Background Individual studies have reported widely variable rates for venous thromboembolism ( VTE ) and bleeding among hospitalized patients with coronavirus disease 2019 ( COVID-19 ). Research question What is the incidence of VTE and bleeding among hospitalized patients with COVID-19? Methods In this systematic review and meta-analysis we searched 15 standard and COVID-19 specific sources between January 1, 2020 and July 31, 2020, with no restriction by language. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I 2 statistic. We assessed publication bias using Begg's and Egger's tests. Results The pooled incidence was 17.0% (95% confidence interval [ CI ], 13.4%-20.9%) for VTE, 12.1% (95% CI, 8.4%-16.4%) for DVT, 7.1% (95% CI, 5.3%-9.1%) for PE, 7.8% (95% CI, 2.6%-15.3%) for bleeding, and 3.9% (95% CI, 1.2%-7.9%) for major bleeding. In subgroup meta-analyses, the incidence of VTE was higher when assessed by screening (33.1% vs. 9.8% by clinical diagnosis), among patients in the ICU (27.9% vs. 7.1% in the ward), in prospective studies (25.5% vs. 12.4% in retrospective studies), and with the inclusion of catheter-associated thrombosis/isolated distal DVTs and isolated subsegmental PEs. The highest pooled incidence estimate of bleeding was reported for patients receiving intermediate- or full-dose anticoagulation (21.4%) and the lowest in the only prospective study that assessed bleeding events (2.7%). Interpretation Among hospitalized patients with COVID-19, the overall estimated pooled incidence of VTE was 17.0%, with higher rates with routine screening, inclusion of distal DVT and subsegmental PE, in critically ill patients, and in prospective studies. Bleeding events were observed in 7.8% of patients and were sensitive to use of escalated doses of anticoagulants, and nature of data collection. Additional studies are required to ascertain the significance of various thrombotic events and to identify strategies to improve patient outcomes.

Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8 T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8 T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8 T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients.

Background and objective: In obstructive sleep apnoea (OSA), intermittent hypoxia (IH) compromises immune surveillance through the upregulation of the programmed cell death-1 (PD-1) receptor and its ligand (PD-L1). Because the risk of OSA-related cancer depends on age, we assessed PD-L1/PD-1 expression in middle-aged and older patients with OSA as well as in a murine model. Methods: PD-L1 expression was studied in 41 patients with severe OSA and 40 healthy volunteers (HV), divided into two groups (≤55 and >55 years of age). We used flow cytometry, quantitative PCR (qPCR) and ELISA to determine PD-L1 expression on monocytes and plasma PD-L1 protein levels. Moreover, we analysed PD-L1 expression on an in vivo IH model with old and young mice. Results: In subjects up to 55 years of age, severe OSA increased PD-L1 surface protein and mRNA level expression on monocytes and soluble-PD-L1 protein concentration in plasma compared to HV. PD-L1 and hypoxia-induced factor (HIF)-1α expression correlated with age in HV, whereas in patients with OSA there was a negative relationship. In the mice exposed to IH, PD-L1 expression on F4/80+ splenocytes was also only increased in young animals. HIF-1α expression was significantly higher in patients with OSA than in HV in subjects up to 55 years of age, while PD-L1 expression in monocytes was related to HIF-1α expression in young patients with OSA. Conclusion: PD-L1 upregulation in patients with OSA as a consequence of HIF-1α activation occurs mainly in young patients. In older patients with OSA, upregulation was not detected, possibly due to impaired oxygen sensitivity. RESULTS Study subjectsForty-one patients with severe OSA were prospectively recruited, including 21 young patients (age < 55 years)Respirology (2019) 24, 684-692Age-dependent PD-L1 upregulation in OSA † † P < 0.01 versus HV younger than 55 years. ‡ ‡ P < 0.01 versus HV older than 55 years. § § P < 0.05 versus patients with OSA older than 55 years. AHI, apnoea-hypopnoea index; FEV 1 , forced expiratory volume at 1 s; FVC, forced vital capacity; HDL, high-density lipoprotein; HV, healthy volunteer; LDL, low-density lipoprotein; OSA, obstructive sleep apnoea; SpO 2 , oxyhaemoglobin saturation.

BackgroundNoninvasive ventilation (NIV) prolongs survival and quality of life in amyotrophic lateral sclerosis (ALS); however, its benefits depend upon the optimisation of both ventilation and adherence. We aimed to identify factors associated with effective initiation and ongoing use of NIV in ALS to develop evidence-based guidance and identify areas for further research.MethodsWe searched 11 electronic databases (January 1998 to May 2018) for all types of quantitative and qualitative studies. Supplementary grey literature searches were conducted. Records were screened against eligibility criteria, data were extracted from included studies and risk of bias was assessed. We present findings using a narrative synthesis.ResultsWe screened 2430 unique records and included 52 quantitative and six qualitative papers. Factors reported to be associated with NIV optimisation included coordinated multidisciplinary care, place of initiation, selection of interfaces, ventilator modes and settings appropriate for the individual patient, and adequate secretion management. The literature indicated that patients with significant bulbar dysfunction can still derive considerable benefit from NIV if their needs are met. Research emphasises that obstructive airway events, mask leak and uncontrolled secretions should be addressed by adjustments to the interface and machine settings, and the concomitant use of cough augmentation.ConclusionThis review highlights that NIV optimisation requires an individualised approach to respiratory management tailored to the differing needs of each patient. Ultimately, this should lead to improved survival and quality of life. This review expands on recommendations in current international guidelines for NIV use in ALS and identifies areas for future research.

Obstructive sleep apnoea (OSA) and pulmonary embolism (PE) remain major health issues worldwide. Data from pathophysiological studies suggest that both intermittent hypoxia and sleep fragmentation are associated with increased blood coagulability, endothelial dysfunction and venous stasis. There is growing evidence that OSA is potentially prevalent in and a risk factor for PE. Conversely, patients with acute PE have two to four times greater risk of moderate-to-severe OSA. The role of continuous positive airway pressure (CPAP) treatment in improving clinically meaningful outcomes in PE patients remains unclear, although some authors have suggested that CPAP could improve the hypercoagulability state and normalise circadian alterations in some of the coagulation molecules, as observed in patients with OSA. Emerging research highlights the complex interdependent relationships between OSA and PE, emphasising the need for rigorous, well-powered trials that address the impact of OSA and its treatment on the prevention and management of PE. Undoubtedly, these will require closer collaboration between the sleep medicine and clinical/venous thromboembolism communities.