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Objectives: Critical illness in COVID-19 is attributed to an exaggerated host immune response. Since neutrophils are the major component of innate immunity, we hypothesize that the quantum of activated neutrophils in the blood may predict an adverse outcome. Design: In a retrospective study of 300 adult patients with confirmed COVID-19, we analyzed the impact of neutrophil activation (NEUT-RI), interleukin-6 (IL-6) and the established clinical risk factors of age, diabetes, obesity and hypertension on the clinical outcome. Results: Significant predictors of the need for mechanical ventilation were NEUT-RI (Odds Ratio (OR) = 1.22, P < 0.001), diabetes (OR = 2.56, P = 0.00846) and obesity (OR = 6.55, P < 0.001). For death, the significant predictors were NEUT-RI (OR = 1.14, P = 0.00432), diabetes (OR = 4.11, P = 0.00185) and age (OR = 1.04, P = 0.00896). The optimal cut-off value for NEUT-RI to predict mechanical ventilation and death was 52 fluorescence intensity units (sensitivity 44%, specificity 88%, area under the curve 0.67 and 44%, 86%, 0.64, respectively). Conclusion: This finding supports an aberrant neutrophil response in COVID-19, likely due to uncontained viral replication, tissue hypoxia and exacerbated inflammation, introduces a novel biomarker for rapid monitoring and opens new avenues for therapeutic strategies.

Summary Background There are no approved treatments for vaso-occlusive crises in sickle cell disease. Sevuparin is a novel non-anticoagulant low molecular weight heparinoid, with anti-adhesive properties. In this study, we tested whether sevuparin could shorten vaso-occlusive crisis duration in hospitalised patients with sickle cell disease. Methods We did a multicentre, double-blinded, placebo-controlled, phase 2 study in 16 public access clinical hospitals in the Netherlands, Lebanon, Turkey, Bahrain, Oman, Saudi Arabia, and Jamaica. Patients aged 12–50 years with a diagnosis of sickle cell disease (types HbSS, HbSC, HbSβ0-thalassaemia, or HbSβ+-thalassaemia) on a stable dose of hydroxyurea, hospitalised with vaso-occlusive crisis for parenteral opioid analgesia with a projected stay of more than 48 h were included in the study. Patients were randomly assigned (1:1) using a computer-generated randomisation scheme to receive sevuparin (18 mg/kg per day) or placebo (NaCl, 0·9% solution) intravenously for 2–7 days until vaso-occlusive crisis resolution. All individuals involved in the trial were masked to treatment allocation. The analysis was done in the intention-to-treat population. The primary endpoint was time to vaso-occlusive crisis resolution defined as freedom from parenteral opioid use (in preceding 6–10 h); and readiness for discharge as judged by the patient or physician. The trial is registered with ClinicalTrials.gov , NCT02515838 . Findings Between Oct 7, 2015, and Feb 10, 2019, 144 patients were randomly assigned and administered sevuparin (n=69) or placebo (n=75). The median age was 22·2 years (range 12·2–33·6), 104 (72%) 144 were adults (18 years or older), and 90 (63%) were male and 54 (37%) were female. The intention-to-treat analysis for the primary endpoint showed no significant difference in median time to vaso-occlusive crisis resolution between the sevuparin and placebo groups (100·4 h [95% CI 85·5–116·8]) vs 86·4 h [70·6–95·1]; hazard ratio 0·89 [0·6–1·3]; p=0·55). Serious adverse events occurred in 16 (22%) of 68 patients in the sevuparin group and in 21 (22%) of patients in the placebo group. The most frequent treatment-emergent adverse events were pyrexia (17 [25%] in the sevuparin group vs 17 [22%] in the placebo group), constipation (12 [18%] vs 17 [22%]), and decreased haemoglobin (18 [26%] vs 9 [12%]). There were no deaths in the sevuparin group and there was one (1%) death in the placebo group after a hyper-haemolytic episode due to alloimmunisation. Interpretation This result, as well as the results seen in other clinical studies of inhibitors of adhesion in sickle cell disease, suggest that selectin-mediated adhesion might be important in the initiation, but not maintenance of vaso-occlusion, indicating that strategies to treat vaso-occlusive crises differ from strategies to prevent this complication. Funding Modus Therapeutics.

Introduction and importance Histiocytic sarcoma (HS) is a rare, aggressive malignant neoplasm of hematopoietic cell origin. Primary HS of the proximal humerus, without involvement of lymph nodes or bone marrow, or systemic features, is very rare. Case presentation We report a rare case of primary bony HS of the proximal humerus without bone marrow involvement in a healthy 33-year-old pregnant woman. She was successfully treated with surgical resection during pregnancy and radiotherapy post-delivery. Clinical discussion This is the first report of a patient with primary bony HS during pregnancy. This highlights the fact that although HS is a neoplasm of hemolymphoid cell lineage, it frequently arises in non-lymphoid organs. Conclusion This case emphasizes the importance of a multidisciplinary approach and the need for balancing treatment risk in a patient with primary bone HS during pregnancy., Highlights • Histiocytic sarcoma is a rare aggressive malignant neoplasm of hematopoietic cell origin. • Primary bony histiocytic sarcoma during pregnancy is extremely rare and difficult to diagnose. • Treatment is challenging in a patient with histiocytic sarcoma during pregnancy.

Introduction We aim to assess the discrimination of transfused salvaged blood in predicting perioperative platelet and plasma transfusion. Methods Retrospective review was performed on all patients undergoing cardiac surgery with cell saver (CS) support. The area under the receiver operating characteristics curve was calculated. Results The discrimination achieved by transfused CS volumes in predicting perioperative platelet and plasma transfusion was poor (AUC 0.642 and 0.613 respectively). None of the covariates included (preoperative platelets, cardiopulmonary bypass use and time, aortic cross clamp time and use of aspirin or clopidogrel within 7 days of surgery) were statistically significant predictors. Conclusion Volumes of transfused CS blood have poor discrimination in predicting platelet and plasma transfusion.

Non-invasive hemoglobin estimation may increase the recruitment of blood donors. CO-oximetry hemoglobin estimation is a non-invasive method used to estimate the hemoglobin level. The primary objective of this study is to validate the pulse CO-oximetry based hemoglobin estimation in normal blood donors.We conducted a prospective observational study on 106 in a tertiary care hospital blood bank over a period of 4 weeks. We performed a Spot Hemoglobin concentration (Sp Hb) using Masimo Pronto-7 Pulse CO-oximetry, and compared it to a venous sample Hb concentration (Reference Hemoglobin; Ref Hb) measured using Abbott CELL-DYN Sapphire hematology analyzer. Age, gender, weight, height, blood pressure and reference hemoglobin were used in the multivariable linear regression model of the difference in measurement.Total of 106 donors (98 males, 8 females) were enrolled with a mean age and Ref Hb of 27 years (SD 6.2; 18-49) and 14.2 g/dL (SD 1.2; 11.5-17) respectively. The mean Sp Hb was 14.4 g/dL (SD 1.2;11.3-16.7). The mean difference between the Sp Hb and Ref Hb was 0.2 g/dL (SD 1.2;-4.5 to 3) with a correlation coefficient of 0.46 (R(2)=21%). In the multivariable model, height (p=0.015) and Hb level (p0.001) were statistically significant predictors. A strong correlation was found between the two CO-oximetry Hb measurements (coefficient 0.78, R(2)=60%).Our study validated the use of the CO-oximetry in blood donors. Larger prospective studies are needed to confirm our results.