Patient-reported disruptions to cancer care during the COVID-19 pandemic: A national cross-sectional study.

BACKGROUND: The aim of this study is to evaluate the extent and associations with patient-reported disruptions to cancer treatment and cancer-related care during the COVID-19 pandemic utilizing nationally representative data. METHODS: This analysis uses data from the 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey of US adults. Adults (age >18) who reported requiring current cancer treatment or other cancer-related medical care in the second half of 2020 were included. Estimated proportions of patients with self-reported changes, delays, or cancelations to cancer treatment or other cancer care due to the COVID-19 pandemic were calculated using sampling weights and associations with sociodemographic and other health-related variables were analyzed. RESULTS: In total, 574 (sample-weighted estimate of 2,867,326) adults reported requiring cancer treatment and/or other cancer care since the start of the COVID-19 pandemic. An estimated 32.1% reported any change, delay, or cancelation. On sample-weighted univariable analysis, patients who were younger, female, had one or fewer comorbidities, and uninsured were significantly more likely to report disruptions. On sample-weighted, multivariable analysis, patients who were younger and female remained significant predictors. Nearly 90% of patients included in the study reported virtual appointment use. Patients reporting disruptions were also significantly more likely to report feelings of anxiety. CONCLUSIONS: An estimated 1/3 of patients experienced disruptions to cancer care due to the COVID-19 pandemic. Patients experiencing disruptions in care were more likely to be female or younger which may reflect risk stratification strategies in the early stages of the pandemic, and also had higher rates of anxiety. The longitudinal impact of these disruptions on outcomes merits further study.

Pretreatment neutrophil-to-lymphocyte ratio as an important prognostic marker in stage III locally advanced non-small cell lung cancer: confirmatory results from the PROCLAIM phase III clinical trial.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is an important pretreatment marker of systemic inflammation and tumor aggressiveness. Increased levels of this ratio have been associated with reduced survival in several observational studies of lung cancer. However, supporting analyses from large clinical trial data are lacking. METHODS: To validate the prognostic role of NLR, the current study evaluated data from a randomized phase III study (PROCLAIM; clinicaltrial.gov ID: NCT00686959) of patients with stage IIIA/B, unresectable, non-squamous, non-small cell lung cancer (NSCLC), originally comparing combination pemetrexed-cisplatin chemoradiotherapy with etoposide-cisplatin chemoradiotherapy. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for survival were estimated using a Cox proportional hazards model. Models were adjusted for age, race, sex, stage, treatment, and body mass index (BMI). Patients were followed for a median of 24 months. RESULTS: Increased NLR levels at baseline were associated with reduced overall (PTrend <0.0001) and progression-free survival (PTrend <0.005). A similar but decreasing linear trend was not observed for lymphocytes count alone. CONCLUSIONS: These findings provide substantiating evidence that NLR, which is routinely available from standard blood testing of patients diagnosed with NSCLC, is an important inflammation-based prognostic marker for survival among patients with locally advanced disease undergoing chemoradiation. Future research will benefit by assessing the prognostic potential of NLR in the context of genetic mutations and molecular markers.

Determination of EPAC2 function using EPAC2 null Min6 sublines generated through CRISPR-Cas9 technology.

Min6 cells, a mouse ß cell line derived from transgenic mouse expressing the large T-antigen of SV40 in pancreatic beta cells, are commonly utilized as an in vitro cellular model for investigating targets involved in insulin secretion. Epac2, an exchange protein that can be directly activated by cyclic AMP (cAMP), is critical for pharmacologic stimuli-induced insulin secretion and has been hypothesized to be a direct target of sulfonylurea. Previous loss of function studies only specifically knocked out EPAC2 isoform A, leaving the other two isoforms intact. In this study, we investigated the function of EPAC2 in Min6 cells by generating EPAC2 knock-out sublines using CRISPR-Cas9 technology, by removing all three isoforms of EPAC2. Our results indicate that Min6 cells can be successfully cloned from a single cell after electroporation with plasmids expressing EPAC2 specific guide RNA, Cas9 and GFP, followed by sorting for GFP expressing single cells. Two clones were found to have a single nucleotide deletion in targeted site of EPAC2 gene by sequencing, therefore creating a frame shift in exon 13. The EPAC2 null clones have an unexpectedly increased secretion of insulin at basal level and an elevated total intracellular insulin content. However, EPAC2 deficiency impaires glucose and sulfonylurea induced insulin secretion without affecting sulfonylurea binding to cells. Potassium chloride induced insulin secretion remains intact. Interestingly, cAMP levels remained unchanged in EPAC2 null cells during these processes. To understand the global function of EPAC2, RNA Seq study was performed, which reveals that EPAC2 deficiency affects expression of multiple previously unrecognized genes, suggesting that EPAC2 can function through multiple pathways in addition to being a cAMP sensor.