Impact of intermediate to high doses of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation.

INTRODUCTION: In addition to respiratory support needs, patients' characteristics to guide indication or timing of corticosteroid treatment in COVID-19 patients are not completely established. This study aimed to evaluate the impact of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation (PI-SSI). METHODS: Between 9 March and 5 May 2020 (final follow-up on 2 July 2020), a retrospective cohort study was conducted in hospitalised patients with COVID-19 PI-SSI (≥2 inflammatory biomarkers [IBs]: temperature ≥38℃, lymphocyte ≤800 cell/µL, C-reactive protein ≥100 mg/L, lactate dehydrogenase ≥300 units/L, ferritin ≥1000 mcg/L, D-dimer ≥500 ng/mL). Patients received 0.5-1.0 mg/kg of methylprednisolone for 5-10 days or standard of care. The primary outcome was 28-day all-cause mortality. Secondary outcomes included ≥2 points improvement on a 7-item WHO-scale (Day 14), transfer to intensive care unit (ICU) (Day 28) and adverse effects. Kaplan-Meier method and Cox proportional hazard regression were implemented to analyse the time to event outcomes. RESULTS: A total of 142 patients (corticosteroid group n = 72, control group n = 70) were included. A significant reduction in 28-day all-cause mortality was shown with methylprednisolone in patients with respiratory support (HR: 0.15; 95% CI 0.03-0.71), with ≥3 (HR: 0.17; 95% CI 0.05-0.61) or ≥4 altered IB (HR: 0.15; 95% CI 0.04-0.54) and in patients with both respiratory support and ≥3 (HR: 0.11; 95% CI 0.02-0.53] or ≥4 altered IB (HR: 0.14; 95% CI 0.04-0.51). No significant differences were found in secondary outcomes. CONCLUSION: Intermediate to high doses of methylprednisolone, initiated between 5 and 12 days after symptom onset, was associated with a significant reduction in 28-day all-cause mortality in patients with COVID-19 pneumonia and ≥3 o ≥ 4 altered IB, independently of the need of respiratory support.

Overview of venous thromboembolism.

Thrombosis occurs at sites of injury to the vessel wall, by inflammatory processes leading to activation of platelets, platelet adherence to the vessel wall and the formation of a fibrin network. A thrombus that goes on to occlude a blood vessel is known as a thromboembolism. Venous thromboembolism begins with deep vein thrombosis (DVT), which forms in the deep veins of the leg (calf) or pelvis. In some cases, the DVT becomes detached from the vein and is transported to the right-hand side of the heart, and from there to the pulmonary arteries, giving rise to a pulmonary embolism (PE). Certain factors predispose patients toward the development of venous thromboembolism (VTE), including surgery, trauma, hospitalization, immobilization, cancer, long-haul travel, increased age, obesity, major medical illness and previous VTE; in addition, there may also be a genetic component to VTE. VTE is responsible for a substantial number of deaths per annum in Europe. Anticoagulants are the mainstay of both VTE treatment and VTE prevention, and many professional organizations have published guidelines on the appropriate use of anticoagulant therapies for VTE. Treatment of VTE aims to prevent morbidity and mortality associated with the disease, and any long-term complications such as VTE recurrence or post-thrombotic syndrome. Generally, guidelines recommend the use of low molecular weight heparins (LMWH), unfractionated heparin (UFH) or fondaparinux for the pharmacological prevention and treatment of VTE, with the duration of therapy varying according to the baseline characteristics and risk profile of the individual. Despite evidence showing that the use of anticoagulation prevents VTE, the availability of several convenient, effective anticoagulant therapies and the existence of clear guideline recommendations, thromboprophylaxis is underused, particularly in patients not undergoing surgery. Greater adherence to guideline-recommended therapies, such as LMWH, which can be administered on an outpatient basis, should reduce the mortality associated with this preventable disease.

Topical issues in venous thromboembolism.

Despite clear guidelines and the availability of effective treatments, venous thromboembolism (VTE) remains relatively common, particularly in the hospital setting. This paper reviews topical issues in VTE, in terms of treatments, data and guidelines. Existing anticoagulants have several limitations. Bleeding risk is a concern with all anticoagulants. Vitamin K antagonists are the mainstay of oral anticoagulant therapy, but they are limited by the need for frequent monitoring. Unfractionated heparin (UFH) is limited by an inconvenient route of administration (continuous intravenous infusion) and a higher risk of heparin-induced thrombocytopenia and bleeding compared with low molecular weight heparins (LMWH). LMWH have a more predictable pharmacokinetic profile and greater bioavailability than UFH, which permits weight-adjusted LMWH dosing without the need for monitoring in most patients. LMWH also have a more convenient dosing strategy than UFH (once-daily subcutaneous injection). Fondaparinux is a selective inhibitor of factor Xa and, like LMWH, does not require monitoring. The efficacy of fondaparinux in long-term VTE treatment remains to be established. The optimal time to initiate thromboprophylaxis in patients undergoing orthopaedic surgery remains controversial. Initiating thromboprophylaxis just before or soon after surgery (the 'just-in-time' strategy) achieves better thromboprophylaxis but could increase the risk of bleeding complications. Balancing the need for extended thromboprophylaxis after major surgery with the need to minimize bleeding remains an important consideration. Despite clear guidelines, thromboprophylaxis is widely underused, particularly in medical patients, in whom rates as low as 28% have been reported. Electronic alert systems may be of value for increasing the use of adequate thromboprophylaxis. The use of different definitions of VTE and bleeding in clinical trials, together with missing venography data, conflicting guidelines in patients undergoing total hip or knee arthroplasty, and the limited amount of data in children, also make VTE prevention and management more difficult. Administering thromboprophylaxis to a wider group of patients, employing the 'just-in-time' protocols, ensuring adequate duration of thromboprophylaxis, combining different methods of thromboprophylaxis and developing new anticoagulants should help to improve thromboprophylaxis.