ARDD 2020: from aging mechanisms to interventions

Aging is emerging as a druggable target with growing interest from academia, industry and investors. New technologies such as artificial intelligence and advanced screening techniques, as well as a strong influence from the industry sector may lead to novel discoveries to treat age-related diseases. The present review summarizes presentations from the 7th Annual Aging Research and Drug Discovery (ARDD) meeting, held online on the 1st to 4th of September 2020. The meeting covered topics related to new methodologies to study aging, knowledge about basic mechanisms of longevity, latest interventional strategies to target the aging process as well as discussions about the impact of aging research on society and economy. More than 2000 participants and 65 speakers joined the meeting and we already look forward to an even larger meeting next year. Please mark your calendars for the 8th ARDD meeting that is scheduled for the 31st of August to 3rd of September, 2021, at Columbia University, USA

Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging

A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly. Endothelial SIRT1 regulates pro-angiogenic signals secreted from myocytes and improves muscle health. Treatment of mice with NAD precursor nicotinamide mononucleotide improves vascular and increases endurance in aging mice.Glenn Foundation for Medical Research (Award RO1 AG028730)Glenn Foundation for Medical Research (Award RO1 DK100263)NIH/NIA (Grant RO1 AG015339

ARDD 2020: from aging mechanisms to interventions

Aging is emerging as a druggable target with growing interest from academia, industry and investors. New technologies such as artificial intelligence and advanced screening techniques, as well as a strong influence from the industry sector may lead to novel discoveries to treat age-related diseases. The present review summarizes presentations from the 7th Annual Aging Research and Drug Discovery (ARDD) meeting, held online on the 1st to 4th of September 2020. The meeting covered topics related to new methodologies to study aging, knowledge about basic mechanisms of longevity, latest interventional strategies to target the aging process as well as discussions about the impact of aging research on society and economy. More than 2000 participants and 65 speakers joined the meeting and we already look forward to an even larger meeting next year. Please mark your calendars for the 8th ARDD meeting that is scheduled for the 31st of August to 3rd of September, 2021, at Columbia University, USA.ISSN:1945-458

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 adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods: A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results: A total of 4164 patients were included, with a median age of 68 (i.q.r. 57\u201375) years (54\ub79 per cent men). Some 1153 (27\ub77 per cent) received NSAIDs on postoperative days 1\u20133, of whom 1061 (92\ub70 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4\ub76 versus 4\ub78 days; hazard ratio 1\ub704, 95 per cent c.i. 0\ub796 to 1\ub712; P = 0\ub7360). There were no significant differences in anastomotic leak rate (5\ub74 versus 4\ub76 per cent; P = 0\ub7349) or acute kidney injury (14\ub73 versus 13\ub78 per cent; P = 0\ub7666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35\ub73 versus 56\ub77 per cent; P < 0\ub7001). Conclusion: NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement

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 < 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

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 center dot 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 < 0 center dot 001). There were no significant differences in rates of readmission between these groups (6 center dot 6 versus 8 center dot 0 per cent; P = 0 center dot 499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0 center dot 90, 95 per cent c.i. 0 center dot 55 to 1 center dot 46; P = 0 center dot 659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34 center dot 7 versus 39 center dot 5 per cent; major 3 center dot 3 versus 3 center dot 4 per cent; P = 0 center dot 110). Conclusion Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

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 < 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