Citations

6010 Background: Definitive or postoperative chemoradiation (CRT) is highly curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a potential deintensification strategy, we studied primary transoral surgery (TOS) and, in intermediate pathologic risk patients, reduced dose postoperative RT (PORT). Methods: E3311 is a phase II trial with randomization to reduced- or standard-dose PORT for resected stage III-IVa (AJCC7) intermediate pathologic risk HPV+ OPC, stratified by smoking history. Primary endpoints have been reported; we now present updated 3-year PFS and patient-reported outcomes (PRO), including head and neck-cancer specific quality of life (FACT-H&N) and swallowing perception and performance (MDADI). Results: Of 519 enrolled patients, 495 underwent TOS. The primary oncologic endpoint was 2-year PFS for 50 Gy (Arm B) or 60Gy (Arm C). Among 360 eligible and treated patients (ETP), Arm A (observation, N = 38) enrolled 11%, Arms B (N = 100) or C (N = 109) randomized 58%, and Arm D (66Gy + weekly cisplatin, N = 113) enrolled 31%. With 35.1 months median follow-up, 3-year PFS Kaplan-Meier estimate is 96.9% (90% CI [91.9%, 100%]) for Arm A; 94.9% (90% CI [91.3%, 98.6%]) for Arm B; 93.5% (90% CI [89.4%, 97.9%]) for Arm C; and 90.7% (90% CI [86.2%, 95.4%]) for Arm D. Recurrences and death without recurrence were 4 and 1 in Arm B, and 5 and one in Arm C. Smokers ( > 10 pack-years) did not have worse 3-year PFS in Arms B or C. Treatment arm distribution and outcome for ineligible patients who started adjuvant therapy mirrored the 360 ETP. A comparison combining arms B/C versus arm D in the proportion of patients stable/improved in FACT-H&N total score, from baseline to 6 months post-treatment as a pre-specified endpoint, was 56% vs. 38% (p value = 0.011, one-sided Fisher’s exact test); however, underlying differences in treatment and risk may be confounding. An exploratory comparison between Arms B and C revealed improvement in FACT H&N (63% in Arm B vs. 49% in Arm C had a stable/improved score, p-value = 0.056). Conclusions: Primary TOS and reduced PORT retained outstanding oncologic outcome at 35 months follow up, with favorable QOL and functional outcomes, in intermediate risk HPV+ OPC. Clinical trial information: NCT 01898494.

1561 Background: Surgical interventions are studied less often than medical or radiation interventions in oncology clinical trials. We characterized surgical oncology trials registered on ClinicalTrials.gov, analyzed funding sources and identified features associated with early discontinuation and results reporting. Methods: We employed a cross-sectional study design with descriptive, logistic regression, cox regression, time series and survival analyses. We downloaded all 270,172 studies registered on the Aggregate Analysis of the ClinicalTrials.gov database from October 1, 2008 to March 9, 2020. After excluding non-interventional trials, applying cancer/oncology specific Medical Subject Heading terms to the remaining trials and excluding phase 1 trials, 27,915 trials were identified for manual review. Primary exposure variables were trial focus: neoplasia site and treatment modality (surgical interventions included investigations of outcomes from surgical resection or intra-operative/peri-operative changes), and funding: industry, U.S. government, academic. Results: 26,815 trials were found to have true oncology content; 1,661 (6.2%) involved surgical oncology, representing 311,789 patients. Funding sources were: 82.7% by academic institutions, 10.9% by industry, and 6.2% by U.S. government. The most studied neoplasia sites were colorectal (17.4% of trials), breast (10.7%), gastric (10.5%), hepatic (8.6%), lung (7.5%), brain/CNS (6.7%) and cervical (6.6%). U.S. government funded surgical oncology trials had the lowest risk of early discontinuation (adjusted HR 0.50, 95% CI: 0.26-0.99, p<0.047) and the highest odds of results reporting (adjusted OR 1.08, 95% CI: 0.55-2.11, p=0.83) (Table 1). Conclusions: There is a paucity of surgical oncology clinical trials compared to other treatment modalities, especially in context of surgery’s role in overall cancer care. From 2008-2020 only 6.2% of trials focused on surgical oncology, and U.S. government funded trials displayed the lowest hazard of early discontinuation and highest odds of results reporting. Stakeholders should look to government funded trials as models of improvement, but must increase representation and results dissemination of surgical oncology trials to guide treatment recommendations. Surgical oncology trial features and associated early discontinuation/results reporting. [Table: see text]

Background The role of race and ethnicity in the outcomes of cardiac arrest (CA) complicating acute myocardial infarction (AMI) is incompletely understood. Methods and Results This was a retrospective cohort study of adult admissions with AMI‐CA from the National Inpatient Sample (2012–2017). Self‐reported race/ethnicity was classified as White, Black, and others (Hispanic, Asian or Pacific Islander, Native American, Other). Outcomes of interest included in‐hospital mortality, coronary angiography, percutaneous coronary intervention, palliative care consultation, do‐not‐resuscitate status use, hospitalization costs, hospital length of stay, and discharge disposition. Of the 3.5 million admissions with AMI, CA was noted in 182 750 (5.2%), with White, Black, and other races/ethnicities constituting 74.8%, 10.7%, and 14.5%, respectively. Black patients admitted with AMI‐CA were more likely to be female, with more comorbidities, higher rates of non–ST‐segment–elevation myocardial infarction, and higher neurological and renal failure. Admissions of patients of Black and other races/ethnicities underwent coronary angiography (61.9% versus 70.2% versus 73.1%) and percutaneous coronary intervention (44.6% versus 53.0% versus 58.1%) less frequently compared to patients of white race ( p <0.001). Admissions of patients with AMI‐CA had significantly higher unadjusted mortality (47.4% and 47.4%) as compared with White patients admitted (40.9%). In adjusted analyses, Black race was associated with lower in‐hospital mortality (odds ratio [OR], 0.95; 95% CI, 0.91–0.99; P =0.007) whereas other races had higher in‐hospital mortality (OR, 1.11; 95% CI, 1.08–1.15; P <0.001) compared with White race. Admissions of Black patients with AMI‐CA had longer length of hospital stay, higher rates of palliative care consultation, less frequent do‐not‐resuscitate status use, and fewer discharges to home (all P <0.001). Conclusions Racial and ethnic minorities received less frequent guideline‐directed procedures and had higher in‐hospital mortality and worse outcomes in AMI‐CA.

Background There are limited contemporary data on the use of emergent coronary artery bypass grafting (CABG) in acute myocardial infarction. Methods and Results Adult (aged >18 years) acute myocardial infarction admissions were identified using the National (Nationwide) Inpatient Sample (2000–2017) and classified by tertiles of admission year. Outcomes of interest included temporal trends of CABG use; age‐, sex‐, and race‐stratified trends in CABG use; in‐hospital mortality; hospitalization costs; and hospital length of stay. Of the 11 622 528 acute myocardial infarction admissions, emergent CABG was performed in 1 071 156 (9.2%). CABG utilization decreased overall (10.5% [2000] to 8.7% [2017]; adjusted odds ratio [OR], 0.98 [95% CI, 0.98–0.98]; P <0.001), in ST‐segment–elevation myocardial infarction (10.2% [2000] to 5.2% [2017]; adjusted OR, 0.95 [95% CI, 0.95–0.95]; P <0.001) and non–ST‐segment–elevation myocardial infarction (10.8% [2000] to 10.0% [2017]; adjusted OR, 0.99 [95% CI, 0.99–0.99]; P <0.001), with consistent age, sex, and race trends. In 2012 to 2017, compared with 2000 to 2005, admissions receiving emergent CABG were more likely to have non–ST‐segment–elevation myocardial infarction (80.5% versus 56.1%), higher rates of noncardiac multiorgan failure (26.1% versus 8.4%), cardiogenic shock (11.5% versus 6.4%), and use of mechanical circulatory support (19.8% versus 18.7%). In‐hospital mortality in CABG admissions decreased from 5.3% (2000) to 3.6% (2017) (adjusted OR, 0.89; 95% CI, 0.88–0.89 [ P <0.001]) in the overall cohort, with similar temporal trends in patients with ST‐segment–elevation myocardial infarction and non–ST‐segment–elevation myocardial infarction. An increase in lengths of hospital stay and hospitalization costs was seen over time. Conclusions Utilization of CABG has decreased substantially in acute myocardial infarction admissions, especially in patients with ST‐segment–elevation myocardial infarction. Despite an increase in acuity and multiorgan failure, in‐hospital mortality consistently decreased in this population.

Introduction: The Mayo Clinic Cardiac Intensive Care Unit Admission Risk Score (M-CARS) has been shown to predict hospital mortality in the CICU population better than conventional critical care scoring models. We tested the hypothesis that M-CARS could similarly be used to predict one-year mortality. Methods: We retrospectively reviewed adult CICU patients admitted from 2007 to 2018. M-CARS was calculated using admission data. Groups were compared using Wilcoxon test for continuous variables and chi-squared test for categorical variables. Results: This study included 12428 unique patients with a mean age of 67 ± 15 years (37% females), of whom 11279 (90.8%) survived hospitalization and 2839 patients (22.8%) died within 1 year of admission. The 1-year survival decreased incrementally as a function of increasing M-CARS ( Figure 1A , p<0.0001), and all components of M-CARS were significant predictors of 1-year mortality (p<0.001). 1690 hospital survivors (15.0%) died within 1 year. The 1-year survival decreased incrementally as a function of increasing M-CARS for scores <3 (all p<0.001); however, there was no further adverse 1-year survival for patients with M-CARS ≥3 ( Figure 1B, p=0.99). M-CARS components associated with 1-year mortality among hospital survivors included blood urea nitrogen, red blood cell distribution width, Braden score, and respiratory failure (all p<0.001), while cardiac arrest, cardiogenic shock, and anion gap were not. Conclusions: M-CARS accurately predicts 1-year mortality among CICU admissions, with a plateau effects at high M-CARS scores ≥3. Significant predictors of 1-year mortality among CICU survivors include frailty markers rather than admission severity.

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced individuals (6,538 ALS patients, 2,415 controls) and the largest cortex-derived eQTL dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, repeat expansions or regulatory effects. ALS associated risk loci were shared with multiple traits within the neurodegenerative spectrum, but with distinct enrichment patterns across brain regions and cell-types. Of the environmental and life-style risk factors obtained from literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. All ALS associated signals combined reveal a role for perturbations in vesicle mediated transport and autophagy, and provide evidence for cell-autonomous disease initiation in glutamatergic neurons.

Abstract Aims There are limited contemporary data on the use of initial fibrinolysis in ST-segment elevation myocardial infarction cardiogenic shock (STEMI-CS). This study sought to compare the outcomes of STEMI-CS receiving initial fibrinolysis vs. primary percutaneous coronary intervention (PPCI). Methods Using the National (Nationwide) Inpatient Sample from 2009 to 2017, a comparative effectiveness study of adult (&gt;18 years) STEMI-CS admissions receiving pre-hospital/in-hospital fibrinolysis were compared with those receiving PPCI. Admissions with alternate indications for fibrinolysis and STEMI-CS managed medically or with surgical revascularization (without fibrinolysis) were excluded. Outcomes of interest included in-hospital mortality, development of non-cardiac organ failure, complications, hospital length of stay, hospitalization costs, use of palliative care, and do-not-resuscitate status. Results During 2009–2017, 5297 and 110 452 admissions received initial fibrinolysis and PPCI, respectively. Compared with those receiving PPCI, the fibrinolysis group was more often non-White, with lower co-morbidity, and admitted on weekends and to small rural hospitals (all P &lt; 0.001). In the fibrinolysis group, 95.3%, 77.4%, and 15.7% received angiography, PCI, and coronary artery bypass grafting, respectively. The fibrinolysis group had higher rates of haemorrhagic complications (13.5% vs. 9.9%; P &lt; 0.001). The fibrinolysis group had comparable all-cause in-hospital mortality [logistic regression analysis: 28.8% vs. 28.5%; propensity-matched analysis: 30.8% vs. 30.3%; adjusted odds ratio 0.97 (95% confidence interval 0.90–1.05); P = 0.50]. The fibrinolysis group had comparable rates of acute organ failure, hospital length of stay, rates of palliative care referrals, do-not-resuscitate status use, and lesser hospitalization costs. Conclusions The use of initial fibrinolysis had comparable in-hospital mortality than those receiving PPCI in STEMI-CS in the contemporary era in this large national observational study.

Abstract Background Residents of nursing homes and long‐term care facilities are at increased risk for severe coronavirus disease‐19 (COVID‐19) but may not be able to access monoclonal antibody therapies offered at outpatient infusion centers due to frailty and logistical issues. We describe a mobile monoclonal antibody infusion program for patients with COVID‐19 in skilled nursing facilities and provide descriptive data on its outcomes. Design Retrospective cohort study. Setting Collaboration between Mayo Clinic and skilled nursing facilities in Southeast Minnesota was developed to administer anti‐spike monoclonal antibodies under the FDA Emergency Use Authorization. Participants Seventy five residents of skilled nursing facilities at high risk of COVID‐19 complications. Exposure Emergency use treatment with bamlanivimab and casirivimab–imdevimab. Measurements Hospitalization and medically attended visits. Results The mobile infusion unit, staffed by Mayo Clinic Infusion Therapy registered nurses and supported by the skilled nursing facility staff, infused anti‐spike monoclonal antibodies to 45 of 75 patients (average age, 77.8 years) in December 2020. The infusions occurred at an average of 4.3 days after COVID‐19 diagnosis. Fourteen days after infusion, there were no deaths, two emergency department visits, and three hospitalizations, for a combined event rate of 11.1%. There was one reported adverse event. Conclusion The implementation of a mobile infusion unit embedded in a collaborative process resulted in rapid infusion of monoclonal antibodies to high‐risk COVID‐19 patients in skilled nursing facilities, who would otherwise be unable to access the novel therapies. The therapies were well tolerated and appear beneficial. Further study is warranted to explore the scalability and efficacy of this program.

Objective: This study aims to determine if outpatient opioid prescriptions are associated with future SUD diagnoses and overdose in injured adolescents 5 years following hospital discharge. Summary of Background Data: Approximately, 1 in 8 adolescents are diagnosed with an SUD and 1 in 10 experience an overdose in the 5 years following injury. State laws have become more restrictive on opioid prescribing by acute care providers for treating pain, however, prescriptions from other outpatient providers are still often obtained. Methods: This was a retrospective cohort study of patients ages 12–18 admitted to 2 level I trauma centers. Demographic and clinical data contained in trauma registries were linked to a regional database containing 5 years of electronic health records and prescription data. Regression models assessed whether number of outpatient opioid prescription fills after discharge at different time points in recovery were associated with a new SUD diagnosis or overdose, while controlling for demographic and injury characteristics, and depression and posttraumatic stress disorder diagnoses. Results: We linked 669 patients (90.9%) from trauma registries to a regional health information exchange database. Each prescription opioid refill in the first 3 months after discharge increased the likelihood of new SUD diagnoses by 55% (odds ratio: 1.55, confidence interval: 1.04–2.32). Odds of overdose increased with ongoing opioid use over 2–4 years post-discharge (P = 0.016–0.025). Conclusions: Short-term outpatient opioid prescribing over the first few months of recovery had the largest effect on developing an SUD, while long-term prescription use over multiple years was associated with a future overdose.

Background: Previous studies have defined preshock as isolated hypotension or isolated hypoperfusion, whereas shock has been variably defined as hypoperfusion with or without hypotension. We aimed to evaluate the mortality risk associated with hypotension and hypoperfusion at the time of admission in a cardiac intensive care unit population. Methods: We analyzed Mayo Clinic cardiac intensive care unit patients admitted between 2007 and 2015. Hypotension was defined as systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg, and hypoperfusion as admission lactate >2 mmol/L, oliguria, or rising creatinine. Associations between hypotension and hypoperfusion with hospital mortality were estimated using multivariable logistic regression. Results: Among 10 004 patients with a median age of 69 years, 43.1% had acute coronary syndrome, and 46.1% had heart failure. Isolated hypotension was present in 16.7%, isolated hypoperfusion in 15.3%, and 8.7% had both hypotension and hypoperfusion. Stepwise increases in hospital mortality were observed with hypotension and hypoperfusion compared with neither hypotension nor hypoperfusion (3.3%; all P <0.001): isolated hypotension, 9.3% (adjusted odds ratio, 1.7 [95% CI, 1.4–2.2]); isolated hypoperfusion, 17.2% (adjusted odds ratio, 2.3 [95% CI, 1.9–3.0]); both hypotension and hypoperfusion, 33.8% (adjusted odds ratio, 2.8 [95% CI, 2.1–3.6]). Adjusted hospital mortality in patients with isolated hypoperfusion was higher than in patients with isolated hypotension ( P =0.02) and not significant different from patients with both hypotension and hypoperfusion ( P =0.18). Conclusions: Hypotension and hypoperfusion are both associated with increased mortality in cardiac intensive care unit patients. Hospital mortality is higher with isolated hypoperfusion or concomitant hypotension and hypoperfusion (classic shock). We contend that preshock should refer to isolated hypotension without hypoperfusion, while patients with hypoperfusion can be considered to have shock, irrespective of blood pressure.