Faculty Bibliography

BACKGROUND:Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS:We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS:A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS:Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

Background and study aims  Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) can be used in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). We performed a systematic review and meta-analysis to evaluate the efficacy of EUS-RFA in treatment of locally advanced unresectable PDAC and other pancreatic tumors. Patients and methods  A comprehensive search was done of multiple electronic databases and conference proceedings including PubMed, EMBASE, Web of Science databases, Google Scholar and manual search of references (from inception through May 2019) to identify the studies reporting use of EUS-RFA for pancreatic lesions. The primary outcome was to evaluate technical and clinical success of the procedure. The secondary outcome was to study overall adverse events (AEs). Results  Thirteen studies reporting 165 EUS-RFA procedures on 134 patients were included. Of 134 patients, 27.94 % (38) had unresectable locally advanced PDAC, 40 % (53) had PNETs, 3 % (4) had metastasis to the pancreas and 30 % (41) had other lesions. The pooled technical success rate calculated out of the total number of procedures was 100 % (95 % CI [99.18 - 100], I2 = 0 %). The pooled clinical success rate calculated out of the total number of patients was 91.58 % (95 % CI [82.5 - 98.08], I2 = 21.5 %). The pooled overall AE rates were 14.67 % (95 % CI [4.77 - 27.46], I2 = 56.19 %) out of which abdominal pain was the most common with 9.82 % (95 % CI [3.34 - 18.24], I2 = 23.76 %). Low to moderate heterogeneity was noted. Conclusion  EUS-RFA has high technical (100 %) and clinical success (91.5 %) rates. Further multicenter trials are needed to further validate our findings.

Taxi and for-hire vehicle (FHV) drivers are a predominantly immigrant population facing a range of occupational stressors, including lack of workplace benefits and increasing financial strain from tumultuous industry changes and now COVID-19's devastating impact. Bilingual research staff surveyed 422 New York City taxi/FHV drivers using a stratified sampling approach in driver-frequented locations to examine drivers' health and financial planning behaviors for the first time. Drivers lacked health insurance at double the NYC rate (20% vs. 10%). Life insurance and retirement savings rates were lower than U.S. averages (20% vs. 60%, 25% vs. 58%, respectively). Vehicle ownership was a significant predictor of health insurance, life insurance, and retirement savings. Compared to South Asian drivers, Sub-Saharan African drivers were significantly less likely to have health insurance and North African, and Middle Eastern drivers were significantly less likely to have retirement savings. Although most drivers indicated the importance of insurance and benefits, < 50% understood how to use them. Drivers felt primary care coverage to be most important followed by other health-related coverage, retirement benefits, and life insurance. Results reveal compelling addressable gaps in insurance and benefits coverage and the need to implement accessible financial literacy with navigation and advising services and programs.

BACKGROUND:Change of the corrected flow time (Ftc) is a surrogate for tracking stroke volume (SV) in the intensive care unit. Multiple Ftc equations have been proposed; many have not had their diagnostic characteristics for detecting SV change reported. Further, little is known about the inherent Ftc variability induced by the respiratory cycle. MATERIALS AND METHODS/METHODS:Using a wearable Doppler ultrasound patch, we studied the clinical performance of 11 Ftc equations to detect a 10% change in SV measured by non-invasive pulse contour analysis; 26 healthy volunteers performed a standardized cardiac preload modifying maneuver. RESULTS:, respectively. As an exploratory analysis, we studied 3335 carotid beats for the dispersion of Ftc during quiet breathing using the equations of Wodey and Bazett. The coefficient of variation of Ftc during quiet breathing for these formulae were 0.06 and 0.07, respectively. CONCLUSIONS:Most of the 11 different equations used to calculate carotid artery Ftc from a wearable Doppler ultrasound patch had similar thresholds and abilities to detect SV change in healthy volunteers. Variation in Ftc induced by the respiratory cycle is important; measuring a clinically significant change in Ftc with statistical confidence requires a large sample of beats.

Background and Aims/UNASSIGNED:To test the feasibility of a novel, wearable carotid Doppler ultrasound to track changes in cardiac output induced by end-inspiratory and end-expiratory occlusion tests. Methods/UNASSIGNED:We observed the pattern of Doppler change of the common carotid artery during a simulated end-inspiratory and expiratory occlusion test (sEIOT/sEEOT) in 10, nonventilated, healthy subjects. Simultaneously, we measured the Doppler signal of the descending aorta using duplex ultrasound (Xario, Toshiba Medical Systems) and stroke volume (SV) using noninvasive pulse contour analysis (Clearsight, Edwards Lifesciences, Irvine, California). Results/UNASSIGNED:= 0.95).The coefficient of variation of the VTI measured by the Doppler patch was roughly 60% less than that of the duplex system. Conclusions/UNASSIGNED:The pattern of SV change induced by a sEIOT/sEEOT in nonmechanically ventilated volunteers is reflected in the common carotid artery and descending aorta. The VTI variability of the Doppler patch was less than that of the traditional, duplex Doppler.

Background: Standard of care (SOC) regimens may contribute to immunosuppression by elevating intratumoral levels of adenosine, which activates the A2a and A2b receptors (R) on immune cells. Extracellular adenosine is primarily produced by the enzyme CD73. In prostate cancer, the activity of the highly expressed protein, prostatic acid phosphatase, produces additional adenosine. AB928, which is the first clinical-stage small molecule dual antagonist of both A2aR and A2bR, is highly potent, pharmacodynamically active, and well tolerated in dose escalation studies in combination with chemo/immunotherapy. Targeting the adenosine axis in combination with SOC regimens or immunotherapy may have a more profound effect on activating and inducing sustained antitumor immunity in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC). Trial design: This is a phase (Ph) 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of AB928-based combination therapy in pts with mCRPC. Eligibility for a specific treatment arm will be informed by prior anticancer therapy. Treatment arms will independently evaluate AB928 + zimberelimab (AB122; anti-PD-1 antibody) alone or in combination with an SOC backbone (enzalutamide or docetaxel) in earlier-line pts or AB928 + AB680 (CD73 inhibitor) +/- zimberelimab in later-line pts. Treatment arms will be conducted in 2 stages: Stage 1 (Ph1b) and Stage 2 (Ph2). In Ph1b, up to 15 pts will receive investigational product(s) at the single agent recommended dose with SOC per label guidance. Provided safety and futility stopping criteria are not met, further accrual in the earlier-line arms will involve randomization to SOC alone; in the later-line arms, upfront randomization to the all-experimental regimens will continue in Ph2. Investigator-assessed antitumor response (radiologic, prostate specific antigen [PSA]) will follow PCWG3 criteria. New treatment arms may be added via protocol amendment. ARC-6 is actively recruiting in the United States, and results will be shared in upcoming scientific conferences (NCT04381832). Clinical trial identification: NCT04381832. Legal entity responsible for the study: Arcus Biosciences.
Funding(s): Arcus Biosciences. Disclosure: S.K. Subudhi: Advisory/Consultancy, Research grant/Funding (self): Janssen Oncology; Advisory/Consultancy: Polaris; Advisory/Consultancy: Dendreon; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Apricity Health; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Dava Oncology; Advisory/Consultancy: Cancer Now; Advisory/Consultancy: MEDACorp; Honoraria (self): Parker Institute of Cancer Immunotherapy; Honoraria (self): SITC. D. Wise: Advisory/Consultancy: ScientiaCME; Advisory/Consultancy: OncLIve; Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: Best Doctors; Advisory/Consultancy: Leap Therapeutics; Advisory/Consultancy: Guidepoint Consulting; Advisory/Consultancy: GLG Consulting; Advisory/Consultancy: Silverlight; Advisory/Consultancy: Alphasights; Advisory/Consultancy: Pfizer. S.T. Liu: Advisory/Consultancy: Merck; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Esai; Advisory/Consultancy: Seattle Genetics. A. Chaudhry: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Astellas Pharma; Shareholder/Stockholder/Stock options: Novartis; Research grant/Funding (institution): Arcus Biosciences; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Abbvie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Basilea; Research grant/Funding (institution): IunoCare; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Novartis. J. Kim: Advisory/Consultancy: Sanofi; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Voluntis; Research grant/Funding (self): Immune Design. O. Gardner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Shareholder/Stockholder/Stock options, Full/Part-time employment: Bellicum Pharmaceuticals; Full/Part-time employment: Aduro Biotech; Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen. H. Gilbert: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy, Full/Part-time employment: Bellicum; Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech; Shareholder/Stockholder/Stock options: Denali; Shareholder/Stockholder/Stock options: Celgene; Shareholder/Stockholder/Stock options: BMS. M. Grady: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Full/Part-time employment: Bellicum; Full/Part-time employment: Biothera. M. Paoloni: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Janssen Oncology; Advisory/Consultancy: Amgen. K. Krishnan: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Full/Part-time employment: Astex; Full/Part-time employment: Roche/Genentech; Full/Part-time employment: Five Prime. M. Carducci: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Medivation; Advisory/Consultancy: Astellas; Advisory/Consultancy: Roche; Advisory/Consultancy: Abbvie; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Merck; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Effector; Non-remunerated activity/ies: ECOG-ACRIN.
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In-hospital cardiac arrest remains a leading cause of death: roughly 300,000 in-hospital cardiac arrests occur each year in the United States, ≈10% of which occur in the emergency department. ED-based cardiac arrest may represent a subset of in-hospital cardiac arrest with a higher proportion of reversible etiologies and a higher potential for neurologically intact survival. Patients presenting to the ED have become increasingly complex, have a high burden of critical illness, and face crowded departments with thinly stretched resources. As a result, patients in the ED are vulnerable to unrecognized clinical deterioration that may lead to ED-based cardiac arrest. Efforts to identify patients who may progress to ED-based cardiac arrest have traditionally been approached through identification of critically ill patients at triage and the identification of patients who unexpectedly deteriorate during their stay in the ED. Interventions to facilitate appropriate triage and resource allocation, as well as earlier identification of patients at risk of deterioration in the ED, could potentially allow for both prevention of cardiac arrest and optimization of outcomes from ED-based cardiac arrest. This review will discuss the epidemiology of ED-based cardiac arrest, as well as commonly used approaches to predict ED-based cardiac arrest and highlight areas that require further research to improve outcomes for this population.

A 66-year-old woman with a history of stage IA mixed endometrioid and serous endometrial cancer presented to our centre with 2 weeks of worsening headaches nearly 4 years after her initial surgery. At admission, she manifested bitemporal hemianopsia, difficulty walking and clinical and laboratory findings of panhypopituitarism, including diabetes insipidus. Magnetic resonance imaging of the brain revealed a 2.7 cm sellar/suprasellar mass compressing the optic chiasm and infiltrating the pituitary stalk. Computerised tomography documented mediastinal, lung, adrenal and liver involvement, including a 2.5 cm palpable left supraclavicular node that on excisional biopsy demonstrated metastatic endometrial adenocarcinoma. Due to the advanced stage of her cancer as well as the presence of multiple metastases, including lung and hepatic metastases causing post-obstructive pneumonia and coagulopathy, the sellar/suprasellar mass was treated with fractionated radiosurgery rather than surgical excision.