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A hypercoagulable state has been described in coronavirus disease 2019 (COVID-19) patients. Others have reported a survival advantage with prophylactic anticoagulation (pAC) and therapeutic anticoagulation (tAC), but these retrospective analyses have important limitations such as confounding by indication. We studied the impact of tAC and pAC compared with no anticoagulation (AC) on time to death in COVID-19. We performed a cross-sectional analysis of 127 deceased COVID-19 patients and compared time to death in those who received tAC (n = 67), pAC (n = 47), and no AC (n = 13). Median time to death was longer with higher doses of AC (11 days for tAC, 8 days for pAC, and 4 days for no AC, p < 0.001). In multivariate analysis, AC was associated with longer time to death, both at prophylactic (hazard ratio [HR] = 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p < 0.001) and therapeutic doses (HR = 0.15; 95% CI: 0.07 to 0.32; p < 0.001) compared with no AC. Bleeding rates were similar among tAC and remaining patients (19 vs. 18%; p = 0.877). In deceased COVID-19 patients, AC was associated with a delay in death in a dose-dependent manner. Randomized trials are required to prospectively investigate the benefit and safety of higher doses of AC in this population.

BackgroundDuring endochondral bone formation, the hypertrophy of chondrocytes is accompanied by selective expression of several genes including type X collagen and alkaline phosphatase. This expression is stimulated by inducers including BMPs and ascorbate. A 316 base pair region of the type X collagen (Col X) promoter has been previously characterized as the site required for BMP regulation. The intent of this study was to examine the role of Mitogen Activated Protein (MAP) and related kinase pathways in the regulation of Col X transcription and alkaline phosphatase activity in pre-hypertrophic chick chondrocytes.ResultsUsing a luciferase reporter regulated by the BMP-responsive region of the type X collagen promoter, we show that promoter activity is increased by inhibition of extra-cellular signal regulated kinases 1 or 2 (ERK1/2). In contrast the ability of BMP-2 to induce alkaline phosphatase activity is little affected by ERK1/2 inhibition. The previously demonstrated stimulatory affect of p38 on Col X was shown to act specifically at the BMP responsive region of the promoter. The inhibitory effect of the ERK1/2 pathway and stimulatory effect of the p38 pathway on the Col X promoter were confirmed by the use of mutant kinases. Inhibition of upstream kinases: protein kinase C (PKC) and phosphatidylinositol 3-(PI3) kinase pathways increased basal Col X activity but had no effect on the BMP-2 induced increase. In contrast, ascorbate had no effect on the BMP-2 responsive region of the Col X promoter nor did it alter the increase in promoter activity induced by ERK1/2 inhibition. The previously shown increase in alkaline phosphatase activity induced by ascorbate was not affected by any kinase inhibitors examined. However some reduction in the alkaline phosphatase activity induced by the combination of BMP-2 and ascorbate was observed with ERK1/2 inhibition.ConclusionOur results demonstrate that ERK1/2 plays a negative role while p38 plays a positive role in the BMP-2 activated transcription of type X collagen. This regulation occurs specifically at the BMP-2 responsive promoter region of Col X. Ascorbate does not modulate Col X at this region indicating that BMP-2 and ascorbate exert their action on chondrocyte hypertrophy via different transcriptional pathways. MAP kinases seem to have only a modest effect on alkaline phosphatase when activity is induced by the combination of both BMP-2 and ascorbate.

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Primary meningococcal pericarditis (PMP) is a rare form of purulent pericarditis that can occur in the event of N. Meningitidis bacteremia without meningitis or fulminant septicemia. This form of pericarditis can be infectious or immunologic and in either form, can cause life threatening tamponade (1). Here described is a case of rapidly evolving purulent pericarditis and pleural effusion in a patient with meningococcal bacteremia.