ABSTRACT
BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19. METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations. RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism. CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results. TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.
ABSTRACT
BACKGROUND: Thromboembolism is more common in patients with critical COVID-19 than in other critically ill patients, and inflammation has been proposed as a possible mechanism. The aim of this study was to investigate if 12 mg vs. 6 mg dexamethasone daily reduced the composite outcome of death or thromboembolism in patients with critical COVID-19. METHODS: Using additional data on thromboembolism and bleeding we did a post hoc analysis of Swedish and Danish intensive care unit patients enrolled in the blinded randomized COVID STEROID 2 trial comparing 12 mg vs. 6 mg dexamethasone daily for up to 10 days. The primary outcome was a composite outcome of death or thromboembolism during intensive care. Secondary outcomes were thromboembolism, major bleeding, and any bleeding during intensive care. RESULTS: We included 357 patients. Whilst in intensive care, 53 patients (29%) in the 12 mg group and 53 patients (30%) in the 6 mg group met the primary outcome with an unadjusted absolute risk difference of - 0.5% (95% CI - 10 to 9.5%, p = 1.00) and an adjusted OR of 0.93 (CI 95% 0.58 to 1.49, p = 0.77). We found no firm evidence of differences in any of the secondary outcomes. CONCLUSIONS: Among patients with critical COVID-19, 12 mg vs. 6 mg dexamethasone daily did not result in a statistically significant difference in the composite outcome of death or thromboembolism. However, uncertainty remains due to the limited number of patients.
ABSTRACT
INTRODUCTION: PD1/PD-L1 pathway targeting therapies are nowadays an established treatment option for patients with NSCLC. We assessed whether PD-L1 expression in NSCLC tumor cells was associated with specific clinical features or overall survival using four different clones. METHODS AND RESULTS: A retrospective study included formalin-fixed paraffin embedded (FFPE) surgical tumors from 482 patients. PD-L1 status was assessed with immunohistochemistry in tumor cells on tissue microarrays using clones 28-8, 22C3, SP263 and SP142. Associations with OS were assessed by Kaplan-Meier and multivariate Cox's regression analysis. Patients' median age: 68 years (39-86); histology: adenocarcinoma (AdCa) 61%, squamous-cell carcinoma (SqCC) 33%, and large cell carcinoma (LCC) 6%; p-stage: IA (46%), IB (30%), IIA (10%), IIB (11,4%), IIIA (1,2%), IIIB - IV (0,4%). PD-L1 positivity (≥1%) in NSCLC for clones 28-8, 22C3, SP263, SP142 was 41.5%, 34.2%, 42.7%, 10.4%, respectively (Pearson Chi-square p < 0.0001). PD-L1 expression was correlated with histology, tumor size and grading. Statistically significant association between PD-L1 expression and OS in NSCLC and Non-AdCa was observed with clone SP142 (log-rank p = 0.045 and p = 0.05, respectively). Statistically significant association between PD-L1 expression and OS in LCC was observed with clones 22C3 (log-rank p = 0.009) and SP263 (log-rank p = 0.050). CONCLUSIONS: Overexpression of the PD-L1 clone SP142 was associated with poor overall survival in NSCLC and Non-AdCa. Clones 22C3 and SP263 were associated with poor prognosis in LCC. PD-L1 status might serve as a prognostic marker in NSCLC.
