Aspirin in prevention of venous thromboembolism following hip fracture surgery: A systematic review and meta-analysis.

Background: Many orthopaedic surgeons routinely prescribe aspirin (ASA) as prophylaxis for venous thromboembolism (VTE) following hip fracture surgery (HFS). The purpose of this study is to assess the effectiveness of aspirin to other agents in preventing VTE and mortality following hip fracture surgery. Methods: Following PRISMA guidelines, we performed a search for HFS studies from 1998 to 2023 reporting comparisons between aspirin and other chemoprophylaxis methods for VTE (DVT - deep vein thrombosis; PE - pulmonary embolism). SPSS Meta-analysis function was used to calculate Mean Effect Size Estimate (MESE) and 95 % Confidence Intervals for each outcome. Reverse Fragility Index (RFI) and Fragility Quotient (FQ) were calculated for each study. Results: Of the 847 articles screened, 4 studies with 5 comparisons met the search criteria to be included for analysis. A total of 1194 participants were included in these studies. There was a decreased risk of mortality seen with use of aspirin compared to other agents (MESE = 0.86, 95 % CI: [0.07-1.66]; p=.03). There was no increased risk of DVT or PE with use of aspirin (both p>.4). The overall RFI and FQ for all 19 outcomes were 12 (IQR: 6.5-15) and 0.080 (IQR: 0.027-0.110), respectively. Ten studies (52.6 %) reported a loss-to-follow-up (LTF) greater than the overall RFI. Conclusions: Aspirin demonstrates similar protective effects on prevention of VTE compared to other agents and may have significant protective effects on overall mortality following surgical intervention for hip fractures. However, the current evidence concerning its use in this arena is less than robust, with more than half of the studied outcomes considered statistically fragile.

Cell-Type-Specific Immune Dysregulation in Severely Ill COVID-19 Patients.

Recent studies have demonstrated immunologic dysfunction in severely ill coronavirus disease 2019 (COVID-19) patients. We use single-cell RNA sequencing (scRNA-seq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMCs) from healthy (n = 3) and COVID-19 patients with moderate disease (n = 5), acute respiratory distress syndrome (ARDS, n = 6), or recovering from ARDS (n = 6). Our data reveal transcriptomic profiles indicative of defective antigen presentation and interferon (IFN) responsiveness in monocytes from ARDS patients, which contrasts with higher responsiveness to IFN signaling in lymphocytes. Furthermore, genes involved in cytotoxic activity are suppressed in both natural killer (NK) and CD8 T lymphocytes, and B cell activation is deficient, which is consistent with delayed viral clearance in severely ill COVID-19 patients. Our study demonstrates that COVID-19 patients with ARDS have a state of immune imbalance in which dysregulation of both innate and adaptive immune responses may be contributing to a more severe disease course.

Cell type-specific immune dysregulation in severely ill COVID-19 patients.

Coronavirus disease 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury called acute respiratory distress syndrome (ARDS) that causes progressive respiratory failure requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease course in COVID-19.