Patent foramen ovale (PFO)-associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. While device closure decreases stroke recurrence risk overall, the best ...treatment for any individual is often unclear.
To evaluate heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems.
Investigators for the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) Consortium pooled individual patient data from all 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, and included a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017.
PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10-point scoring system in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) Classification System, which combines the RoPE Score with high-risk PFO features (either an atrial septal aneurysm or a large-sized shunt) to classify patients into 3 categories of causal relatedness: unlikely, possible, and probable.
Ischemic stroke.
Over a median follow-up of 57 months (IQR, 24-64), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09% (95% CI, 0.88%-1.36%) and with device closure was 0.47% (95% CI, 0.35%-0.65%) (adjusted hazard ratio HR, 0.41 95% CI, 0.28-0.60). The subgroup analyses showed statistically significant interaction effects. Patients with low vs high RoPE Score had HRs of 0.61 (95% CI, 0.37-1.00) and 0.21 (95% CI, 0.11-0.42), respectively (P for interaction = .02). Patients classified as unlikely, possible, and probable using the PASCAL Classification System had HRs of 1.14 (95% CI, 0.53-2.46), 0.38 (95% CI, 0.22-0.65), and 0.10 (95% CI, 0.03-0.35), respectively (P for interaction = .003). The 2-year absolute risk reduction was -0.7% (95% CI, -4.0% to 2.6%), 2.1% (95% CI, 0.6%-3.6%), and 2.1% (95% CI, 0.9%-3.4%) in the unlikely, possible, and probable PASCAL categories, respectively. Device-associated adverse events were generally higher among patients classified as unlikely; the absolute risk increases in atrial fibrillation beyond day 45 after randomization with a device were 4.41% (95% CI, 1.02% to 7.80%), 1.53% (95% CI, 0.33% to 2.72%), and 0.65% (95% CI, -0.41% to 1.71%) in the unlikely, possible, and probable PASCAL categories, respectively.
Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO. Application of this classification system has the potential to guide individualized decision-making.
Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4⁺T cells. Some of ...these CD4⁺T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4⁺ T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1–infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4⁺T cells can be a reservoir of infectious HIV-1.
A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute ...sequelae of SARS-CoV-2 infection (PASC).
To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls.
Cohort study. (ClinicalTrials.gov: NCT04411147).
National Institutes of Health Clinical Center, Bethesda, Maryland.
Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area.
All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations.
189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC.
Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment.
A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19.
Division of Intramural Research, National Institute of Allergy and Infectious Diseases.
The discovery of potent and broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) has made passive immunization a potential strategy for the prevention and treatment of ...HIV infection. We sought to determine whether passive administration of VRC01, a bNAb targeting the HIV CD4-binding site, can safely prevent or delay plasma viral rebound after the discontinuation of antiretroviral therapy (ART).
We conducted two open-label trials (AIDS Clinical Trials Group ACTG A5340 and National Institutes of Health NIH 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART.
A total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 μg per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P=0.04 by a two-sided Fisher's exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher's exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus.
VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326 .).
Nearly all chronic human infections are associated with alterations in the memory B cell (MBC) compartment, including a large expansion of CD19
T-bet
MBC in the peripheral blood of HIV-infected ...individuals with chronic viremia. Despite their prevalence, it is unclear how these B cells arise and whether they contribute to the inefficiency of antibody-mediated immunity in chronic infectious diseases. We addressed these questions by characterizing T-bet-expressing B cells in lymph nodes (LN) and identifying a strong T-bet signature among HIV-specific MBC associated with poor immunologic outcome. Confocal microscopy and quantitative imaging revealed that T-bet
B cells in LN of HIV-infected chronically viremic individuals distinctly accumulated outside germinal centers (GC), which are critical for optimal antibody responses. In single-cell analyses, LN T-bet
B cells of HIV-infected individuals were almost exclusively found among CD19
MBC and expressed reduced GC-homing receptors. Furthermore, HIV-specific B cells of infected individuals were enriched among LN CD19
T-bet
MBC and displayed a distinct transcriptome, with features similar to CD19
T-bet
MBC in blood and LN GC B cells (GCBC). LN CD19
T-bet
MBC were also related to GCBC by B cell receptor (BCR)-based phylogenetic linkage but had lower BCR mutation frequencies and reduced HIV-neutralizing capacity, consistent with diminished participation in GC-mediated affinity selection. Thus, in the setting of chronic immune activation associated with HIV viremia, failure of HIV-specific B cells to enter or remain in GC may help explain the rarity of high-affinity protective antibodies.
Self-oxidative copolymerization of dopamine with α-cyano-4-hydroxycinnamic acid (CHCA) provides an efficient and multifunctional platform for laser desorption/ionization time-of-flight mass ...spectrometry (LDI-TOF-MS) analysis. The polydopamine coating layer embedded with the CHCA matrix can be readily formed on nanomaterials and solid substrates without additional surface treatments to generate an efficient LDI-TOF-MS platform for the analysis of small molecules as well as synthetic polymers. This coating can be further functionalized with specific ligands for target enrichment from complex biological media, providing analyte capture for subsequent LDI-TOF-MS analysis.
The Patent Foramen Ovale (PFO)-Associated Stroke Causal Likelihood classification system combines information regarding noncardiac patient features (vascular risk factors, infarct topography) and PFO ...features (shunt size and presence of atrial septal aneurysm ASA) to classify patients into 3 validated categories of responsiveness to treatment with PFO closure. However, the distinctive associations of shunt size and ASA, alone and in combination, have not been completely delineated.
To evaluate the association of PFO closure with stroke recurrence according to shunt size and/or the presence of an ASA.
Pooled individual patient data from 6 randomized clinical trials conducted from February 2000 to October 2017 that compared PFO closure with medical therapy. Patients in North America, Europe, Australia, Brazil, and South Korea with PFO-associated stroke were included. Analysis was completed in January 2022.
Transcatheter PFO closure plus antithrombotic therapy vs antithrombotic therapy alone, stratified into 4 groups based on the combination of 2 features: small vs large PFO shunt size and the presence or absence of an ASA.
Recurrent ischemic stroke.
A total of 121 recurrent ischemic strokes occurred in the pooled 3740 patients (mean SD age, 45 10 years; 1682 45% female) during a median (IQR) follow-up of 57 (23.7-63.8) months. Treatment with PFO closure was associated with reduced risk for recurrent ischemic stroke (adjusted hazard ratio aHR, 0.41 95% CI, 0.28-0.60; P < .001). The reduction in hazard for recurrent stroke was greater for patients with both a large shunt and an ASA (aHR, 0.15 95% CI, 0.06-0.35) than for large shunt without ASA (aHR, 0.27 95% CI, 0.14-0.56), small shunt with ASA (aHR, 0.36 95% CI, 0.17-0.78), and small shunt without ASA (aHR, 0.68 95% CI, 0.41-1.13) (interaction P = .02). At 2 years, the absolute risk reduction of recurrent stroke was greater (5.5% 95% CI, 2.7-8.3) in patients with large shunt and ASA than for patients in the other 3 categories (1.0% for all).
Patients with both a large shunt and an ASA showed a substantially greater beneficial association with PFO closure than patients with large shunt alone, patients with small shunt and ASA, and patients with neither large shunt nor ASA. These findings, combined with other patient features, may inform shared patient-clinician decision-making.
Self-enhancement bias has been studied from 2
perspectives:
L. Festinger's
(1954)
social comparison theory (self-enhancers
perceive themselves more positively than they perceive others) and
G. W. ...Allport's
(1937)
self-insight theory
(self-enhancers perceive themselves more positively than they are
perceived by others). These 2 perspectives are theoretically and
empirically distinct, and the failure to recognize their differences has
led to a protracted debate. A new interpersonal approach to
self-enhancement decomposes self-perception into 3
components: perceiver effect, target effect, and unique
self-perception. Both theoretical derivations and an illustrative
study suggest that this resulting measure of self-enhancement is less
confounded by unwanted components of interpersonal perception than previous
social comparison and self-insight measures. Findings help
reconcile conflicting views about whether self-enhancement is adaptive
or maladaptive.
Conceptualizing and Assessing Self-Enhancement Bias Kwan, Virginia S. Y; John, Oliver P; Robins, Richard W ...
Journal of personality and social psychology,
06/2008, Letnik:
94, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Four studies implemented a componential approach to assessing self-enhancement and contrasted this approach with 2 earlier ones: social comparison (comparing self-ratings with ratings of others) and ...self-insight (comparing self-ratings with ratings by others). In Study 1, the authors varied the traits being rated to identify conditions that lead to more or less similarity between approaches. In Study 2, the authors examined the effects of acquaintance on the conditions identified in Study 1. In Study 3, the authors showed that using rankings renders the self-insight approach equivalent to the component-based approach but also has limitations in assessing self-enhancement. In Study 4, the authors compared the social-comparison and the component-based approaches in terms of their psychological implications; the relation between self-enhancement and adjustment depended on the self-enhancement approach used, and the positive-adjustment correlates of the social-comparison approach disappeared when the confounding influence of the target effect was controlled.
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