Outcome after heart-lung or lung transplantation in patients with Eisenmenger syndrome

Objective The optimal timing for transplantation is unclear in patients with Eisenmenger syndrome (ES). We investigated post-transplantation survival and transplantation-specific morbidity after heart-lung transplantation (HLTx) or lung transplantation (LTx) in a cohort of Nordic patients with ES to aid decision-making for scheduling transplantation. Methods We performed a retrospective, descriptive, population-based study of patients with ES who underwent transplantation from 1985 to 2012. Results Among 714 patients with ES in the Nordic region, 63 (9%) underwent transplantation. The median age at transplantation was 31.9 (IQR 21.1-42.3) years. Within 30 days after transplantation, seven patients (11%) died. The median survival was 12.0 (95% CI 7.6 to 16.4) years and the overall 1-year, 5-year, 10-year and 15-year survival rates were 84.1%, 69.7%, 55.8% and 40.6%, respectively. For patients alive 1 year post-transplantation, the median conditional survival was 14.8 years (95% CI 8.0 to 21.8), with 5-year, 10-year and 15-year survival rates of 83.3%, 67.2% and 50.0%, respectively. There was no difference in median survival after HLTx (n=57) and LTx (n=6) (14.9 vs 10.6 years, p=0.718). Median cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis/kidney transplantation-free survival rates were 11.2 (95% CI 7.8 to 14.6), 6.9 (95% CI 2.6 to 11.1) and 11.2 (95% CI 8.8 to 13.7) years, respectively. The leading causes of death after the perioperative period were infection (36.7%), bronchiolitis obliterans syndrome (23.3%) and heart failure (13.3%). Conclusions This study shows that satisfactory post-transplantation survival, comparable with contemporary HTx and LTx data, without severe comorbidities such as cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis, is achievable in patients with ES, with a conditional survival of nearly 15 years.Peer reviewe

Smoking trends and health equity in Switzerland between 1992 and 2017: dependence of smoking prevalence on educational level and social determinants

BackgroundSwitzerland ranks among the top three healthcare systems in the world with regards to healthcare access, suggesting a high degree of health equity. However, Switzerland has few preventive strategies against smoking abuse. The aim of this study is to clarify whether educational level and citizenship status have an influence on the prevalence of smoking in Switzerland and whether there is health inequity related to a lack of preventive strategies.MethodsWe based our analysis on publicly available health data published in the Swiss government's Swiss health survey (1992–2017). We compared the prevalence of smoking across the years and correlated these data with levels of educational attainment, citizenship status and age.ResultsA continuous significant decline in smokers is observed in the highest education group (TERT). Over time, prevalence was reduced from 29% in 1992 to 23% in 2017 (p < 0.001). The intermediate-level educational group (SEK 2) showed smaller but also significant decline on a 0.05 sigificance level over the same period, from 31% to 29% (p = 0.003). The lowest educational group showed a nonsignificant decline from 28% to 27% (p = 0.6). The population who holds Swiss citizenship showed a decrease in smoking from 28% to 26% within the time frame (p < 0.001). People without Swiss citizenship had a much higher prevalence of smokers, at 38% in 1992 and declining to 32% in 2017 (p < 0.001). All cohorts from age 15 to age 64 have a far higher prevalence of smokers than cohorts at an older age, with the highest prevalence in the 25–34 age group.ConclusionIn Switzerland, individuals with lower levels of education and non-Swiss populations are more susceptible to health risk of smoking. This is despite the existence of a high-quality healthcare system that has nevertheless failed to negated health inequities

HIV-1 Env associates with HLA-C free-chains at the cell membrane modulating viral infectivity

HLA-C has been demonstrated to associate with HIV-1 envelope glycoprotein (Env). Virions lacking HLA-C have reduced infectivity and increased susceptibility to neutralizing antibodies. Like all others MHC-I molecules, HLA-C requires \u3b22-microglobulin (\u3b22m) for appropriate folding and expression on the cell membrane but this association is weaker, thus generating HLA-C free-chains on the cell surface. In this study, we deepen the understanding of HLA-C and Env association by showing that HIV-1 specifically increases the amount of HLA-C free chains, not bound to \u3b22m, on the membrane of infected cells. The association between Env and HLA-C takes place at the cell membrane requiring \u3b22m to occur. We report that the enhanced infectivity conferred to HIV-1 by HLA-C specifically involves HLA-C free chain molecules that have been correctly assembled with \u3b22m. HIV-1 Env-pseudotyped viruses produced in the absence of \u3b22m are less infectious than those produced in the presence of \u3b22m. We hypothesize that the conformation and surface expression of HLA-C molecules could be a discriminant for the association with Env. Binding stability to \u3b22m may confer to HLA-C the ability to preferentially act either as a conventional immune-competent molecule or as an accessory molecule involved in HIV-1 infectivity

First two decades of paediatric heart transplantation in Sweden - outcome of listing and post-transplant results.

Aims: To evaluate outcome in the first generation of children with end-stage heart disease to whom heart transplantation was available. Methods: Retrospective review of all 135 Swedish children <18 years old listed for heart transplantation 1989-2009, followed to December 31, 2009, including 74 (55%) with cardiomyopathy and 61 (45%) with congenital heart disease; 34 (25%) were infants (<1 year). Cumulative risk of requiring heart transplantation was 1:17 300 (11 patients who improved were omitted from outcome analysis). Results: Waiting-list mortality was 31% (44% in infants). Median waiting time in 82 transplanted patients was 57 days (0-585 days). Post-transplant follow-up time was median 5.9 years (0.03-20.1 years), and actuarial survival was 92% at 1 year, 82% at 5 years, 76% at 10 years and 58% at 15 years. Survival after listing was 64% at 1 year, 58% at 5 years, 52% at 10 years and 40% at 15 years. Post-transplant complications included rejections (34%), malignancies (12%), renal failure (8%), coronary artery vasculopathy (6%) and re-transplantation (5%). Among 64 survivors, 84% were free of complications affecting prognosis. Conclusion: High waiting-list mortality and post-transplant attrition precluded 60% of this pioneer population from reaching adulthood. Functional status in survivors is generally good

QT correction using Bazett's formula remains preferable in long QT syndrome type 1 and 2

Background: The heart rate (HR) corrected QT interval (QTc) is crucial for diagnosis and risk stratification in the long QT syndrome (LQTS). Although its use has been questioned in some contexts, Bazett's formula has been applied in most diagnostic and prognostic studies in LQTS patients. However, studies on which formula eliminates the inverse relation between QT and HR are lacking in LQTS patients. We therefore determined which QT correction formula is most appropriate in LQTS patients including the effect of beta blocker therapy and an evaluation of the agreement of the formulae when applying specific QTc limits for diagnostic and prognostic purposes. Methods: Automated measurements from routine 12-lead ECGs from 200 genetically confirmed LQTS patients from two Swedish regions were included (167 LQT1, 33 LQT2). QT correction was performed using the Bazett, Framingham, Fridericia, and Hodges formulae. Linear regression was used to compare the formulae in all patients, and before and after the initiation of beta blocking therapy in a subgroup (n = 44). Concordance analysis was performed for QTc &gt;= 480 ms (diagnosis) and &gt;= 500 ms (prognosis). Results: The median age was 32 years (range 0.1-78), 123 (62%) were female and 52 (26%) were children &lt;= 16 years. Bazett's formula was the only method resulting in a QTc without relation with HR. Initiation of beta blocking therapy did not alter the result. Concordance analyses showed clinically significant differences (Cohen's kappa 0.629-0.469) for diagnosis and prognosis in individual patients. Conclusion: Bazett's formula remains preferable for diagnosis and prognosis in LQT1 and 2 patients

Effectiveness of tobacco cessation interventions for different groups of tobacco users in Sweden : A study protocol for a national prospective cohort study

INTRODUCTION: Tobacco is still one of the single most important risk factors among the lifestyle habits that cause morbidity and mortality in humans. Furthermore, tobacco has a heavy social gradient, as the consequences are even worse among disadvantaged and vulnerable groups. To reduce tobacco-related inequity in health, those most in need should be offered the most effective tobacco cessation intervention. The aim of this study is to facilitate and improve the evaluation of already implemented national tobacco cessation efforts, focusing on 10 disadvantaged and vulnerable groups of tobacco users. METHODS AND ANALYSIS: This is a prospective cohort study. Data will be collected by established tobacco cessation counsellors in Sweden. The study includes adult tobacco or e-cigarette users, including disadvantaged and vulnerable patients, receiving in-person interventions for tobacco or e-cigarette cessation (smoking, snus and/or e-cigarettes). Patient inclusion was initiated in April 2020. For data analyses patients will be sorted into vulnerable groups based on risk factors and compared with tobacco users without the risk factor in question.The primary outcome is continuous successful quitting after 6 months, measured by self-reporting. Secondary outcomes include abstinence at the end of the treatment programme, which could be from minutes over days to weeks, 14-day point prevalence after 6 months, and patient satisfaction with the intervention. Effectiveness of successful quitting will be examined by comparing vulnerable with non-vulnerable patients using a mixed-effect logistic regression model adjusting for potential prognostic factors and known confounders. ETHICS AND DISSEMINATION: The project will follow the guidelines from the Swedish Data Protection Authority and have been approved by the Swedish Ethical Review Authority before patient inclusion (Dnr: 2019-02221). Only patients providing written informed consent will be included. Both positive and negative results will be published in scientific peer-reviewed journals and presented at national and international conferences. Information will be provided through media available to the public, politicians, healthcare providers and planners as these are all important stakeholders. TRIAL REGISTRATION NUMBER: NCT04819152