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The CTLA-4 and PD-1 checkpoints control immune responses and are key targets in immunotherapy. Both pathways are connected via a cis interaction between CD80 and PD-L1, the ligands for CTLA-4 and PD-1, respectively. This cis interaction prevents PD-1-PD-L1 binding but is reversed by CTLA-4 trans-endocytosis of CD80. However, how CTLA-4 selectively removes CD80, but not PD-L1, is unclear. Here, we show CTLA-4-CD80 interactions are unimpeded by PD-L1 and that CTLA-4 binding with CD80 does not displace PD-L1 per se. Rather, both rigidity and bivalency of CTLA-4 molecules are required to orientate CD80 such that PD-L1 interactions are no longer permissible. Moreover, soluble CTLA-4 released PD-L1 only at specific expression levels of CD80 and PD-L1, whereas CTLA-4 trans-endocytosis released PD-L1 in all conditions. These data show that PD-L1 release from CD80 is driven by orientation and bivalent cross-linking of membrane proteins and that trans-endocytosis of CD80 efficiently promotes PD-L1 availability.

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IL-1ß is a principal proinflammatory cytokine underlying multiple local and systemic chronic inflammatory conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and type 2 diabetes. Passive immunotherapies and biologic drugs targeting IL-1ß, while offering significant clinical benefit, nevertheless have limitations such as significant non-response rates, induction of anti-drug antibodies, and high costs. Here, an active immunotherapy raising antibody responses against IL-1ß employing self-assembling peptide nanofibers is described. The nanofibers contain defined quantities of B-cell epitopes from IL-1ß and exogenous T helper epitopes and employ the Q11 self-assembling peptide platform. Without adjuvant, the nanofibers raised durable anti-IL-1ß antibody responses that inhibit IL-1ß activity in vitro and in vivo. In a mouse model of imiquimod-induced psoriasis, prophylactic immunizations with the nanofibers diminished symptoms of epidermal thickening. This therapeutic effect is associated with biasing the immune response toward an anti-inflammatory IgG1/Th2 phenotype and a lowered expression of proinflammatory genes in the skin. Further, anti-IL-1ß nanofibers induced therapeutic immunosuppressive CD62L+ Treg cells. This technology represents a potential alternative for passive immunotherapies and other biologics for treating chronic inflammatory conditions.

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Escherichia coli (E. coli) was among the first organisms to have its complete genome published (Genome Sequence of E. coli 1997 Science). It is used as a model system in microbiology research. E. coli can cause life-threatening illnesses, particularly in children and the elderly. Possible contamination by the bacteria also results in product recalls, which, alongside the potential danger posed to individuals, can have significant financial consequences. We report the detection of live Escherichia coli (E. coli) in liquid samples using a biosensor based on a field-effect transistor (FET) biosensor with B/N co-coped reduced graphene oxide (rGO) gel (BN-rGO) as the transducer material. The FET was functionalized with antibodies to detect E. coli K12 O-antigens in phosphate-buffered saline (PBS). The biosensor detected the presence of planktonic E. coli bacterial cells within a mere 2 min. The biosensor exhibited a limit of detection (LOD) of 10 cells per sample, which can be extrapolated to a limit of detection at the level of a single cell per sample and a detection range of at least 10-108 CFU/mL. The selectivity of the biosensor for E. coli was demonstrated using Bacillus thuringiensis (B. thuringiensis) as a sample contaminant. We also present a comparison of our functionalized BN-rGO FET biosensor with established detection methods of E. coli k12 bacteria, as well as with state-of-the-art detection mechanisms.

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BACKGROUND: The aim of this study was to understand the experiences of young men with a diagnosis of testicular cancer (TC) using a narrative approach, with the intention of informing models of care and support in clinical services. METHODS: TC patients were recruited to participate in one of four focus groups examining their lived experiences from diagnosis. Focus groups were recorded and transcribed and analyzed using a narrative approach. RESULTS: A total of 4 focus groups were held from March to May 2019, involving 21 participants. Participants were currently on treatment (n = 2), < 2 years from treatment completion (n = 7), or > 2 years from treatment completion (n = 12). Two overarching meta-themes were identified: Negotiating Identity (comprising "recovery, repair and control"; "breaking the news"; "threats to fertility and virility"; "multiple masculinities") and Needing to Adjust (comprising "trauma and post-traumatic growth"; "facing vulnerability"; "managing to cope"; "secrecy vs. privacy"). Shared themes relating to environments for support, conversations about cancer, and time stress were also identified. CONCLUSIONS: Despite the significant cure rates for testicular cancer, the psychosocial needs of patients diagnosed with TC are paramount and potentially long-lasting. Improved clinical care for these patients includes exploration of both physical and psychosocial concerns over multiple timepoints. Opportunities for peer support and mentorship may be essential to support these vulnerable patients.

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BACKGROUND AND AIMS: Citation scores (CS) have been traditionally used to measure the impact of scientific publications. Sourced from the Internet, Altmetric Attention Scores (AAS) are complementary metrics that assess how often publications are discussed and used globally. We compared by rank the top 500 papers by CS and AAS published in Clinical Nutrition with corresponding AAS and CS. METHODS: A search for all publications in Clinical Nutrition was performed on Dimensions (https://app.dimensions.ai/discover/publication) on 3rd April 2024. Outputs were ranked according to CS and then by AAS with the top 500 in each category selected. Scores, year and type of publication were recorded. Correlation was expressed as the Spearman's rank coefficient (ϱ). RESULTS: We identified 18,790 outputs. Within the top 500 publications ranked by CS, there was a significant weak positive correlation (ϱ = 0.235, P < 0.0001) between CS [median (IQR) 149 (116-223)] and AAS [7 (3-22)]. Ranked by AAS, there was a non-significant very weak positive correlation (ϱ = 0.072, P = 0.106) between AAS [55.5 (36-115)] and CS [42 (16.5-94.5)]. Trends remained similar when grouped by publication type. Guidelines, ranked by CS, had the highest CS and ranked by AAS, the highest CS and AAS. Publications per year, by year, ranked by CS, had a negatively skewed distribution peaking in 2012 and declined thereafter, but when ranked by AAS, had a moderately positive linear trend from 2001 to 2024 (ϱ = 0.513, P < 0.0001). CONCLUSION: Correlation between CS and AAS was weak. Guidelines had the highest CS and AAS. CS are iterative taking years to mature while AAS are immediate.

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INTRODUCTION: A noncoding variant (rs35349669) within INPP5D, a lipid and protein phosphatase restricted to microglia in the brain, is linked to increased susceptibility to Alzheimer's disease (AD). While Inpp5d is well-studied in amyloid pathology, its role in tau pathology remains unclear. METHODS: PS19 Tauopathy mice were crossed with Inpp5d-haplodeficient (Inpp5d+/-) mice to examine the impact of Inpp5d in tau pathology. RESULTS: Increased INPP5D expression correlated positively with phospho-Tau AT8 in PS19 mice. Inpp5d haplodeficiency mitigated hyperphosphorylated tau levels (AT8, AT180, AT100, and PHF1) and motor deficits in PS19 mice. Transcriptomic analysis revealed an up-regulation of genes associated with immune response and cell migration. DISCUSSION: Our findings define an association between INPP5D expression and tau pathology in PS19 mice. Alleviation in hyperphosphorylated tau, motor deficits, and transcriptomics changes in haplodeficient-Inpp5d PS19 mice indicate that modulation in INPP5D expression may provide therapeutic potential for mitigating tau pathology and improving motor deficits. HIGHLIGHTS: The impact of Inpp5d in the context of tau pathology was studied in the PS19 mouse model. INPP5D expression is associated with tau pathology. Reduced Inpp5d expression in PS19 mice improved motor functions and decreased total and phospho-Tau levels. Inpp5d haplodeficiency in PS19 mice modulates gene expression patterns linked to immune response and cell migration. These data suggest that inhibition of Inpp5d may be a therapeutic approach in tauopathies.

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INTRODUCTION: MODEL-AD (Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late-onset Alzheimer's disease (LOAD) more accurately. METHODS: We created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid-beta (Aß). Mice were subjected to a control diet or a high-fat/high-sugar diet (LOAD2+HFD). We assessed disease-relevant outcome measures in plasma and brain including neuroinflammation, Aß, neurodegeneration, neuroimaging, and multi-omics. RESULTS: By 18 months, LOAD2+HFD mice exhibited sex-specific neuron loss, elevated insoluble brain Aß42, increased plasma neurofilament light chain (NfL), and altered gene/protein expression related to lipid metabolism and synaptic function. Imaging showed reductions in brain volume and neurovascular uncoupling. Deficits in acquiring touchscreen-based cognitive tasks were observed. DISCUSSION: The comprehensive characterization of LOAD2+HFD mice reveals that this model is important for preclinical studies seeking to understand disease trajectory and progression of LOAD prior to or independent of amyloid plaques and tau tangles. HIGHLIGHTS: By 18 months, unlike control mice (e.g., LOAD2 mice fed a control diet, CD), LOAD2+HFD mice presented subtle but significant loss of neurons in the cortex, elevated levels of insoluble Ab42 in the brain, and increased plasma neurofilament light chain (NfL). Transcriptomics and proteomics showed changes in gene/proteins relating to a variety of disease-relevant processes including lipid metabolism and synaptic function. In vivo imaging revealed an age-dependent reduction in brain region volume (MRI) and neurovascular uncoupling (PET/CT). LOAD2+HFD mice also demonstrated deficits in acquisition of touchscreen-based cognitive tasks.

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BACKGROUND: Diabetes mellitus is a significant modulator of postoperative outcomes and is an important risk factor in the patient selection process. We aimed to investigate the effect of diabetes mellitus and use of insulin on outcomes after colorectal resection using a national cohort. METHODS: Adults with a recorded colorectal resection in England between 2010 and 2020 were identified from Hospital Episode Statistics data linked to the Clinical Practice Research Database. The primary outcome was 90-day mortality. Secondary outcomes included hospital length of stay (LOS) and readmission within 90 days. RESULTS: Of the 106 139 (52 875, 49.8% male) patients included, diabetes mellitus was prevalent in 10 931 (10.3%), 2145 (19.6%) of whom had a record of use of insulin. Unadjusted 90-day mortality risk was 5.7%, with an increased adjusted hazard ratio (aHR) for people with diabetes mellitus (aHR 1.28, 95% confidence interval [CI] 1.19-1.37, P<0.001). This risk was higher in both people with diabetes using insulin (aHR 1.51, 95% CI 1.31-1.74, P<0.001) and not using insulin (aHR 1.22, 95% CI 1.13-1.33, P<0.001), compared with those without diabetes. Ninety-day readmission occurred in 20 542 (19.4%) patients and this was more likely in those with diabetes mellitus (aHR 1.23, 95% CI 1.18-1.29, P<0.001). Median (inter-quartile range) LOS was 8 (5-15) days and was higher in people with diabetes mellitus (adjusted time ratio 1.10, 95% CI 1.08-1.11, P<0.001). CONCLUSIONS: People with diabetes mellitus undergoing colorectal resection are at a higher risk of 90-day mortality, prolonged LOS, and 90-day readmission, with use of insulin associated with additional risk.

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Background: Individuals with chronic kidney disease (CKD) on dialysis are at an increased risk of stroke and embolic events especially in the presence of atrial fibrillation (AF). Vitamin K antagonists (VKA), including warfarin, have been used for decades for anticoagulation among CKD patients on dialysis with AF but recent evidence has shown increased bleeding. Direct oral anticoagulants (DOAC) have been emerging as an alternative to VKA which, based on several observational cohort studies, are at least as efficacious and safe as VKA. This meta-analysis looked into the safety and efficacy of DOACs compared to VKA among CKD patients on dialysis with non-valvular AF. Methodology: This study used a random-effects meta-analysis using RevMan 5.4. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were searched from their dates of inception to June 2023. The risk of bias was assessed using Cochrane RoB2 and the certainty of evidence was assessed using GRADE. Results: This meta-analysis showed that DOACs when compared to VKA have no significant difference in terms of risk for major bleeding (RR = 0.81, 95% CI 0.46-1.43), ischemic stroke (RR = 0.5, 95% CI 0.19-1.35), and cardiovascular death (RR = 1.34, 95% CI 0.69-2.60). Discussion: This meta-analysis adds to the growing body of evidence supporting that the use of DOACs has similar efficacy and safety outcomes in CKD patients on dialysis with non-valvular AF patients compared to VKA. The findings need to be replicated in larger and more adequately powered clinical trials in order to ascertain its level of evidence.

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BACKGROUND: Venous thromboembolism is a well-established preventable complication after colectomy. Specific guidance on venous thromboembolism prevention after colectomy for benign disease is limited. OBJECTIVE: This meta-analysis aimed to quantify the venous thromboembolism risk after benign colorectal resection and determine its variability. DATA SOURCES: Following Preferred Reporting Items for Systematic Review and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology Guidelines (PROSPERO: CRD42021265438), Embase, MEDLINE, and 4 other registered medical literature databases were searched from the database inception to June 21, 2021. STUDY SELECTION: Inclusion criteria: randomized controlled trials and large population-based database cohort studies reporting 30-day and 90-day venous thromboembolism rates after benign colorectal resection in patients aged ≥18 years. Exclusion criteria: patients undergoing colorectal cancer or completely endoscopic surgery. MAIN OUTCOME MEASURES: Thirty- and 90-day venous thromboembolism incidence rates per 1000 person-years after benign colorectal surgery. RESULTS: Seventeen studies were eligible for meta-analysis reporting on 250,170 patients. Pooled 30-day and 90-day venous thromboembolism incidence rates after benign colorectal resection were 284 (95% CI, 224-360) and 84 (95% CI, 33-218) per 1000 person-years. Stratified by admission type, 30-day venous thromboembolism incidence rates per 1000 person-years were 532 (95% CI, 447-664) for emergency resections and 213 (95% CI, 100-453) for elective colorectal resections. Thirty-day venous thromboembolism incidence rates per 1000 person-years after colectomy were 485 (95% CI, 411-573) for patients with ulcerative colitis, 228 (95% CI, 181-288) for patients with Crohn's disease, and 208 (95% CI, 152-288) for patients with diverticulitis. LIMITATIONS: High degree of heterogeneity was observed within most meta-analyses attributable to large cohorts minimizing within-study variance. CONCLUSIONS: Venous thromboembolism rates remain high up to 90 days after colectomy and vary by indication for surgery. Emergency resections compared to elective benign resections have higher rates of postoperative venous thromboembolism. Further studies reporting venous thromboembolism rates by type of benign disease need to stratify rates by admission type to more accurately define venous thromboembolism risk after colectomy. REGISTRATION NO: CRD42021265438.

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AIM: This study reports venous thromboembolism (VTE) rates following colectomy for diverticular disease to explore the magnitude of postoperative VTE risk in this population and identify high risk subgroups of interest. METHOD: English national cohort study of colectomy patients between 2000 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type, absolute incidence rates (IR) per 1000 person-years and adjusted incidence rate ratios (aIRR) were calculated for 30- and 90-day post-colectomy VTE. RESULTS: Of 24,394 patients who underwent colectomy for diverticular disease, over half (57.39%) were emergency procedures with the highest VTE rate seen in patients ≥70-years-old (IR 142.27 per 1000 person-years, 95%CI 118.32-171.08) at 30 days post colectomy. Emergency resections (IR 135.18 per 1000 person-years, 95%CI 115.72-157.91) had double the risk (aIRR 2.07, 95%CI 1.47-2.90) of developing a VTE at 30 days following colectomy compared to elective resections (IR 51.14 per 1000 person-years, 95%CI 38.30-68.27). Minimally invasive surgery (MIS) was shown to be associated with a 64% reduction in VTE risk (aIRR 0.36 95%CI 0.20-0.65) compared to open colectomies at 30 days post-op. At 90 days following emergency resections, VTE risks remained raised compared to elective colectomies. CONCLUSION: Following emergency colectomy for diverticular disease, the VTE risk is approximately double compared to elective resections at 30 days while MIS was found to be associated with a reduced risk of VTE. This suggests advancements in postoperative VTE prevention in diverticular disease patients should focus on those undergoing emergency colectomies.

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PaxlovidTM (nirmaltrelvir/ritonavir) received emergency use authorization from the Food and Drug Administration (FDA) in December 2021 to treat coronavirus disease 2019 (COVID-19). Given the actions of Paxlovid on cytochrome P450-3A4 (CYP3A4) enzymes, it is imperative to check for potential drug-drug interactions before prescribing. We describe a case in which the common emergency department presentation of generalized weakness was found to be caused by interactions between Paxlovid and a patient's home medications resulting in tacrolimus toxicity.

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Innovative approaches to prevent catheter-associated urinary tract infections (CAUTIs) are urgently required. Here, we describe the discovery of an acrylate copolymer capable of resisting single- and multispecies bacterial biofilm formation, swarming, encrustation, and host protein deposition, which are major challenges associated with preventing CAUTIs. After screening ~400 acrylate polymers, poly(tert-butyl cyclohexyl acrylate) was selected for its biofilm- and encrustation-resistant properties. When combined with the swarming inhibitory poly(2-hydroxy-3-phenoxypropyl acrylate), the copolymer retained the bioinstructive properties of the respective homopolymers when challenged with Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Urinary tract catheterization causes the release of host proteins that are exploited by pathogens to colonize catheters. After preconditioning the copolymer with urine collected from patients before and after catheterization, reduced host fibrinogen deposition was observed, and resistance to diverse uropathogens was maintained. These data highlight the potential of the copolymer as a urinary catheter coating for preventing CAUTIs.

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INTRODUCTION: MODEL-AD is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to more accurately mimic LOAD than commonly used transgenic models. METHODS: We created the LOAD2 model by combining APOE4, Trem2*R47H, and humanized amyloid-beta. Mice aged up to 24 months were subjected to either a control diet or a high-fat/high-sugar diet (LOAD2+HFD) from two months of age. We assessed disease-relevant outcomes, including in vivo imaging, biomarkers, multi-omics, neuropathology, and behavior. RESULTS: By 18 months, LOAD2+HFD mice exhibited cortical neuron loss, elevated insoluble brain Aß42, increased plasma NfL, and altered gene/protein expression related to lipid metabolism and synaptic function. In vivo imaging showed age-dependent reductions in brain region volume and neurovascular uncoupling. LOAD2+HFD mice also displayed deficits in acquiring touchscreen-based cognitive tasks. DISCUSSION: Collectively the comprehensive characterization of LOAD2+HFD mice reveal this model as important for preclinical studies that target features of LOAD independent of amyloid and tau.

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INTRODUCTION: In this study we aimed to determine the impact of the mandatory coronavirus disease 2019 (COVID-19) pandemic stay-at-home order on the proportional makeup of emergency department (ED) visits by frequent users and super users. METHODS: We conducted a secondary analysis of existing data using a multisite review of the medical records of 280,053 patients to measure the impact of the COVID-19 pandemic stay-at-home order on ED visits. The primary outcomes included analysis before and during the lockdown in determining ED use and unique characteristics of non-frequent, frequent, and super users of emergency services. RESULTS: During the mandatory COVID-19 stay-at-home order (lockdown), the percentage of frequent users increased from 7.8% (pre-lockdown) to 21.8%. Super users increased from 0.7% to 4.7%, while non-frequent users dropped from 91.5% to 73.4%. Frequent users comprised 23.7% of all visits (4% increase), while super user encounters (4.7%) increased by 53%. Patients who used Medicaid and Medicare increased by 39.3% and 4.6%, respectively, while those who were uninsured increased ED use by 190.3% during the lockdown. CONCLUSION: When barriers to accessing healthcare are implemented as part of a broader measure to reduce the spread of an infectious agent, individuals reliant on these services are more likely to seek out the ED for their medical needs. Policymakers considering future pandemic planning should consider this finding to ensure that vital healthcare resources are allocated appropriately.

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Anti-CTLA-4 antibodies have pioneered the field of tumour immunotherapy. However, despite impressive clinical response data, the mechanism by which anti-CTLA-4 antibodies work is still controversial. Two major checkpoint antibodies (ipilimumab and tremelimumab) have been trialled clinically. Both have high affinity binding to CTLA-4 and occupy the ligand binding site, however recently it has been suggested that in some settings such antibodies may not block ligand-CTLA-4 interactions. Here we evaluated blocking capabilities of these antibodies in a variety of settings using both soluble and cell bound target proteins. We found that when ligands (CD80 or CD86) were expressed on cells, soluble CTLA-4-Ig bound in line with affinity expectations and that this interaction was effectively disrupted by both ipilimumab and tremelimumab antibodies. Similarly, cellular CTLA-4 binding to soluble ligands was comparably prevented. We further tested the ability of these antibodies to block transendocytosis, whereby CTLA-4 captures ligands from target cells during a cognate cell-cell interaction. Once again ipilimumab and tremelimumab were similar in preventing removal of ligand by transendocytosis. Furthermore, even once transendocytosis was ongoing and cell contact was fully established, the addition of these antibodies could prevent further ligand transfer. Together these data indicate that the above checkpoint inhibitors performed in-line with predictions based on affinity and binding site data and are capable of blocking CTLA-4-ligand interactions in a wide range of settings tested.

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Obesity is recognized as a significant risk factor for Alzheimer's disease (AD). Studies have supported the notion that obesity accelerates AD-related pathophysiology in mouse models of AD. The majority of studies, to date, have focused on the use of early-onset AD models. Here, we evaluate the impact of genetic risk factors on late-onset AD (LOAD) in mice fed with a high fat/high sugar diet (HFD). We focused on three mouse models created through the IU/JAX/PITT MODEL-AD Center. These included a combined risk model with APOE4 and a variant in triggering receptor expressed on myeloid cells 2 (Trem2R47H ). We have termed this model, LOAD1. Additional variants including the M28L variant in phospholipase C Gamma 2 (Plcg2M28L ) and the 677C > T variant in methylenetetrahydrofolate reductase (Mthfr 677C > T ) were engineered by CRISPR onto LOAD1 to generate LOAD1.Plcg2M28L and LOAD1.Mthfr 677C > T . At 2 months of age, animals were placed on an HFD that induces obesity or a control diet (CD), until 12 months of age. Throughout the study, blood was collected to assess the levels of cholesterol and glucose. Positron emission tomography/computed tomography (PET/CT) was completed prior to sacrifice to image for glucose utilization and brain perfusion. After the completion of the study, blood and brains were collected for analysis. As expected, animals fed a HFD, showed a significant increase in body weight compared to those fed a CD. Glucose increased as a function of HFD in females only with cholesterol increasing in both sexes. Interestingly, LOAD1.Plcg2M28L demonstrated an increase in microglia density and alterations in regional brain glucose and perfusion on HFD. These changes were not observed in LOAD1 or LOAD1.Mthfr 677C > T animals fed with HFD. Furthermore, LOAD1.Plcg2M28L but not LOAD1.Mthfr 677C > T or LOAD1 animals showed transcriptomics correlations with human AD modules. Our results show that HFD affects the brain in a genotype-specific manner. Further insight into this process may have significant implications for the development of lifestyle interventions for the treatment of AD.

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OBJECTIVE: To assess the impact of current guidelines by reporting weekly postoperative postdischarge venous thromboembolism (VTE) rates. SUMMARY BACKGROUND DATA: Disparity exists between the postoperative thromboprophylaxis duration colectomy patients receive based on surgical indication, where malignant resections routinely receive 28 days extended thromboprophylaxis into the postdischarge period and benign resections do not. METHODS: English national cohort study of colectomy patients between 2010 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type and surgical indication, absolute incidence rates (IRs) per 1000 person-years and adjusted incidence rate ratios (aIRRs) for postdischarge VTE were calculated for the first 4 weeks following resection and postdischarge VTE IRs for each postoperative week to 12 weeks postoperative. RESULTS: Of 104,744 patients, 663 (0.63%) developed postdischarge VTE within 12 weeks after colectomy. Postdischarge VTE IRs per 1000 person-years for the first 4 weeks postoperative were low following elective resections [benign: 20.66, 95% confidence interval (CI): 13.73-31.08; malignant: 28.95, 95% CI: 23.09-36.31] and higher following emergency resections (benign: 47.31, 95% CI: 34.43-65.02; malignant: 107.18, 95% CI: 78.62-146.12). Compared with elective malignant resections, there was no difference in postdischarge VTE risk within 4 weeks following elective benign colectomy (aIRR=0.92, 95% CI: 0.56-1.50). However, postdischarge VTE risks within 4 weeks following emergency resections were significantly greater for benign (aIRR=1.89, 95% CI: 1.22-2.94) and malignant (aIRR=3.13, 95% CI: 2.06-4.76) indications compared with elective malignant colectomy. CONCLUSIONS: Postdischarge VTE risk within 4 weeks of colectomy is ∼2-fold greater following emergency benign compared with elective malignant resections, suggesting emergency benign colectomy patients may benefit from extended VTE prophylaxis.

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AIM: It is important for patient safety to assess if international changes in perioperative care, such as the focus on venous thromboembolism (VTE) prevention and minimally invasive surgery, have reduced the high post colectomy VTE risks previously reported. This study assesses the impact of changes in perioperative care on VTE risk following colorectal resection. METHOD: This was a population-based cohort study of colectomy patients in England between 2000 and 2019 using a national database of linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Within 30 days following colectomy, absolute VTE rates per 1000 person-years and adjusted incidence rate ratios (aIRRs) using Poisson regression for the per year change in VTE risk were calculated. RESULTS: Of 183 791 patients, 1337 (0.73%) developed 30-day postoperative VTE. Overall, VTE rates reduced over the 20-year study period following elective (relative risk reduction 31.25%, 95% CI 5.69%-49.88%) but not emergency surgery. Similarly, yearly changes in VTE risk reduced following minimally invasive resections (elective benign, aIRR 0.93, 95% CI 0.90-0.97; elective malignant, aIRR 0.94, 95% CI 0.91-0.98; and emergency benign, aIRR 0.96, 95% CI 0.92-1.00) but not following open resections. There was a per year VTE risk increase following open emergency malignant resections (aIRR 1.02, 95% CI 1.00-1.04). CONCLUSION: Yearly VTE risks reduced following minimally invasive surgeries in the elective setting yet in contrast were static following open elective colectomies, and following emergency malignant resections increased by almost 2% per year. To reduce VTE risk, further efforts are required to implement advances in surgical care for those having emergency and/or open surgery.

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