Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels.

BACKGROUND: Experimental evidence suggests a key role of SIRT1 (silent information regulator 1) in age- and metabolic-related vascular dysfunction. Whether these effects hold true in the human microvasculature is unknown. We aimed to investigate the SIRT1 role in very early stages of age- and obesity-related microvascular dysfunction in humans. METHODS: Ninety-five subjects undergoing elective laparoscopic surgery were recruited and stratified based on their body mass index status (above or below 30 kg/m2) and age (above or below 40 years) in 4 groups: Young Nonobese, Young Obese, Old Nonobese, and Old Obese. We measured small resistance arteries' endothelial function by pressurized micromyography before and after incubation with a SIRT1 agonist (SRT1720) and a mitochondria reactive oxygen species (mtROS) scavenger (MitoTEMPO). We assessed vascular levels of mtROS and nitric oxide availability by confocal microscopy and vascular gene expression of SIRT1 and mitochondrial proteins by qPCR. Chromatin immunoprecipitation assay was employed to investigate SIRT1-dependent epigenetic regulation of mitochondrial proteins. RESULTS: Compared with Young Nonobese, obese and older patients showed lower vascular expression of SIRT1 and antioxidant proteins (FOXO3 [forkhead box protein O3] and SOD2) and higher expression of pro-oxidant and aging mitochondria proteins p66Shc and Arginase II. Old Obese, Young Obese and Old Nonobese groups endothelial dysfunction was rescued by SRT1720. The restoration was comparable to the one obtained with mitoTEMPO. These effects were explained by SIRT1-dependent chromatin changes leading to reduced p66Shc expression and upregulation of proteins involved in mitochondria respiratory chain. CONCLUSIONS: SIRT1 is a novel central modulator of the earliest microvascular damage induced by age and obesity. Through a complex epigenetic control mainly involving p66Shc and Arginase II, it influences mtROS levels, NO availability, and the expression of proteins of the mitochondria respiratory chain. Therapeutic modulation of SIRT1 restores obesity- and age-related endothelial dysfunction. Early targeting of SIRT1 might represent a crucial strategy to prevent age- and obesity-related microvascular dysfunction.

Laparoscopic bariatric surgery is safe during phase 2-3 of COVID-19 pandemic in Italy: A multicenter, prospective, observational study.

BACKGROUND: Sars-Cov-2 epidemic in Italy caused one of the greatest 2020 European outbreaks, with suspension of elective bariatric/metabolic surgery (BMS). From May 2020 a significant decline of the epidemic has been observed (phase 2); National Health Service protocols permitted elective BMS' resumption. A new, more severe COVID-19 surge, the "second wave", started on October 2020 (phase 3). AIM: The primary end point was to analyze the outcomes of any Sars-Cov-2 infection and related morbidity/mortality within 30 POD after laparoscopic BMS during phase 2-3; secondary end points were readmission and reoperation rates. METHODS: Study design prospective, multicenter, observational. SETTING: Eight Italian high-volume bariatric centers. All patients undergoing BMS from July 2020 through January 2021 were enrolled according to the following criteria: no Sars-Cov-2 infection; primary procedures; no concomitant procedure; age > 18 < 60 years; compensated comorbidities; informed consent including COVID-19 addendum; adherence to specific admission, in-hospital and follow-up protocols. Data were collected in a prospective database. Patients undergone BMS during July-December 2019 were considered a control group. RESULTS: 1258 patients were enrolled and compared with 1451 operated on in 2019, with no differences for demographics, complications, readmission, and reintervention rates. Eight patients (0·6%) tested positive for Sars-Cov-2 infection after discharge, as well as and 15 healthcare professionals, with no related complications or mortality. CONCLUSIONS: Introduction of strict COVID-19 protocols concerning the protection of patients and health-care professionals guaranteed a safe resumption of elective BMS in Italy. The safety profile was, also, maintained during the second wave of outbreak, thus allowing access to a cure for the obese population.

Abdominal pain and internal hernias after Roux-en-Y Gastric Bypass: are we dealing with the tip of an iceberg?

BACKGROUND: Abdominal pain is the most frequent cause of hospital admission after Roux-en-y gastric bypass (RYGB). Among numerous possible underlying causes, internal hernias represent one of the most peculiar and insidious conditions, setting challenging diagnostic and therapeutic problems for the surgeon. The aim of this study is to analyze aspecific abdominal pain incidence and characteristics after RYGB, discriminating peculiar aspects suggestive of internal hernias. METHODS: 13 patients submitted to internal hernia repair after laparoscopic antecolic RYGB and a group of 49 controls (non-complicated RYGB) have been assessed using a specific questionnaire. Overall aspecific abdominal pain incidence and characteristics have been analysed. Typical pain traits and predisposing conditions for internal hernias have been investigated. RESULTS: 33% of controls reported aspecific abdominal pain after RYGB, mainly early postprandial, deep, remittent, colicky, located in the upper left abdomen. 77% of the case patients reported prodromal episodes of pain similar to the controls. The only significant differences between prodromal and acute episodes were pain intensity and quality (continuous). Excess weight lost at 3 months significantly correlated with internal hernia occurrence (p: 0.002). CONCLUSIONS: Based on abdominal pain characteristics, we can reasonably postulate the presence of remittent bowel torsions (remittent internal hernia) in many patients after antecolic RYGB, only occasionally complicating. Therapeutic management of these cases remains controversial, being laparoscopic exploration a reasonable option when symptomatology is suggestive.