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Background: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Testing for plasma tumor tissue modified viral (TTMV)-HPV DNA has emerged as a biomarker strategy for post-treatment surveillance to identify recurrent disease. We aimed to understand the prognostic and predictive potential of TTMV-HPV DNA when monitoring patients who had developed recurrent or metastatic (R/M) HPV+OPSCC., Methods: This retrospective observational cohort study included 80 patients from 4 academic centers with R/M HPV+OPSCC if they had ≥ 1 plasma TTMV-HPV DNA test obtained at any point during their R/M disease course. Physician-reported clinical data and treatment history were captured in a centralized database, along with investigator-assessed response to therapy and survival. Descriptive statistics and non-parametric tests of association were employed along with survival analyses (Kaplan-Meier method)., Results: Sixteen (20 %) patients had ≥ 5 test results over time. Consecutive TTMV-HPV DNA tests were performed a median of 73 days apart. Median TTMV-HPV DNA scores were higher with an increasing per-patient number of metastatic sites (<2 vs. 2+; p < 0.01). Score changes over time were influenced by R/M treatment modality and became undetectable in 67 % (12/18) of patients who achieved a complete response to R/M therapy. Patients with detectable scores at last follow-up had significantly worse survival compared with those who were undetectable (log-rank test, p < 0.01)., Conclusions: TTMV-HPV DNA appears useful as a prognostic tool for monitoring response to therapy in the R/M setting. In the future, TTMV-HPV DNA could be explored as an exploratory clinical trial endpoint in the metastatic setting., Competing Interests: Declaration of competing interest CDF and JJ are employees or contractors for Naveris, Inc. with stock holdings. GH and MRP receive research support from, and have consulted for Naveris in the past, unrelated to the work presented here. ER receives in-kind support from Naveris only. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Traditionally, patients undergoing free flap reconstruction for oral cavity defects have been given nothing by mouth for 6-14 days post-operatively due to concern for orocutaneous fistula development., Methods: Multiple databases were screened for studies assessing the rate of orocutaneous fistula formation in early (≤5 days) versus late (>5 days) feeding groups following oral cavity free flap reconstruction. Fixed- and random-effects meta-analyses were used., Results: One randomized controlled trial, one prospective cohort, and three retrospective cohort studies were included. The early feeding group displayed no significant increase in orocutaneous fistula formation (RD = -0.02, p = 0.06) or free flap failure (RD = -0.01, p = 0.39), with a significantly shorter hospital length of stay (mean difference [days] = -2.43, p < 0.01)., Conclusions: While further prospective trials are necessary, initiation of oral intake before post-operative day 5 may be appropriate in properly selected patients following oral reconstruction., (© 2024 Wiley Periodicals LLC.)

Circulating tumor human papillomavirus DNA (ctHPVDNA) testing using digital-droplet polymerase chain reaction (PCR) detects fragments of tumor-modified human papillomavirus (HPV) in the plasma of patients with HPV-associated head and neck squamous cell carcinomas (HNSCCs). Its impact on tumor surveillance and primary diagnosis is limited by unresolved issues relating to sensitivity and specificity. The study population consisted of patients with HNSCC who had undergone ctHPVDNA testing. HPV status was determined by p16 immunohistochemistry and PCR-HPV genotyping on the tumor samples. For discrepant cases (HPV-positive/ctHPVDNA-negative), HPV status was confirmed by RNA in situ hybridization and, when possible, targeted single-nucleotide polymorphisms genotyping. A total of 167 patients had ctHPVDNA testing, and 141 tumors were HPV positive by p16 immunohistochemistry and PCR genotyping. Genotypes included types 16 (91.5%), 33 (4.3%), 35 (2.1%), and 18 (2.1%). ctHPVDNA was detected in 133 (94.3%) of HPV-positive HNSCCs but in none of the HPV-negative HNSCCs. Four of the 5 p16-positive cases that were negative by PCR and ctHPVDNA were positive by RNA in situ hybridization, and in 2 of these cases, rare high-risk genotypes were identified. ctHPVDNA had a sensitivity of 91.7%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 63.6%. The likelihood that patients with HPV-positive HNSCC have detectable ctHPVDNA is high. Non-HPV16 genotypes contribute to discrepancies but only in a small subset of cases. This finding validates ongoing efforts to use ctHPVDNA as a surveillance tool, and even as a primary diagnostic assay in patients presenting with masses in the neck and/or oropharynx., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance., Experimental Design: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154)., Results: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively., Conclusions: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only sequencing, which were based on an analysis of 17 152 cancers., Methods: We analysed an expanded dataset including 49 264 paired tumour-normal samples. We applied filters to tumour-detected variants based on variant allele frequency, predicted pathogenicity and population variant frequency. For 58 cancer-susceptibility genes, we then examined the proportion of filtered tumour-detected variants of true germline origin [germline conversion rate (GCR)]. We conducted subanalyses based on the age of cancer diagnosis, specific tumour types and 'on-tumour' status (established tumour-gene association)., Results: Analysis of 45 472 nonhypermutated solid malignancy tumour samples yielded 21 351 filtered tumour-detected variants of which 3515 were of true germline origin. 3.1% of true germline pathogenic variants were absent from the filtered tumour-detected variants. For genes such as BRCA1, BRCA2 and PALB2, the GCR in filtered tumour-detected variants was >80%; conversely for TP53, APC and STK11 this GCR was <2%., Conclusion: Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2, (iii) definition of a set of seven 'most actionable' cancer-susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6 and RET) in which germline follow-up is recommended regardless of tumour type., Competing Interests: Disclosure AGe reports receipt of honoraria for participation in advisory board from AstraZeneca, receipt of honoraria as invited speaker from GSK and receipt of honoraria for performing editorial and research review from Roche. HH reports receipt of honoraria for participation in advisory board from AstraZeneca and nonfinancial interest for leadership role as Chair of the UK Cancer Genetics Group. KS reports receipt of honoraria for providing expert testimony from Axa-PPP and receipt of honoraria as invited speaker from Everything Genetic, Merck, Pfizer. AK reports receipt of honoraria as invited speaker from AstraZeneca, receipt of honoraria for professional service agreement with HCA Healthcare and owning stocks/shares in Perci Health. CBW reports receipt of honoraria for participation in advisory board from BMS, Celgene, Rafael, RedHill, Roche, Shire/Baxalta; receipt of honoraria for providing expert testimony from Janssen; receipt of honoraria as invited speaker from Amgen, Bayer, BMS, Celgene, Chugai, Falk, GSK, Janssen, Merck, MSD, Roche, Servier, Sirtex and Taiho; receipt of travel support from Bayer, Celgene, RedHill, Roche, Servier and Taiho; receipt of personal and institutional research grant with no financial interest from Roche and nonfinancial interest as officer in the AIO – Arbeitsgemeinschaft Internistische Onkologie. EC reports receipt of honoraria for participation in advisory board from Astellas, AstraZeneca, Bayer, Janssen, MSD and Pfizer; receipt of honoraria as invited speaker from Astellas, AstraZeneca, Clovis, Janssen and Pfizer; receipt of honoraria for writing engagement from Pfizer; institutional funding from AstraZeneca and Pfizer; research grants to institution from Bayer and Janssen and institutional financial interest as local principal investigator from Janssen and Pfizer. JR reports receipt of honoraria for participation in advisory board from Ellipses Pharma, iOnctura SA, Kelun Pharmaceuticals/KLUS Pharma, Molecular Partners and Peptomyc; receipt of institutional research grant with no financial interest for clinical research from Aadi Bioscience, Amgen, Bicycle Therapeutics, BioMed Valley Discoveries, Cellestia, Curis, Deciphera, ForeBio, Hutchison MediPharma, Ideaya, Linnaeus Therapeutics, Loxo Oncology, Merus, Mirati, Nuvation, Roche Pharmaceuticals, Taiho and Tango Therapeutics; receipt of institutional research grant with no financial interest for research funding/clinical research from Hummingbird and Yingli; receipt of institutional research grant with no financial interest for research funding from Vall d’Hebron Institute of Oncology/Cancer Core Europe; receipt of institutional nonfinancial interest for clinical research from Bayer, BioAtla, CytomX, Genmab, GlaxoSmithKline, Kelun-Biotech, Novartis, Pfizer, Spectrum Pharmaceuticals, Symphogen and Takeda-Millennium; receipt of institutional financial interest for research funding from Black Diamond, Blueprint Medicines, Merck Sharp & Dohme; receipt of consultancy fees from Boxer Capital, LLC and Tang Advisors, LLC; receipt of travel reimbursement from the European Society for Medical Oncology and reports academic collaborations with Chinese University of Hong Kong, VHIO/Ministerio De Empleo Y Seguridad Social. JM reports receipt of honoraria for participation in advisory board from Amgen, AstraZeneca, Clovis Oncology, Janssen and Roche; receipt of honoraria as invited speaker from AstraZeneca, Guardant Health and MSD; no financial interest for serving as a steering committee member from AstraZeneca and Pfizer Oncology; receipt of research grant to institution from AstraZeneca and Pfizer Oncology and nonfinancial interest for receipt of product samples, access to drugs in early development for preclinical testing from AstraZeneca. GJB reports receipt of honoraria as invited speaker from AstraZeneca. MFB reports receipt of honoraria for participation in advisory board from Eli Lilly and PetDx. CT reports receipt of honoraria for participation in advisory board from Roche and receipt of honoraria as invited speaker from AstraZeneca. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To characterize and analyze variation in price markup of seven common otologic surgeries by procedure and geographic region., Study Design: Retrospective Analysis of the Centers for Medicare and Medicaid Services database of 2017 Medicare Provider Utilization and Payment Public File., Setting: Inpatient and outpatient centers delivering Medicare-reimbursed services., Patients: Full sample of patients undergoing procedures with Medicare fee-for-service final action claims during 2017., Interventions: Seven procedures (myringotomy, tympanoplasty, mastoidectomy, tympanomastoidectomy stapedotomy/stapedectomy, cochlear implant, bone-anchored hearing aid)., Main Outcome Measures: Markup ratio (MUR) is defined as the ratio of total charges to Medicare-allowable-costs; Variation in MUR was measured using coefficient of variation (CoV)., Results: Among all providers, the median MUR was 2.4 (interquartile range: 1.9-3.1). MUR varied significantly by procedure, from 2.3 for myringotomy to 8.7 for mastoidectomy (p < 0.01). MUR also varied significantly within procedure, with the least variation found in myringotomy (CoV = 0.46), and the greatest in cochlear implants (CoV = 0.92). Using the national average as baseline, MUR varied 71% between states, ranging from 1.75 to 6.24. Within the same state, significant variation was also noted, varying by 4% (CoV = 0.04) in Montana compared with 138% (CoV = 1.38) in Pennsylvania. MUR was not significantly correlated with patient comorbidity or Centers for Medicare and Medicaid Services risk scores., Conclusions: There was significant variation in the price of otologic surgery across geographic regions and procedures. The MUR for otology is lower or comparable to that reported in other surgical fields., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Background: Donor site pain after osteocutaneous free flap surgery contributes to postoperative morbidity and impairs recovery. We evaluated the efficacy of local infusion of ropivacaine for treating donor-site pain after surgery., Methods: We conducted a randomized, double-blind, placebo-controlled trial of patients undergoing osteocutaneous fibula or scapular tip free flaps for head and neck reconstruction at Mount Sinai Hospital. Patients were randomized to receive local infusion of ropivacaine or saline. We compared Visual Analog Scale pain scores for donor-site specific pain 48 hours after surgery., Results: There were 8 fibular free flap and 10 scapular free flap reconstructions. Average donor-site pain scores were 29 ± 22 and 31 ± 28 mm (P = .88) for placebo and ropivacaine arms, respectively. The trial was stopped after the planned interim analysis for futility of the intervention., Conclusions: Local infusion of ropivacaine did not affect donor-site specific pain scores in this population. ClinicalTrials.gov Identifier: NCT03349034., (© 2021 Wiley Periodicals LLC.)

Objective: To evaluate the utility of lymph node ratio (LNR) as a prognostic factor for survival and recurrence in surgically treated patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC)., Study Design: Retrospective cohort study., Methods: In this retrospective cohort study of a tertiary healthcare system in a major metropolitan area, we reviewed 169 consecutive patients with HPV-related OPSCC treated using transoral robotic surgery. Univariable and multivariable Cox proportional hazards regression analysis with stratified models were used to compare LNR with other traditional clinicopathologic risk factors forrecurrence and survival. An LNR cutoff was found using the minimal P approach., Results: Multivariable Cox regression models showed that each additional percentage increase in LNR corresponded to an adjusted hazard ratio (HR) of 1.04 (confidence interval [CI] 1.02-1.07). LNR was more significant when adjusted for adequate lymph node yield of ≥ 18 nodes (HR 5.05, 95% confidence interval [CI] 1.38-18.47). The minimal P generated cutoff point at LNR ≥ 17% demonstrated a HR 4.34 (95% CI 1.24-15.2) for disease-free survival., Conclusion: For HPV-related OPSCC, continuous LNR and an LNR threshold of 17% could be helpful in identifying recurrent disease in addition to measures such as lymph node number alone., Level of Evidence: 4., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To determine independent risk factors for 30-day readmission, prolonged length of stay (PLOS), and discharge to a rehabilitation facility for those with malignant otitis externa., Methods: Retrospective cohort study of patients hospitalized with malignant otitis externa (International Classification of Diseases, 9th edition, code 380.14) in the Nationwide Readmissions Database (2013-2014). Overall and disease-specific complication and mortality data were analyzed using chi-squared and multivariate analysis., Results: There were 1267 cases of malignant otitis externa extracted. A PLOS of ≥8 days (90th percentile) was found in 14.2% (n = 180) of patients, and 13.7% (n = 174) were discharged to a facility. Patients were readmitted within 30 days at a rate of 12.5% (n = 159). The overall rates of uncomplicated and complicated diabetes were found to be 42.1% and 17.8%, respectively. Factors independently associated with PLOS included undergoing a surgical procedure (odds ratio [OR] 2.08, P < .001), and having central nervous system complications (OR 3.21, P < .001). Independent risk factors for disposition to a facility included nutritional deficiency (OR 1.91, P = .029), PLOS (OR 4.61, P < .001), and age 65-79 years (OR 6.57, P = .001). Readmission was independently linked to PLOS (OR 3.14, P < .001). Diabetes was not an independent risk factor for any outcome., Conclusions: Thirty-day readmission, PLOS, and ultimate discharge to a rehabilitation facility were common and closely intertwined. Despite the classic association between diabetes and malignant otitis externa, diabetes was not an independent risk factor for any of our outcomes., Level of Evidence: 4 Laryngoscope, 130:2220-2228, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To determine risk factors for readmission, prolonged length of stay, and discharge to a rehabilitation facility in patients with acute mastoiditis. Trends in treatment and complication rates were also examined., Study Design: Retrospective cohort study., Setting: Nationwide Readmissions Database (2013, 2014)., Patients: Pediatric and adult patients in the Nationwide Readmissions Database with a primary diagnosis of acute mastoiditis., Interventions: Medical treatment, surgical intervention., Outcome Measures: Rates of and risk factors for readmission, prolonged length of stay, and discharge to a rehabilitation facility. Procedure and complication rates were also examined., Results: Four thousand two hundred ninety-five pediatric and adult admissions for acute mastoiditis were analyzed. The overall rates of readmission, prolonged length of stay, and discharge to a rehabilitation facility were 17.0, 10.4, and 10.2%, respectively. Children 4 to 17 years of age had the highest rates of intracranial complications, and children ≤3 years were most likely to undergo operative intervention. Any procedure was performed in 31.2% of cases, and undergoing myringotomy or mastoidectomy was associated with lower rates of readmission but higher rates of prolonged length of stay. Those with intracranial complications and subperiosteal abscesses had the highest surgical intervention rates., Conclusions: Readmission, prolonged length of stay, and discharge to a rehabilitation facility are common in patients with acute mastoiditis with various sociodemographic and disease-related risk factors. While once a primarily surgical disease, a minority of patients in our cohort underwent procedures. Undergoing a surgical procedure was protective against readmission but a risk factor for prolonged length of stay.

Objective: Although the prognostic role of human papilloma virus (HPV) status in oropharyngeal head and neck squamous cell carcinoma (SCC) is well established, growing evidence shows that there may be a prognostic role for HPV status in hypopharyngeal SCC. The objective of this study was to determine the prognostic role of HPV status in hypopharyngeal SCC., Methods: We performed a retrospective, population-based analysis of 1934 adult patients with HNSCC diagnosed between 2010-2016 and treated with a combination of surgery and/or radiotherapy, with or without chemotherapy, and a subset of 641 patients with hypopharyngeal SCC and known HPV status included in the Surveillance, Epidemiology, and End Results (SEER) Head and Neck with HPV Status Database. Patient data were used to determine the adjusted 2-year cancer-specific survival (CSS) and overall survival (OS) for the entire cohort and the specific subgroup of hypopharyngeal cancer patients with known HPV status., Results: Of the 1934 hypopharynx SCC cases, HPV status was unknown in 1294 (66.9%), and 167 (8.6%) were HPV positive; among hypopharynx cases with known HPV status, 21.6% were HPV positive. In models adjusting for sex, age, race/ethnicity, marital status and stage, patients with HPV-positive hypopharyngeal tumors had improved CSS compared with patients with HPV-negative tumors (CSS: HR: .57, 95% CI = .38 to .86, P = .008; OS: HR: .49, 95% CI = .34 to .71, P = <.001)., Conclusion: Our findings in a large cohort of hypopharyngeal SCC with known HPV status and cancer-specific survival support the hypothesis that HPV has a prognostic role in hypopharyngeal cancer. Consideration should be given to increased testing for HPV in hypopharyngeal SCC., Level of Evidence: 4., Competing Interests: Dr. Wisnivesky has received consulting honorarium from Sanofi, Galaxosmithkline, and Banook and research grants from Sanofi and Quorum unrelated to the manuscript. All other authors have no financial conflicts of interest to disclose., (© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Purpose: To determine the risk factors for unanticipated readmission, prolonged index admission, and discharge to a facility after vestibular schwannoma surgery., Materials and Methods: Retrospective cohort study of those undergoing surgery for vestibular schwannoma in the Nationwide Readmissions Database (2013-2014). Main outcome measures included readmission rate, length of stay, discharge destination., Results: There were 4585 cases identified. The overall unanticipated readmission rate was 8.1%, and 9.1% had a prolonged length of stay (PLOS) of ≥7 days. Mean and median LOS were 4.63 and 4.00 days, respectively, and >90% of patients were discharged after 7 days. Disposition to a facility occurred in 6.7% of cases. Teaching hospitals were protective against unintended readmission (odds ratio [OR] 0.44, p < .001). Major functional loss was associated with PLOS (OR 12.55, p < .001). High volume centers were associated with decreased risk of PLOS (OR 0.46, p < .001) and facility discharge (OR 0.68, p < .001). The most common readmission diagnoses included "other nervous system complications" (n = 128), cerebrospinal fluid leak (n = 71), "other postoperative infection" (n = 61), and meningitis (n = 59)., Conclusions: Unanticipated readmission and prolonged LOS following vestibular schwannoma surgery are common, with varied sociodemographic, hospital, and patient factors independently associated with each. Further studies are needed to investigate targeted interventions aimed at minimizing readmission and prolonged LOS using the factors outlined above., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Concurrent chemoradiotherapy is an established component of the nonoperative management of locally advanced head and neck squamous cell carcinoma (HNSCC), but the standard dose of 100 mg/m2 cisplatin every 3 weeks is associated with clinically significant toxicity. Interest in a more tolerable regimen has led to the widespread use of weekly lower dose cisplatin, but few randomized trials have compared these approaches., Methods: We examined outcomes of patients with stage III-IVb HNSCC treated with definitive intent chemoradiotherapy using either high-dose cisplatin (HDC) or low-dose cisplatin (LDC), using population-based Veterans Affairs data. In an intent-to-treat analysis, patients were assigned to the HDC vs LDC group according to the dose of their first cycle. Variables potentially influencing treatment decisions including cancer site, stage, smoking/alcohol use, and comorbidities were used to generate propensity scores (PS) for the use of HDC. We compared overall survival (OS) by treatment group using Cox regression, adjusting for PS. We then determined the risk of toxicities using PS-adjusted logistic regression., Results: A total of 2901 patients were included in the analysis; 2200 received HDC (mean initial dose 100 mg/m2). The mean initial dose of LDC was 40 mg/m2. After PS adjustment, HDC was not associated with improved OS over LDC (hazard ratio = 0.94, 95% confidence interval = 0.80 to 1.04). Adjusting for PS, HDC was associated with an increased risk of acute kidney injury, neutropenia, dehydration/electrolyte disturbance, and hearing loss., Conclusion: In this large, population-based study of US military veterans, LDC was associated with similar survival to HDC in the nonoperative definitive management of locally advanced HNSCC of the oral cavity, oropharynx, and hypopharynx/larynx. HDC was associated with statistically significantly more toxicity than LDC. Adoption of LDC may reduce toxicity burden while maintaining OS., (Published by Oxford University Press 2018.)

Background: Transsphenoidal pituitary surgery has evolved into a safe procedure with shorter hospitalizations, yet unplanned readmissions remain a quality measure for which there is a paucity of data. We sought to examine rates, timing, etiologic factors, and costs surrounding readmission after transsphenoidal pituitary surgery., Methods: The Nationwide Readmissions Database (NRD) was queried for patients who underwent transsphenoidal pituitary between January 2013 and November 2013. Patient, procedure, admission, and hospital-level characteristics were compared for patients with and without unplanned 30-day readmission. Multivariate logistic regression was used to identify readmission predictors. A total of 8546 patients were included in this retrospective study., Results: A total of 8546 patients with a median age of 54 years and female predominance were identified, with 742 patients experiencing at least 1 unplanned readmission within 30 days of index admission. Hypertension, hypothyroidism, diabetes, and obesity were common comorbidities among readmitted patients. Readmission was most frequently because of nervous system complications, followed by neurohypophyseal or electrolyte disorders, cerebrospinal fluid leak, hemorrhage, and meningitis. Median length and cost of stay of index admission was greater in the readmission group (p < 0.001). Fluid and electrolyte disorders as well as neurologic disease (most commonly epilepsy or convulsions) present on initial admission were predictive of length of initial stay and readmission (p < 0.001). Median readmission cost was $7723 and was expected to occur within 7 days., Conclusion: Approximately 8.7% of patients undergoing transsphenoidal pituitary surgery experience an unplanned readmission within 30 days of discharge. Risk factors identified should be considered to reduce preventable readmissions and identify medically complex patients., (© 2018 ARS-AAOA, LLC.)

Objectives/hypothesis: Examine rates of readmission after total laryngectomy and determine primary etiologies, timing, and risk factors for unplanned readmission., Study Design: Retrospective cohort study., Methods: The Nationwide Readmissions Database was queried for patients who underwent total laryngectomy between January 2013 and November 2013. Patient-, procedure-, admission-, and institution-level characteristics were compared for patients with and without unplanned 30-day readmission. Outcomes of interest included rates, etiology, and timing of readmission. Multivariate logistic regression was used to identify predictors of 30-day readmission., Results: There were 2,931 total laryngectomies performed in 2013 with an unplanned readmission rate of 17.5%. Postoperative fistula accounted for 13.7% of readmissions. The odds of readmission were elevated for patients undergoing concurrent procedures, including primary tracheoesophageal fistulization (adjusted odds ratio [aOR]: 2.44, 95% confidence interval [CI]: 1.15-5.18, P = .02) and/or pedicle graft or flap procedures (aOR: 1.73, 95% CI: 1.13-2.66, P = .01). Additionally, patients with comorbid coagulopathy (aOR: 3.04, 95% CI: 1.13-8.22, P = .03), liver disease (aOR: 2.48, 95% CI: 1.08-5.71, P = .03), and valvular heart disease (aOR: 3.18, 95% CI: 1.20-8.41, P = .02) had increased risk for unplanned 30-day readmission. Private insurance and longer lengths of stay were associated with decreased odds of readmission., Conclusions: Nearly one-fifth of total laryngectomy patients are readmitted to the hospital within 30 days of discharge. Risk factors identified in this nationally representative cohort should be carefully considered during the postoperative period to reduce preventable readmissions after total laryngectomy., Level of Evidence: 2c Laryngoscope, 1842-1850, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

The number of patients with advanced heart failure receiving left ventricular assist device (LVAD) implantation has increased dramatically over the last decade. There are limited data available about the nationwide trends of complications leading to readmissions after implantation of contemporary devices. Patients who underwent LVAD implantation from January 2013 to December 2013 were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 37.66 from the Healthcare Cost and Utilization Project's National Readmission Database. The top causes of unplanned 30-day readmission after LVAD implantation were determined. Survey logistic regression was used to analyze the significant predictors of readmission. In 2013, there were 2,235 patients with an LVAD implantation. Of them, 665 (29.7%) had at least 1 unplanned readmission within 30 days, out of which 289 (43.4%) occurred within 10 days after discharge. Implant complications (14.9%), congestive heart failure (11.7%), and gastrointestinal bleeding (8.4%) were the top 3 diagnoses for the first readmission and accounted for more than a third of all readmissions. Significant predictors of readmissions included a prolonged length of stay during the index admission, Medicare insurance, and discharge to short-term facility. In conclusion, despite increased experience with LVADs, unplanned readmissions within 30 days of implantation remain significantly high., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective To examine rates of readmission after parathyroidectomy in patients with chronic kidney disease and determine primary etiologies, timing, and risk factors for these unplanned readmissions. Study Design Retrospective cohort study. Setting Nationwide Readmissions Database. Subjects and Methods The Nationwide Readmissions Database was queried for parathyroidectomy procedures performed in patients with chronic kidney disease between January 2013 and November 2013. Patient-, admission-, and hospital-level characteristics were compared for patients with and without at least 1 unplanned 30-day readmission. Outcomes of interest included rates, etiology, and timing of readmission. Multivariate logistic regression was used to identify predictors of 30-day readmission. Results There were 2756 parathyroidectomies performed in patients with chronic kidney disease with an unplanned readmission rate of 17.2%. Hypocalcemia/hungry bone syndrome accounted for 40% of readmissions. Readmissions occurred uniformly throughout the 30 days after discharge, but readmissions for hypocalcemia/hungry bone syndrome peaked in the first 10 days and decreased over time. Weight loss/malnutrition at time of parathyroidectomy and length of stay of 5 to 6 days conferred increased risk of readmission with adjusted odds ratios (aOR) of 3.31 (95% confidence interval [CI], 1.55-7.05; P = .002) and 1.87 (95% CI, 1.10-3.19; P = .02), respectively. Relative to primary hyperparathyroidism, parathyroidectomies performed for secondary hyperparathyroidism (aOR, 2.53; 95% CI, 1.07-5.95; P = .03) were associated with higher risk of readmission. Conclusion Postparathyroidectomy readmission rates for patients with chronic kidney disease are nearly 5 times that of the general population. Careful consideration of postoperative care and electrolyte management is crucial to minimize preventable readmissions in this vulnerable population.

Objective: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D., Research Design and Methods: We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort. We selected SGLT inhibitor users and nonusers (patients with T2D without SGLT2 inhibitor prescription). We determined AKI by the KDIGO (Kidney Disease: Improving Global Outcomes) definition (AKI KDIGO ). We performed 1:1 nearest-neighbor propensity matching and calculated unadjusted hazard ratios (HRs) and adjusted HRs (aHRs; accounting for covariates poorly balanced) for AKI in primary and sensitivity analyses., Results: We identified 377 SGLT2 inhibitor users and 377 nonusers in the Mount Sinai cohort, of whom 3.8 and 9.7%, respectively, had an AKI KDIGO event over a median follow-up time of 14 months. The unadjusted hazards of AKI KDIGO were 60% lower in users (HR 0.4 [95% CI 0.2-0.7]; P = 0.01), which was unchanged (aHR 0.4 [95% CI 0.2-0.7]; P = 0.004) postadjustment. Similarly, we identified 1,207 SGLT2 inhibitor users and 1,207 nonusers in the Geisinger cohort, of whom 2.2 and 4.6% had an AKI KDIGO event. AKI KDIGO unadjusted hazards were lower in users (HR 0.5 [95% CI 0.3-0.8]; P < 0.01) with modest attenuation postadjustment for covariates (aHR 0.6 [95% CI 0.4-1.1]; P = 0.09). These estimates did not qualitatively change across several sensitivity analyses., Conclusions: Our findings do not suggest an increased risk of AKI associated with SGLT2 inhibitor use in patients with T2D in two large health systems., (© 2017 by the American Diabetes Association.)

Background: The number of patients with end-stage renal disease (ESRD) on peritoneal dialysis (PD) has increased by over 30% between 2007 and 2014. The Centers for Medicare and Medicaid has identified readmissions in ESRD patients to be a quality measure; however, there is a paucity of studies examining readmissions in PD patients., Methods: Utilizing the National Readmission Database for the year 2013, we aimed to determine reasons for admission, the associated rates of unplanned readmission and independent predictors of readmissions in PD patients., Results: The top 10 reasons for initial hospitalization were implant/PD catheter complications (23.22%), hypertension (5.47%), septicemia (5.18%), diabetes mellitus (DM) (5.12%), complications of surgical procedures/medical care (3.50%), fluid and electrolyte disorders (4.29%), peritonitis (3.76%), congestive heart failure (3.25%), pneumonia (2.90%) and acute myocardial infarction (AMI) (2.01%). The overall 30-day readmission rate was 14.6%, with the highest rates for AMI (21.8%), complications of surgical procedure/medical care (19.6%) and DM (18.4%). Concordance among the top 10 reasons for index admission and readmission was 22.6% and varied by admission diagnosis. Independent predictors of readmissions included age 35-49 years compared with 18-34 years [adjusted odds ratio (aOR) 1.35; 95% confidence interval (CI) 1.09-1.68; P  = 0.006], female gender (aOR 1.27; 95% CI 1.12-1.44; P < 0.001), and comorbidities including liver disease (aOR 1.39; 95% CI 1.07-1.81; P  = 0.01), peripheral vascular disease (aOR 1.33; 95% CI 1.14-1.56; P  < 0.001) and depression (aOR 1.22; 95% CI 1.00-1.48; P  = 0.04)., Conclusions: This study demonstrates the most common reasons for admission and readmissions in PD patients and several comorbidities that are predictive of readmissions. Targeted interventions towards these patients may be of benefit in reducing readmission in this growing population.

Background: The epidemiology and outcomes of acute kidney injury (AKI) in prevalent non-renal solid organ transplant recipients is unknown., Methods: We assessed the epidemiology of trends in acute kidney injury (AKI) in orthotopic cardiac and liver transplant recipients in the United States. We used the Nationwide Inpatient Sample to evaluate the yearly incidence trends (2002 to 2013) of the primary outcome, defined as AKI requiring dialysis (AKI-D) in hospitalizations after cardiac and liver transplantation. We also evaluated the trend and impact of AKI-D on hospital mortality and adverse discharge using adjusted odds ratios (aOR)., Results: The proportion of hospitalizations with AKI (9.7 to 32.7% in cardiac and 8.5 to 28.1% in liver transplant hospitalizations; p trend <0.01) and AKI-D (1.63 to 2.33% in cardiac and 1.32 to 2.65% in liver transplant hospitalizations; p trend <0.01) increased from 2002-2013. This increase in AKI-D was explained by changes in race and increase in age and comorbidity burden of transplant hospitalizations. AKI-D was associated with increased odds of in hospital mortality (aOR 2.85; 95% CI 2.11-3.80 in cardiac and aOR 2.00; 95% CI 1.55-2.59 in liver transplant hospitalizations) and adverse discharge [discharge other than home] (aOR 1.97; 95% CI 1.53-2.55 in cardiac and 1.91; 95% CI 1.57-2.30 in liver transplant hospitalizations)., Conclusions: This study highlights the growing burden of AKI-D in non-renal solid organ transplant recipients and its devastating impact, and emphasizes the need to develop strategies to reduce the risk of AKI to improve health outcomes.

Background/aims: Depression is common in patients with end-stage renal disease (ESRD) on hemodialysis (HD). Although, depression is associated with mortality, the effect of depression on in-hospital outcomes has not been studied as yet., Methods: We analyzed the National Inpatient Sample for trends and outcomes of hospitalizations with depression in patients with ESRD., Results: The proportion of ESRD hospitalizations with depression doubled from 2005 to 2013 (5.01-11.78%). Hospitalized patients on HD with depression were younger (60.47 vs. 62.70 years, p < 0.0001), female (56.93 vs. 47.81%, p < 0.0001), white (44.92 vs. 34.01%, p < 0.0001), and had higher proportion of comorbidities. However, there was a statistically significant lower risk of mortality in HD patients within the top 5 reasons for admissions., Conclusion: There were significant differences in demographics and comorbidities for hospitalized HD patients with depression. Depression was associated with an increased rate of adverse effects in discharged patients, and decreased in-hospital mortality., (© 2017 S. Karger AG, Basel.)

Candida glabrata is an important human fungal pathogen whose incidence continues to rise. Because many clinical isolates are resistant to azole drugs, the drugs of choice to treat such infections are members of the echinocandin family, although there are increasing reports of resistance to these drugs as well. In efforts to better understand the genetic changes that lead to altered responses to echinocandins, we screened a transposon-insertion library of mutants for strains to identify genes that are important for cellular responses to caspofungin, a member of this drug family. We identified 16 genes that, when disrupted, caused increased tolerance, and 48 genes that, when disrupted, caused increased sensitivity compared to the wild-type parental strain. Four of the genes identified as causing sensitivity are orthologs of Saccharomyces cerevisiae genes encoding proteins important for the cell wall integrity (CWI) pathway. In addition, several other genes are orthologs of the high affinity Ca(2+) uptake system (HACS) complex genes. We analyzed disruption mutants representing all 64 genes under 33 different conditions, including the presence of cell wall disrupting agents and other drugs, a variety of salts, increased temperature, and altered pH. Further, we generated knockout mutants in different genes within the CWI pathway and the HACS complex, and found that they too exhibited phenotypes consistent with defects in cell wall construction. Our results indicate that small molecules that inhibit the CWI pathway, or that the HACS complex, may be an important means of increasing the efficacy of caspofungin., (Copyright © 2016 Rosenwald et al.)

Type II restriction endonucleases require metal ions to specifically cleave DNA at canonical sites. Despite the wealth of structural and biochemical information, the number of Mg(2+) ions used for cleavage by EcoRV, in particular, at physiological divalent ion concentrations has not been established. In this work, we employ a single-turnover technique that uses osmotic stress to probe reaction kinetics between an initial specific EcoRV-DNA complex formed in the absence of Mg(2+) and the final cleavage step. With osmotic stress, complex dissociation before cleavage is minimized and the reaction rates are slowed to a convenient time scale of minutes to hours. We find that cleavage occurs by a two-step mechanism that can be characterized by two rate constants. The dependence of these rate constants on Mg(2+) concentration and osmotic pressure gives the number of Mg(2+) ions and water molecules coupled to each kinetic step of the EcoRV cleavage reaction. Each kinetic step is coupled to the binding 1.5-2.5 Mg(2+) ions, the uptake of ∼30 water molecules, and the cleavage of a DNA single strand. We suggest that each kinetic step reflects an independent, rate-limiting conformational change of each monomer of the dimeric enzyme that allows Mg(2+) ion binding. This modified single-turnover protocol has general applicability for metalloenzymes.