BACKGROUND: Optimal timing of mechanical ventilation in COVID-19 is uncertain. We sought to evaluate outcomes of delayed intubation and examine the ROX index (ie, [S pO 2 =F IO 2 ]/breathing frequency) to predict weaning from high-flow nasal cannula (HFNC) in patients with COVID-19. METHODS: We performed a multicenter, retrospective, observational cohort study of subjects with respiratory failure due to COVID-19 and managed with HFNC. The ROX index was applied to predict HFNC success. Subjects that failed HFNC were divided into early HFNC failure (^48 h of HFNC therapy prior to mechanical ventilation) and late failure (> 48 h). Standard statistical comparisons and regression analyses were used to compare overall hospital mortality and secondary end points, including time-specific mortality, need for extracorporeal membrane oxygenation, and ICU length of stay between early and late failure groups. RESULTS: 272 subjects with COVID-19 were managed with HFNC. One hundred sixty-four (60.3%) were successfully weaned from HFNC, and 111 (67.7%) of those weaned were managed solely in non-ICU settings. ROX index >3.0 at 2, 6, and 12 hours after initiation of HFNC was 85.3% sensitive for identifying subsequent HFNC success. One hundred eight subjects were intubated for failure of HFNC (61 early failures and 47 late failures). Mortality after HFNC failure was high (45.4%). There was no statistical difference in hospital mortality (39.3% vs 53.2%, P 5 .18) or any of the secondary end points between early and late HFNC failure groups. This remained true even when adjusted for covariates. CONCLUSIONS: In this retrospective review, HFNC was a viable strategy and mechanical ventilation was unecessary in the majority of subjects. In the minority that progressed to mechanical ventilation, duration of HFNC did not differentiate subjects with worse clinical outcomes. The ROX index was sensitive for the identification of subjects successfully weaned from HFNC. Prospective studies in COVID-19 are warranted to confirm these findings and to optimize patient selection for use of HFNC in this disease.

We have previously shown that local application at the time of operation of Staphylococcus aureus, nonviable S. aureus, its cell wall, or S. aureus peptidoglycan accelerates wound healing. We hypothesized that this effect is due to both direct and indirect mechanisms, among which is an increase in the inflammatory response to wounding, resulting in an increase in macrophages, angiogenesis, and fibroblasts. Twenty-seven Sprague-Dawley male rats were anesthetized, and two 7-cm paravertebral skin incisions were made. Four polyvinyl alcohol sponges, two on each side, containing either 100 microliter of isotonic saline or 0.5 mg of nonviable S. aureus or S. aureus peptidoglycan in 100-microliter saline were implanted subcutaneously. Nonviable S. aureus or S. aureus peptidoglycan (860 microgram/cm incision) in 200-microliter saline were inoculated into the incisions at closure. The rats ate a commercial rat chow and drank tap water ad libitum throughout. After days 3 and 7 postwounding, rats were euthanized, and tissues were examined for immunohistochemical features of reparative tissue using ED-1, Factor VIII, and vimentin antibodies, markers for monocyte/macrophages, endothelial cells, and mesenchymal cells (including fibroblasts), respectively. Incisions treated with nonviable S. aureus or S. aureus peptidoglycan showed more macrophages along and deep in the wound tract 7 days postoperatively. Nonviable S. aureus or S. aureus peptidoglycan-treated sponges were surrounded and penetrated by much larger capsules of reparative tissue than saline-treated sponges at both 3 and 7 days. Neutrophil influx was much greater in nonviable S. aureus or S. aureus peptidoglycan-treated sponges, especially in central regions, and there were many more ED-1-stained macrophages in distinct geographic locations, specifically, the more peripheral-cortical areas. Some clustering of macrophages occurred around areas of invasion by reparative tissue into the surrounding subcutaneous fat and within the interstices of the sponges at the interface between reparative tissue and acute inflammatory cells. In contrast, saline-treated sponge reparative tissue had significantly fewer macrophages, much thinner and flimsy reparative tissue, with proportionately fewer macrophages clustering centrally. There were many more mesenchymal cells (notably fibroblasts) and new blood vessels and much more reparative collagen in the nonviable S. aureus or S. aureus peptidoglycan-treated sponges. We conclude that local application of nonviable S. aureus or S. aureus peptidoglycan at wounding induces an increased number and alteration in location of macrophages, increased influx (or proliferation) of mesenchymal cells (notably fibroblasts), and increased angiogenesis and reparative collagen accumulation, as well as increasing the overall acute inflammatory response to wounding.

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Objective Intensive care for organ preservation (ICOP) is defined as the initiation or pursuit of intensive care not to save the patient's life, but to protect and optimize organs for transplantation. Analysis When a patient has devastating brain injury that might progress to organ donation this can be conceptualized as evolving through four consecutive stages: (1) instability, (2) stability, (3) futility and (4) finality. ICOP might be applied at any of these stages, raising different ethical issues. Only in the stage of finality is the switch from neurointensive care to ICOP ethically justified. Conclusion The difference between the stages is that during instability, stability and futility the focus must be neurointensive care which seeks the patient's recovery or an accurate neurological prognostication, while finality focuses on withdrawal of life-sustaining therapy and commencement of comfort care, which may include ICOP for deceased donation.

Harry was found near a smoking gun with his face severed from his skull. He was still breathing, so paramedics inserted an endotracheal tube and took him to the emergency room, where he displayed strong vital signs and ventilated well, with normal oxygen saturation. Surgical evaluation revealed that he had succeeded in removing everything from his chin to his ears and to his eyebrows, and had exposed and damaged numerous cranial nerves. In addition, no normal anatomical landmarks could be discerned. Debridement and a permanent tracheostomy were performed, and the remaining skin folded over.By way of past history; Harry never got much of a break in his 46 years of life. Unsuccessful marriages, failed jobs, and severe depression resulted in multiple psychiatrists and multiple suicide attempts. On this occasion, emergency teams were called to investigate a gunshot reported by his neighbours.As the anaesthesia wore off, recovery room staff were horrified to see Harry raise his left hand and examine his facial packing. An immediate neurological examination showed that he used his left arm in a semi-purposeful manner, but was otherwise unresponsive -he had deep tendon reflexes all around, and did not withdraw from painful stimuli.An electroencephalograph demonstrated 'diffuse slowing', but no other acute abnormality. Auditory evoked stimuli showed no hearing function, and coded commands on Harry's palms and chest did not result in a response in the good arm. Occasionally, Harry raised his left arm briefly into the void, but he was otherwise unresponsive. Commentary'Round- AbstractLiving wills are often considered by physicians who are faced with a dying patient. Although popular with the general public, they remain problems of authenticity and authority. It is difficult for the examining physician to know whether the patient understood the terms of the advance directive when they signed it, and whether they still consider it authoritative at the time that it is produced. Also, there is little consensus on what spectrum of instruments constitutes a binding advance directive in real life. Does a 'suicide note' constitute an authentic and authoritative 'living will'? Our panel of authorities considers this problem in a round-table discussion.