@ERSpublications These data showed that age ⩾65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3 + CD8 + T-cells ⩽75 cells·μL −1 and cardiac troponin I ⩾0.05 ng·mL −1 were four risk factors predicting high mortality of COVID-19 pneumonia patients https://bit.ly/2Rh6NqvABSTRACT The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ⩾65 years (OR 3.765, 95% CI 1.146-17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755-8.044; p=0.007), CD3 + CD8 + T-cells ⩽75 cells·μL −1 (OR 3.982, 95% CI 1.132-14.006; p<0.001) and cardiac troponin I ⩾0.05 ng·mL −1 (OR 4.077, 95% CI 1.166-14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age-and comorbid illness-matched case-control study, CD3 + CD8 + T-cells ⩽75 cells·μL −1 and cardiac troponin I ⩾0.05 ng·mL −1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ⩾65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3 + CD8 + T-cells ⩽75 cells·μL −1 and cardiac troponin I ⩾0.05 ng·mL −1 . The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.

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Purpose: Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that ascorbate concentrations achievable with i.v. dosing would be cytotoxic in pancreatic cancer for which the 5-year survival is <3%.Experimental Design: Pancreatic cancer cell lines were treated with ascorbate (0, 5, or 10 mmol/L) for 1 hour, then viability and clonogenic survival were determined. Pancreatic tumor cells were delivered s.c. into the flank region of nude mice and allowed to grow at which time they were randomized to receive either ascorbate (4 g/kg) or osmotically equivalent saline (1 mol/L) i.p. for 2 weeks.Results: There was a time-and dose-dependent increase in measured H 2 O 2 production with increased concentrations of ascorbate. Ascorbate decreased viability in all pancreatic cancer cell lines but had no effect on an immortalized pancreatic ductal epithelial cell line. Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines, which was reversed by treatment of cells with scavengers of H 2 O 2 . Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy. In vivo, treatment with ascorbate inhibited tumor growth and prolonged survival.Conclusions: These results show that pharmacologic doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer. Clin Cancer Res; 16(2); 509-20.

Background Treatment of pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in pre-clinical models. A phase I clinical trial was performed to establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma. Design Nine subjects received twice weekly intravenous ascorbate (15–125 g) employing Simon’s Accelerated Titration design to achieve a targeted post-infusion plasma level of ≥ 350 mg/dL (≥20 mM). Subjects received concurrent gemcitabine. Disease burden, weight, performance status, hematologic and metabolic labs, time to progression and overall survival were monitored. Results Mean plasma ascorbate trough levels were significantly higher than baseline (1.46 ± 0.02 vs. 0.78 ± 0.09 mg/dL, i.e. 83 vs. 44μM, p < 0.001). Adverse events attributable to the drug combination were rare and included diarrhea (n = 4) and dry mouth (n = 6). Dose-limiting criteria were not met for this study. Mean survival of subjects completing at least 2 cycles (8 weeks) of therapy was 13 ± 2 months. Conclusions Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well-tolerated. Initial data from this small sampling suggest some efficacy. Further studies powered to determine efficacy should be conducted.

Ascorbate (AscH−) functions as a versatile reducing agent. At pharmacological doses (P-AscH−; [plasma AscH−] ≥≈20 mM), achievable through intravenous delivery, oxidation of P-AscH− can produce a high flux of H2O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We hypothesize that sensitivity of tumor cells to P-AscH− compared to normal cells is due to their lower capacity to metabolize H2O2. Rate constants for removal of H2O2 (kcell) and catalase activities were determined for 15 tumor and 10 normal cell lines of various tissue types. A differential in the capacity of cells to remove H2O2 was revealed, with the average kcell for normal cells being twice that of tumor cells. The ED50 (50% clonogenic survival) of P-AscH− correlated directly with kcell and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH−.