The synthesis of oxidized graphene nanoribbons (O-GNR) via longitudinal unzipping of carbon nanotubes opens avenues for their further development for a variety of biomedical applications. Evaluation of the cyto- and bio-compatibility is necessary to develop any new material for in vivo biomedical applications. In this study, we report the cytotoxicity screening of O-GNRs water-solubilized with PEG-DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)]), using six different assays, in four representative cell lines; Henrietta Lacks cells (HeLa) derived from cervical cancer tissue, National Institute of Health 3T3 mouse fibroblast cells (NIH-3T3), Sloan Kettering breast cancer cells (SKBR3) and Michigan cancer foundation-7 breast cancer cells (MCF7). These cell lines significantly differed in their response to O-GNR-PEG-DSPE formulations; assessed and evaluated using various endpoints (lactate dehydrogenase (LDH) release, cellular metabolism, lysosomal integrity and cell proliferation) for cytotoxicity. In general, all the cells showed a dose-dependent (10–400 μg/ml) and time-dependent (12–48 h) decrease in cell viability. However, the degree of cytotoxicity was significantly lower in MCF7 or SKBR3 cells compared to HeLa cells. These cells were 100% viable upto 48 hours, when incubated at 10μg/ml O-GNR-PEG-DSPE concentration, and showed decrease in cell viability above this concentration with ~78% of cells viable at the highest concentration (400 μg/ml). In contrast, significant cell death (5–25% cell death depending on the time point, and the assay) was observed for HeLa cells even at a low concentration of 10μg/ml. The decrease in cell viability was steep with increase in concentration with the CD50 values ≥ 100μg/ml depending on the assay, and time point. Transmission electron microscopy of the various cells treated with the O-GNR solutions show higher uptake of the O-GNR-PEG-DSPEs into HeLa cells compared to other cell types. Additional analysis indicates that this increased uptake is the dominant cause of the significantly higher toxicity exhibited by HeLa cells. The results suggest that water-solubilized O-GNR-PEG-DSPEs have a heterogeneous cell-specific cytotoxicity, and have significantly different cytotoxicity profile compared to graphene nanoparticles prepared by the modified Hummer’s method (graphene nanoparticles prepared by oxidation of graphite, and its mechanical exfoliation) or its variations.

Background and aims The prevalence and significance of digestive manifestations in COVID-19 remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. Methods Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were manually abstracted from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. Findings A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were elevated to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio 0.93, 95% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death. Conclusion Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common but the majority were mild and their presence was not associated with a more severe clinical course.

Background: The prevalence and significance of digestive manifestations in COVID-19 remain uncertain. Methods: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were manually abstracted from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. Results: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were elevated to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio 0.93, 95% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death. Conclusions: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common but the majority were mild and their presence was not associated with a more severe clinical course.

Key Points Question Are health care workers (HCWs) at risk of worse outcomes associated with coronavirus disease 2019 (COVID-19) compared with the general population? Findings This propensity-matched multicenter cohort study included 122 HCWs hospitalized with COVID-19 matched to 366 non-HCWs hospitalized with COVID-19. The odds of the primary outcome—mechanical ventilation or death—were not significantly different for HCWs compared with non-HCWs. Meaning This study finds that HCW status is not associated with poorer outcomes among patients hospitalized with COVID-19.

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Measurements: We captured baseline demographic, pre-hospitalization antiplatelet medication use, and clinical encounter data for all patients who met inclusion criteria. The primary endpoint was peak score on a 6point modified ordinal scale (MOS), which is based on World Health Organization blueprint R&S groups, used to grade severity of illness through clinical outcomes of interest. Scores indicate the following: 1 À COVID-19 infection not requiring hospitalization, 2 À requiring hospitalization but not supplemental oxygen, 3 À hospitalization requiring supplemental oxygen, 4 À hospitalization requiring high-flow nasal cannula (HFNC) or non-invasive positive pressure ventilation (NIPPV), 5 À hospitalization requiring intubation or extracorporeal membrane oxygenation (ECMO), 6 À death. Multivariable adjusted partial proportional odds model (PPOM) was performed to examine the association between pre-hospitalization antiplatelet medication use and likelihood of each MOS score. Main Results: Of 762 people admitted with COVID-19, 239 (31.4%) used antiplatelet medications pre-hospitalization while 523 (68.6%) did not. Antiplatelet users were older and had more co-morbidities at baseline. Before adjusting for covariates, patients who used antiplatelet medications pre-hospitalization were more likely than non-users to have peak MOS score 6 (death, OR 1.75, 95% CI 1.21À2.52), peak MOS score 5 (intubation/ECMO or death, OR 1.4, 95% CI 1.00À1.98) and peak MOS score 4 (HFNC, NIPPV, intubation/ECMO or death, OR 1.40, 95% CI 1.01À1.94). On multivariable adjusted PPOM analysis controlling for 13 covariates, there were no longer any significant differences in peak MOS scores between users and non-users. Conclusions: After adjusting for covariates, pre-hospital antiplatelet use was not associated with COVID-19 severity in hospitalized patients.

Background & Aims Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous neoplasms. Although some have a relatively benign and indolent natural history, others can be aggressive and ultimately fatal. Somatostatin analogues (SSAs) improve both quality of life and survival for these patients once they develop metastatic disease. However, these drugs are costly and their cost-effectiveness is not known. Methods A decision-analytic model was developed and analyzed to compare two treatment strategies for patients with Stage IV GEP-NETs. The first strategy had all patients start SSA immediately while the second strategy waited, reserving SSA initiation until the patient showed signs of progression. Sensitivity analysis was performed to explore model parameter uncertainty. Results Our model of patients age 60 with metastatic GEP-NETs suggests empiric initiation of SSA led to an increase 0.62 unadjusted life-years and incremental increase in quality-adjusted life years (QALYs) of 0.44. The incremental costs were $388,966 per QALY and not cost-effective at a willingness-to-pay threshold of $100,000. Death was attributed to GEP-NETs for 94.1% of patients in the SSA arm vs. 94.9% of patients in the DELAY SSA arm. Sensitivity analysis found that the model was most sensitive to costs of SSAs. Using probabilistic sensitivity analysis, the SSA strategy was only cost-effective 1.4% of the time at a WTP threshold of $100,000 per QALY. Conclusions Our modeling study finds it is not cost-effective to initiate SSAs at time of presentation for patients with metastatic GEP-NETs. Further clinical studies are needed to identify the optimal timing to initiate these drugs.