Mitophagy is a selective mode of autophagy in which mitochondria are specifically targeted for degradation at the autophagolysosome. Mitophagy is activated by stresses such as hypoxia, nutrient deprivation, DNA damage, inflammation and mitochondrial membrane depolarization and plays a role in maintaining mitochondrial integrity and function. Defects in mitophagy lead to mitochondrial dysfunction that can affect metabolic reprogramming in response to stress, alter cell fate determination and differentiation, which in turn affects disease incidence and etiology, including cancer. Here, we discuss how different mitophagy adaptors and modulators, including Parkin, BNIP3, BNIP3L, p62/SQSTM1 and OPTN, are regulated in response to physiological stresses and deregulated in cancers. Additionally, we explore how these different mitophagy control pathways coordinate with each other. Finally, we review new developments in understanding how mitophagy affects stemness, cell fate determination, inflammation and DNA damage responses that are relevant to understanding the role of mitophagy in cancer.

The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pan-demic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, David C. Fajgenbaum and Johnson S. Khor contributed equally to this study.

Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-Lactobacillus bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing Lactobacillus or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1LAI virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women.

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Background and Aim This study quantifies how changes in healthcare utilization and delivery during the first months of the COVID‐19 pandemic have altered the presentation, treatment, and management of patients with gastrointestinal (GI) malignancies within an academic health system. Methods and results Patients diagnosed with a GI malignancy (ICD10: C15‐C26) who received medical care within the health system during the observation period (first 44 weeks of 2019 and 2020) were identified for a retrospective cohort study. Deidentified patient encounter parameters were collected for this observation period and separated into pre‐pandemic (weeks 1–10) and early pandemic (weeks 11–20) study periods. Difference‐in‐difference analyses adjusted for week‐specific and year‐specific effects quantified the impact of the COVID‐19 pandemic on care delivery between pre‐pandemic and early pandemic study periods in 2020. Across all GI malignancies, the COVID‐19 pandemic has been associated with a significant decline in the number of patients with new patient visits (NPVs) ( p = 1.2 × 10 −4 ), Radiology encounters ( p = 1.9 × 10 −7 ), Surgery encounters ( p = 1.6 × 10 −3 ), Radiation Oncology encounters ( p = 4.1 × 10 −3 ), and infusion visits (6.1 × 10 −5 ). Subgroup analyses revealed cancer‐specific variations in changes to delivery. Patients with colorectal cancer (CRC) had the most significant decrease in NPVs ( p = 7.1 × 10 −5 ), which was significantly associated with a concomitant decrease in colonoscopies performed during the early pandemic period (r 2 = 0.722, p = 2.1 × 10 −10 ). Conclusions The COVID‐19 pandemic has been associated with significant disruptions to care delivery. While these effects were appreciated broadly across GI malignancies, CRC, diagnosed and managed by periodic screening, has been affected most acutely.

awarded to Dr. Ying Cheng. We would like to thank members of the Learning Analytics and Measurement in Behavioral Sciences (LAMBS) Lab at the University of Notre Dame for their contributions to the broader discussion of the topic. We would also like to thank the high school statistics teachers who contributed to this project.

30 Background: Changes in healthcare utilization and delivery during the first months of the COVID-19 pandemic have altered the presentation, treatment, and management of patients with gastrointestinal (GI) malignancies. We hypothesize this has contributed to diagnostic and treatment delays that will increase disease morbidity and mortality. Methods: We performed a retrospective cohort study comparing healthcare utilization of patients with diagnosed GI malignancy (ICD10:C15-C26) during and prior to the COVID-19 pandemic within our health system. Deidentified patient encounter parameters were collected for the first 20 weeks of both 2019 and 2020, including the number of: new patient visits (NPVs), hospital admissions, and specialty encounters. Difference-in-difference analyses adjusted for week-specific and year-specific effects quantified the impact of the COVID-19 pandemic on care delivery, with week 11 of 2020 marking the start of the pandemic period. Results: The 2019 and 2020 cohorts of patients had similar demographic compositions on the basis of sex and ethnicity (2019: n = 23,536, 56.8% M, 70.4/16.3/1.9% White/Black/Hispanic; 2020: n = 25,773, 57.0% M, 70.3/16.3/2.0% White/Black/Hispanic). Across all GI malignancies, the COVID-19 pandemic period was associated with a significant decrease in NPVs (-50.0/week, -45% from 2019, p < 1e-3). Colorectal cancer (CRC) had the largest decrease in NPVs among GI malignancies (-25.3/week, -53% from 2019, p < 1e-4). Of note, there was a parallel decrease in colonoscopies during this time (-682/week, -91% from 2019, p < 1e-11). For patients with diagnosed GI malignancies, the COVID-19 pandemic was associated with statistically significant declines in hospital admissions (-31.7/week, -37% from 2019, p < 1e-5), radiology encounters (-177/week, -38% from 2019, p < 1e-6), radiation oncology encounters (-18.2/week, -12% from 2019, p < 0.01), chemotherapy infusion visits (-62.2/week, -17% from 2019, p < 1e-4), and surgery encounters (-71.1/week, -15.7% from 2019, p < 0.01). Subgroup analyses revealed these reductions were most significant in patients with CRC (radiology encounters, surgery encounters, hospital admissions), anal cancer (radiation oncology encounters), and pancreatic cancer (chemotherapy infusion visits). Conclusions: These data demonstrate that the COVID-19 pandemic is associated with significant disruptions to care delivery. While these effects were appreciated broadly across GI malignancies, CRC—diagnosed and managed by periodic screening—has been affected most acutely. The precipitous drop in screening colonoscopies likely contributed to the decline in NPVs, specialty encounters and hospital admissions. These findings underscore the importance of reinstating regular GI cancer screening and management. Future work will assess the impact of these and other changes to cancer care delivery on long term morbidity and mortality.

A cross-sectional survey study of inpatient prescribers in a university health system was performed to assess the importance they place on different clinical risk factors when making empiric antibiotic decisions. Our findings show that these clinical risk factors were weighted differently based on the clinical scenario and the type of prescriber.