Operative versus conservative management for inguinal hernia: a methodology scoping review of randomized controlled trials.

Introduction: There is a lack of consensus on the management of inguinal hernia with limited symptoms. To address this issue a systematic review of existing randomized clinical trials (RCTs) was performed to critically appraise all existing data on asymptomatic hernia management, focusing on generalizability.

Methods: A scoping review to identify all RCTs comparing surgical and conservative management of patients with inguinal hernias was undertaken.

Randomized controlled trials comparing gastric bypass, gastric band, and sleeve gastrectomy: A systematic review examining validity and applicability to wider clinical practice.

Consideration of how applicable the results of surgical trials are to clinical practice is important to inform decision-making. Randomized controlled trials comparing at least two surgical interventions (of gastric bypass, gastric band, and sleeve gastrectomy) for severe and complex obesity were examined using the PRagmatic Explanatory Continuum Indicator Summary-2 tool, to consider how applicable the trial results are to clinical practice, and the Risk of Bias 2 tool, to examine validity. MEDLINE, Embase, and CENTRAL databases were searched for studies published between November 2013 and June 2021, and 15 were identified.

Development and pilot testing of a patient-reported outcome measure to assess symptoms of parastomal hernia.

Aim: The aim was to develop and pilot a patient-reported outcome measure (PROM) to assess symptoms of parastomal hernia (PSH).

Methods: Standard questionnaire development was undertaken (phases 1-3). An initial list of questionnaire domains was identified from validated colorectal cancer PROMs and from semi-structured interviews with patients with a PSH and health professionals (phase 1).

How do pilot and feasibility studies inform randomised placebo-controlled trials in surgery? A systematic review.

Introduction: Randomised controlled trials (RCTs) with a placebo comparator are considered the gold standard study design when evaluating healthcare interventions. These are challenging to design and deliver in surgery. Guidance recommends pilot and feasibility work to optimise main trial design and conduct; however, the extent to which this occurs in surgery is unknown.

Development of a Bariatric Surgery Core Data Set for an International Registry.

Purpose: Bariatric and metabolic surgery is an effective treatment for severe and complex obesity; however, robust long-term data comparing operations is lacking. Clinical registries complement clinical trials in contributing to this evidence base. Agreement on standard data for bariatric registries is needed to facilitate comparisons.

Impact on Health-Related Quality of Life of Video-Assisted Thoracoscopic Surgery for Lung Cancer.

Background: Video-assisted thoracoscopic surgery (VATS) approaches are increasingly used in lung cancer surgery, but little is known about their impact on patients' health-related quality of life (HRQL). This prospective study measured recovery and HRQL in the year after VATS for non-small cell lung cancer (NSCLC) and explored the feasibility of HRQL data collection in patients undergoing VATS or open lung resection.

Patients And Methods: Consecutive patients referred for surgical assessment (VATS or open surgery) for proven/suspected NSCLC completed HRQL and fatigue assessments before and 1, 3, 6 and 12 months post-surgery.

Reporting of key methodological issues in placebo-controlled trials of surgery needs improvement: a systematic review.

Objectives: To examine key methodological considerations for using a placebo intervention in randomized controlled trials (RCTs) evaluating invasive procedures, including surgery.

Study Design And Setting: RCTs comparing an invasive procedure with a placebo were included in this systematic review. Articles published from database inception to December 31, 2017, were retrieved from Ovid MEDLINE, Ovid EMBASE and CENTRAL electronic databases, by handsearching references and expert knowledge.

Laparoscopically assisted versus open oesophagectomy for patients with oesophageal cancer-the Randomised Oesophagectomy: Minimally Invasive or Open (ROMIO) study: protocol for a randomised controlled trial (RCT).

Introduction: Surgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK.

Impact of question order on prioritisation of outcomes in the development of a core outcome set: a randomised controlled trial.

Background: Core outcome set (COS) developers increasingly employ Delphi surveys to elicit stakeholders' opinions of which outcomes to measure and report in trials of a particular condition or intervention. Research outside of Delphi surveys and COS development demonstrates that question order can affect response rates and lead to 'context effects', where prior questions determine an item's meaning and influence responses. This study examined the impact of question order within a Delphi survey for a COS for oesophageal cancer surgery.

Development of a Core Outcome Set for Clinical Effectiveness Trials in Esophageal Cancer Resection Surgery.

Objective: Development of a core outcome set (COS) for clinical effectiveness trials in esophageal cancer resection surgery.

Background: Inconsistency and heterogeneity in outcome reporting after esophageal cancer resection surgery hampers comparison of trial results and undermines evidence synthesis. COSs provide an evidence-based approach to these challenges.

A Core Outcome Set for the Benefits and Adverse Events of Bariatric and Metabolic Surgery: The BARIACT Project.

Background: Bariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this.

A Comparison of Health Professionals' and Patients' Views of the Importance of Outcomes of Bariatric Surgery.

Background: A comprehensive evaluation of bariatric surgery is required to inform decision-making. This will include measures of benefit and risk. It is possible that stakeholders involved with surgery value these outcomes differently, although this has not previously been explored.

Erratum: Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue.

In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers.

What are important outcomes of bariatric surgery? An in-depth analysis to inform the development of a core outcome set and a comparison between the views of surgeons and other health professionals (the BARIACT study).

Background: Outcome reporting in bariatric surgery needs uniformity. A core outcome set is an agreed minimum set of outcomes reported in all studies of a particular condition, but members of the bariatric multidisciplinary team might value outcomes differently. The aim of this study was to summarise existing outcome reporting in bariatric surgery, to inform the development of a core outcome set, and to compare outcomes selected as important by type of health professional.

Regional Increase in the Expression of the BCAT Proteins in Alzheimer's Disease Brain: Implications in Glutamate Toxicity.

Background: The human branched chain aminotransferases (hBCATm, mitochondrial and hBCATc, cytosolic) are major contributors to brain glutamate production. This excitatory neurotransmitter is thought to contribute to neurotoxicity in neurodegenerative conditions such as Alzheimer's disease (AD) but the expression of hBCAT in this disease has not previously been investigated.

Objective: The objective of investigating hBCAT expression is to gain insight into potential metabolic pathways that may be dysregulated in AD brain, which would contribute to glutamate toxicity.

Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue.

In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers.

Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation.

The branched chain aminotransferase enzymes (BCAT) serve as nitrogen donors for the production of 30% of de novo glutamate synthesis in rat brain. Despite the importance of this major metabolite and excitatory neurotransmitter, the distribution of BCAT proteins in the human brain (hBCAT) remains unreported. We have studied this and report, for the first time, that the mitochondrial isoform, hBCATm is largely confined to vascular endothelial cells, whereas the cytosolic hBCATc is restricted to neurons.

LRP-1 variation is not associated with risk of Alzheimer's disease.

Alzheimer's disease (AD) is characterised by the extensive deposition of amyloid beta (Aβ) within the parenchyma and vasculature of the brain. It is hypothesised that a dysfunction in Aβ degradation and/or its removal from the brain may result in accumulation as plaques. Low density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional receptor shown to be involved in cholesterol metabolism but also the removal of Aβ from the brain.

Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy.

Amyloid-beta (Abeta) cerebral amyloid angiopathy (CAA) affects most Alzheimer's disease (AD) patients and ~30% of otherwise-normal elderly people. APOE epsilon 4 is a major risk factor for CAA in AD. Neurons are probably the source of the vascular Abeta.

Cholinesterase inhibitors may increase phosphorylated tau in Alzheimer's disease.

Cholinesterase inhibitors (ChEIs) are widely used for the symptomatic treatment of Alzheimer's disease (AD). In vitro and in animal studies, ChEIs have been shown to influence the processing of Abeta and the phosphorylation of tau, proteins that are the principal constituents of the plaques and neurofibrillary tangles, respectively, in AD brain. However, little is known about the effects of these drugs on Abeta and tau pathology in AD.

Phosphorylated Smad 2/3 colocalizes with phospho-tau inclusions in Pick disease, progressive supranuclear palsy, and corticobasal degeneration but not with alpha-synuclein inclusions in multiple system atrophy or dementia with Lewy bodies.

Impaired transduction of transforming growth factor-beta signaling has recently been implicated in Alzheimer disease. Transforming growth factor-beta signals are transduced by Smads, which are phosphorylated and translocated to the nucleus, where they initiate gene transcription. In Alzheimer disease, neurofibrillary tangles sequester phosphorylated Smad 2/3 (pSmad2/3) and reduce its nuclear translocation.

Neurofibrillary tangles may interfere with Smad 2/3 signaling in neurons.

Transforming growth factor (TGF)-beta is a multifunctional cytokine with anti-inflammatory, reparative and neuroprotective functions. Increased levels of TGFbeta in Alzheimer disease (AD) are associated with perivascular deposition of extracellular matrix, which may impair clearance of beta-amyloid and contribute to the development of cerebral amyloid angiopathy. TGFbeta signaling is transduced by Smad proteins: on TGFbeta receptor activation, Smads 2 and 3 are released from sequestration by microtubules, phosphorylated (forming pSmad2/3), and, together with Smad 4, translocated to the nucleus, where they initiate the transcription of multiple genes.

Decreased expression and activity of neprilysin in Alzheimer disease are associated with cerebral amyloid angiopathy.

Neprilysin (NEP) degrades amyloid-beta (Abeta) and is thought to contribute to its clearance from the brain. In Alzheimer disease (AD), downregulation of NEP has been suggested to contribute to the development of cerebral amyloid angiopathy (CAA). We examined the relationship among NEP, CAA, and APOE status in AD and elderly control cases.

Sequence variants of IDE are associated with the extent of beta-amyloid deposition in the Alzheimer's disease brain.

Insulin degrading enzyme, encoded by IDE, plays a primary role in the degradation of amyloid beta-protein (A beta), the deposition of which in senile plaques is one of the defining hallmarks of Alzheimer's disease (AD). We recently identified haplotypes in a broad linkage disequilibrium (LD) block encompassing IDE that associate with several AD-related quantitative traits. Here, by examining 32 polymorphic markers extending across IDE and testing quantitative measures of plaque density and cognitive function in three independent Swedish AD samples, we have refined the probable position of pathogenic sequences to a 3' region of IDE, with local maximum effects in the proximity of marker rs1887922.

APOE promoter, ACE1 and CYP46 polymorphisms and beta-amyloid in Alzheimer's disease.

Polymorphisms in the APOE promoter, ACE1 and CYP46 genes have all been reported to be associated with Alzheimer's disease (AD). We studied the relationship of these polymorphisms to the presence of AD in 86 neuropathologically confirmed cases of AD and 58 controls. In addition, we assessed the effects of these polymorphisms on the accumulation of beta-amyloid (Abeta) in the cerebral parenchyma and vasculature.