The EVEREST II (Endovascular Valve Edge-to-Edge REpair STudy) High-Risk registry and REALISM Continued Access Study High-Risk Arm are prospective registries of patients who received the MitraClip ...device (Abbott Vascular, Santa Clara, California) for mitral regurgitation (MR) in the United States.
The purpose of this study was to report 12-month outcomes in high-risk patients treated with the percutaneous mitral valve edge-to-edge repair.
Patients with grades 3 to 4+ MR and a surgical mortality risk of ≥12%, based on the Society of Thoracic Surgeons risk calculator or the estimate of a surgeon coinvestigator following pre-specified protocol criteria, were enrolled.
In the studies, 327 of 351 patients completed 12 months of follow-up. Patients were elderly (76 ± 11 years of age), with 70% having functional MR and 60% having prior cardiac surgery. The mitral valve device reduced MR to ≤2+ in 86% of patients at discharge (n = 325; p < 0.0001). Major adverse events at 30 days included death in 4.8%, myocardial infarction in 1.1%, and stroke in 2.6%. At 12 months, MR was ≤2+ in 84% of patients (n = 225; p < 0.0001). From baseline to 12 months, left ventricular (LV) end-diastolic volume improved from 161 ± 56 ml to 143 ± 53 ml (n = 203; p < 0.0001) and LV end-systolic volume improved from 87 ± 47 ml to 79 ± 44 ml (n = 202; p < 0.0001). New York Heart Association functional class improved from 82% in class III/IV at baseline to 83% in class I/II at 12 months (n = 234; p < 0.0001). The 36-item Short Form Health Survey physical and mental quality-of-life scores improved from baseline to 12 months (n = 191; p < 0.0001). Annual hospitalization rate for heart failure fell from 0.79% pre-procedure to 0.41% post-procedure (n = 338; p < 0.0001). Kaplan-Meier survival estimate at 12 months was 77.2%.
The percutaneous mitral valve device significantly reduced MR, improved clinical symptoms, and decreased LV dimensions at 12 months in this high-surgical-risk cohort. (Endovascular Valve Edge-to-Edge REpair STudy EVERESTIIRCT; NCT00209274).
Abstract Background Public health statistics are often released too late to affect reversible societal factors affecting suicide. Increasingly, internet search volume is used in epidemiology, but ...this method has not yet been applied to suicide. Methods Google internet search engine activity for suicide-related terms from the years 2004–2009 was measured and correlated to available suicide and intentional self-injury data from the Centers of Disease Control (CDC). Results Google search volumes correlated to CDC statistics for both suicide and self-injury, but in patterns that differed by age. Whereas internet search activity was negatively correlated to the suicide rate in the general population, it was positively correlated to both intentional self-injury and completed suicides among youth. Conclusions Monitoring changes in search volumes on the internet may provide an early indicator of suicide risk within the population. Furthermore, youth may utilize the internet in ways that differ from the general population with respect to suicide.
Bipolar disorder (BD) and major depressive disorder (MDD) are heritable neuropsychiatric disorders associated with disrupted circadian rhythms. The hypothesis that circadian clock dysfunction plays a ...causal role in these disorders has endured for decades but has been difficult to test and remains controversial. In the meantime, the discovery of clock genes and cellular clocks has revolutionized our understanding of circadian timing. Cellular circadian clocks are located in the suprachiasmatic nucleus (SCN), the brain’s primary circadian pacemaker, but also throughout the brain and peripheral tissues. In BD and MDD patients, defects have been found in SCN-dependent rhythms of body temperature and melatonin release. However, these are imperfect and indirect indicators of SCN function. Moreover, the SCN may not be particularly relevant to mood regulation, whereas the lateral habenula, ventral tegmentum, and hippocampus, which also contain cellular clocks, have established roles in this regard. Dysfunction in these non-SCN clocks could contribute directly to the pathophysiology of BD/MDD. We hypothesize that circadian clock dysfunction in non-SCN clocks is a trait marker of mood disorders, encoded by pathological genetic variants. Because network features of the SCN render it uniquely resistant to perturbation, previous studies of SCN outputs in mood disorders patients may have failed to detect genetic defects affecting non-SCN clocks, which include not only mood-regulating neurons in the brain but also peripheral cells accessible in human subjects. Therefore, reporters of rhythmic clock gene expression in cells from patients or mouse models could provide a direct assay of the molecular gears of the clock, in cellular clocks that are likely to be more representative than the SCN of mood-regulating neurons in patients. This approach, informed by the new insights and tools of modern chronobiology, will allow a more definitive test of the role of cellular circadian clocks in mood disorders.
Abstract Background The TRANSFORM (Multicen t er Experience With R apid Deployment Edw a rds I N TUITY Valve S ystem for Aortic Valve Replace m ent) trial ( NCT01700439 ) evaluated the performance of ...the INTUITY rapid deployment aortic valve replacement (RDAVR) system in patients with severe aortic stenosis. Methods TRANSFORM was a prospective, nonrandomized, multicenter (n = 29), single-arm trial. INTUITY is comprised of a cloth-covered balloon-expandable frame attached to a Carpentier-Edwards PERIMOUNT Magna Ease aortic valve. Primary and effectiveness endpoints were evaluated at 1 year. Results Between 2012 and 2015, 839 patients underwent RDAVR. Mean age was 73.5 ± 8.3 years. Full sternotomy (FS) was used in 59% and minimally invasive surgical incisions in 41%. Technical success rate was 95%. For isolated RDAVR, mean crossclamp and cardiopulmonary bypass times for FS were 49.3 ± 26.9 minutes and 69.2 ± 34.7 minutes, respectively, and for minimally invasive surgical 63.1 ± 25.4 minutes and 84.6 ± 33.5 minutes, respectively. These times were favorable compared with Society of Thoracic Surgeons database comparators for FS: 76.3 minutes and 104.2 minutes, respectively, and for minimally invasive surgical, 82.9 minutes and 111.4 minutes, respectively ( P < .001). At 30 days, all-cause mortality was 0.8%; valve explant, 0.1%; thromboembolism, 3.5%; and major bleeding, 1.3%. In patients with isolated aortic valve replacement, the rate of permanent pacemaker implantation was 11.9%. At 1 year, mean effective orifice area was 1.7 cm2 ; mean gradient, 10.3 mm Hg; and moderate and severe paravalvular leak, 1.2% and 0.4%, respectively. Conclusions INTUITY RDAVR performed effectively in this North American trial. It may lead to a relative reduction in aortic crossclamp time and cardiopulmonary bypass time and has excellent hemodynamic performance. Pacemaker implantation rate observed was somewhat greater than European trials and requires further investigation.
Stroke family caregiver and dyad literature has expanded over the past few years. The purpose of this review was to build upon 2 prior systematic reviews to critique, analyze, and synthesize the ...evidence pertaining to the impact of family caregiver and dyad interventions on stroke survivor and family caregiver outcomes. CINAHL, PsychINFO, PubMed, and reference lists were searched from December 1, 2016 through March 31, 2021. Using PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), articles were identified that tested outcomes from stroke family caregiver or dyad interventions that targeted the health or well-being of family caregivers. Data from the articles were abstracted into tables for analysis, then compared with recommendations from the 2 prior systematic reviews. A total of 18 articles met inclusion criteria (10 caregiver interventions; 8 dyad interventions) representing sample sizes ranging from 7 to 349 caregivers or dyads. Most were randomized controlled trials (n=13); 2 were cluster randomized trials; and 3 were single-group quasi-experimental designs. Of the 18 studies, 8 had <50 caregivers or dyads and 5 were small feasibility studies that reported data trends rather than testing for significance. Only 6 studies reported significant survivor outcomes. Eleven studies reported significant caregiver outcomes, the most common being burden. A number of survivor and caregiver outcomes were not significant, or only significant for certain subgroups. The limited number of studies, small sample sizes, and conflicting results, made it difficult to draw firm conclusions regarding the impact of these interventions on outcomes. Based on the available evidence from these 18 studies, recommendations from the 2 prior reviews were generally supported. Well-designed and well-powered randomized controlled clinical trials are still needed to confirm efficacy of stroke family caregiver and dyad interventions.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a common and disabling disorder primarily characterized by persistent fatigue and exercise intolerance, with associated sleep ...disturbances, autonomic dysfunction, and cognitive problems. The causes of ME/CFS are not well understood but may coincide with immune and inflammatory responses following viral infections. During the current SARS-CoV2 coronavirus pandemic, ME/CFS has been increasingly reported to overlap with persistent “long COVID” symptoms, also called the post-acute sequelae of COVID-19 (PASC). Given the prominence of activity and sleep problems in ME/CFS, circadian rhythm disruption has been examined as a contributing factor in ME/CFS. While these studies of circadian rhythms have been pursued for decades, evidence linking circadian rhythms to ME/CFS remains inconclusive. A major limitation of older chronobiology studies of ME/CFS was the unavailability of modern molecular methods to study circadian rhythms and incomplete understanding of circadian rhythms outside the brain in peripheral organ systems. Major methodological and conceptual advancements in chronobiology have since been made. Over the same time, biomarker research in ME/CFS has progressed. Together, these new developments may justify renewed interest in circadian rhythm research in ME/CFS. Presently, we review ME/CFS from the perspective of circadian rhythms, covering both older and newer studies that make use of modern molecular methods. We focus on transforming growth factor beta (TGFB), a cytokine that has been previously associated with ME/CFS and has an important role in circadian rhythms, especially in peripheral cells. We propose that disrupted TGFB signaling in ME/CFS may play a role in disrupting physiological rhythms in sleep, activity, and cognition, leading to the insomnia, energy disturbances, cognition problems, depression, and autonomic dysfunction associated with ME/CFS. Since SARS-like coronavirus infections cause persistent changes in TGFB and previous coronavirus outbreaks have caused ME/CFS-like syndromes, chronobiological considerations may have immediate implications for understanding ME/CFS in the context of the COVID-19 pandemic and possibly suggest new avenues for therapeutic interventions.
•Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by disrupted sleep and activity implicating circadian clocks.•The incidence of ME/CFS is expected to increase as a result of the post-acute sequelae of COVID-19.•Biomarker studies in ME/CFS patients implicate Transforming Growth Factor B (TGFB).•TGFB has roles in synchronizing circadian rhythms in peripheral cells.•Identification of biomarkers and new methodologies may facilitate progress in the chronobiological basis of ME/CFS.
We reconstruct crustal structure along the Lesser Antilles island arc using an inversion approach combining constraints from petrology of magmatic crustal xenoliths and seismic receiver functions. ...Xenoliths show considerable island-to-island variation in xenolith petrology from plagioclase-free ultramafic lithologies to gabbros and gabbronorites with variable proportions of amphibole, indicative of changing magma differentiation depths. Xenoliths represent predominantly cumulate compositions with equilibration depths in the range 5 to 40 km. We use xenolith mineral modes and compositions to calculate seismic velocities (vP,vS) and density at the estimated equilibration depths. We create a five-layer model of crustal structure for testing against receiver functions (RF) from island seismic stations along the arc. Lowermost layer (5) comprises peridotite with physical characteristics of mantle xenoliths from Grenada. Uppermost layer (1) consists of 5 km of volcaniclastics and sediments, whose physical properties are determined via a grid inversion routine. The three middle layers (2) to (4) comprise igneous arc crust with compositions corresponding to the xenoliths sampled at each island. By inversion we obtain a petrological best-fit for the RF on each island to establish the nature and thicknesses of layers (2) to (4).
Along the arc we see variations in the depth and strength of both Moho and mid-crustal discontinuity (MCD) on length-scales of tens of km. Moho depths vary from 25 to 37 km; MCD from 11 and 32 km. The Moho is the dominant discontinuity beneath some islands (St. Kitts, Guadeloupe, Martinique, Grenada), whereas the MCD dominates beneath others (Saba, St. Eustatius). Along-arc variability in MCD depth and strength is consistent with variation in estimated magmatic H2O contents and differentiations depths that, in turn, influence xenolith lithologies. A striking feature is steep, along-arc gradients in vP similar to those observed at other oceanic arcs. These gradients reflect abrupt changes in rates and processes of magma generation in the underlying crust and mantle. We find no evidence for large, interconnected bodies of partial melt beneath the Lesser Antilles. Instead, the crustal velocity structure is consistent with magma differentiation in vertically-extensive, crystal mush-dominated reservoirs. Along-arc variation in crustal structure may reflect heterogeneous upwelling within the mantle wedge, itself driven by variation in slab-derived H2O fluxes.
•Arc crustal structure modelled by integrating petrology of 230 igneous xenoliths with seismic data from 23 islands.•Crust comprises four layers defined on basis of xenolith composition, calculated seismic properties and receiver functions.•Steep lateral velocity gradients and irregular along-arc variations in depth to Moho and mid-crustal discontinuity.•Lateral variation consistent with island-to-island variation in xenolith petrology.•Velocity structure reflects heterogeneous upwelling within the mantle wedge, driven by variation in slab-derived H2O fluxes.
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