Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since it was first recognized in December 2019, it has resulted in the ongoing worldwide pandemic. Although acute hypoxic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) are the main features of the disease, the involvement of other organs needs to be explored. There has been a growing concern regarding the association between acute kidney injury (AKI) and poor outcomes in SARS-CoV-2 patients. Based on current observational data, AKI is the 2nd most common cause of morbidity and mortality behind ARDS in SARS-CoV-2 patients. Angiotensin-converting enzyme 2 (ACE2) receptor has been shown to be the cornerstone of SARS-CoV-2 infection and possibly plays a significant role in the occurrence of renal injury. The pathogenesis of AKI is likely multifactorial that involves not only direct viral invasion but also dysregulated immune response in the form of cytokine storm, ischemia to kidneys, hypercoagulable state, and rhabdomyolysis, among others. We performed a literature search of the Pubmed and Google Scholar database from 1996 to 2020 using the following keywords: severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, angiotensin-converting enzyme 2 receptor, and acute kidney injury to find the most pertinent and highest-quality of evidence. Any cited references were reviewed to identify relevant literature. The purpose of this review is to discuss, explore, and summarize the relationship between AKI in SARS-CoV-2 patients, with a focus on its epidemiology, association with ACE2 receptors, and pathophysiology of AKI. 相似文献
Background Poly(ADP-ribose) polymerase inhibitors (PARPi) target tumours defective in homologous recombination (HR). Most BRCA-wild-type (WT) HR-proficient breast cancers are intrinsically resistant to PARP inhibitors, e.g., talazoparib. We evaluated the role of autophagy in this de novo resistance and determined the underlying mechanism to overcome this.Methods Autophagosome formation and autophagic flux were assessed by evaluating endogenous LC3-II levels and ectopic expression of EGFP-LC3 and mRFP-EGFP-LC3 in breast cancer cells. Autophagy-defective cells were generated by genetic depletion of BECN1, ATG5, p62/SQSTM1 and LAMP1 by using CRISPR-Cas9 double nickase system. The response of PARPi was evaluated in autophagy-proficient and -defective breast cancer cells and in xenograft SCID-mice model.Results Pro-survival autophagy was significantly enhanced upon talazoparib treatment in BRCA-WT breast cancer cell lines. Autophagy-deficient cells were hypersensitive to talazoparib. Targeting autophagy synergistically enhanced the therapeutic efficacy of talazoparib in BRCA1-WT breast cancer cells in vitro and in vivo xenograft tumour mouse model. Mechanistically, autophagy inhibition by chloroquine promoted deleterious NHEJ mediated DSB-repair, leading to extensive genomic instability and mitotic catastrophe.Conclusions Autophagy confers de novo resistance to PARP inhibitor, talazoparib. Autophagy inhibition improves the therapeutic outcome of PARPi treatment in preclinical mice model, bearing HR-proficient breast tumours, warranting its usage in the clinical settings.Subject terms: Breast cancer, Cancer therapy相似文献
Social Psychiatry and Psychiatric Epidemiology - Our study explored whether aspects of veterans’ social connectedness (social support, interpersonal conflict, loneliness, social norms, number... 相似文献
Prolonged mechanical ventilation (MV) is a major complication following cardiac surgery. We conducted a secondary analysis of the Transfusion Requirements in Cardiac Surgery (TRICTS) III trial to describe MV duration, identify factors associated with prolonged MV, and examine associations of prolonged MV with mortality and complications.
Methods
Four thousand, eight hundred and nine participants undergoing cardiac surgery at 71 hospitals worldwide were included. Prolonged MV was defined based on the Society of Thoracic Surgeons definition as MV lasting 24 hr or longer. Adjusted associations of patient and surgical factors with prolonged MV were examined using multivariable logistic regression. Associations of prolonged MV with complications were assessed using odds ratios, and adjusted associations between prolonged MV and mortality were evaluated using multinomial regression. Associations of shorter durations of MV with survival and complications were explored.
Results
Prolonged MV occurred in 15% (725/4,809) of participants. Prolonged MV was associated with surgical factors indicative of complexity, such as previous cardiac surgery, cardiopulmonary bypass duration, and separation attempts; and patient factors such as critical preoperative state, left ventricular impairment, renal failure, and pulmonary hypertension. Prolonged MV was associated with perioperative but not long-term complications. After risk adjustment, prolonged MV was associated with perioperative mortality; its association with long-term mortality among survivors was weaker. Shorter durations of MV were not associated with increased risk of mortality or complications.
Conclusion
In this substudy of the TRICS III trial, prolonged MV was common after cardiac surgery and was associated with patient and surgical risk factors. Although prolonged MV showed strong associations with perioperative complications and mortality, it was not associated with long-term complications and had weaker association with long-term mortality among survivors.
Study registration
www.ClinicalTrials.gov (NCT02042898); registered 23 January 2014. This is a substudy of the Transfusion Requirements in Cardiac Surgery (TRICS) III trial.
Pituitary - To provide an overview of fundamental concepts in machine learning (ML), review the literature on ML applications in imaging analysis of pituitary tumors for the last 10 years, and... 相似文献