ObjectiveTo evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function.Methods and materialCOVID-19 patients were prospectively followed up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020.Results647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitation and 56 (9%) with dyspnea. Prevalences of the three symptoms were markedly higher in severe patients than non-severe patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitation, p=0.007; 12% versus 7% for dyspnea, p=0.014). Results of multivariable regression showed an increased odd in the ongoing symptoms among severe patients (OR: 1.7, 95%CI: 1.1–2.6, p=0.026) or patients with longer hospital stay (OR: 1.03, 95%CI: 1.00–1.05, p=0.041). Pulmonary function test results were available for 81 patients, including 41 non-severe and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusion capacity for carbon monoxide (DLCO) (68% severe versus 42% non-severe patients, p=0.019). Chest CT total severity score (TSS)>10.5 (OR: 10.4; 95%CI: 2.5–44.1; p=0.001) on admission and ARDS (OR: 4.6; 95%CI: 1.4–15.5; p=0.014) were significantly associated with impaired DLCO. Pulmonary interstitial damage may be associated with abnormal DLCO.ConclusionPulmonary function, particularly DLCO, declined in COVID-19 survivors. This decrease was associated with TSS of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied DLCO.

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The goal of the current investigation was to evaluate the mechanisms through which administration of a selective cannabinoid-2 (CB2) agonist (O-1966) modifies inflammatory responses and helps to improve function following spinal cord injury. A comparison of motor function, autonomic function, and inflammatory responses was made between animals treated with O-1966 (5 mg/kg IP) and animals treated with vehicle 1 h and 24 h following contusion injury to the spinal cord. Motor function was significantly improved in the treated animals at each time point during the 14 days of evaluation. The percentage of animals able to spontaneously void their bladder was also greater over the entire study period in the group treated with the selective CB2 agonist. Seven days following injury there was a significant reduction in both hematopoietic and myeloid cell invasion of the spinal cord, and a reduction in the number of immunoreactive microglia. The results of the evaluation of chemokine/cytokine expression and inflammatory cell invasion also demonstrated a significant effect of treatment on inflammatory reactions following injury. Two days after injury, animals treated with O-1966 had significant reductions in CXCL-9 and CXCL-11, and dramatic reductions in IL-23p19 expression and its receptor IL-23r. Treatment with O-1966 also caused inhibition of toll-like receptor expression (TLR1, TLR4, TLR6 and TLR7) following injury. These results demonstrate that the improvement in motor and autonomic function resulting from treatment with a selective CB2 agonist is associated with a significant effect on inflammatory responses in the spinal cord following injury.

Coagulation factor XI (FXI) plays an important part in both venous and arterial thrombosis, rendering FXIa a potential target for the development of antithrombotic therapy. The kunitz protease inhibitor (KPI) domain of protease nexin-2 (PN2) is a potent, highly specific inhibitor of FXIa, suggesting its possible role in the inhibition of FXI-dependent thrombosis in vivo. Therefore, we examined the effect of PN2KPI on thrombosis in the murine carotid artery and the middle cerebral artery. Intravenous administration of PN2KPI prolonged the clotting time of both human and murine plasma, and PN2KPI inhibited FXIa activity in both human and murine plasma in vitro. The intravenous administration of PN2KPI into WT mice dramatically decreased the progress of FeCl 3 -induced thrombus formation in the carotid artery. After a similar initial rate of thrombus formation with and without PN2KPI treatment, the propagation of thrombus formation after 10 minutes and the amount of thrombus formed were significantly decreased in mice treated with PN2KPI injection compared with untreated mice. In the middle cerebral artery occlusion model, the volume and fraction of ischemic brain tissue were significantly decreased in PN2KPI-treated compared with untreated mice. Thus, inhibition of FXIa by PN2KPI is a promising approach to antithrombotic therapy. (Blood. 2012;120(3):671-677) IntroductionCoagulation factor XI (FXI) has an essential role both in maintaining normal hemostasis and in the pathogenesis of thrombosis. 1 Because deficiencies of factor XII (FXII), prekallikrein, and high M r kininogen are not associated with hemostatic abnormalities but FXI deficiency produces relatively mild, posttraumatic bleeding complications in ϳ 50% of affected individuals, 2-4 the more relevant pathway for activation of plasma FXI might be via feedback activation by thrombin or possibly autoactivation by FXIa. 5,6 High levels of FXI constitute a risk factor for deep venous thrombosis (DVT) 7 and cardiovascular disease in women. 8 Although inherited FXI deficiency confers no protection against acute myocardial infarction (AMI), 9 a large clinical study showed that the risk of DVT in the 10% of individuals in a population with the highest levels of FXI was Ͼ 2-fold greater than that for the remaining 90% of the population, supporting the conclusion that elevated FXI levels constitute an important risk factor for venous thrombosis. 7,8,10 There is also a reduced incidence of ischemic stroke in patients with severe FXI deficiency. 11 One study followed 600 patients with a first episode of venous thromboembolism and found an increased risk of recurrence, especially among those with increased levels of thrombin-activatable fibrinolysis inhibitor (TAFI) and FXI, 12 whereas another study showed that increased levels of TAFI, but not FXI, increased the risk of venous thromboembolism in patients with FV Leiden carrier status. 10 These studies are consistent with the results of studies demonstrating increased rabbit jugular vein thrombolysis by FXI Ab neutrali...

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