Scientific reports
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Gene editing using CRISPR/Cas9 is a promising method to cure many human genetic diseases. We have developed an efficient system to deliver Cas9 into the adeno-associated virus integration site 1 (AAVS1) locus, known as a safe harbor, using lentivirus and AAV viral vectors, as a step toward future in vivo transduction. ⋯ Then, Cas9v1 was removed from the genome by another AAV vector containing sgRNA targeting the long terminal repeat of the lentivirus vector. The reconstituted Cas9v2 in the AAVS1 locus was functional and gene editing was efficient.
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Currently, infections with SARS-Coronavirus-2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, are responsible for substantial morbidity and mortality worldwide. Older adults subjects > 60 years of age account for > 95% of the over one million fatal cases reported to date. It is unclear why in this age group SARS-CoV-2 infection causes more severe disease than in young adults. ⋯ To the best of our knowledge, this is the first time that the presence of cross-reactive T cells to SARS-CoV-2 is compared in young and older adults. Our findings provide at least a partial explanation for the more severe clinical outcome of SARS-CoV-2 infection observed in the elderly. Moreover, this information could help to design efficacious vaccines for this age group, aiming at the induction of cell-mediated immunity.
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The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. ⋯ According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 > 200 mmHg, and a lymphocyte count at admission > 1.0 × 109/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.
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Multicenter Study Historical Article
Improvement in fast-track hip and knee arthroplasty: a prospective multicentre study of 36,935 procedures from 2010 to 2017.
"Fast-track" protocols has improved surgical care with a reduction in length of hospital stay (LOS) in total hip (THA) and knee arthroplasty (TKA). However, the effects of continuous refinement of perioperative care lack detailed assessment. We studied time-related changes in LOS and morbidity after THA and TKA within a collaboration with continuous scientific refinement of perioperative care. ⋯ LOS declined from three [two to three] days in 2010 to one [one to two] day in 2017. LOS > 4 days due to "medical" or "surgical" complications, and "with no recorded morbidity" declined from 4.4 to 2.7%, 1.5 to 0.6%, and 3.8 to 1.3%, respectively. 90-days readmission rate declined from 8.6 to 7.7%. Our multicentre study in a socialized healthcare setting was associated with a continuous reduction in LOS and morbidity after THA and TKA.
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Although both pre- and postoperative myocardial injuries are strongly associated with an increased postoperative mortality, no study has directly compared the effects of pre- and postoperative myocardial injuries on 30-day mortality after non-cardiac surgery. Therefore, we evaluated and compared the effects of pre- and postoperative myocardial injury on 30-day mortality after non-cardiac surgery. From January 2010 to December 2016, patients undergoing non-cardiac surgery were stratified into either the normal (n = 3182), preoperative myocardial injury (n = 694), or postoperative myocardial injury (n = 756) groups according to the peak cardiac troponin value. ⋯ In patients undergoing non-cardiac surgery, preoperative myocardial injury also increased postoperative 30-day mortality to a similar degree of postoperative myocardial injury. Further studies on the importance of preoperative myocardial injury are needed. Clinical trial number and registry URL: KCT0004348 ( www.cris.nih.go.kr ).