Search

Objectives: (1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity., Methods: Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed-effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses., Results: The primary vaccination induced an 11- to 208-fold increase in binding and neutralizing antibody levels and a 3- to 4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3- to 5-fold increase in binding antibodies and 4- to 5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity., Interpretation: Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To compare "hybrid immunity" (prior COVID-19 infection plus vaccination) and post-vaccination immunity to SARS CoV-2 in MS patients on different disease-modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post-vaccination immune responses., Methods: Consecutive MS patients from NYU MS Care Center (New York, NY), aged 18-60, who completed primary COVID-19 vaccination series ≥6 weeks previously were evaluated for SARS CoV-2-specific antibody responses with electro-chemiluminescence and multiepitope bead-based immunoassays and, in a subset, live virus immunofluorescence-based microneutralization assay. SARS CoV-2-specific cellular responses were assessed with cellular stimulation TruCulture IFNγ and IL-2 assay and, in a subset, with IFNγ and IL-2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID-19 infection while controlling for age, sex, DMT at vaccination, time-to-vaccine, and vaccine product., Results: Between 6/01/2021 and 11/11/2021, 370 MS patients were recruited (mean age 40.6 years; 76% female; 53% non-White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine-1-phosphate receptor modulators 13%; and no DMT 8%). Vaccine-to-collection time was 18.7 (±7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory-confirmed prior COVID-19 infection had significantly increased antibody and cellular post-vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of antibody and cellular responses, while race/ethnicity was not., Interpretation: Prior COVID-19 infection is associated with enhanced antibody and cellular post-vaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: The objective of this study was to determine the impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection., Methods: Patients with MS aged 18 to 60 years were evaluated for anti-nucleocapsid and anti-Spike receptor-binding domain (RBD) antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture enzyme-linked immunosorbent assay (ELISA); and IL-2 and IFNγ ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity., Results: Between January 6, 2021, and July 21, 2021, 389 patients with MS were recruited (mean age 40.3 years; 74% women; 62% non-White). Most common DMTs were ocrelizumab (OCR)-40%; natalizumab -17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. One hundred seventy-seven patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, and 47 were asymptomatic. Antibody responses were markedly attenuated in OCR compared with other groups (p ≤0.0001). T-cell responses (IFNγ) were decreased in S1P (p = 0.03), increased in natalizumab (p <0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r = 0.45, p = 0.0002) and non-OCR (r = 0.64, p <0.0001). Immune responses did not differ by race/ethnicity. Coronavirus disease 2019 (COVID-19) clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized., Interpretation: DMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and nondisabled group of patients with MS. ANN NEUROL 2022;91:782-795., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Objectives: Research indicates the value of targeting emotional regulation (ER) skills in psychological interventions for psychosis. These skills can be delivered in a group format, thereby increasing access to therapy. This pilot study examined the acceptability and clinical effects of teaching ER skills in The Living Through Psychosis (LTP) group programme., Methods: Patients with a psychotic illness were offered the LTP programme, comprising eight sessions over four weeks. Measures were completed by 55 participants. Acceptability was assessed by attendance rates and group cohesion. Measures of intervention targets, recovery and clinical outcomes were completed at baseline, pre-group, post-group, and one-month follow-up., Results: High group attendance and cohesion support the acceptability of the group. Participants reported less difficulty with ER (Coeff. = -8.29, 95% CI: -13.40 to -3.18, within participant uncontrolled effect size (ES) d = 0.29), increased mindful relating to distressing symptoms (Coeff. = 11.20, 95% CI: 7.02 to 15.38, d = 0.65), and improvements in recovery dimensions (Coeff. = 10.07, 95% CI: 5.6 to 14.54, d = 0.42) from pre-to post-intervention, and maintained at one-month follow-up. Participants' hallucinations and delusions reduced from pre-intervention to follow-up (t(18) = 4.64, p < 0.001; t(18) = 5.34, p < 0.001). There was no change in fear of relapse., Limitations: The uncontrolled, pre-post design precluded blinded assessments, and may have inflated effect sizes. Other factors may have contributed to the improvements., Conclusions: The LTP programme was acceptable to people with psychosis. The preliminary findings indicate the potential utility of teaching ER and mindfulness skills in a brief group programme. Findings require replication in a randomized controlled trial., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Tobacco smoking is a leading public health concern and is the most preventable cause of morbidity and mortality worldwide. Sportspeople are no exception and those who smoke are predisposed to the same hazardous health effects as the general public, in addition to the potential effects it may have on their sporting performance., Aim: We aimed to ascertain the prevalence of tobacco consumption in a sporting population. We also endeavoured to quantify the use of electronic cigarettes (e-cigarettes) and assess exposure to passive smoking., Design: Observational study., Methods: A web-based e-questionnaire was distributed to participants from various sports across Ireland between November 2017 and January 2018, and data were analysed using SPSS., Results: A total of 546 sportspeople completed the survey with more than twice as many male respondents. Of whom, 16% of participants were current smokers, with males significantly more likely to smoke (P < 0.001), 26% of rugby players were current smokers which was significantly higher when compared with other sports (P < 0.01), 10% of all participants were exposed to second-hand smoke for more than 1 h per day and 2% of all participants were current users of e-cigarettes., Conclusion: The prevalence of smoking in our study population was higher than other literature reports. Further studies are essential to evaluate the potential negative effects this may be having on sporting performance, career progression and indeed injury occurrence/rehabilitation. It is imperative to address the matter of smoking in athletes, not only for public health concerns but also considering they are important role models in our society., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Limited data are available regarding real-world prescribing in patients with an indication for oral anticoagulation (OAT) who undergo percutaneous coronary intervention (PCI). Most current guidelines recommend a period of triple therapy with OAT and dual antiplatelet (DAPT) agents over dual therapy with an OAT and DAPT but the clinical benefit is still unclear giving rise to limited evidence-based recommendations., Aim: To analyze the appropriateness of OAT and anti-platelet strategies post PCI in a real-world cohort of patients in 2 academic teaching hospitals., Methods and Results: In total, 103 patients were retrospectively analyzed. As the initial 3 month stragey, 97 patients (94.2%) received triple therapy, 4 received Dual Therapy (3.9%) and 2 received DAPT (1.9%). Patients with predominant bleeding risk were significantly less likely to receive triple therapy (75% vs. 95.7% vs. 95.8%, P < 0.05). Apixaban was the most common OAT (65.7%) which in most cases was prescribed at an inappropriately reduced dose of 2.5 mg BD (80.4%). The MACE, bleeding and all-cause mortality rates did not differ significantly between groups., Discussion: Our study demonstrates the widespread use of triple therapy for the first 3 months of treatment in 2 Irish academic hospitals. DOACs were prescribed in most cases at reduced doses not currently known to prevent stroke. This study highlights the need for more explicit management algorithms to improve evidence-based management in this area.

Atrial fibrillation can be managed with anticoagulation and restoration of normal sinus rhythm using direct current cardioversion (DCCV). To reduce the risk of thromboembolism, anticoagulation pre-and-post DCCV is recommended. This study investigates the cost effectiveness of using NOACs compared to warfarin to attain therapeutic anticoagulation amongst AF patients pre-and-post DCCV. Propensity score matching revealed no statistically significant difference in outcomes from using NOACs and Warfarin. A cost minimisation study was performed; demonstrating a cost differential of €209 between those administered NOACs and warfarin pre- and post-DCCV. This study demonstrates how using NOACs compared to warfarin to attain therapeutic anticoagulation amongst AF patients pre-and-post DCCV is cost effective.

An 18-year-old man presented to hospital following an out of hospital ventricular fibrillation cardiac arrest, with successful resuscitation at the scene. The incident happened during a competitive football match in which the man was playing. In the course of an extensive work up, a CT coronary angiogram demonstrated an anomalous right coronary artery (RCA) origin in the left coronary sinus. The RCA followed an initial intramural and subsequent interarterial course between the ascending aorta and pulmonary artery trunk. Cardiac MRI showed a small subendocardial area of delayed gadolinium enhancement in the inferoseptal wall, consistent with a small infarct. Treatment involved elective coronary artery bypass of the RCA with a right internal mammary artery graft. The patient made a full recovery. An implantable cardioverter-defibrillator was not inserted and he was advised not to return to competitive sports., (2016 BMJ Publishing Group Ltd.)

Objectives: To relate cardiovascular magnetic resonance-derived segmental wall motion and myocardial scarring and determine whether they are associated with postoperative mitral regurgitation following coronary artery bypass grafting and annuloplasty for severe functional ischemic mitral regurgitation., Methods: From January 2001 to October 2006, 29 patients with grade >or=3+ chronic functional ischemic mitral regurgitation were studied using cardiovascular magnetic resonance. Wall motion abnormality was graded for 17 standard left ventricular myocardial segments (0 = none, 1+ = hypokinesis, 2+ = severe hypokinesis, 3+ = akinesis, 4+ = dyskinesis), as was degree of hyperenhancement (scarring). Postoperative mitral regurgitation was assessed longitudinally by 71 transthoracic echocardiograms., Results: Wall motion abnormalities grade >or=2+ were present in most myocardial segments (median 13). Scar >25% was present in a median of 3 segments, and 44% of those were in the territory of the posterior papillary muscle. Nearly all segments (95%) with >25% scar had >or=2+ wall motion abnormality. Although 90% of patients had no mitral regurgitation at hospital discharge, by 6 months, 34% had mitral regurgitation grade >or=2+. There was little association between wall motion abnormality and recurrence of mitral regurgitation (P > .1). Seventy percent of patients with scar >25% in the posterior papillary muscle region exhibited postoperative mitral regurgitation of grade >or=2+ by 6 months, compared with 15% with score

Background: Both platelet function and heart disease show strong genetic components, many of which remain to be elucidated., Materials and Methods: The roles of candidate polymorphisms in ten platelet-associated genes were compared between 1,237 Acute Coronary Syndrome (ACS) cases (with myocardial infarction and unstable angina) and 386 controls, from an Irish Caucasian population. Additionally, 361 stable angina patients were investigated. Two genes of interest were followed up in a separate Irish study of 1,484 individuals (577 with IHD and 907 unaffected)., Results: The GALNT4 (N-acetyl galactosaminyl transferase 4) 506I allele was significantly underrepresented in ACS (OR = 0.66, CI = 0.52-0.84; P = 0.001; P = 0.01 after correction for multiple testing), while the SULT1A1 (Sulphotransferase 1A1) 213H allele was associated with risk of ACS (OR = 1.37, CI = 1.08-1.74; P = 0.01; P = 0.1 after correction for multiple testing). Subsequent genotyping of further SNPs in GALNT4 in the family-based (IHD) group revealed that the 506I allele showed the same trend towards protecting against ACS but the haplotypic test over the four commonest haplotypes was not significant (P = 0.55). In contrast, the SULT1A1/SULT1A2 gene complex showed suggestive haplotypic association in the family-based study (P = 0.07), with the greatest increase in risk conferred by the SULT1A2 235T allele (P = 0.025)., Conclusion: We have identified two risk genes for cardiovascular disease, one of whose (GALNT4) effects may be on either platelet or endothelial function through modifications of PSGL1 or other important glycosylated proteins. The role of sulphotransferases (SULT1A1/2) in cardiovascular disease requires further exploration. Further validation of cardiovascular risks conferred by both genes in other populations (including gene copy number variation) is warranted.