High-dose intravenous vitamin C attenuates hyperinflammation in severe coronavirus disease 2019.

OBJECTIVE: High-dose intravenous vitamin C (HIVC) is a major concern when treating patients with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the clinical efficacy of HIVC on hyperinflammation in patients with severe COVID-19. METHODS: This retrospective cohort study included hospitalized patients with severe COVID-19, a subset of whom was treated with HIVC. The medical records were screened for demographic data, laboratory findings, and medications, as well as initial and repeated values of multiple inflammatory markers for analysis. RESULTS: A high percentage of patients presented with hyperinflammation based on inflammatory marker levels above the upper limit of normal (high-sensitivity C-reactive protein, 80.1%; interleukin-6, 91.5%; and tumor necrosis factor-α, 67.4%). Eighty-five (36%) patients received HIVC therapy. After treatment with HIVC, the levels of inflammatory markers displayed a significant decrease compared with those of patients without HIVC. Furthermore, the percentages of reduction in inflammatory marker levels were higher in patients receiving HIVC compared with those in patients treated without HIVC. Stepwise multiple linear regression analysis revealed that HIVC was independently associated with percentages of reduction in levels of inflammatory markers. CONCLUSIONS: HIVC has the potential benefit of attenuating hyperinflammation by reducing inflammatory marker levels in patients with severe COVID-19.

Prevention of neointimal formation after angioplasty using tetramethylpyrazine-coated balloon catheters in a rabbit iliac artery model.

BACKGROUND: Restenosis remains a clinical problem; drug-coated balloons (DCBs) have demonstrated high efficiency in this situation. DCBs prevent neointimal hyperplasia by inhibiting cell proliferation and migration. Tetramethylpyrazine (TMP) is a traditional Chinese medicine originally isolated from the rhizome of Ligusticum Walliichii, which can inhibit platelet aggregation and smooth muscle cell proliferation. We hypothesized that TMP-coated balloons (TCB) could reduce neointimal hyperplasia through the NF-κB signalling pathway. METHODS: Twenty-one New-Zealand White rabbits (2.5-3.0 kg, male) were fed high-fat diets; 36 bilateral iliac artery stenosis models were successfully established by balloon straining. Rabbits were randomly treated with TCB (n=20) or plain balloons (PBA, n=16) (3 died during model construction). Angiographies were recorded at baseline, the immediate period, and 4 weeks later. Animals were euthanized and arteries collected for histological analysis and immunohistochemical staining. Protein expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 of the vessel samples were analyzed using Western blotting. RESULTS: No difference existed in the baseline lesion characteristics or procedural results. Angiographic follow-up was successfully performed on 18 rabbits (TCB: n=20, PBA: n=16), except for 3 deaths related to the operation. Treatment with TCB was superior to that with PBA, with lower late lumen loss (0.45±0.23 vs. 0.84±0.17 mm, P<0.01). Pathological analysis confirmed the efficiency of TCB through decreasing the area stenosis rate compared with PBA (46.48%±8.22% vs. 75.24%±6.10%, P<0.01). As determined by Western blotting, significant reductions occurred in PCNA and NF-κB p65 protein intensity in the TCB group versus the PBA group (all P<0.01). TCB efficiently mitigated restenosis in the rabbit iliac artery model. CONCLUSIONS: This study elucidated that TCB could restrain intimal hyperplasia of vessels by inhibiting the activation of the NF-κB pathway to reduce inflammatory response and decrease the rate of cell proliferation through suppressing PCNA expression.