Background Wiskott-Aldrich syndrome (WAS) is a severe X-linked immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and susceptibility to autoimmunity and lymphomas. ...Hematopoietic stem cell transplantation is the treatment of choice; however, administration of WAS gene–corrected autologous hematopoietic stem cells has been demonstrated as a feasible alternative therapeutic approach. Objective Because B-cell homeostasis is perturbed in patients with WAS and restoration of immune competence is one of the main therapeutic goals, we have evaluated reconstitution of the B-cell compartment in 4 patients who received autologous hematopoietic stem cells transduced with lentiviral vector after a reduced-intensity conditioning regimen combined with anti-CD20 administration. Methods We evaluated B-cell counts, B-cell subset distribution, B cell–activating factor and immunoglobulin levels, and autoantibody production before and after gene therapy (GT). WAS gene transfer in B cells was assessed by measuring vector copy numbers and expression of Wiskott-Aldrich syndrome protein. Results After lentiviral vector-mediated GT, the number of transduced B cells progressively increased in the peripheral blood of all patients. Lentiviral vector-transduced progenitor cells were able to repopulate the B-cell compartment with a normal distribution of B-cell subsets both in bone marrow and the periphery, showing a WAS protein expression profile similar to that of healthy donors. In addition, after GT, we observed a normalized frequency of autoimmune-associated CD19+ CD21− CD35− and CD21low B cells and a reduction in B cell–activating factor levels. Immunoglobulin serum levels and autoantibody production improved in all treated patients. Conclusions We provide evidence that lentiviral vector-mediated GT induces transgene expression in the B-cell compartment, resulting in ameliorated B-cell development and functionality and contributing to immunologic improvement in patients with WAS.
Recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines highlighted some concerns about the randomized clinical trials (RCTs) comparing ...transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for aortic stenosis. Quantification of these biases has not been previously performed.
To assess whether randomization protects RCTs comparing TAVI and SAVR from biases other than nonrandom allocation.
A systematic review of the literature between January 1, 2007, and June 6, 2022, on MEDLINE, Embase, and Cochrane Central Register of Controlled Trials was performed. Specialist websites were also checked for unpublished data.
The study included RCTs with random allocation to TAVI or SAVR with a maximum 5-year follow-up.
Data extraction was performed by 2 independent investigators following the PRISMA guidelines. A random-effects meta-analysis was used for quantifying pooled rates and differential rates between treatments of deviation from random assigned treatment (DAT), loss to follow-up, and receipt of additional treatments.
The primary outcomes were the proportion of DAT, loss to follow-up, and patients who were provided additional treatments and myocardial revascularization, together with their ratio between treatments. The measures were the pooled overall proportion of the primary outcomes and the risk ratio (RR) in the TAVI vs SAVR groups.
The search identified 8 eligible trials including 8849 participants randomly assigned to undergo TAVI (n = 4458) or SAVR (n = 4391). The pooled proportion of DAT among the sample was 4.2% (95% CI, 3.0%-5.6%), favoring TAVI (pooled RR vs SAVR, 0.16; 95% CI, 0.08-0.36; P < .001). The pooled proportion of loss to follow-up was 4.8% (95% CI, 2.7%-7.3%). Meta-regression showed a significant association between the proportion of participants lost to follow-up and follow-up time (slope, 0.042; 95% CI, 0.017-0.066; P < .001). There was an imbalance of loss to follow-up favoring TAVI (RR, 0.39; 95% CI, 0.28-0.55; P < .001). The pooled proportion of patients who had additional procedures was 10.4% (95% CI, 4.4%-18.5%): 4.6% (95% CI, 1.5%-9.3%) in the TAVI group and 16.5% (95% CI, 7.5%-28.1%) in the SAVR group (RR, 0.27; 95% CI, 0.15-0.50; P < .001). The imbalance between groups also favored TAVI for additional myocardial revascularization (RR, 0.40; 95% CI, 0.24-0.68; P < .001).
This study suggests that, in RCTs comparing TAVI vs SAVR, there are substantial proportions of DAT, loss to follow-up, and additional procedures together with systematic selective imbalance in the same direction characterized by significantly lower proportions of patients undergoing TAVI that might affect internal validity.
Abstract
Background
Positive mental health effects of nature have been studied before with relevant associations between the two easily found in literature. However, there is still a lack of ...population based studies that focus on the effect that the amount of surrounding greenness might have on well-being.
Objectives
This study aims to evaluate the effects of exposure to surrounding greenness in the residential area with well-being based on the Mental Health Inventory 5-items (MHI-5) score from 0-100 (less to more well-being).
Methods
We used data from participants of the 2015 National Health Examination Survey (INSEF) which uses complex sampling methods to represent the Portuguese population and includes 4911 participants. Data regarding socioeconomic status, urbanization level, education, sex, age, postal code and well-being score was extracted. We then calculated the average surrounding greenness using the Normalized Difference Vegetation Index (NDVI) in a 300m and 1km buffer around each participant's residency and divided it by tertiles (from less green to most green). Log linear regression models controlling for confounder effects were applied.
Results
For the 300m buffer living in the 2nd tertile of greeness compared to the 1st tercile decreased the average well-being score by around 4% (ExpB=0.969, 95% p < 0.05). Living in the 3rd tercile (most green) had less to almost no effect (ExpB=0.989, 95% p < 0.05). Sensitivity analysis in a 1km buffer and the stratified analysis for sex and urbanization, also show a 4% decrease in well-being in the 2nd tertile and little to no effect in the 3rd.
Discussion
This study has found an association that is contrary to most literature on this subject, the study design might be subject to selection biases and misclassification of exposure. Further analysis should be done with relation to qualitative aspects of green space, accessibility to green areas and the roles of social cohesion and physical activity.
Key messages
• Population based study done in Portugal regarding the association between well-being and surrounding greenness.
• Findings point to a negative association between increased surrounding greeness and well-being.
Abstract
Introduction
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the cornerstone of antithrombotic therapy in patients with ST-segment elevation myocardial infarction ...(STEMI). Yet, there is uncertainty surrounding the optimal timing for the initiation of the P2Y12 inhibitor. This study aims to evaluate the effectiveness and safety of P2Y12 pretreatment by means of a systematic review and meta-analysis of studies in primary percutaneous coronary intervention (PCI) in STEMI.
Methods
We performed a systematic search of electronic databases Pubmed, CENTRAL and Scopus until March of 2021. Studies were considered eligible if they were: a) comparing P2Y12 inhibitor upstream administration vs. treatment during PCI; b) patients enrolled for STEMI and submitted to primary PCI. Studies with patients treated with fibrinolysis or medical therapy only were excluded. Major clinical outcomes included 30-day occurrence of all-cause death, definite stent thrombosis and re-infarction. Thrombolysis in myocardial infarction (TIMI) flow-grade pre-PCI and post-PCI, in-hospital cardiogenic shock and major bleeding events were analysed.
Results
Out of 2193 articles, 18 studies were included (1 randomized clinical trial RCT and 17 observational studies non-RCT), with a total of 76,836 patients, 52,181 in the pretreatment arm. At 30 days, pretreatment was associated with a reduction in definite stent thrombosis (1 RCT & 4 Non-RCT: OR 0.40; 95% CI 0.18–0.90), but no significant reduction in all-cause death (1 RCT & 7 Non-RCT: OR 0.77; 95% CI 0.56–1.04) or re-infacrtion (1 RCT & 4 Non-RCT: OR 0.73; 95% CI 0.49–1.09). Regarding in-hospital outcomes, pretreatment showed a significant reduction in the occurrence of cardiogenic shock (5 Non-RCT: 0.62; 95% CI 0.51–0.79), major bleeding events (1 RCT & 14 Non-RCT: 0.83; 95% CI 0.75–0.92) and in the number of patients with TIMI flow <3 postPCI (1 RCT & 8 Non-RCT: 0.82; 95% CI 0.73–0.93). Pretreatment was not associated with lower number of patients with TIMI flow <3 pre-PCI (1 RCT & 5 Non-RCT: 0.85; 95% CI 0.66–1.09).
Conclusion
Pretreatment with DAPT, including a P2Y12 inhibitor, was associated with lower risk for definite stent thrombosis and cardiogenic shock, but was not associated with lower all-cause death or re-infarction.
Funding Acknowledgement
Type of funding sources: None.
Guidelines on myocardial revascularization Kolh, Philippe; Wijns, William; Danchin, Nicolas ...
European journal of cardio-thoracic surgery,
09/2010, Letnik:
38, Številka:
Supplement-1
Journal Article, Web Resource
PDF
