IntroductionPneumothorax and pneumomediastinum have both been noted to complicate cases of COVID-19 requiring hospital admission. We report the largest case series yet described of patients with both these pathologies that includes non-ventilated patients.MethodsCases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival.ResultsSeventy-one patients from 16 centres were included in the study, of whom 60 patients had pneumothoraces (six also with pneumomediastinum), whilst 11 patients had pneumomediastinum alone. Two of these patients had two distinct episodes of pneumothorax, occurring bilaterally in sequential fashion, bringing the total number of pneumothoraces included to 62. Clinical scenarios included patients who had presented to hospital with pneumothorax, patients who had developed pneumothorax or pneumomediastinum during their inpatient admission with COVID-19 and patients who developed their complication whilst intubated and ventilated, either with or without concurrent extracorporeal membrane oxygenation. Survival at 28 days was not significantly different following pneumothorax (63.1%±6.5%) or isolated pneumomediastinum (53.0%±18.7%; p=0.854). The incidence of pneumothorax was higher in males. The 28-day survival was not different between the sexes (males 62.5%±7.7% versus females 68.4%±10.7%; p=0.619). Patients above the age of 70 had a significantly lower 28-day survival than younger individuals (≥70 years 41.7%±13.5% survival versus <70 years 70.9%±6.8% survival; p=0.018 log-rank).ConclusionThese cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and we encourage active treatment to be continued where clinically possible.

During heart transplantation, storage in cold preservation solution is thought to protect the organ by slowing metabolism; by providing osmotic support; and by minimising ischaemia-reperfusion (IR) injury upon transplantation into the recipient 1,2 . Despite its widespread use our understanding of the metabolic changes prevented by cold storage and how warm ischaemia leads to damage is surprisingly poor. Here, we compare the metabolic changes during warm ischaemia (WI) and cold Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Aims Succinate accumulates several-fold in the ischemic heart and is then rapidly oxidised upon reperfusion, contributing to reactive oxygen species (ROS) production by mitochondria. In addition, a significant amount of the accumulated succinate is released from the heart into the circulation at reperfusion, potentially activating the G-protein coupled succinate receptor (SUCNR1). However, the factors that determine the proportion of succinate oxidation or release, and the mechanism of this release, are not known. Methods and results To address these questions, we assessed the fate of accumulated succinate upon reperfusion of anoxic cardiomyocytes, and of the ischemic heart both ex vivo and in vivo. The release of accumulated succinate was selective and was enhanced by acidification of the intracellular milieu. Furthermore, pharmacological inhibition, or haploinsufficiency of the monocarboxylate transporter 1 (MCT1) significantly decreased succinate efflux from the reperfused heart. Conclusion Succinate release upon reperfusion of the ischemic heart is mediated by MCT1 and is facilitated by the acidification of the myocardium during ischemia. These findings will allow the signalling interaction between succinate released from reperfused ischemic myocardium and SUCNR1 to be explored. Translational Perspectives In this study we demonstrate that succinate efflux upon reperfusion of the ischemic myocardium is mediated by the monocarboxylate transporter 1 (MCT1) and is enhanced by the ischemic acidification of the heart. These findings are an important advance in understanding how succinate is released upon reperfusion of ischemic organs. While this pathway is therapeutically tractable, greater understanding of the effects of succinate release is required before exploring this possibility.

Studies from a number of laboratories have shown that the myeloid lineage is prominent in human cytomegalovirus (HCMV) latency, reactivation, dissemination, and pathogenesis. Existing as a latent infection in CD34؉ progenitors and circulating CD14 ؉ monocytes, reactivation is observed upon differentiation to mature macrophage or dendritic cell (DC) phenotypes. Langerhans' cells (LCs) are a subset of periphery resident DCs that represent a DC population likely to encounter HCMV early during primary infection. Furthermore, we have previously shown that CD34؉ derived LCs are a site of HCMV reactivation ex vivo. Accordingly, we have utilized healthy-donor CD34 ؉ cells to study latency and reactivation of HCMV in LCs. However, the increasing difficulty acquiring healthy-donor CD34؉ cells-particularly from seropositive donors due to the screening regimens used-led us to investigate the use of CD14 ؉ monocytes to generate LCs. We show here that CD14 ؉ monocytes cultured with transforming growth factor ␤ generate Langerin-positive DCs (MoLCs). Consistent with observations using CD34 ؉ derived LCs, only mature MoLCs were permissive for HCMV infection. The lytic infection of mature MoLCs is productive and results in a marked inhibition in the capacity of these cells to promote T cell proliferation. Pertinently, differentiation of experimentally latent monocytes to the MoLC phenotype promotes reactivation in a maturation and interleukin-6 (IL-6)-dependent manner. Intriguingly, however, IL-6-mediated effects were restricted to mature LCs, in contrast to observations with classical CD14؉ derived DCs. Consequently, elucidation of the molecular basis behind the differential response of the two DC subsets should further our understanding of the fundamental mechanisms important for reactivation. Human cytomegalovirus (HCMV) represents an opportunistic pathogen that is a major cause of disease in a number of immunocompromised patient populations (30,60). A significant contribution to morbidity in the clinical setting results from the reactivation of latent HCMV, particularly in seropositive bone marrow transplant recipients (40). Although the mechanisms that govern HCMV reactivation have not been fully elucidated, work from a number of laboratories has shown that CD34 ϩ hematopoietic cells, and the early granulocyte-macrophage progenitors derived from them, which are normally resident in the bone marrow are an important site for the carriage of HCMV latency in vivo (27,34,53) and that reactivation is intrinsically linked with the differentiation to a more mature myeloid cell phenotype (19,37,45,56,59,64).Langerhans' cells (LCs) are a unique population of dendritic cells (DCs) resident in the epidermis and a number of mucosal tissues (e.g., nasal, oral, vaginal, and corneal). They are derived from bone marrow progenitors (26) and exhibit a capacity for self-renewal (11, 36), as well as exhibiting prodigious longevity for a DC, with a half-life of up to 78 days documented (62) and, in one case, a donor's LCs were observed to persis...