Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease

AbstractAlzheimer’s disease (AD) is increasingly prevalent worldwide, and disease-modifying treatments may soon be at hand; hence, now, more than ever, there is a need to develop techniques that allow earlier and more secure diagnosis. Current biomarker-based guidelines for AD diagnosis, which have replaced the historical symptom-based guidelines, rely heavily on neuroimaging and cerebrospinal fluid (CSF) sampling. While these have greatly improved the diagnostic accuracy of AD pathophysiology, they are less practical for application in primary care, population-based and epidemiological settings, or where resources are limited. In contrast, blood is a more accessible and cost-effective source of biomarkers in AD. In this review paper, using the recently proposed amyloid, tau and neurodegeneration [AT(N)] criteria as a framework towards a biological definition of AD, we discuss recent advances in biofluid-based biomarkers, with a particular emphasis on those with potential to be translated into blood-based biomarkers. We provide an overview of the research conducted both in CSF and in blood to draw conclusions on biomarkers that show promise. Given the evidence collated in this review, plasma neurofilament light chain (N) and phosphorylated tau (p-tau; T) show particular potential for translation into clinical practice. However, p-tau requires more comparisons to be conducted between its various epitopes before conclusions can be made as to which one most robustly differentiates AD from non-AD dementias. Plasma amyloid beta (A) would prove invaluable as an early screening modality, but it requires very precise tests and robust pre-analytical protocols.</div

Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery.

Background: Ileus is common after elective colorectal surgery, and is associated with increased adverseevents and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatorydrugs (NSAIDs) for reducing ileus after surgery.Methods: A prospective multicentre cohort study was delivered by an international, student- andtrainee-led collaborative group. Adult patients undergoing elective colorectal resection between Januaryand April 2018 were included. The primary outcome was time to gastrointestinal recovery, measuredusing a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs wasexplored using Cox regression analyses, including the results of a centre-specific survey of complianceto enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acutekidney injury.Results: A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54⋅9 percent men). Some 1153 (27⋅7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92⋅0per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, themean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDsand those who did not (4⋅6 versus 4⋅8 days; hazard ratio 1⋅04, 95 per cent c.i. 0⋅96 to 1⋅12; P = 0⋅360). Therewere no significant differences in anastomotic leak rate (5⋅4 versus 4⋅6 per cent; P = 0⋅349) or acute kidneyinjury (14⋅3 versus 13⋅8 per cent; P = 0⋅666) between the groups. Significantly fewer patients receivingNSAIDs required strong opioid analgesia (35⋅3 versus 56⋅7 per cent; P &lt; 0⋅001).Conclusion: NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, butthey were safe and associated with reduced postoperative opioid requirement.</p

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function.Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system.Results: A total of 3288 patients were included in the analysis, of whom 301 (9.2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P &lt; 0.001). There were no significant differences in rates of readmission between these groups (6.6 versus 8.0 per cent; P = 0.499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0.90, 95 per cent c.i. 0.55 to 1.46; P = 0.659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34.7 versus 39.5 per cent; major 3.3 versus 3.4 per cent; P = 0.110).Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients