Osteosarcoma is a highly aggressive cancer for which treatment has remained essentially unchanged for more than 30 years. Osteosarcoma is characterized by widespread and recurrent somatic copy-number ...alterations (SCNA) and structural rearrangements. In contrast, few recurrent point mutations in protein-coding genes have been identified, suggesting that genes within SCNAs are key oncogenic drivers in this disease. SCNAs and structural rearrangements are highly heterogeneous across osteosarcoma cases, suggesting the need for a genome-informed approach to targeted therapy. To identify patient-specific candidate drivers, we used a simple heuristic based on degree and rank order of copy-number amplification (identified by whole-genome sequencing) and changes in gene expression as identified by RNA sequencing. Using patient-derived tumor xenografts, we demonstrate that targeting of patient-specific SCNAs leads to significant decrease in tumor burden, providing a road map for genome-informed treatment of osteosarcoma. SIGNIFICANCE: Osteosarcoma is treated with a chemotherapy regimen established 30 years ago. Although osteosarcoma is genomically complex, we hypothesized that tumor-specific dependencies could be identified within SCNAs. Using patient-derived tumor xenografts, we found a high degree of response for "genome-matched" therapies, demonstrating the utility of a targeted genome-informed approach.
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Objective
Determine the effect of patient demographics and surgical approach on patient outcomes after tracheal resection in the management of thyroid cancer.
Study Design
Systematic review and ...meta‐analysis.
Methods
Systematic review of literature was performed using PubMed, Embase, and Cochrane Library to identify patients with thyroid carcinoma who underwent tracheal resection. Pooled estimates for patient demographics, presenting findings, complications, and outcomes are determined using random‐effects meta‐analyses.
Results
Ninety‐six relevant studies encompassing 1,179 patients met inclusion criteria. Meta‐analysis pooled rates of complications: 1.7% (confidence interval CI 0.8–2.5; P < .001; I2 = 1.85%) airway complications, 2.8% (CI 1.6–3.9; P < .001; I2 = 13.34%) bilateral recurrent laryngeal nerve paralysis, 2.2% (CI 1.2–3.1; P < .001; I2 = 6.72%) anastomotic dehiscence. Circumferential resection pooled estimates major complications, locoregional recurrence, distal recurrence, overall survival: 14.1% (CI 8.3–19.9; P < .001; I2 = 35.26%), 15% (CI 9.6–20.3; P < .001; I2 = 38.2%), 19.7% (CI 13.7–25.8; P < .001; I2 = 28.83%), 74.5% (CI 64.4–84.6; P < .001; I2 = 85.07%). Window resection estimates: 19.8% (CI 6.9–32.8; P < .001; I2 = 18.83%) major complications, 25.6% (CI 5.1–46.1; P < .014; I2 = 84.68%) locoregional recurrence, 15.6% (CI 9.7–21.5; P < .001; I2 = 0%) distal recurrence, 77.1% (CI 58–96.2; P < .001; I2 = 78.77%) overall survival.
Conclusion
Management of invasive thyroid carcinoma may require tracheal resection to achieve locoregional control. Nevertheless, postoperative complications are not insignificant, and therefore this risk cannot be overlooked when counseling patients perioperatively. Laryngoscope, 131:932–946, 2021
This study aims to describe presenting characteristics of patients diagnosed with non-invasive chronic rhinosinusitis (CRS) following liver or kidney transplant and determine factors associated with ...disease-related complications, selection of endoscopic sinus surgery (ESS), and disease resolution in this population.
Retrospective chart review.
An academic tertiary care center (Mayo Clinic, Rochester, Minnesota).
Liver and kidney transplant recipients evaluated by Mayo Clinic otolaryngologists for CRS between 1998 and 2018 were identified. Univariate and multivariate logistic regression analyses were used to determine patient factors and treatment modalities associated with developing complications, selection of ESS, and disease resolution.
Fifty-seven patients met inclusion criteria. No patients developed intraorbital or intracranial complications of their CRS. Multivariate modeling demonstrated that the presence of polyps (P = 0.036) was associated with undergoing ESS within one year of presentation. A higher Lund–Mackay (LM) computed tomography score (P = 0.023) and older age (P = 0.018) were significantly associated with decreased disease resolution. No other factors were significantly associated with the use of endoscopic sinus surgery within one year of otolaryngology presentation or resolution of CRS in this cohort.
The risk of developing CRS-related intraorbital or intracranial complications in this immunecompromised patient cohort may be lower than originally thought. For liver- and kidney-recipients stable on immunosuppressive medication for many years, prognostic factors for CRS may mirror those for immunocompetent patients.
Purpose
Odontogenic sinusitis (ODS) is underrepresented in the literature compared to other forms of rhinosinusitis, specifically in sinusitis guidelines and position statements. ODS publication ...characteristics could help explain why ODS has received less attention in sinusitis guidelines and position statements. The purpose of this study was to explore trends in the quantity and quality of ODS studies over 3 decades from 1990 to 2019.
Methods
A systematic review was performed to identify all ODS studies from 1990 to 2019. The following variables from all ODS studies were compared between and across the 3 decades: authors’ specialties, journal specialties, authors’ geographic origins (continents), study topics, study designs, and evidence levels.
Results
From 1990 to 2019, there were 254 ODS studies that met inclusion criteria. Numbers of publications increased each decade, with 161 being published from 2010 to 2019. Otolaryngologists and dental authors published over 75% of ODS studies each decade, with 60–75% of ODS articles being published in otolaryngology or dental journals. European and Asian authors published the most ODS studies each decade. Overall, 92–100% of ODS publications per decade were level 4 and 5 evidence, with no significant changes between or across decades.
Conclusion
While numbers of ODS publications increased each decade from 1990 to 2019, evidence levels remained low without significant changes over time. Otolaryngologists and dental authors published the majority of ODS studies each decade, with a minority of these studies being multidisciplinary. More ODS studies are needed across all aspects of the condition, and future projects would benefit from improved study designs and multidisciplinary collaboration.
Purpose
To evaluate the cost-effectiveness of obtaining a preoperative type and screen (T/S) for common urologic procedures.
Methods
A decision tree model was constructed to track surgical patients ...undergoing two preoperative blood ordering strategies as follows: obtaining a preoperative T/S versus not doing so. The model was applied to the National (Nationwide) Inpatient Sample (NIS) data, from January 1, 2006 to September 30, 2015. Cost estimates for the model were created from combined patient-level data with published costs of a T/S, type and crossmatch (T/C), a unit of pRBC, and one unit of emergency-release transfusion (ERT). The primary outcome was the incremental cost per ERT prevented, expressed as an incremental cost-effectiveness ratio (ICER) between the two preoperative blood ordering strategies. A cost-effectiveness analysis determined the ICER of obtaining preoperative T/S to prevent an emergency-release transfusion (ERT), with a willingness-to-pay threshold of $1,500.00.
Results
A total of 4,113,144 surgical admissions from 2006 to 2015 were reviewed. The overall transfusion rate was 10.54% (95% CI, 10.17–10.91) for all procedures. The ICER of preoperative T/S was $1500.00 per ERT prevented. One-way sensitivity analysis demonstrated that the risk of transfusion should exceed 4.12% to justify preoperative T/S.
Conclusion
Routine preoperative T/S for radical prostatectomy (rate = 3.88%) and penile implants (rate = .91%) does not represent a cost-effective practice for these surgeries. It is important for urologists to review their institution T/S policy to reduce inefficiencies within the preoperative setting.
Most circulating tumor DNA (ctDNA) assays are designed to detect recurrent mutations. Pediatric sarcomas share few recurrent mutations but rather are characterized by translocations and copy-number ...changes. We applied Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) for detection of translocations found in the most common pediatric sarcomas. We also applied ichorCNA to the combined off-target reads from our hybrid capture to simultaneously detect copy-number alterations (CNA). We analyzed 64 prospectively collected plasma samples from 17 patients with pediatric sarcoma. Translocations were detected in the pretreatment plasma of 13 patients and were confirmed by tumor sequencing in 12 patients. Two of these patients had evidence of complex chromosomal rearrangements in their ctDNA. We also detected copy-number changes in the pretreatment plasma of 7 patients. We found that ctDNA levels correlated with metastatic status and clinical response. Furthermore, we detected rising ctDNA levels before relapse was clinically apparent, demonstrating the high sensitivity of our assay. This assay can be utilized for simultaneous detection of translocations and CNAs in the plasma of patients with pediatric sarcoma. While we describe our experience in pediatric sarcomas, this approach can be applied to other tumors that are driven by structural variants.
Evaluate trends in mortality due to acute epiglottitis before and after adoption of Haemophilus influenza Type b vaccination (Hib) in pediatric and adult populations.
Patients who died from acute ...epiglottis from 1979 to 2017 identified using National Vital Statistics System. Mortality rates calculated using age-adjusted US census data expressed in rate per 100,000 individuals. Trends analyzed using the National Cancer Institute Joinpoint Regression Program (version 4.7.0; Bethesda, Maryland).
1187 epiglottitis-related deaths were identified over thirty-nine years. Total deaths decreased from 65 in 1979 to 15 in 2017. Adult deaths accounted for 63.5% and decreased from 0.015 per 100,000 individuals (24 deaths) in 1979 to 0.006 per 100,000 individuals (14 deaths) in 2017. Best fitting log-liner regression model showed APC of −3.5% (95% CI, −4.2 to −2.7%) from 1979 to 2017. Pediatric and adolescent deaths accounted for 443 (37.3%) deaths, decreasing from 0.064 per 100,000 individuals (41 deaths) in 1979 to 0.001 per 100,000 individuals (1 death) in 2017. APC was −11.1% (95% CI, −13.8% to −8.3%) in 1979 to 1990; 46.5% (95% CI, −16.6% to 157.3%) in 1990 to 1993; −61.6% (95% CI, −88% to 23%) in 1993 to 1996; and 1.1% (95% CI, −2.4% to 4.7%) in 1996 to 2017.
Mortality from acute epiglottitis decreased after widespread adoption of Hib vaccination in the US. Adults are now more likely than children to die of acute epiglottitis. Further research including multi-institutional cohort studies must be done to elucidate causative factors contributing to remaining cases of mortality.
•Mortality from acute epiglottitis decreased in the US after widespread Hib vaccination.•Epiglottitis mortality has decreased in children and adolescents and in adults in the US.•The rate of decline in acute epiglottitis mortality was steepest in children.•Adults are now more likely than children to die from acute epiglottitis in the US.•Acute epiglottitis should be considered in anyone presenting with acute airway symptoms.
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