The effect of diabetes mellitus on perioperative outcomes after colorectal resection: a national cohort study.

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.

Inpp5d haplodeficiency alleviates tau pathology in the PS19 mouse model of Tauopathy.

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.

Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.

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.

Risk of Postoperative Venous Thromboembolism After Benign Colorectal Surgery: Systematic Review and Meta-analysis.

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.

Venous thromboembolism following colectomy for diverticular disease: an English population-based cohort study.

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.

The Duration and Magnitude of Postdischarge Venous Thromboembolism Following Colectomy.

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.

Time trends in the incidence rates of venous thromboembolism following colorectal resection by indication and operative technique.

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.

Hypokalemic Cardiac Arrest: Narrative Review of Case Reports and Current State of Science.

PURPOSE: Hypokalemic cardiac arrest is an uncommon occurrence in the emergency department. Electrocardiogram findings related to hypokalemic cardiac arrest include prolonged QT, U waves, and preventricular contractions leading to Torsades de Pointes and then arrest. Literature evaluating the prevalence of hypokalemic cardiac arrest is scarce, and its management is lacking. This review provides a summary of current literature, recommendations from current guidelines, and proposed management strategies of hypokalemic cardiac arrest. SUMMARY: Intravenous potassium administration is the treatment for hypokalemic cardiac arrest. Although the treatment for hypokalemic cardiac arrest is known, there is limited evidence on the proper procedure for administering intravenous potassium appropriately and safely. Owing to the time-sensitive nature of treating hypokalemic cardiac arrest, rapid administration of intravenous potassium (10 mEq/100 mL of potassium chloride over 5 minutes) is warranted. Concerns regarding rapid potassium administration are not without merit; however, a risk-benefit analysis and potential mitigation strategies for unwanted side effects need to be considered if hypokalemic cardiac arrest is to remain a reversible cause. It is imperative to identify hypokalemia as the cause for arrest as soon as possible and administer potassium before systemic acidosis, ischemia, and irreversible cell death. CONCLUSIONS: More evidence is necessary to support treatment recommendations for hypokalemic cardiac arrest; however, it is the authors' opinion that, if identified early during cardiac arrest, intravenous potassium should be administered to treat a reversible cause for cardiac arrest.

Risk of Postoperative Venous Thromboembolism After Surgery for Colorectal Malignancy: A Systematic Review and Meta-analysis.

BACKGROUND: Colorectal cancer has the second highest mortality of any malignancy, and venous thromboembolism is a major postoperative complication. OBJECTIVE: This study aimed to determine the variation in incidence of venous thromboembolism after colorectal cancer resection. DATA SOURCES: Following PRISMA and MOOSE guidelines (PROSPERO, ID: CRD42019148828), Medline and Embase databases were searched from database inception to August 2019 including 3 other registered medical databases. STUDY SELECTION: Two blinded reviewers screened studies with a third reviewer adjudicating any discordance. Eligibility criteria: Patients post colorectal cancer resection aged ≥18 years. Exclusion criteria: Patients undergoing completely endoscopic surgery and those without cancer resection. Selected studies were randomized controlled trials and population-based database/registry cohorts. MAIN OUTCOME MEASURES: Thirty- and 90-day incidence rates of venous thromboembolism per 1000 person-years following colorectal cancer surgery. RESULTS: Of 6441 studies retrieved, 28 met inclusion criteria. Eighteen were available for meta-analysis reporting on 539,390 patients. Pooled 30- and 90-day incidence rates of venous thromboembolism following resection were 195 (95% CI, 148-256, I2 99.1%) and 91 (95% CI, 56-146, I2 99.2%) per 1000 person-years. When separated by United Nations Geoscheme Areas, differences in the incidence of postoperative venous thromboembolism were observed with 30- and 90-day pooled rates per 1000 person-years of 284 (95% CI, 238-339) and 121 (95% CI, 82-179) in the Americas and 71 (95% CI, 60-84) and 57 (95% CI, 47-69) in Europe. LIMITATIONS: A high degree of heterogeneity was observed within meta-analyses attributable to large cohorts minimizing within-study variance. CONCLUSION: The incidence of venous thromboembolism following colorectal cancer resection is high and remains so more than 1 month after surgery. There is clear disparity between the incidence of venous thromboembolism after colorectal cancer surgery by global region. More robust population studies are required to further investigate these geographical differences to determine valid regional incidence rates of venous thromboembolism following colorectal cancer resection.

Publication Rates, Ethnic and Sex Disparities in UK and Ireland Surgical Research Prize Presentations: An Analysis of Data From the Moynihan and Patey Prizes From 2000 to 2020.

BACKGROUND: Presentation at academic conferences is an important marker of research productivity. However, not all accepted abstracts progress to full publication, and there is anecdotal evidence suggesting an imbalance in sex and ethnicity amongst presenters. There is a lack of data evaluating the outcome of prize presentation sessions at academic surgical conferences in the UK. This study aimed to analyse the outcomes and demographics from presentations at prize sessions at two prestigious UK surgical conferences. METHODS: This retrospective observational study compared data on all Moynihan (Association of Surgeons of Great Britain and Ireland) and Patey (Surgical Research Society) prize presentations from 2000 to 2020. The primary outcome was rate of publication. Secondary outcomes included demographic differences in sex and ethnicity, publication according to prize outcome, academic affiliation, time to publication, and journal impact factor. RESULTS: Some 442 accepted abstracts were identified over the 21-year period, with 71.0% from the Moynihan sessions and 79.3% from the Patey sessions leading to full publications, with a median time to publication of 448 days (IQR 179-859) in journals with relatively high impact factors (median 5.00; IQR 3.15-6.36). Of the 442 prize presenters, 85 (19.2%) were female. The majority of the presenters were White males (211, 47.7%), followed by Asian males (112, 25.3%). However, there was a continuously increasing overall trend of female presenters from 2000 to 2020 (P = 0.019). CONCLUSION: Publication rates from the two prize sessions were high, with presenters publishing in journals with high impact factors. There, however, was a disparity in sex and ethnicity amongst presenters.

Contending with Spiritual Reductionism: Demons, Shame, and Dividualising Experiences Among Evangelical Christians with Mental Distress.

The belief that mental distress is caused by demons, sin, or generational curses is commonplace among many evangelical Christian communities. These beliefs may have positive or negative effects for individuals and groups. Phenomenological descriptions of these experiences and the subjective meanings associated with them, however, remain somewhat neglected in the literature. The current study employed semi-structured interviews with eight evangelical Christians in order to idiographically explore their experiences of mental distress in relation to their faith and wider communities. Through an interpretative phenomenological analysis, two superordinate themes were constructed: negative spiritualisation and negotiating the dialectic between faith and the lived experience of mental distress. Participants variously experienced a climate of negative spiritualisation, whereby their mental distress was demonised and dismissed, and they were further discouraged from seeking help in secular institutions and environments. Participants often considered such dismissals of their mental distress as unhelpful and stigmatising and experienced heightened feelings of shame and suffering as a result. Such discouragement also contributed to the process of othering and relational disconnection. Alongside a rejection of church teachings, which exclusively spiritualised psychological distress, participants negotiated a nuanced personal synthesis of faith, theology, and distress, which assumed a localised and idiographic significance. This synthesis included advocating for the uptake of aetiological accounts, which contextualised mental distress in terms of the whole person and resisted de-politicised, dichotomised, and individualistic narratives. Results are discussed in relation to a broad range of literature in the field, while further research suggestions are provided.

Preclinical development of a high affinity α-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo.

There are no approved drug therapies that can prevent or slow the progression of Parkinson's disease (PD). Accumulation and aggregation of α-synuclein protein is observed throughout the nervous system in PD. α-Synuclein is a core component of Lewy bodies and neurites that neuropathologically define PD, suggesting that α-synuclein may be a key causative agent in PD. Recent experimental data suggest that PD progression may arise due to spreading of pathological forms of extracellular α-synuclein throughout the brain via a cellular release, uptake and seeding mechanism. We have developed a high affinity α-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo. MEDI1341 binds both monomeric and aggregated forms of α-synuclein. In vitro, MEDI1341 blocks cell-to-cell transmission of pathologically relevant α-synuclein preformed fibrils (pffs). After intravenous injection into rats and cynomolgus monkeys, MEDI1341 rapidly enters the central nervous system and lowers free extracellular α-synuclein levels in the interstitial fluid (ISF) and cerebrospinal fluid (CSF) compartments. Using a novel lentiviral-based in vivo mouse model of α-synuclein spreading in the brain, we show that treatment with MEDI1341 significantly reduces α-synuclein accumulation and propagation along axons. In this same model, we demonstrate that an effector-null version of the antibody was equally as effective as one with effector function. MEDI1341 is now in Phase 1 human clinical trial testing as a novel treatment for α-synucleinopathies including PD with the aim to slow or halt disease progression.

A comparison of the top 500 papers in Clinical Nutrition ranked by citation and Altmetric Attention Scores.

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.

Paxlovid-Induced Tacrolimus Toxicity in the Treatment of COVID-19: A Case Report.

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.

The safety and efficacy of direct oral anticoagulants among chronic kidney disease patients on dialysis with non-valvular atrial fibrillation: a meta-analysis.

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.

Discovery of a polymer resistant to bacterial biofilm, swarming, and encrustation.

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.

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

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.

Mycotic Aortic Aneurysm: A Rare Etiology of Septic Shock.

Mycotic aneurysm of the aorta is a rare disease with a high mortality rate due to its likelihood of aneurysmal rupture. This syndrome is predominantly seen in patients over age 65 with the most common presenting symptoms being fever and back pain. Our case illustrates a mycotic aneurysm of the aorta presenting in an elderly female with vague abdominal pain, flank pain, and generalized weakness. We review the investigative approach, diagnostic modalities, and treatment options in patient management. This case emphasizes the need for a high index of suspicion of mycotic aneurysms of the aorta in critically ill elderly patients as early antibiotic therapy can be crucial for source control.

"His Main Problem Was Not Being in a Relationship With God": Perceptions of Depression, Help-Seeking, and Treatment in Evangelical Christianity.

Some Christian communities may understand mental illness as the result of spiritual causes, such as sin, demons, or a lack of faith. Such perceptions are likely to influence how Christian individuals conceptualise and experience their mental health and enact help-seeking behaviours. This study explores perceptions of depression and mental health help-seeking in evangelical Christianity by using a novel qualitative story completion task. A convenience sample of 110 Christian participants from the United Kingdom completed a third-person, fictional story stem featuring a male with depression who entered his local church. A contextualist-informed thematic analysis illustrated how the disclosure of depression was represented as eliciting negative social reactions, potentially rendering individuals with depression as socially dislocated. Stories suggested that, increasingly, evangelical Christians may perceive a spiritualisation of mental illness, which negates reference to psychological, social, and biomedical representations, as unhelpful. Findings reveal the risks of a solely spiritual aetiology of depression and highlight how existing mental ill-health can be exacerbated if fundamentalist beliefs and approaches to therapeutic care are prioritised over holistic models of care. Methodologically, this study demonstrates the value of a rarely-used tool in psychology-the story completion task-for examining socio-cultural discourses and dominant meanings surrounding stigmatised topics or populations.

"It's easy to dismiss it as simply a spiritual problem." Experiences of mental distress within evangelical Christian communities: A qualitative survey.

Evidence suggests that faith communities can support psychological wellbeing but can also potentially diminish wellbeing through stigma, imposed spiritualization, and marginalization. In particular, for evangelical Christianity, whose theological praxis typically accentuates literalist spiritual onto-etiologies, including the belief that mental distress can be treated solely through spiritual intervention (prayer, fasting, and deliverance), there may be negative implications for Christians with mental distress. The current qualitative survey examined the responses of 293 self-identified evangelical Christians, concerning their experiences of mental distress in relation to their church community. An inductive thematic analysis revealed five themes: 1) Tensions between Faith and Suffering; 2) Cautions about a Reductive Spiritualization; 3) Feeling Othered and Disconnected; 4) Faith as Alleviating Distress; and 5) Inviting an Integrationist Position. Findings reveal stigma and the totalizing spiritualization of mental distress can be experienced as both dismissive and invalidating and can problematize secular help-seeking. This lends support to previous research which has suggested that evangelical Christian communities tend to link mental distress to spiritual deficiencies, which can hold potentially negative consequences for their wellbeing. Nevertheless, a degree of complexity and nuance emerged whereby spiritual explanations and interventions were also experienced as sometimes helpful in alleviating suffering. Overall, findings suggest evangelical communities are increasingly adopting integrationist understandings of mental distress, whereby spiritual narratives are assimilated alongside the biopsychosocial. We argue that church communities and psychotherapeutic practitioners should support movement from a position of dichotomizing psychological suffering (e.g., spiritual vs. biopsychosocial) towards a spiritually syntonic frame, which contextualizes distress in terms of the whole person. Considerations for psychotherapeutic practice and further research are made.