Employing innovation to enhance the safety and reliability of restorative surgical techniques for patients with familial adenomatous polyposis at a national referral centre.

Introduction: Restorative proctocolectomy (RPC) and total colectomy with ileorectal anastomosis (TC-IRA) are traditional surgical options for individuals with familial adenomatous polyposis (FAP). Re-appraisal and modification to these techniques, such as near-total colectomy with ileo-distal sigmoid anastomosis (NT-IDSA) and RPC with robotic intracorporeal single-stapled anastomosis (RPC-RiSSA), have been implemented in recent years. This study aimed to evaluate the early postoperative outcomes associated with novel techniques employed in a single centre for restorative surgery in patients with FAP.

Climate sensitivity and relative humidity changes in global storm-resolving model simulations of climate change.

The climate simulation frontier of a global storm-resolving model (GSRM; or -scale model because of its kilometer-scale horizontal resolution) is deployed for climate change simulations. The climate sensitivity, effective radiative forcing, and relative humidity changes are assessed in multiyear atmospheric GSRM simulations with perturbed sea-surface temperatures and/or carbon dioxide concentrations. Our comparisons to conventional climate model results can build confidence in the existing climate models or highlight important areas for additional research.

PIGA Mutations and Glycosylphosphatidylinositol Anchor Dysregulation in Polyposis-Associated Duodenal Tumorigenesis.

Unlabelled: The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS.

Human mRNA in saliva can correctly identify individuals harboring acute infection.

There are a variety of clinical and laboratory criteria available to clinicians in controlled healthcare settings to help them identify whether an infectious disease is present. However, in situations such as a new epidemic caused by an unknown infectious agent, in health screening contexts performed within communities and outside of healthcare facilities or in battlefield or potential biowarfare situations, this gets more difficult. Pathogen-agnostic methods for rapid screening and triage of large numbers of people for infection status are needed, in particular methods that might work on an easily accessible biospecimen like saliva.

The Diagnostic Yield of Genetic Testing in Patients With Multiple Colorectal Adenomas: A Specialist Center Cohort Study.

Introduction: Adenoma multiplicity is associated with increased colorectal cancer (CRC) risk. The utility of genetic testing in patients with multiple colorectal adenomas (MCRA) remains uncertain. We evaluated the diagnostic yield of mutations in polyposis- and CRC-associated genes in patients with MCRA.

Long-term outcomes of pouch surveillance and risk of neoplasia in familial adenomatous polyposis.

Background: Long-term pouch surveillance outcomes for familial adenomatous polyposis (FAP) are unknown. We aimed to quantify surveillance outcomes and to determine which of selected possible predictive factors are associated with pouch dysplasia.

Methods: Retrospective analysis of collected data on 249 patients was performed, analyzing potential risk factors for the development of adenomas or advanced lesions ( ≥ 10 mm/high grade dysplasia (HGD)/cancer) in the pouch body and cuff using Cox proportional hazards models.

Gastrointestinal aspects of Peutz-Jeghers syndrome.

There are two main problems in the clinical management of the gastrointestinal (GI) tract in patients with Peutz-Jeghers syndrome (PJS), namely long-term cancer risk and managing polyp related complications (of which the most important clinically is intussusception). Given the rarity of this condition, the evidence base upon which to make recommendations is small. Furthermore, controversies persist regarding the relationship between PJ polyps, cancer development and cancer risk.

Altered Mucosal Immune-Microbiota Interactions in Familial Adenomatous Polyposis.

Introduction: Familial adenomatous polyposis (FAP) is a condition caused by a constitutional pathogenic variant of the adenomatous polyposis coli gene that results in intestinal adenoma formation and colorectal cancer, necessitating pre-emptive colectomy. We sought to examine interaction between the mucosal immune system and commensal bacteria in FAP to test for immune dysfunction that might accelerate tumorigenesis.

Methods: Colonic biopsies were obtained from macroscopically normal mucosal tissue from 14 healthy donors and 13 patients with FAP during endoscopy or from surgical specimens.

Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues.

Molecular clocks that record cell ancestry mutate too slowly to measure the short-timescale dynamics of cell renewal in adult tissues. Here, we show that fluctuating DNA methylation marks can be used as clocks in cells where ongoing methylation and demethylation cause repeated 'flip-flops' between methylated and unmethylated states. We identify endogenous fluctuating CpG (fCpG) sites using standard methylation arrays and develop a mathematical model to quantitatively measure human adult stem cell dynamics from these data.

Attenuated Familial Adenomatous Polyposis: A Phenotypic Diagnosis but Obsolete Term?

Background: Attenuated familial adenomatous polyposis is characterised by low number (≤100) and delayed development of colorectal adenomas. Various definitions have been used, and genotype-phenotype correlations have been suggested.

Objective: We aimed to evaluate phenotypic and genotypic correlation in patients with presumed attenuated familial adenomatous polyposis and assess familial variability.

Regular endoscopic surveillance and polypectomy is effective in managing rectal adenoma progression following colectomy and ileorectal anastomosis in patients with familial adenomatous polyposis.

Aim: Total colectomy with ileorectal anastomosis (TC-IRA) is a surgical option for patients with familial adenomatous polyposis (FAP). Regular endoscopic surveillance of the rectum is recommended to prevent rectal cancer. We aimed to document polyp progression in the rectum following TC-IRA and evaluate the role of polypectomy during surveillance.

Risk of colorectal adenomas and cancer in monoallelic carriers of MUTYH pathogenic variants: a single-centre experience.

Purpose: The carrier frequency of MUTYH pathogenic variants in the population may be as high as one in 45. Some studies have found an increased risk of colorectal cancer (CRC) in monoallelic carriers of MUTYH pathogenic variants, but the role of early surveillance colonoscopy is not conclusive. This study aimed to assess the outcomes of colonoscopy surveillance in MUTYH carriers.

-------A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS--.

Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation.

Presentation, management and outcomes of ileoanal pouch cancer: a single-centre experience.

Aim: This study aimed to determine the clinical presentation, management and outcomes for patients with ileoanal pouch cancer.

Method: Patients who were diagnosed with ileoanal pouch cancer were identified from our polyposis registry (1978-2019) and operative and referral records (2006-2019). Details of presentation, endoscopic surveillance, cancer staging and management were retrieved from hospital records.

Just 2% of SARS-CoV-2-positive individuals carry 90% of the virus circulating in communities.

We analyze data from the fall 2020 pandemic response efforts at the University of Colorado Boulder, where more than 72,500 saliva samples were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using qRT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified.

The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management.

Pathogenic germline exonuclease domain (ED) variants of POLE and POLD1 cause the Mendelian dominant condition polymerase proof-reading associated polyposis (PPAP). We aimed to describe the clinical features of all PPAP patients with probably pathogenic variants. We identified patients with a variants mapping to the EDs of POLE or POLD1 from cancer genetics clinics, a colorectal cancer (CRC) clinical trial, and systematic review of the literature.

Saliva TwoStep for rapid detection of asymptomatic SARS-CoV-2 carriers.

Here, we develop a simple molecular test for SARS-CoV-2 in saliva based on reverse transcription loop-mediated isothermal amplification. The test has two steps: (1) heat saliva with a stabilization solution and (2) detect virus by incubating with a primer/enzyme mix. After incubation, saliva samples containing the SARS-CoV-2 genome turn bright yellow.

Just 2% of SARS-CoV-2-positive individuals carry 90% of the virus circulating in communities.

We analyze data from the Fall 2020 pandemic response efforts at the University of Colorado Boulder (USA), where more than 72,500 saliva samples were tested for SARS-CoV-2 using quantitative RT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified.

Saliva TwoStep for rapid detection of asymptomatic SARS-CoV-2 carriers.

Here, we develop a simple molecular test for SARS-CoV-2 in saliva based on reverse transcription loop-mediated isothermal amplification (RT-LAMP). The test has two steps: 1) heat saliva with a stabilization solution, and 2) detect virus by incubating with a primer/enzyme mix. After incubation, saliva samples containing the SARS-CoV-2 genome turn bright yellow.

Implications for the colorectal surgeon following the 100 000 Genomes Project.

Aim: The 100 000 Genomes Project was completed in 2019 with the objective of integrating genomic medicine into routine National Health Service (NHS) clinical pathways. This project and genomic research will revolutionize the way we practice colorectal surgery in the 21st century. This paper aims to provide an overview of genomic medicine and its implications for the colorectal surgeon.

Polyp Progression in Paediatric Patients With Familial Adenomatous Polyposis: A Single-centre Experience.

Objectives: Prophylactic colectomy at a premalignant stage is the cornerstone of management of familial adenomatous polyposis (FAP). Before surgery, colonoscopy surveillance is recommended in children with FAP. This study aimed to examine the natural history of FAP in children by evaluating adenoma progression and factors influencing timing of colectomy.

Gastric adenomas and their management in familial adenomatous polyposis.

Background: Patients with familial adenomatous polyposis (FAP) are at increased risk of developing gastric adenomas. There is limited understanding of their clinical course and no consensus on management. We reviewed the management of gastric adenomas in patients with FAP from two centers.