be associated with adverse short-term outcomes after ORIF of ankle fractures, and that machine learning can accurately predict these outcomes.

Identifying Risk Factors for 30-Day Readmissions After Triple Arthrodesis Surgery.

Rigid flatfoot deformity is a debilitating condition that can be managed by triple arthrodesis surgery. Triple arthrodesis has the potential to restore health-related quality of life, but it is also associated with several complications. Few studies have examined the 30-day readmission rates after triple arthrodesis. The objective of this study was to investigate risk factors for 30-day all-cause readmissions after triple arthrodesis. The nationwide readmission database was queried from 2013. By using International Classification of Disease, Ninth Revision, procedure codes, all triple arthrodesis procedures were identified. Demographic factors, comorbidities, insurance status, and hospital characteristics were statistically compared between patients who experienced a 30-day readmission and those who did not. Multivariable logistic regression was used to identify independent risk factors for 30-day readmission. Overall, 1916 triple arthrodesis cases were identified. The overall 30-day readmission rate after triple arthrodesis was 4.6%. Univariate analysis revealed a statistically higher proportion of patients with electrolyte abnormalities (13.8% vs 4.6%; p < .01) in the patients who were readmitted within 30 days compared with those who were not. Multivariable analysis demonstrated Medicaid insurance, relative to private insurance, as the only statistically significant predictor of 30-day readmission with an odds ratio of 4.43 (p < .05). These results suggest that patients of lower socioeconomic status may be at a greater risk for development of a short-term readmission after triple arthrodesis surgery. These findings are important for surgeon and patient communication, counseling, and postoperative care when choosing to pursue triple arthrodesis surgery.

Comparing 30-day all-cause readmission rates between tibiotalar fusion and total ankle replacement.

BACKGROUND: End-stage ankle arthritis is a debilitating condition that negatively impacts patient quality of life. Tibiotalar fusion and total ankle replacement are treatment options for managing ankle arthritis. Few studies have examined short term readmission rates of these two procedures. The objective of this study was compare all-cause 30-day readmission rates between patients undergoing tibiotalar fusion vs. total ankle replacement. METHODS: This study queried the Nationwide Readmission Database (NRD) from 2013-2014 and used international classification of disease, 9th revision (ICD-9) procedure codes to identify all patients who underwent a tibiotalar fusion or a total ankle replacement. Comorbidities, insurance status, hospital characteristics, and readmission rates were statistically compared between the two cohorts. Risk factors were then identified for 30-day readmission. RESULTS: A total of 5660 patients were analyzed with 2667 in the tibiotalar fusion cohort and 2993 in the total ankle replacement cohort. Univariate analysis revealed that the readmission rate after tibiotalar fusion (4.4%) was statistically greater than after total ankle replacement (1.4%). Multivariable regression analysis indicated that deficiency anemia (OR 2.18), coagulopathy (OR 3.51), renal failure (OR 2.83), other insurance relative to private (OR 3.40), and tibiotalar fusion (OR 2.51) were all statistically significant independent risk factors for having a readmission within 30-days. CONCLUSIONS: These findings suggest that during the short-term period following discharge from the hospital, patients who received a tibiotalar fusion are more likely to experience a 30-day readmission. These findings are important for decision making when a surgeon encounters a patient with end stage ankle arthritis. LEVEL OF EVIDENCE: Level III, cohort study.