Mucosal biomarkers of colorectal cancer risk do not increase at 6 months following sleeve gastrectomy, unlike gastric bypass

YesObjective The hypothesis that sleeve gastrectomy (SG) is not associated with an increase in mucosal colorectal cancer (CRC) biomarkers, unlike Roux-en-Y gastric bypass (RYGB), was tested. Design and Methods Rectal mucosa, blood, and urine were obtained from morbidly obese patients (n = 23) before and after (median 28 months) SG, as well as from nonobese controls (n = 20). Rectal epithelial cell mitosis and apoptosis, crypt size/fission, and pro-inflammatory gene expression were measured, as well as systemic inflammatory biomarkers, including C-reactive protein (CRP). Results The mean pre-operative body mass index in SG patients was 65.7 kg/m2 (24.7 kg/m2 in controls). Mean excess weight loss post-SG was 38.2%. There was a significant increase in mitosis frequency, crypt size, and crypt fission (all P < 0.01) in SG patients versus controls, as well as evidence of a chronic inflammatory state (raised CRP and mononuclear cell p65 NFκB binding), but there was no significant change in these biomarkers after SG, except CRP reduction. Macrophage migration inhibitory factor mRNA levels were increased by 39% post-SG (P = 0.038). Conclusions Mucosal biomarkers of CRC risk do not increase at 6 months following SG, unlike RYGB. Biomarkers of rectal crypt proliferation and systemic inflammation are increased in morbidly obese patients compared with controls

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A genetic reconstruction of the invasion of the calanoid copepod Pseudodiaptomus inopinus across the North American Pacific Coast

The rate of aquatic invasions by planktonic organisms has increased considerably in recent decades. In order to effectively direct funding and resources to control the spread of such invasions, a methodological framework for identifying high-risk transport vectors, as well as ruling out vectors of lesser concern will be necessary. A number of estuarine ecosystems on the North American Pacific Northwest coast have experienced a series of high impact planktonic invasions that have slowly unfolded across the region in recent decades, most notably, that of the planktonic copepod crustacean Pseudodiaptomus inopinus. Although introduction of P. inopinus to the United States almost certainly occurred through the discharge of ballast water from commercial vessels originating in Asia (the species' native range), the mechanisms and patterns of subsequent spread remain unknown. In order to elucidate the migration events shaping this invasion, we sampled the genomes of copepods from seven invasive and two native populations using restriction-site associated DNA sequencing. This genetic data was evaluated against spatially-explicit genetic simulation models to evaluate competing scenarios of invasion spread. Our results indicate that invasive populations of P. inopinus exhibit a geographically unstructured genetic composition, likely arising from infrequent and large migration events. This pattern of genetic patchiness was unexpected given the linear geographic structure of the sampled populations, and strongly contrasts with the clear invasion corridors observed in many aquatic systems

Video assisted esophagectomy for esophageal cancer

Video assisted surgery for esophageal cancer is an advanced surgical technique. It is being adopted with a concept of minimally invasive surgery. Since there are several options of the operative procedure for thoracic esophageal cancer, there are several laparoscopic approaches. The first VATS esophagectomy through a right thoracoscopic approach and the first transhiatal esophagectomy were reported in early 1990's. Mediastinoscope-assisted esophagectomy is also reported as a substitute of the blunt dissection of the esophagus. Moreover, video assisted Ivor-Lewis esophagectomy by right thoracotomy with intrathoracic anastomosis has also been tried. Furthermore, laparoscopic gastric mobilization and gastroplasty is also widely accepted as a substitution for open laparotomy. This article serves to review the literature on laparoscopic approaches for esophageal cancer