ORCID Profile
0000-0002-5983-9674
Current Organisation
Università degli Studi di Milano
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Publisher: Springer Science and Business Media LLC
Date: 22-11-2019
DOI: 10.1038/S41467-019-13180-8
Abstract: Histone deacetylase 3 ( Hdac3 ) regulates the expression of lipid metabolism genes in multiple tissues, however its role in regulating lipid metabolism in the intestinal epithelium is unknown. Here we demonstrate that intestine-specific deletion of Hdac3 ( Hdac3 IKO ) protects mice from diet induced obesity. Intestinal epithelial cells (IECs) from Hdac3 IKO mice display co-ordinate induction of genes and proteins involved in mitochondrial and peroxisomal β-oxidation, have an increased rate of fatty acid oxidation, and undergo marked remodelling of their lipidome, particularly a reduction in long chain triglycerides. Many HDAC3-regulated fatty oxidation genes are transcriptional targets of the PPAR family of nuclear receptors, Hdac3 deletion enhances their induction by PPAR-agonists, and pharmacological HDAC3 inhibition induces their expression in enterocytes. These findings establish a central role for HDAC3 in co-ordinating PPAR-regulated lipid oxidation in the intestinal epithelium, and identify intestinal HDAC3 as a potential therapeutic target for preventing obesity and related diseases.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Oxford University Press (OUP)
Date: 25-09-2020
DOI: 10.1002/BJS.12050
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2021
DOI: 10.1200/JCO.20.01933
Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9% adjusted odds ratio [aOR], 0.62 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6% aOR, 0.53 95% CI, 0.36 to 0.76). Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
Publisher: Wiley
Date: 21-12-2020
DOI: 10.1002/CNCR.33320
Abstract: 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. 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. 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. 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. 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.
Publisher: Elsevier BV
Date: 11-2021
No related grants have been discovered for ALDO BRUNO GIANNI'.