Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity

Specific functions of the immune system are essential to protect us from infections caused by pathogens such as viruses and bacteria. However, as we age, the immune system shows a functional decline that can be attributed in large part to age-associated defects in hematopoietic stem cells (HSCs)-the cells at the apex of the immune cell hierarchy. Here, we find that the Hippo pathway coactivator TAZ is potently induced in old HSCs and protects these cells from functional decline. We identify Clca3a1 as a TAZ-induced gene that allows us to trace TAZ activity in vivo. Using CLCA3A1 as a marker, we can isolate "young-like" HSCs from old mice. Mechanistically, Taz acts as coactivator of PU.1 and to some extent counteracts the gradual loss of PU.1 expression during HSC aging. Our work thus uncovers an essential role for Taz in a previously undescribed fail-safe mechanism in aging HSCs. Immune system function declines with age, a consequence of defects in hematopoietic stem cells (HSCs). Here the authors show that TAZ buffers age-related loss of PU.1 activity to maintain HSC functionality and identify the surface protein Clca3a1 as a marker of "young-like" HSCs, even in old mice

Head and neck cancer surgery during the COVID-19 pandemic: An international, multicenter, observational cohort study

Background: The aims of this study were to provide data on the safety of head and neck cancer surgery currently being undertaken during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This international, observational cohort study comprised 1137 consecutive patients with head and neck cancer undergoing primary surgery with curative intent in 26 countries. Factors associated with severe pulmonary complications in COVID-19–positive patients and infections in the surgical team were determined by univariate analysis. Results: Among the 1137 patients, the commonest sites were the oral cavity (38%) and the thyroid (21%). For oropharynx and larynx tumors, nonsurgical therapy was favored in most cases. There was evidence of surgical de-escalation of neck management and reconstruction. Overall 30-day mortality was 1.2%. Twenty-nine patients (3%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 30 days of surgery; 13 of these patients (44.8%) developed severe respiratory complications, and 3.51 (10.3%) died. There were significant correlations with an advanced tumor stage and admission to critical care. Members of the surgical team tested positive within 30 days of surgery in 40 cases (3%). There were significant associations with operations in which the patients also tested positive for SARS-CoV-2 within 30 days, with a high community incidence of SARS-CoV-2, with screened patients, with oral tumor sites, and with tracheostomy. Conclusions: Head and neck cancer surgery in the COVID-19 era appears safe even when surgery is prolonged and complex. The overlap in COVID-19 between patients and members of the surgical team raises the suspicion of failures in cross-infection measures or the use of personal protective equipment. Lay Summary: Head and neck surgery is safe for patients during the coronavirus disease 2019 pandemic even when it is lengthy and complex. This is significant because concerns over patient safety raised in many guidelines appear not to be reflected by outcomes, even for those who have other serious illnesses or require complex reconstructions. Patients subjected to suboptimal or nonstandard treatments should be carefully followed up to optimize their cancer outcomes. The overlap between patients and surgeons testing positive for severe acute respiratory syndrome coronavirus 2 is notable and emphasizes the need for fastidious cross-infection controls and effective personal protective equipment

Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic.

BACKGROUND: Surgical services are preparing to scale up in areas affected by COVID-19. This study aimed to evaluate the association between preoperative SARS-CoV-2 testing and postoperative pulmonary complications in patients undergoing elective cancer surgery. METHODS: This international cohort study included adult patients undergoing elective surgery for cancer in areas affected by SARS-CoV-2 up to 19 April 2020. Patients suspected of SARS-CoV-2 infection before operation were excluded. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery. Preoperative testing strategies were adjusted for confounding using mixed-effects models. RESULTS: Of 8784 patients (432 hospitals, 53 countries), 2303 patients (26.2 per cent) underwent preoperative testing: 1458 (16.6 per cent) had a swab test, 521 (5.9 per cent) CT only, and 324 (3.7 per cent) swab and CT. Pulmonary complications occurred in 3.9 per cent, whereas SARS-CoV-2 infection was confirmed in 2.6 per cent. After risk adjustment, having at least one negative preoperative nasopharyngeal swab test (adjusted odds ratio 0.68, 95 per cent confidence interval 0.68 to 0.98; P = 0.040) was associated with a lower rate of pulmonary complications. Swab testing was beneficial before major surgery and in areas with a high 14-day SARS-CoV-2 case notification rate, but not before minor surgery or in low-risk areas. To prevent one pulmonary complication, the number needed to swab test before major or minor surgery was 18 and 48 respectively in high-risk areas, and 73 and 387 in low-risk areas. CONCLUSION: Preoperative nasopharyngeal swab testing was beneficial before major surgery and in high SARS-CoV-2 risk areas. There was no proven benefit of swab testing before minor surgery in low-risk areas