The rapidly increasing number of patients with implantable cardioverter-defibrillators (ICD) places a large burden on follow-up providers. This study investigated the possibility of longer in-office ...follow-up intervals in primary prevention ICD patients under remote monitoring with automatic daily data transmissions from the implant memory.
Conducted in 155 ICD recipients with MADIT II indications, the study compared the burden of scheduled and unscheduled ICD follow-up visits, quality of life (SF-36), and clinical outcomes in patients randomized to either 3- or 12-month follow-up intervals in the period between 3 and 27 months after implantation. Remote monitoring (Biotronik Home Monitoring) was used equally in all patients. In contrast to previous clinical studies, no calendar-based remote data checks were performed between scheduled in-office visits. Compared with the 3-month follow-up interval, the 12-month interval resulted in a minor increase in the number of unscheduled follow-ups (0.64 vs. 0.27 per patient-year; P = 0.03) and in a major reduction in the total number of in-office ICD follow-ups (1.60 vs. 3.85 per patient-year; P < 0.001). No significant difference was found in mortality, hospitalization rate, or hospitalization length during the 2-year observation period, but more patients were lost to follow-up in the 12-month group (10 vs. 3; P = 0.04). The SF-36 scores favoured the 12-month intervals in the domains 'social functioning' and 'mental health'.
In prophylactic ICD recipients under automatic daily remote monitoring, the extension of the 3-month in-office follow-up interval to 12 months appeared to safely reduce the ICD follow-up burden during 27 months after implantation.
NCT00401466 (http://www.clinicaltrials.gov/ct2/show/NCT00401466).
Cytokines released during chronic inflammatory diseases induce pro-inflammatory properties in polymorphonuclear neutrophils (PMNs). Here, we describe the development of a subgroup of human PMNs ...expressing CCR5, termed CCR5+ PMNs. Auto- and paracrine tumor necrosis factor (TNF) signaling increases intracellular neutrophil elastase (ELANE) abundance and induces neutrophil extracellular traps formation (NETosis) in CCR5+ PMNs, and triggering of CCR5 amplifies NETosis. Membranous TNF (mTNF) outside-in signaling induces the formation of reactive oxygen species, known activators of NETosis. In vivo, we find an increased number of CCR5+ PMNs in the peripheral blood and inflamed lamina propria of patients with ulcerative colitis (UC). Notably, failure of anti-TNF therapy is associated with higher frequencies of CCR5+ PMNs. In conclusion, we identify a phenotype of pro-NETotic, CCR5+ PMNs present in inflamed tissue in vivo and inducible in vitro. These cells may reflect an important component of tissue damage during chronic inflammation and could be of diagnostic value.
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•Priming induces neutrophil diversification into CCR5− and CCR5+ cells•TNFR2 signaling renders CCR5+ neutrophils pro-NETotic by ELANE upregulation•CCR5+ neutrophils appear in the lamina propria of ulcerative colitis patients•Retrograde TNF signaling induces NETosis of CCR5+ neutrophils
Neuenfeldt et al. show that neutrophil priming induces dichotomous expression of CCR5. TNFR2 signaling increases ELANE expression in CCR5+ neutrophils. CCR5 triggering or reverse signaling of membrane-bound TNF activates ELANE, leading to enhanced NETosis. Pro-NETotic CCR5+ neutrophils in the lamina propria of ulcerative colitis patients may affect the success of anti-TNF therapies.
Digital-Humanities-Infrastrukturen tendieren dazu, ihr eigentliches Klientel - den einzelnen Fachwissenschaftler - aus den Augen zu verlieren. In diesem Beitrag sollen die Bestrebungen DARIAH-DEs ...aufgezeigt werden, solchen Entwicklungen entgegenzuwirken. Aufgabe und Ziel des eigens eingerichteten Stakeholdergremiums „Fachgesellschaften“ werden ebenso dargestellt wie die Verbindungen zwischen DHd und DARIAH-DE.
Axon loss determines persistent disability in multiple sclerosis patients. Here, we use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the ...choice between axon loss and survival. We rule out the endoplasmic reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the axonal plasma membrane as the critical path of calcium entry.
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•Cytoplasmic calcium accumulations predict axon degeneration in neuroinflammation•Release from the axoplasmic reticulum does not explain calcium accumulations•Calcium influx from the extracellular space drives axon degeneration•Nanoscale ruptures allow entry of calcium across the axonal plasma membrane
Witte et al. identify cytoplasmic calcium accumulations as a key driver of axon degeneration in a model of multiple sclerosis. Calcium accumulates in the axoplasm because nanoscale ruptures of the axonal plasma membrane provide an entry path for extracellular calcium.
To analyse the incidental findings during computed tomographic angiography (CTA) diagnostic work-up in patients with arteriogenic erectile dysfunction (ED).
The medical records of all patients with ...suspected arteriogenic ED were entered into a database. Risk factors and underlying comorbidities were also collected. Pathological CTA findings were extracted from the CT readings and entered into the database. Incidental findings on CTA were classified as those requiring immediate medical treatment, requiring deferred medical treatment or of no clinical importance.
A total of 200 patients underwent CTA for suspected arteriogenic ED. Mean patient age was 59.6 ± 11.7 years. Of these, 181 patients (90.5%) had obstructions of erection-related arteries. In 168 patients (84.0%), CTA showed multiple incidental pathological findings. Eighty-five of 200 patients (42.5%) exhibited incidental findings requiring immediate further medical workup and/or treatment: coronary artery calcification was diagnosed in 75/200 (37.5%), aorto-iliac aneurysms in 8/200 (4%) of patients and incidentally detected embolism in 1/200 patient. Pancreatic and liver tumours were less frequent (incidence 1.5% and 1%, respectively). Incidental findings requiring deferred medical workup and/or treatment were detected in 175/200 patients (87.5%). The findings with the highest prevalence were liver steatosis followed by colon diverticulosis and prostate hyperplasia. Findings of little to no clinical importance were reported in 117 (58.5%) patients. These included uncomplicated renal cysts, spinal degeneration and renal vascular anomalies. Almost every second patient presenting with ED had an incidental finding which required immediate treatment.
Incidental findings not directly related to ED were common among patients undergoing CTA scans for suspected arterial obstructions. Coronary artery calcification was the leading finding requiring further medical workup and/or treatment. Thus, the benefit of CTA investigations extends beyond the anatomic description of arterial obstructions of erection-related arteries.
Myocardial infarction is a leading cause of death worldwide
. Although advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness ...of therapies to reduce late-stage mortality
. Here we generate an integrative high-resolution map of human cardiac remodelling after myocardial infarction using single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of multiple physiological zones at distinct time points in myocardium from patients with myocardial infarction and controls. Multi-modal data integration enabled us to evaluate cardiac cell-type compositions at increased resolution, yielding insights into changes of the cardiac transcriptome and epigenome through the identification of distinct tissue structures of injury, repair and remodelling. We identified and validated disease-specific cardiac cell states of major cell types and analysed them in their spatial context, evaluating their dependency on other cell types. Our data elucidate the molecular principles of human myocardial tissue organization, recapitulating a gradual cardiomyocyte and myeloid continuum following ischaemic injury. In sum, our study provides an integrative molecular map of human myocardial infarction, represents an essential reference for the field and paves the way for advanced mechanistic and therapeutic studies of cardiac disease.
The corticotropin-releasing hormone receptor 1 (CRHR1) critically controls behavioral adaptation to stress and is causally linked to emotional disorders. Using neurochemical and genetic tools, we ...determined that CRHR1 is expressed in forebrain glutamatergic and γ-aminobutyric acid— containing (GABAergic) neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs neurotransmission in the amygdala and hippocampus. Selective deletion of CRHR1 in midbrain dopaminergic neurons increases anxiety-like behavior and reduces dopamine release in the prefrontal cortex. These results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders.
We report on electronic transport measurements in rotational square probe configuration in combination with scanning tunneling potentiometry of epitaxial graphene monolayers which were fabricated by ...polymer-assisted sublimation growth on SiC substrates. The absence of bilayer graphene on the ultralow step edges of below 0.75 nm scrutinized by atomic force microscopy and scanning tunneling microscopy result in a not yet observed resistance isotropy of graphene on 4H- and 6H-SiC(0001) substrates as low as 2%. We combine microscopic electronic properties with nanoscale transport experiments and thereby disentangle the underlying microscopic scattering mechanism to explain the remaining resistance anisotropy. Eventually, this can be entirely attributed to the resistance and the number of substrate steps which induce local scattering. Thereby, our data represent the ultimate limit for resistance isotropy of epitaxial graphene on SiC for the given miscut of the substrate.
Competing risks methodology allows for an event-specific analysis of the single components of composite time-to-event endpoints. A key feature of competing risks is that there are as many hazards as ...there are competing risks. This is not always well accounted for in the applied literature.
We advocate a simulation point of view for understanding competing risks. The hazards are envisaged as momentary event forces. They jointly determine the event time. Their relative magnitude determines the event type. 'Empirical simulations' using data from a recent study on cardiovascular events in diabetes patients illustrate subsequent interpretation. The method avoids concerns on identifiability and plausibility known from the latent failure time approach.
The 'empirical simulations' served as a proof of concept. Additionally manipulating baseline hazards and treatment effects illustrated both scenarios that require greater care for interpretation and how the simulation point of view aids the interpretation. The simulation algorithm applied to real data also provides for a general tool for study planning.
There are as many hazards as there are competing risks. All of them should be analysed. This includes estimation of baseline hazards. Study planning must equally account for these aspects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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