Objective To determine the pooled global prevalence of olfactory and gustatory dysfunction in patients with the 2019 novel coronavirus (COVID-19). Data Sources Literature searches of PubMed, Embase, and Scopus were conducted on April 19, 2020, to include articles written in English that reported the prevalence of olfactory or gustatory dysfunction in COVID-19 patients. Review Methods Search strategies developed for each database contained keywords such as anosmia, dysgeusia, and COVID-19. Resulting articles were imported into a systematic review software and underwent screening. Data from articles that met inclusion criteria were extracted and analyzed. Meta-analysis using pooled prevalence estimates in a random-effects model were calculated. Results Ten studies were analyzed for olfactory dysfunction (n = 1627), demonstrating 52.73% (95% CI, 29.64%-75.23%) prevalence among patients with COVID-19. Nine studies were analyzed for gustatory dysfunction (n = 1390), demonstrating 43.93% (95% CI, 20.46%-68.95%) prevalence. Subgroup analyses were conducted for studies evaluating olfactory dysfunction using nonvalidated and validated instruments and demonstrated 36.64% (95% CI, 18.31%-57.24%) and 86.60% (95% CI, 72.95%-95.95%) prevalence, respectively. Conclusions Olfactory and gustatory dysfunction are common symptoms in patients with COVID-19 and may represent early symptoms in the clinical course of infection. Increased awareness of this fact may encourage earlier diagnosis and treatment, as well as heighten vigilance for viral transmission. To our knowledge, this is the first meta-analysis to report on the prevalence of these symptoms in COVID-19 patients.

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Purpose: Targeted agents and immunotherapies promise to transform the treatment of metastatic bladder cancer, but therapy selection will depend on practical tumor molecular stratification. Circulating tumor DNA (ctDNA) is established in several solid malignancies as a minimally invasive tool to profile the tumor genome in real-time, but is critically underexplored in bladder cancer.Experimental Design: We applied a combination of wholeexome sequencing and targeted sequencing across 50 bladder cancer driver genes to plasma cell-free DNA (cfDNA) from 51 patients with aggressive bladder cancer, including 37 with metastatic disease.Results: The majority of patients with metastasis, but only 14% of patients with localized disease, had ctDNA proportions above 2% of total cfDNA (median 16.5%, range 3.9%-72.6%). Twelve percent of estimable samples had evidence of genome hypermutation. We reveal an aggressive mutational landscape in metastatic bladder cancer with 95% of patients harboring deleterious alterations to TP53, RB1, or MDM2, and 70% harboring a mutation or disrupting rearrangement affecting chromatin modifiers such as ARID1A. Targetable alterations in MAPK/ERK or PI3K/AKT/ mTOR pathways were robustly detected, including amplification of ERBB2 (20% of patients) and activating hotspot mutations in PIK3CA (20%), with the latter mutually exclusive to truncating mutations in TSC1. A novel FGFR3 gene fusion was identified in consecutive samples from one patient.Conclusions: Our study demonstrates that ctDNA provides a practical and cost-effective snapshot of driver gene status in metastatic bladder cancer. The identification of a wide spectrum of clinically informative somatic alterations nominates ctDNA as a tool to dissect disease pathogenesis and guide therapy selection in patients with metastatic bladder cancer.

Objective To determine whether radiologically defined sarcopenia at the C3 or L3 level as measured by computed tomography or magnetic resonance imaging is prognostic of overall survival (OS) in head and neck cancers (HNCs). Methods Literature searches of PubMed, Embase, and Scopus were conducted on July 12, 2019, to include articles written in the English language with no constraints on publication date. To be included in the analysis, articles had to report the prognostic impact of skeletal muscle mass measured radiologically at the C3 or L3 vertebral level in HNC patients; hazard ratios (HRs) for OS; 95% confidence intervals (CIs); be from a clinical trial, cohort, or case–control study; and have English full‐text availability. Articles were reviewed in consensus by two reviewers, with disagreements reviewed by a third reviewer. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses and Meta‐analysis Of Observational Studies in Epidemiology Checklist guidelines were used for reporting. Study quality assessment was performed using Quality In Prognosis Studies tool. The random‐effects DerSimonian and Laird method was used for meta‐analysis. Results Ten articles, nine retrospective and one prospective, were included in this meta‐analysis (n = 2,181 patients). Significant differences were found in OS for HNC patients with sarcopenia (HR = 1.98; 95% CI: 1.64‐2.39; P < .00001). No heterogeneity was detected in either the overall or subgroup analyses. Conclusions Radiologically defined sarcopenia is a negative predictor of OS in patients with HNC. Early detection of sarcopenia in cancer patients may help guide nutritional and adjuvant support to improve treatment outcomes. Level of Evidence NA Laryngoscope, 131:333–341, 2021

Purpose: Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). We sought to determine acquired genomic contributors to cross-resistance. Experimental Design: We collected 458 serial plasma cell-free DNA samples at baseline and progression timepoints from 202 patients with mCRPC receiving sequential AR signaling inhibitors (abiraterone and enzalutamide) in a randomized phase II clinical trial (NCT02125357). We utilized deep targeted and whole-exome sequencing to compare baseline and posttreatment somatic genomic profiles in circulating tumor DNA (ctDNA). Results: Patient ctDNA abundance was correlated across plasma collections and independently prognostic for sequential therapy response and overall survival. Most driver alterations in established prostate cancer genes were consistently detected in ctDNA over time. However, shifts in somatic populations after treatment were identified in 53% of patients, particularly after strong treatment responses. Treatment-associated changes converged upon the AR gene, with an average 50% increase in AR copy number, changes in AR mutation frequencies, and a 2.5-fold increase in the proportion of patients carrying AR ligand binding domain truncating rearrangements. Conclusions: Our data show that the dominant AR genotype continues to evolve during sequential lines of AR inhibition and drives acquired resistance in patients with mCRPC.