Faecal immunochemical tests for patients with symptoms suggestive of colorectal cancer: An updated systematic review and multiple-threshold meta-analysis of diagnostic test accuracy studies.

Aim: Extending faecal immunochemical tests for haemoglobin (FIT) to all primary care patients with symptoms suggestive of colorectal cancer (CRC) could identify people who are likely to benefit from colonoscopy and facilitate earlier treatment. The aim of this work was to investigate the diagnostic accuracy of FIT across different analysers at different thresholds, as a single test or in duplicate (dual FIT).

Method: This systematic review and meta-analysis searched 10 sources (December 2022).

Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying abnormal neuronal connectivity remain unclear.

Lynch syndrome diagnostic testing pathways in endometrial cancers: a nationwide English registry-based study.

Background: For female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS.

Methods: A retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset.

Intraoperative computerised tomography scan for percutaneous fixation of the pelvis: a retrospective case series.

Purpose: Fractures and dislocations of the pelvic ring are complex injuries that when treating require meticulous attention to detail and often specialized technical skill. These injuries can be the result of high-energy trauma, particularly in younger patients, or low energy trauma more often found in the elderly. Regardless of mechanism, these injuries lie on a spectrum of severity and can be treated conservatively or surgically.

Extra-articular proximal tibia fracture fixation with locked plating versus intramedullary nailing: A meta-analysis.

Objectives: This study compared outcomes of locked plating (LP) versus intramedullary nailing (IMN) techniques for treatment of extra-articular proximal-third tibia fractures.

Methods: Data Sources: PubMed, Ovid MEDLINE STUDY SELECTION: Studies were included if they compared LP and IMN fixation for proximal one third tibial shaft fractures without articular extension or with simple articular extension into the tibial plateau. Minimum 1 year of clinical and radiographic follow up was used.

Retrieval of Embolized WATCHMAN Flex Atrial Appendage Occlusion Device.

This case report documents the management of a 66-year old man with atrial fibrillation with recent placement of a WATCHMAN Flex atrial appendage occlusion device. The patient presented with renal failure, abdominal pain, and difficulty walking 2 months after placement. The WATCHMAN Flex device was found to have embolized to his abdominal aorta at the level of the renal arteries with associated thrombus.

Cognitive impairment and treatment strategy for atrial fibrillation in older adults: The SAGE-AF study.

Background: Cognitive impairment is strongly associated with atrial fibrillation (AF). Rate and rhythm control are the two treatment strategies for AF and the effect of treatment strategy on risk of cognitive decline and frailty is not well established. We sought to determine how treatment strategy affects geriatric-centered outcomes.

Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated "Big Bang" pathway to CRC in three of the four Lynch syndromes.

Background: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas.

study of radiosensitivity in colorectal cancer cell lines associated with Lynch syndrome.

Introduction: Lynch syndrome patients have an inherited predisposition to cancer due to a deficiency in DNA mismatch repair (MMR) genes which could lead to a higher risk of developing cancer if exposed to ionizing radiation. This pilot study aims to reveal the association between MMR deficiency and radiosensitivity at both a CT relevant low dose (20 mGy) and a therapeutic higher dose (2 Gy).

Methods: Human colorectal cancer cell lines with (dMMR) or without MMR deficiency (pMMR) were analyzed before and after exposure to radiation using cellular and cytogenetic analyses i.

Extent of investigation and management of cases of 'unexplained' mismatch repair deficiency (u-dMMR): a UK Cancer Genetics Group consensus.

Background: Mismatch repair deficiency (dMMR) is a characteristic feature of cancers linked to Lynch syndrome. However, in most cases, it results from sporadic somatic events rather than hereditary factors. The term 'Lynch-like syndrome' (LLS) has been used to guide colorectal cancer surveillance for relatives of individuals with a dMMR tumour when somatic and germline genomic testing is uninformative.

The comprehensive English National Lynch Syndrome Registry: development and description of a new genomics data resource.

Background: Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established.

Identification of people with Lynch syndrome from those presenting with colorectal cancer in England: baseline analysis of the diagnostic pathway.

It is believed that >95% of people with Lynch syndrome (LS) remain undiagnosed. Within the National Health Service (NHS) in England, formal guidelines issued in 2017 state that all colorectal cancers (CRC) should be tested for DNA Mismatch Repair deficiency (dMMR). We used a comprehensive population-level national dataset to analyse implementation of the agreed diagnostic pathway at a baseline point 2 years post-publication of official guidelines.

The diagnostic yield of colonoscopic surveillance following resection of early age onset colorectal cancer.

Background: The primary benefit of post-colorectal cancer (CRC) colonoscopic surveillance is to detect and remove premalignant lesions to prevent metachronous CRC. Current guidelines for long-term colonoscopic surveillance post early age onset CRC (EOCRC) resection are based on limited evidence. The aims of this study were to assess the diagnostic yield of colonoscopic surveillance post-EOCRC resection and identify molecular and clinicopathological risk factors associated with advanced neoplasia.

RNA-mediated symmetry breaking enables singular olfactory receptor choice.

Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, where every olfactory neuron stably transcribes one of approximately 2,000 or more OR alleles. OR gene choice is mediated by a multichromosomal enhancer hub that activates transcription at a single OR, followed by OR-translation-dependent feedback that stabilizes this choice. Here, using single-cell genomics, we show formation of many competing hubs with variable enhancer composition, only one of which retains euchromatic features and transcriptional competence.

Opposing, spatially-determined epigenetic forces impose restrictions on stochastic olfactory receptor choice.

Olfactory receptor (OR) choice represents an example of genetically hardwired stochasticity, where every olfactory neuron expresses one out of ~2000 OR alleles in the mouse genome in a probabilistic, yet stereotypic fashion. Here, we propose that topographic restrictions in OR expression are established in neuronal progenitors by two opposing forces: polygenic transcription and genomic silencing, both of which are influenced by dorsoventral gradients of transcription factors NFIA, B, and X. Polygenic transcription of OR genes may define spatially constrained OR repertoires, among which one OR allele is selected for singular expression later in development.

Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying aberrant neuronal connectivity remains unclear.

Genetic predisposition to gastrointestinal polyposis: syndromes, tumour features, genetic testing, and clinical management.

Gastrointestinal tract polyposis is characterised by the presence of multiple polyps, particularly in the colorectum, and encompasses both cancer predisposition genetic syndromes and non-syndromic clinical manifestations. The sources of the heterogeneity observed in polyposis syndromes relate to genetic cause, mode of inheritance, polyp burden and histological type, and spectrum and frequency of extracolonic manifestations. These features determine the clinical management of carriers, including strategies for cancer prevention and early detection, and oncological treatments.