Toll-like receptors in atherosclerosis: a 'Pandora's box' of advances and controversies

n/

Using EMR to Implement and Track Compliance of a Unique Colon Bundle That Reduced Surgical Site Infection in Colorectal Surgery: A Single Institution Review

Background: Surgical site infections (SSI) remain a common complication of colorectal surgery and are associated with an increase in cost, hospital LOS and an increased risk of postoperative morbidity and mortality. It is well studied that surgical care bundles reduce infection, there is no established consensus on the optimal amalgamation of variables. Increasing the number of measures within the bundle is associated with a stepwise reduction in SSI. This review presents the efficacy and implementation of a detailed surgical bundle to reduce SSIs in patients undergoing colorectal surgery. We illustrate how the use of EMR aids in implementation and the ability to easily record and track compliance, leading to dramatic reductions in SSIs during colon surgery. Methods: Our 700+ bed tertiary care center performs over 25,000 surgeries per year and approximately 280 colon cases. In 2015 our institution had a rise in the rate of SSI in colorectal surgeries prompting our institution to reevaluate their practices and initiate a Colon Bundle. A multidisciplinary team evaluated the current process and reviewed best practice guidelines and prevention bundles at other high performing institutions. The current Colon Bundle consists of various features including; standardized preoperative bowel prep, hair removal outside of OR, CHG prep, intraop wound protectors and an incision closing protocol . The benefit of this bundle focuses on continued surveillance of compliance with the incorporation directly into the EMR system. Intraop nursing staff are required to document key components of the bundle as part of their intraop paperwork, generating monthly reports that track surgeon specific compliance and fallouts. Results: The rate of SSI prior to implementation of the Colon Bundle, was 7.82% for 243 colon cases with a SIR of 2.431. The bundle was implemented in 2015 and the rate of SSI dropped to 3.52% with a SIR of 1.25 in 2016. The SSI rate continued to drop, in 2017 to 1.96% with a decrease in SIR to 0.68. When compliance was evaluated for specific components, most showed an increase between July 2017 and September 2018. Adherence to the intraop closure went from an average of 93% to 97%, wound protector use went from 85% to 90%. Preop CHG wipes went from 89% to 92%. A few areas had a decrease in compliance, including changing of gown and gloves intraop at the initiation of closing bundle from 99% to 97% and use of new instruments intraop when closing went from 98% to 96%. Conclusions: The implementation of a unique colon bundle at hospital dramatically reduced the incidence of SSI. Ongoing surveillance of compliance is tracked through the EMR allowing for immediate recognition of fall outs, reporting of SSI directly to the surgeons and a way to quickly address issues with compliance. We show that EMR is a helpful tool to track compliance and can be used effectively to improve adherence to aspects of a Colon Bundle in order to effectively reduce SSI

Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity

Aims: Atherosclerosis is characterised by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis. Methods and Results: Apolipoprotein E-deficient (ApoE-/-) mice were fed a chow or a high fat (western) diet for 12 weeks. Single cell aortic preparations were probed with a panel of 35 metal-conjugated antibodies using Cytometry by time of flight (CyTOF). Clustering of marker expression on live CD45+ cells from the aortas of ApoE-/- mice identified 13 broad populations of leucocytes. Monocyte, macrophage, type 1 and type 2 conventional dendritic cell (cDC1 and cDC2), plasmacytoid dendritic cell (pDC), neutrophil, eosinophil, B cell, CD4+ and CD8+ T cell, γδ T cell, natural killer (NK) cell and innate lymphoid (ILC) cell populations accounted for approximately 95% of the live CD45+ aortic cells. Automated clustering algorithms applied to the Lin-CD11blo-hi cells revealed 20 clusters of myeloid cells. Comparison between chow and high fat fed animals revealed increases in monocytes (both Ly6C+ and Ly6C-), pDC and a CD11c+ macrophage subset with high fat feeding. Concomitantly, the proportions of CD206+ CD169+ subsets of macrophages were significantly reduced as were cDC2. Conclusions: A CyTOF-based comprehensive mapping of the immune cell subsets within atherosclerotic aortas from ApoE-/- mice offers tools for myeloid cell discrimination within the vascular compartment and it reveals that high fat feeding skews the myeloid cell repertoire towards inflammatory monocyte-macrophage populations rather than resident macrophage phenotypes and cDC2 during atherogenesis

A Combined Therapeutic Regimen of Buspirone and Environmental Enrichment is more Efficacrious than Either Alone in Enhancing Spatial Learning in Brain-Injured Rats

Abstract Buspirone, a 5-HT1A receptor agonist, and environmental enrichment (EE) enhance cognition and reduce histopathology after traumatic brain injury (TBI) in adult rats, but have not been fully evaluated after pediatric TBI, which is the leading cause of death in children. Hence, the aims of this study were to assess the efficacy of buspirone alone (Experiment 1) and in combination with EE (Experiment 2) in TBI postnatal day-17 male rats. The hypothesis was that both therapies would confer cognitive and histological benefits when provided singly, but their combination would be more efficacious. Anesthetized rats received a cortical impact or sham injury and then were randomly assigned to receive intraperitoneal injections ofbuspirone (0.08 mg/kg, 0.1 mg/kg, and 0.3 mg/kg) or saline vehicle (1.0 mL/kg) 24 h after surgery and once daily for 16 days (Experiment 1). Spatial learning and memory were assessed using the Morris water maze (MWM) on post-operative days 11-16, and cortical lesion volume was quantified on day 17. Sham controls for each condition were significantly better than all TBI groups. In the TBI groups, buspirone (0.1 mg/kg) enhanced MWM performance versus vehicle and buspirone (0.08 mg/kg and 0.3 mg/kg) (p\u3c0.05) and reduced lesion volume relative to vehicle (p=0.038). In Experiment 2, buspirone (0.1 mg/kg) or vehicle was combined with EE after TBI, and the data were compared to the standard (STD)-housed groups from Experiment 1. EE lead to a significant enhancement of spatial learning and a reduction in lesion size versus STD. Moreover, the combined treatment group (buspirone+EE) performed markedly better than the buspirone+STD and vehicle+EE groups, which suggests an additive effect and supports the hypothesis. The data replicate previous studies assessing these therapies in adult rats. These novel findings may have important rehabilitation-relevant implications for clinical pediatric TBI

The comorbidity of depression and neurocognitive disorder in persons with HIV infection: call for investigation and treatment

Depression and neurocognitive disorder continue to be the major neuropsychiatric disorders affecting persons with HIV (PWH). The prevalence of major depressive disorder is two to fourfold higher among PWH than the general population (∼6.7%). Prevalence estimates of neurocognitive disorder among PWH range from 25 to over 47% – depending upon the definition used (which is currently evolving), the size of the test battery employed, and the demographic and HIV disease characteristics of the participants included, such as age range and sex distribution. Both major depressive disorder and neurocognitive disorder also result in substantial morbidity and premature mortality. However, though anticipated to be relatively common, the comorbidity of these two disorders in PWH has not been formally studied. This is partly due to the clinical overlap of the neurocognitive symptoms of these two disorders. Both also share neurobehavioral aspects — particularly apathy — as well as an increased risk for non-adherence to antiretroviral therapy. Shared pathophysiological mechanisms potentially explain these intersecting phenotypes, including neuroinflammatory, vascular, and microbiomic, as well as neuroendocrine/neurotransmitter dynamic mechanisms. Treatment of either disorder affects the other with respect to symptom reduction as well as medication toxicity. We present a unified model for the comorbidity based upon deficits in dopaminergic transmission that occur in both major depressive disorder and HIV-associated neurocognitive disorder. Specific treatments for the comorbidity that decrease neuroinflammation and/or restore associated deficits in dopaminergic transmission may be indicated and merit study

The comorbidity of depression and neurocognitive disorder in persons with HIV infection: call for investigation and treatment

Depression and neurocognitive disorder continue to be the major neuropsychiatric disorders affecting persons with HIV (PWH). The prevalence of major depressive disorder is two to fourfold higher among PWH than the general population (∼6.7%). Prevalence estimates of neurocognitive disorder among PWH range from 25 to over 47% – depending upon the definition used (which is currently evolving), the size of the test battery employed, and the demographic and HIV disease characteristics of the participants included, such as age range and sex distribution. Both major depressive disorder and neurocognitive disorder also result in substantial morbidity and premature mortality. However, though anticipated to be relatively common, the comorbidity of these two disorders in PWH has not been formally studied. This is partly due to the clinical overlap of the neurocognitive symptoms of these two disorders. Both also share neurobehavioral aspects — particularly apathy — as well as an increased risk for non-adherence to antiretroviral therapy. Shared pathophysiological mechanisms potentially explain these intersecting phenotypes, including neuroinflammatory, vascular, and microbiomic, as well as neuroendocrine/neurotransmitter dynamic mechanisms. Treatment of either disorder affects the other with respect to symptom reduction as well as medication toxicity. We present a unified model for the comorbidity based upon deficits in dopaminergic transmission that occur in both major depressive disorder and HIV-associated neurocognitive disorder. Specific treatments for the comorbidity that decrease neuroinflammation and/or restore associated deficits in dopaminergic transmission may be indicated and merit study

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes

Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P=0.10) for major bleedings. Results—The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P=0.009) for ischemic outcome events and 0.407 (0.275–0.540; P=0.14) for hemorrhagic outcome events. Conclusions—In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings

Diagnosis of Imported Dengue and Zika Virus Infections in Italy from November 2015 to November 2022: Laboratory Surveillance Data from a National Reference Laboratory

Dengue (DENV) and Zika (ZIKV) viruses are mosquito-borne human pathogens. In Italy, the presence of the competent vector Aedes albopictus increases the risk of autochthonous transmission, and a national plan for arboviruses prevention, surveillance, and response (PNA 2020–2025) is in place. The results of laboratory diagnosis of both viruses by the National Reference Laboratory for arboviruses (NRLA) from November 2015 to November 2022 are presented. Samples from 655 suspected cases were tested by both molecular and serological assays. Virus and antibody kinetics, cross-reactivity, and diagnostic performance of IgM ELISA systems were analysed. Of 524 cases tested for DENV, 146 were classified as confirmed, 7 as probable, while 371 were excluded. Of 619 cases tested for ZIKV, 44 were classified as confirmed, while 492 were excluded. All cases were imported. Overall, 75.3% (110/146) of DENV and 50% (22/44) of ZIKV cases were confirmed through direct virus detection methods. High percentages of cross reactivity were observed between the two viruses. The median lag time from symptoms onset to sample collection was 7 days for both DENV molecular (range 0–20) and NS1 ELISA (range 0–48) tests, with high percentages of positivity also after 7 days (39% and 67%, respectively). For ZIKV, the median lag time was 5 days (range 0–22), with 16% positivity after 7 days. Diagnostic performance was assessed with negative predictive values ranging from 92% to 95% for the anti-DENV systems, and of 97% for the ZIKV one. Lower positive predictive values were seen in the tested population (DENV: 55% to 91%, ZIKV: 50%). DENV and ZIKV diagnosis by molecular test is the gold standard, but sample collection time is a limitation. Serological tests, including Plaque Reduction Neutralization Test, are thus necessary. Co-circulation and cross-reactivity between the two viruses increase diagnostic difficulty. Continuous evaluation of diagnostic strategies is essential to improve laboratory testing

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT