Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Facilitating the validation of novel protein biomarkers for dementia: an optimal workflow for the development of sandwich immunoassays

Different neurodegenerative disorders, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), lead to dementia syndromes. Dementia will pose a huge impact on society and thus it is essential to develop novel tools that are able to detect the earliest, most sensitive, discriminative, and dynamic biomarkers for each of the disorders. To date, the most common assays used in large-scale protein biomarker analysis are enzyme-linked immunosorbent assays (ELISA), such as the sandwich immunoassays, which are sensitive, practical, and easily implemented. However, due to the novelty of many candidate biomarkers identified during proteomics screening, such assays or the antibodies that specifically recognize the desired marker are often not available. The development and optimization of a new ELISA should be carried out with considerable caution since a poor planning can be costly, ineffective, time consuming, and it may lead to a misinterpretation of the findings. Previous guidelines described either the overall biomarker development in more general terms (i.e., the process from biomarker discovery to validation) or the specific steps of performing an ELISA procedure. However, a workflow describing and guiding the main issues in the development of a novel ELISA is missing. Here, we describe a specific and detailed workflow to develop and validate new ELISA for a successful and reliable validation of novel dementia biomarkers. The proposed workflow highlights the main issues in the development of an ELISA and covers several critical aspects, including production, screening, and selection of specific antibodies until optimal fine-tuning of the assay. Although these recommendations are designed to analyze novel biomarkers for dementia in cerebrospinal fluid, they are generally applicable for the development of immunoassays for biomarkers in other human body fluids or tissues. This workflow is designed to maximize the quality of the developed ELISA using a time- and cost-efficient strategy. This will facilitate the validation of the dementia biomarker candidates ultimately allowing accurate diagnostic conclusions

Vascular Endothelial Growth Factor remains unchanged in cerebrospinal fluid of patients with Alzheimer's disease and vascular dementia

Background: Increasing evidence suggests that cerebral vascular dysfunction is associated with the early stages of Alzheimer's disease (AD). Vascular endothelial growth factor (VEGF) is one of the key players involved in the development and maintenance of the vasculature. Here, we hypothesized that VEGF levels in cerebrospinal fluid (CSF) may be altered in AD patients with vascular involvement, characterized by the presence of microbleeds (MB), and in vascular dementia (VaD) patients compared to controls. Methods: VEGF levels were determined by electrochemilumiscence Meso Scale Discovery (MULTI-SPOT Assay System) in CSF from age-matched groups of controls with subjective cognitive decline (n = 21), AD without MB (n = 25), AD with MB (n = 25), and VaD (n = 21) patients. Results: The average level of VEGF in the different groups was 2.8 ± 1 pg/ml CSF. Adjusted for age and gender, no significant differences were detected between groups (p > 0.5). However, we detected a significant correlation between the concentration of VEGF in the CSF and age (r = 0.22, p = 0.03). In addition, males (n = 54) revealed higher VEGF levels in their CSF compared to females (n = 38) (males = 3.08 ± 0.769 pg/ml (mean ± SD), females = 2.6 ± 0.59; p = 0.006), indicating a gender-related regulation. Conclusion: Our study suggests that VEGF levels in the CSF do not reflect the cerebral vascular alterations in either AD or VaD patients. The observed associations of VEGF with age and gender may indicate that VEGF reflects normal aging and that males and females may differ in their aging process

BRI2 ectodomain affects Aβ42 fibrillation and tau truncation in human neuroblastoma cells.

Alzheimer's disease (AD) is pathologically characterized by the presence of misfolded proteins such as amyloid beta (Aβ) in senile plaques, and hyperphosphorylated tau and truncated tau in neurofibrillary tangles (NFT). The BRI2 protein inhibits Aβ aggregation via its BRICHOS domain and regulates critical proteins involved in initiating the amyloid cascade, which has been hypothesized to be central in AD pathogenesis. We recently detected the deposition of BRI2 ectodomain associated with Aβ plaques and concomitant changes in its processing enzymes in early stages of AD. Here, we aimed to investigate the effects of recombinant BRI2 ectodomain (rBRI

CDH6 and HAGH protein levels in plasma associate with Alzheimer's disease in APOE epsilon 4 carriers

Many Alzheimer's disease (AD) genes including Apolipoprotein E (APOE) are found to be expressed in blood-derived macrophages and thus may alter blood protein levels. We measured 91 neuro-proteins in plasma from 316 participants of the Rotterdam Study (incident AD=161) using Proximity Extension Ligation assay. We studied the association of plasma proteins with AD in the overall sample and stratified by APOE. Findings from the Rotterdam study were replicated in 186 AD patients of the BioFINDER study. We further evaluated the correlation of these protein biomarkers with total tau (t-tau), phosphorylated tau (p-tau) and amyloid-beta (A beta) 42 levels in cerebrospinal fluid (CSF) in the Amsterdam Dementia Cohort (N=441). Finally, we conducted a genome-wide association study (GWAS) to identify the genetic variants determining the blood levels of AD-associated proteins. Plasma levels of the proteins, CDH6 (beta =0.638, P=3.33x10(-4)) and HAGH (beta =0.481, P=7.20x10(-4)), were significantly elevated in APOE epsilon 4 carrier AD patients. The findings in the Rotterdam Study were replicated in the BioFINDER study for both CDH6 (beta =1.365, P=3.97x10(-3)) and HAGH proteins (beta =0.506, P=9.31x10(-7)) when comparing cases and controls in APOE epsilon 4 carriers. In the CSF, CDH6 levels were positively correlated with t-tau and p-tau in the total sample as well as in APOE epsilon 4 stratum (P<1x10(-3)). The HAGH protein was not detected in CSF. GWAS of plasma CDH6 protein levels showed significant association with a cis-regulatory locus (rs111283466, P=1.92x10(-9)). CDH6 protein is implicated in cell adhesion and synaptogenesis while HAGH protein is related to the oxidative stress pathway. Our findings suggest that these pathways may be altered during presymptomatic AD and that CDH6 and HAGH may be new blood-based biomarkers

CDH6 and HAGH protein levels in plasma associate with Alzheimer’s disease in APOE ε4 carriers

Many Alzheimer’s disease (AD) genes including Apolipoprotein E (APOE) are found to be expressed in blood-derived macrophages and thus may alter blood protein levels. We measured 91 neuro-proteins in plasma from 316 participants of the Rotterdam Study (incident AD = 161) using Proximity Extension Ligation assay. We studied the association of plasma proteins with AD in the overall sample and stratified by APOE. Findings from the Rotterdam study were replicated in 186 AD patients of the BioFINDER study. We further evaluated the correlation of these protein biomarkers with total tau (t-tau), phosphorylated tau (p-tau) and amyloid-beta (Aβ) 42 levels in cerebrospinal fluid (CSF) in the Amsterdam Dementia Cohort (N = 441). Finally, we conducted a genome-wide association study (GWAS) to identify the genetic variants determining the blood levels of AD-associated proteins. Plasma levels of the proteins, CDH6 (β = 0.638, P = 3.33 × 10−4) and HAGH (β = 0.481, P = 7.20 × 10−4), were significantly elevated in APOE ε4 carrier AD patients. The findings in the Rotterdam Study were replicated in the BioFINDER study for both CDH6 (β = 1.365, P = 3.97 × 10−3) and HAGH proteins (β = 0.506, P = 9.31 × 10−7) when comparing cases and controls in APOE ε4 carriers. In the CSF, CDH6 levels were positively correlated with t-tau and p-tau in the total sample as well as in APOE ε4 stratum (P < 1 × 10−3). The HAGH protein was not detected in CSF. GWAS of plasma CDH6 protein levels showed significant association with a cis-regulatory locus (rs111283466, P = 1.92 × 10−9). CDH6 protein is implicated in cell adhesion and synaptogenesis while HAGH protein is related to the oxidative stress pathway. Our findings suggest that these pathways may be altered during presymptomatic AD and that CDH6 and HAGH may be new blood-based biomarkers