Influence of Apolipoprotein E Plasma Levels and Tobacco Smoking on the Induction of Neutralising Antibodies to Interferon-Beta

Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta

A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis

The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Health care costs and disease severity of relapsing-remitting multiple sclerosis in Portugal

Objective: In Portugal, the prevalence rate for multiple sclerosis (MS) has been estimated at 47 per 100,000 population and there are around 700 annual MS inpatient episodes in public hospitals. Though the number of patients is small, the costs to the health system are potentially large. The present study measures the average health care cost per patient with relapsing remitting multiple sclerosis (RRMS) by level of severity in Portugal. Additionally, and in contrast to previous studies, the health care cost of a relapse by severity level is also calculated. Methods: The study adopts the perspective of the National Health Service (NHS) and carries out a cost of care analysis. Information concerning treatment profiles and resource use was gathered through a modified Delphi Panel involving seven experienced neurologists and a physiatrician from eight hospitals throughout the country. Each completed a questionnaire based on four clinical cases chosen to represent different levels of the Expanded Disability Severity Scale (EDSS). Information was collected on the use of inpatient care, pharmaceuticals, ambulatory visits, diagnostic tests, therapeutic procedures, nursing and other resources. Resources were valued using national information on unit costs from a variety of sources. Results: Total health care costs per patient, in 2003, were estimated to range from _11,515 (EDSS less or equal (LE) 3) to _22,876 (EDSS greater or equal (GE) 6.5). At each level of EDSS the cost of care rises with the most significant increase occurring between EDSS LE 3 and EDSS 3.5 /4.5. The highest expenditures are associated with the use of interferons (between 44% and 82% of the total costs), followed by inpatient care or ambulatory care, depending on the level of severity. When patients have a relapse, health care costs vary between _3,412 (EDSS LE 3) and _6,718 (EDSS GE 6.5). At intermediate EDSS levels the costs of a relapse are _4,422 for EDSS 3.5 /4.5 and _6,495 for EDSS 5 /6. The most significant cost component for relapses is that related to inpatient stays followed by ambulatory care. Conclusion: In Portugal around 5,000 people suffer from MS. The disease imposes enormous costs on the health service. Therapeutic strategies that reduce the impact of the disease (eg. relapse avoidance) can bring about potentially significant cost-savings. The results may be used as input to cost-effectiveness analyses and more widely in health care planning and policy

Epicardial Fat Volume Is Associated with Endothelial Dysfunction, but not with Coronary Calcification: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Abstract Background The increase in epicardial fat volume (EFV) is related to coronary artery disease (CAD), independent of visceral or subcutaneous fat. The mechanism underlying this association is unclear. Coronary artery calcium (CAC) score and endothelial dysfunction are related to coronary events, but whether EFV is related to these markers needs further clarification. Objectives To evaluate the association between automatically measured EFV, cardiovascular risk factors, CAC, and endothelial function. Methods In 470 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) with measures of EFV, CAC score and endothelial function, we performed multivariable models to evaluate the relation between cardiovascular risk factors and EFV (response variable), and between EFV (explanatory variable) and endothelial function variables or CAC score. Two-sided p 0. Conclusion Higher EFV was associated with impaired endothelial function, but not with CAC. The results suggest that EFV is related to the development of CAD through a pathway different from the CAC pathway, possibly through aggravation of endothelial dysfunction and microvascular disease