2 days versus 5 days of postoperative antibiotics for complex appendicitis:a pragmatic, open-label, multicentre, non-inferiority randomised trial

Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development.</p

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Ultrafiltration of polysaccharide-protein mixtures: Elucidation of fouling mechanisms and fouling control by membrane surface modification

This work describes the fouling b ehavior of polysaccharideâprotein mixture solutions by investigation of adsorptive and ultraï¬ltration fouling. Alginate, dextran, myoglobin and bovine serum albumin were used as model foulants. Three commercial poly(ether sulfone) (PES) ultraï¬ltration (UF) membranes with nominal cut-off of 10, 30 and 10 0 kg/mol and a PES-base d thin layer hydrogel composite (TLHC) membrane,synthesize d by photo-initiated graft copolymerization of poly(ethylene glycol) methacrylate (PEGMA) and having a cut-off of 10 kg/mol were used. The effects of pH, foulant concentration, ionic content and pro-portion of protein to polysaccharide in the solution on fouling we re investigated . The results showed that signiï¬cant water ï¬ux reductions and changes in membrane surface property were observed after static adsorption for PES membranes for all feed solution conditions. This water ï¬ux reduction decreased with increasing the pH of the solution. Addition of monovalent ions could either increase or decrease the water ï¬ux reduction. Synergistic effects between polysaccharide and protein with respect to forming a mixed fouling layer with stronger reduction of ï¬ux than for the individual solutes under the same conditions have also been verified for PES UF membranes. UF experiments using a stirred dead-end UF suggested that both reversible and irreversible fouling have contributed to the overall fouling. The antifouling efï¬ciency of the TLHC membrane with respect to both adsorptive and ultrafiltration fouling has been demonstrated for the strong foulant alginate as well as for polysaccharideâprotein mixtures

Inactivation and Site-specific Oxidation of Aquatic Extracellular Bacterial Leucine Aminopeptidase by Singlet Oxygen

Extracellular enzymes are master recyclers of organic matter, and to predict their functional lifetime, we need to understand their environmental transformation processes. In surface waters, direct and indirect photochemical transformation is a known driver of inactivation. We investigated molecular changes that occur along with inactivation in aminopeptidase, an abundant class of extracellular enzymes. We studied the inactivation kinetics and localized oxidation caused by singlet oxygen, 1O2, a major photochemically derived oxidant toward amino acids. Aminopeptidase showed second-order inactivation rate constants with 1O2 comparable to those of free amino acids. We then visualized site-specific oxidation kinetics within the three-dimensional protein and demonstrated that fastest oxidation occurred around the active site and at other reactive amino acids. However, second-order oxidation rate constants did not correlate strictly with the 1O2-accessible surface areas of those amino acids. We inspected site-specific processes by a comprehensive suspect screening for 723,288 possible transformation products. We concluded that histidine involved in zinc coordination at the active site reacted slower than what was expected by its accessibility, and we differentiated between two competing reaction pathways of 1O2 with tryptophan residues. This systematic analysis can be directly applied to other proteins and transformation reactions.ISSN:0013-936XISSN:1520-585

Environmental photochemistry of fenamate NSAIDs and their radical intermediates

ISSN:2050-7887ISSN:2050-789

Inhibition of Extracellular Enzymes Exposed to Cyanopeptides

Harmful cyanobacterial blooms in freshwater ecosystems produce bioactive secondary metabolites including cyanopeptides that pose ecological and human health risks. Only adverse effects of one class of cyanopeptides, microcystins, have been studied extensively and have consequently been included in water quality assessments. Inhibition is a commonly observed effect for enzymes exposed to cyanopeptides and has mostly been investigated for human biologically relevant model enzymes. Here, we investigated the inhibition of ubiquitous aquatic enzymes by cyanobacterial metabolites. Hydrolytic enzymes are utilized in the metabolism of aquatic organisms and extracellularly by heterotrophic bacteria to obtain assimilable substrates. The ubiquitous occurrence of hydrolytic enzymes leads to the co-occurrence with cyanopeptides especially during cyanobacterial blooms. Bacterial leucine aminopeptidase and alkaline phosphatase were exposed to cyanopeptide extracts of different cyanobacterial strains ( Microcystis aeruginosa wild type and microcystin-free mutant, Planktothrix rubescens) and purified cyanopeptides. We observed inhibition of aminopeptidase and phosphatase upon exposure, especially to the apolar fractions of the cyanobacterial extracts. Exposure to the dominant cyanopeptides in these extracts confirmed that purified microcystins, aerucyclamide A and cyanopeptolin A inhibit the aminopeptidase in the low mg L–1 range while the phosphatase was less affected. Inhibition of aquatic enzymes can reduce the turnover of nutrients and carbon substrates and may also impair metabolic functions of grazing organisms.ISSN:0009-429

Multicenter cohort study on the presentation and treatment of acute appendicitis during the COVID-19 pandemic

Purpose: Current studies have demonstrated conflicting results regarding surgical care for acute appendicitis during the COVID-19 pandemic. This study aimed to assess trends in diagnosis as well as treatment of acute appendicitis in the Netherlands during the first and second COVID-19 infection wave. Methods: All consecutive patients that had an appendectomy for acute appendicitis in nine hospitals from January 2019 to December 2020 were included. The primary outcome was the number of appendectomies for acute appendicitis. Secondary outcomes included time between onset of symptoms and hospital admission, proportion of complex appendicitis, postoperative length of stay and postoperative infectious complications. Outcomes were compared between the pre-COVID group and COVID group. Results: A total of 4401 patients were included. The mean weekly rate of appendectomies during the COVID period was 44.0, compared to 40.9 in the pre-COVID period. The proportion of patients with complex appendicitis and mean postoperative length of stay in days were similar in the pre-COVID and COVID group (respectively 35.5% vs 36.8%, p = 0.36 and 2.0 ± 2.2 vs 2.0 ± 2.6, p = 0.93). There were no differences in postoperative infectious complications. A computed tomography scan was used more frequently as a diagnostic tool after the onset of COVID-19 compared to pre-COVID (13.8% vs 9.8%, p < 0.001, respectively). Conclusion: No differences were observed in number of appendectomies, proportion of complex appendicitis, postoperative length of stay or postoperative infectious complications before and during the COVID-19 pandemic. A CT scan was used more frequently during the COVID-19 pandemic

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial

Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development