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"Winter, Klaus Dieter"
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Impact of COVID-19 outbreak on regional STEMI care in Germany
AimsTo assess the impact of the lockdown due to coronavirus disease 2019 (COVID-19) on key quality indicators for the treatment of ST-segment elevation myocardial infarction (STEMI) patients.MethodsData were obtained from 41 hospitals participating in the prospective Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) study, including 15,800 patients treated for acute STEMI from January 2017 to the end of March 2020.ResultsThere was a 12.6% decrease in the total number of STEMI patients treated at the peak of the pandemic in March 2020 as compared to the mean number treated in the March months of the preceding years. This was accompanied by a significant difference among the modes of admission to hospitals (p = 0.017) with a particular decline in intra-hospital infarctions and transfer patients from other hospitals, while the proportion of patients transported by emergency medical service (EMS) remained stable. In EMS-transported patients, predefined quality indicators, such as percentages of pre-hospital ECGs (both 97%, 95% CI = − 2.2–2.7, p = 0.846), direct transports from the scene to the catheterization laboratory bypassing the emergency department (68% vs. 66%, 95% CI = − 4.9–7.9, p = 0.641), and contact-to-balloon-times of less than or equal to 90 min (58.3% vs. 57.8%, 95%CI = − 6.2–7.2, p = 0.879) were not significantly altered during the COVID-19 crisis, as was in-hospital mortality (9.2% vs. 8.5%, 95% CI = − 3.2–4.5, p = 0.739).ConclusionsClinically important indicators for STEMI management were unaffected at the peak of COVID-19, suggesting that the pre-existing logistic structure in the regional STEMI networks preserved high-quality standards even when challenged by a threatening pandemic.Clinical trial registrationNCT00794001
Journal Article
Twelve-month efficacy of second-generation cryoballoon ablation for atrial fibrillation performed at community hospitals: results of the German register on cryoballoon ablation in local hospitals (regional)
Background
The 12-month follow-up (F/U) efficacy of CBA PVI performed at community hospitals for treatment of symptomatic paroxysmal and persistent atrial fibrillation (AF) is unknown. This study determined the 12-month efficacy of pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) performed at community hospitals with limited annual case numbers.
Methods
This registry study included 983 consecutive patients (pts) from 19 hospitals, each with an annual procedural volume of < 100 PVI procedures/year. Pts underwent CBA PVI for paroxysmal AF (
n
= 520), persistent AF (
n
= 423), or redo PVI (
n
= 40). The primary endpoint was frequency of documented recurrent AF, the occurrence of atrial flutter or tachycardia following a 90-day period after the index ablation and up to 12 months. The frequency of repeat ablation was determined.
Results
Isolation of all PVs was documented in 98% of pts at the end of the procedure. Twelve-month F/U data could be obtained in 916 pts. A 24-h ECG registration was performed in 641 pts (70.0%); in 107 pts (16.7%) of them, recurrent AF was documented. The primary endpoint was met in 193 F/U pts (21.1%). It occurred in 80/486 F/U pts with paroxysmal AF (16.4%), and in 107/390 F/U pts with persistent AF (27.4%). Redo PVI was performed in 71 pts (7.8%), and atrial flutter ablation was performed in 12 pts (1.4%).
Conclusions
CBA PVI for paroxysmal or persistent AF can be performed at community hospitals with adequate rates of 12-month symptom freedom and arrhythmia recurrence. The study was registered at the German register of clinical studies (DRKS00016504).
Journal Article
Patient delay and benefit of timely reperfusion in ST-segment elevation myocardial infarction
BackgroundIn patients with ST-segment elevation myocardial infarction (STEMI), it is unknown how patient delay modulates the beneficial effects of timely reperfusion.AimsTo assess the prognostic significance of a contact-to-balloon time of less than 90 min on in-hospital mortality in different categories of symptom-onset-to-first-medical-contact (S2C) times.MethodsA total of 20 005 consecutive patients from the Feedback Intervention and Treatment Times in ST-segment Elevation Myocardial Infarction (FITT-STEMI) programme treated with primary percutaneous coronary intervention (PCI) were included.ResultsThere were 1554 deaths (7.8%) with a J-shaped relationship between mortality and S2C time. Mortality was 10.0% in patients presenting within 1 hour, and 4.9%, 6.0% and 7.3% in patient groups with longer S2C intervals of 1–2 hours, 2–6 hours and 6–24 hours, respectively. Patients with a short S2C interval of less than 1 hour (S2C<60 min) had the highest survival benefit from timely reperfusion with PCI within 90 min (OR 0.27, 95% CI 0.23 to 0.31, p<0.0001) as compared with the three groups with longer S2C intervals of 1 hour
Journal Article
Identification of novel small ncRNAs in pollen of tomato
Background
The unprecedented role of sncRNAs in the regulation of pollen biogenesis on both transcriptional and epigenetic levels has been experimentally proven. However, little is known about their global regulation, especially under stress conditions. We used tomato pollen in order to identify pollen stage-specific sncRNAs and their target mRNAs. We further deployed elevated temperatures to discern stress responsive sncRNAs. For this purpose high throughput sncRNA-sequencing as well as Massive Analysis of cDNA Ends (MACE) were performed for three-replicated sncRNAs libraries derived from tomato tetrad, post-meiotic, and mature pollen under control and heat stress conditions.
Results
Using the omiRas analysis pipeline we identified known and predicted novel miRNAs as well as sncRNAs from other classes, responsive or not to heat. Differential expression analysis revealed that post-meiotic and mature pollen react most strongly by regulation of the expression of coding and non-coding genomic regions in response to heat. To gain insight to the function of these miRNAs, we predicted targets and annotated them to Gene Ontology terms. This approach revealed that most of them belong to protein binding, transcription, and Serine/Threonine kinase activity GO categories. Beside miRNAs, we observed differential expression of both tRNAs and snoRNAs in tetrad, post-meiotic, and mature pollen when comparing normal and heat stress conditions.
Conclusions
Thus, we describe a global spectrum of sncRNAs expressed in pollen as well as unveiled those which are regulated at specific time-points during pollen biogenesis. We integrated the small RNAs into the regulatory network of tomato heat stress response in pollen.
Journal Article
The coupling of transcriptome and proteome adaptation during development and heat stress response of tomato pollen
Background
Pollen development is central for plant reproduction and is assisted by changes of the transcriptome and proteome. At the same time, pollen development and viability is largely sensitive to stress, particularly to elevated temperatures. The transcriptomic and proteomic changes during pollen development and of different stages in response to elevated temperature was targeted to define the underlying molecular principles.
Results
The analysis of the transcriptome and proteome of
Solanum lycopersicum
pollen at tetrad, post-meiotic and mature stage before and after heat stress yielded a decline of the transcriptome but an increase of the proteome size throughout pollen development. Comparison of the transcriptome and proteome led to the discovery of two modes defined as direct and delayed translation. Here, genes of distinct functional processes are under the control of direct and delayed translation. The response of pollen to elevated temperature occurs rather at proteome, but not as drastic at the transcriptome level. Heat shock proteins, proteasome subunits, ribosomal proteins and eukaryotic initiation factors are most affected. On the example of heat shock proteins we demonstrate a decoupling of transcript and protein levels as well as a distinct regulation between the developmental stages.
Conclusions
The transcriptome and proteome of developing pollen undergo drastic changes in composition and quantity. Changes at the proteome level are a result of two modes assigned as direct and delayed translation. The response of pollen to elevated temperature is mainly regulated at the proteome level, whereby proteins related to synthesis and degradation of proteins are most responsive and might play a central role in the heat stress response of pollen.
Journal Article
Multimodal Nonlinear Microscopy for Therapy Monitoring of Cold Atmospheric Plasma Treatment
Here we report on a non-linear spectroscopic method for visualization of cold atmospheric plasma (CAP)-induced changes in tissue for reaching a new quality level of CAP application in medicine via online monitoring of wound or cancer treatment. A combination of coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence lifetime imaging (2P-FLIM) and second harmonic generation (SHG) microscopy has been used for non-invasive and label-free detection of CAP-induced changes on human skin and mucosa samples. By correlation with histochemical staining, the observed local increase in fluorescence could be assigned to melanin. CARS and SHG prove the integrity of the tissue structure, visualize tissue morphology and composition. The influence of plasma effects by variation of plasma parameters e.g., duration of treatment, gas composition and plasma source has been evaluated. Overall quantitative spectroscopic markers could be identified for a direct monitoring of CAP-treated tissue areas, which is very important for translating CAPs into clinical routine.
Journal Article
A New Isoleucine Substitution of Val-20 in Transthyretin Tetramers Selectively Impairs Dimer--Dimer Contacts and Causes Systemic Amyloidosis
The most frequent form of inherited amyloidoses is associated with mutations in the transthyretin (TTR) gene coding for 127-amino acid residues of four identical, noncovalently linked subunits that form a pair of dimers in the plasma protein complex. Amyloid fibrils containing the variant and to a lesser extent the wild-type form of the TTR molecule are deposited in various organs, including peripheral nerves and the myocardium, with polyneuropathy and cardiomyopathy as major clinical manifestations. So far, more than 40 distinct amino acid substitutions distributed throughout the TTR sequence over 30 positions have been found to be correlated with an increased amyloidogenicity of TTR. Most of these amyloidogenic amino acid substituions are suspected to alter the conformation and stability of the monomer. Here we identify and characterize by protein and DNA analysis a novel amyloidogenic Val-20 to Ile mutation in a German three-generation family. The index patient suffered from severe amyloid cardiomyopathy at the age of 60. Conformational stability and unfolding behavior of the Ile-20 monomer in urea gradients was found to be almost indistinguishable from that of wild-type TTR. In contrast, tetramer stability was significantly reduced in agreement with the expected change in the interactions between the two opposing dimers via the side chain of Ile-20. Our observations provide strong evidence for the view that amyloidogenic amino acid substitutions in TTR facilitate the conversion of tetrameric TTR complexes into those conformational intermediates of the TTR folding pathway that have an intrinsic amyloidogenic potential.
Journal Article
