Rationale: Recruited leukocytes play an important role in ventilatorinduced lung injury, although studies have focused predominantly on neutrophils. Inflammatory subset Gr-1 high monocytes are recruited to sites of inflammation and have been implicated in acute lung injury induced by systemic endotoxin. Objectives: To investigate the recruitment and role of Gr-1 high monocytes in an in vivo mouse model of ventilator-induced lung injury. Methods: Anesthetized mice were ventilated with low or high stretch. Flow cytometry was used to quantify monocyte subset margination to the lungs, and to assess their in situ cellular activation in response to mechanical stretch. To investigate monocyte involvement in lung injury progression, a two-hit model was used, with a subclinical dose of lipopolysaccharide (intraperitoneal) given 2 hours prior to highstretch ventilation. In some animals, monocytes were depleted using intravenous clodronate liposomes. Development of lung injury was assessed in ventilated animals by peak inspiratory pressure and respiratory system mechanics. Measurements and Main Results: High-stretch ventilation induced significant pulmonary margination of Gr-1 high but not Gr-1 low monocytes compared with nonventilated mice. These monocytes displayed increased activation status, with higher CD11b (vs. nonventilated mice) and lower L-selectin expression (vs. low-stretch ventilation). Lipopolysaccharide challenge led to enhanced lung margination of Gr-1 high monocytes and neutrophils, and sensitized the lungs to high stretch-induced pulmonary edema. Clodronate-liposome pretreatment depleted lung monocytes (but not neutrophils) and significantly attenuated lung injury. Conclusions: High-stretch mechanical ventilation promotes pulmonary margination of activated Gr-1 high monocytes, which play a role in the progression of ventilator-induced lung injury.

Introduction The aim of this study is to report the 30 day COVID-19 related morbidity and mortality of patients assessed as SARS-CoV-2 negative who underwent emergency or urgent orthopaedic surgery in the NHS during the peak of the COVID-19 pandemic. Method A retrospective, single centre, observational cohort study of all patients undergoing surgery between 17 March 2020 and 3May 2020 was performed. Outcomes were stratified by British Orthopaedic Association COVID-19 Patient Risk Assessment Tool. Patients who were SARS-CoV-2 positive at the time of surgery were excluded. Results Overall, 96 patients assessed as negative for SARS-CoV-2 at the time of surgery underwent 100 emergency or urgent orthopaedic procedures during the study period. Within 30 days of surgery 9.4% of patients (n = 9) were found to be SARS-CoV-2 positive by nasopharyngeal swab. The overall 30 day mortality rate across the whole cohort of patients during this period was 3% (n = 3). Of those testing positive for SARS-CoV-2 66% (n = 6) developed significant COVID-19 related complications and there was a 33% 30-day mortality rate (n = 3). Overall, the 30-day mortality in patients classified as BOA low or medium risk (n = 69) was 0%, whereas in those classified as high or very high risk (n = 27) it was 11.1%. Conclusion Orthopaedic surgery in SARS-CoV-2 negative patients who transition to positive within 30 days of surgery carries a significant risk of morbidity and mortality. In lower risk groups, the overall risk of becoming SARS-CoV-2 positive, and subsequently developing a significant postoperative related complication, was low even during the peak of the pandemic. In addition to ensuring patients are SARS-CoV-2 negative at the time of surgery it is important that the risk of acquiring SARS-CoV-2 is minimized through their recovery. Cite this article: Bone Joint Open 2020;1-8:474–480.

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