Same-day discharge after percutaneous coronary procedures-Consensus statement of the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology.

INTRODUCTION: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. Recent technical advances such as radial access, third generation drug-eluting stents and highly effective antiplatelet therapy have substantially improved the safety profile of coronary procedures. Despite several practice guidelines and a clear patient preference of early hospital discharge, the percentage of coronary procedures performed in an outpatient setting in Austria remains low, mostly due to safety concerns. METHODS: The aim of this consensus statement is to provide a practical framework for the safe and effective implementation of coronary outpatient clinics in Austria. Based on a structured literature review and an in-depth analysis of available practice guidelines a consensus statement was developed and peer-reviewed within the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology. RESULTS: Based on the available literature same-day discharge coronary procedures show a favorable safety profile with no increase in the risk of major adverse events compared to an overnight stay. This document provides a detailed consensus in various clinical settings. The most important prerequisite for same-day discharge is, however, adequate selection of suitable patients and a structured peri-interventional and postinterventional management plan. CONCLUSION: Based on the data analysis this consensus document provides detailed practice guidelines for the safe operation of daycare cathlab programs in Austria.

Same-day discharge after percutaneous coronary procedures-Structured review and comprehensive meta-analysis.

INTRODUCTION: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. The safety and feasibility of performing these procedures on a same-day discharge basis for selected patients has been studied in a large number of mostly nonrandomized trials. An up to date literature review should focus on trials with radial access, representing the current standard for coronary procedures in Austria and other European countries. METHODS: The aim of this consensus statement is to review the most recent evidence for the safety and feasibility of performing same-day discharge procedures in selected patients. A structured literature search was performed using prespecified search criteria, focusing on trials with radial access procedures. RESULTS: A total of 44 clinical trials and 4 large meta-analyses were retrieved, spanning 21 years of clinical evidence from 2001 to 2022. The outcome data from a wide range of clinical settings were unanimous in showing no negative effect on early (24 h) or late (30 day) major adverse events after same-day discharge coronary procedures. Based on nine prospective trials a comprehensive meta-analysis was compiled. Using 1­month major adverse events data the pooled odds ratio of same-day discharge versus overnight stay procedures was 0.66 (95% confidence interval, CI 0.35-01.24; p = 0.19; I2 0%), indicating a noninferiority in carefully selected patients. CONCLUSION: Outcome data from same-day discharge coronary intervention trials with radial access confirm the robust safety profile showing no increase in the risk of major adverse events compared to overnight stay.

Linking the Autotaxin-LPA Axis to Medicinal Cannabis and the Endocannabinoid System.

Over the past few decades, many current uses for cannabinoids have been described, ranging from controlling epilepsy to neuropathic pain and anxiety treatment. Medicines containing cannabinoids have been approved by both the FDA and the EMA for the control of specific diseases for which there are few alternatives. However, the molecular-level mechanism of action of cannabinoids is still poorly understood. Recently, cannabinoids have been shown to interact with autotaxin (ATX), a secreted lysophospholipase D enzyme responsible for catalyzing lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a pleiotropic growth factor that interacts with LPA receptors. In addition, a high-resolution structure of ATX in complex with THC has recently been published, accompanied by biochemical studies investigating this interaction. Due to their LPA-like structure, endocannabinoids have been shown to interact with ATX in a less potent manner. This finding opens new areas of research regarding cannabinoids and endocannabinoids, as it could establish the effect of these compounds at the molecular level, particularly in relation to inflammation, which cannot be explained by the interaction with CB1 and CB2 receptors alone. Further research is needed to elucidate the mechanism behind the interaction between cannabinoids and endocannabinoids in humans and to fully explore the therapeutic potential of such approaches.

Challenges in oncology career: are we closing the gender gap? Results of the new ESMO Women for Oncology Committee survey.

BACKGROUND: Following a European Society for Medical Oncology Women for Oncology (ESMO W4O) survey in 2016 showing severe under-representation of female oncologists in leadership roles, ESMO launched a series of initiatives to address obstacles to gender equity. A follow-up survey in October 2021 investigated progress achieved. MATERIALS AND METHODS: The W4O questionnaire 2021 expanded on the 2016 survey, with additional questions on the impact of ethnicity, sexual orientation and religion on career development. Results were analysed according to respondent gender and age. RESULTS: The survey sample was larger than in 2016 (n = 1473 versus 482), especially among men. Significantly fewer respondents had managerial or leadership roles than in 2016 (31.8% versus 51.7%). Lack of leadership development for women and unconscious bias were considered more important in 2021 than in 2016. In 2021, more people reported harassment in the workplace than in 2016 (50.3% versus 41.0%). In 2021, ethnicity, sexual orientation and religion were considered to have little or no impact on professional career opportunities, salary setting or related potential pay gap. However, gender had a significant or major impact on career development (25.5% of respondents), especially in respondents ≤40 years of age and women. As in 2016, highest ranked initiatives to foster workplace equity were promotion of work-life balance, development and leadership training and flexible working. Significantly more 2021 respondents (mainly women) supported the need for culture and gender equity education at work than in 2016. CONCLUSIONS: Gender remains a major barrier to career progression in oncology and, although some obstacles may have been reduced since 2016, we are a long way from closing the gender gap. Increased reporting of discrimination and inappropriate behaviour in the workplace is a major, priority concern. The W4O 2021 survey findings provide new evidence and highlight the areas for future ESMO interventions to support equity and diversity in oncology career development.

Linking medicinal cannabis to autotaxin-lysophosphatidic acid signaling.

Autotaxin is primarily known for the formation of lysophosphatidic acid (LPA) from lysophosphatidylcholine. LPA is an important signaling phospholipid that can bind to six G protein-coupled receptors (LPA1-6). The ATX-LPA signaling axis is a critical component in many physiological and pathophysiological conditions. Here, we describe a potent inhibition of Δ9-trans-tetrahydrocannabinol (THC), the main psychoactive compound of medicinal cannabis and related cannabinoids, on the catalysis of two isoforms of ATX with nanomolar apparent EC50 values. Furthermore, we decipher the binding interface of ATX to THC, and its derivative 9(R)-Δ6a,10a-THC (6a10aTHC), by X-ray crystallography. Cellular experiments confirm this inhibitory effect, revealing a significant reduction of internalized LPA1 in the presence of THC with simultaneous ATX and lysophosphatidylcholine stimulation. Our results establish a functional interaction of THC with autotaxin-LPA signaling and highlight novel aspects of medicinal cannabis therapy.

Machine Learning Algorithms for Classification of MALDI-TOF MS Spectra from Phylogenetically Closely Related Species Brucella melitensis, Brucella abortus and Brucella suis.

(1) Background: MALDI-TOF mass spectrometry (MS) is the gold standard for microbial fingerprinting, however, for phylogenetically closely related species, the resolution power drops down to the genus level. In this study, we analyzed MALDI-TOF spectra from 44 strains of B. melitensis, B. suis and B. abortus to identify the optimal classification method within popular supervised and unsupervised machine learning (ML) algorithms. (2) Methods: A consensus feature selection strategy was applied to pinpoint from among the 500 MS features those that yielded the best ML model and that may play a role in species differentiation. Unsupervised k-means and hierarchical agglomerative clustering were evaluated using the silhouette coefficient, while the supervised classifiers Random Forest, Support Vector Machine, Neural Network, and Multinomial Logistic Regression were explored in a fine-tuning manner using nested k-fold cross validation (CV) with a feature reduction step between the two CV loops. (3) Results: Sixteen differentially expressed peaks were identified and used to feed ML classifiers. Unsupervised and optimized supervised models displayed excellent predictive performances with 100% accuracy. The suitability of the consensus feature selection strategy for learning system accuracy was shown. (4) Conclusion: A meaningful ML approach is here introduced, to enhance Brucella spp. classification using MALDI-TOF MS data.

Telemedical cardiac risk assessment by implantable cardiac monitors in patients after myocardial infarction with autonomic dysfunction (SMART-MI-DZHK9): a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial.

BACKGROUND: Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events. METHODS: We did a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial at 33 centres in Germany and Austria. Survivors of acute myocardial infarction with left ventricular ejection fraction of 36-50% had biosignal analysis for assessment of cardiac autonomic function. Patients with abnormal periodic repolarisation dynamics (≥5·75 deg2) or abnormal deceleration capacity (≤2·5 ms) were randomly assigned (1:1) to telemedical monitoring with implantable cardiac monitors or conventional follow-up. Primary endpoint was time to detection of serious arrhythmic events defined by atrial fibrillation 6 min or longer, atrioventricular block class IIb or higher and fast non-sustained (>187 beats per min; ≥40 beats) or sustained ventricular tachycardia or fibrillation. This study is registered with ClinicalTrials.gov, NCT02594488. FINDINGS: Between May 12, 2016, and July 20, 2020, 1305 individuals were screened and 400 patients at high risk were randomly assigned (median age 64 years [IQR 57-73]); left ventricular ejection fraction 45% [40-48]) to telemedical monitoring with implantable cardiac monitors (implantable cardiac monitor group; n=201) or conventional follow-up (control group; n=199). During median follow-up of 21 months, serious arrhythmic events were detected in 60 (30%) patients of the implantable cardiac monitor group and 12 (6%) patients of the control group (hazard ratio 6·33 [IQR 3·40-11·78]; p<0·001). An improved detection rate by implantable cardiac monitors was observed for all types of serious arrhythmic events: atrial fibrillation 6 min or longer (47 [23%] patients vs 11 [6%] patients; p<0·001), atrioventricular block class IIb or higher (14 [7%] vs 0; p<0·001) and ventricular tachycardia or ventricular fibrillation (nine [4%] patients vs two [1%] patients; p=0·054). INTERPRETATION: In patients at high risk after myocardial infarction and cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction, telemedical monitoring with implantable cardiac monitors was highly effective in early detection of subclinical, prognostically relevant serious arrhythmic events. FUNDING: German Centre for Cardiovascular Research (DZHK) and Medtronic Bakken Research Center.

In-Depth Analysis of Bacillus anthracis 16S rRNA Genes and Transcripts Reveals Intra- and Intergenomic Diversity and Facilitates Anthrax Detection.

Analysis of 16S rRNA (rRNA) genes provides a central means of taxonomic classification of bacterial species. Based on presumed sequence identity among species of the Bacillus cereus sensu lato group, the 16S rRNA genes of B. anthracis have been considered unsuitable for diagnosis of the anthrax pathogen. With the recent identification of a single nucleotide polymorphism in some 16S rRNA gene copies, specific identification of B. anthracis becomes feasible. Here, we designed and evaluated a set of in situ, in vitro, and in silico assays to assess the unknown 16S state of B. anthracis from different perspectives. Using a combination of digital PCR, fluorescence in situ hybridization, long-read genome sequencing, and bioinformatics, we were able to detect and quantify a unique 16S rRNA gene allele of B. anthracis (16S-BA-allele). This allele was found in all available B. anthracis genomes and may facilitate differentiation of the pathogen from any close relative. Bioinformatics analysis of 959 B. anthracis SRA data sets inferred that abundances and genomic arrangements of the 16S-BA-allele and the entire rRNA operon copy numbers differ considerably between strains. Expression ratios of 16S-BA-alleles were proportional to the respective genomic allele copy numbers. The findings and experimental tools presented here provide detailed insights into the intra- and intergenomic diversity of 16S rRNA genes and may pave the way for improved identification of B. anthracis and other pathogens with diverse rRNA operons. IMPORTANCE For severe infectious diseases, precise pathogen detection is crucial for antibiotic therapy and patient survival. Identification of Bacillus anthracis, the causative agent of the zoonosis anthrax, can be challenging when querying specific nucleotide sequences such as in small subunit rRNA (16S rRNA) genes, which are commonly used for typing of bacteria. This study analyzed on a broad genomic scale a cryptic and hitherto underappreciated allelic variant of the bacterium's 16S rRNA genes and their transcripts using a set of in situ, in vitro, and in silico assays and found significant intra- and intergenomic heterogeneity in the distribution of the allele and overall rRNA operon copy numbers. This allelic variation was uniquely species specific, which enabled sensitive pathogen detection on both DNA and transcript levels. The methodology used here is likely also applicable to other pathogens that are otherwise difficult to discriminate from their less harmful relatives.

Occupational contact dermatitis: Retrospective analysis of North American Contact Dermatitis Group Data, 2001 to 2016.

BACKGROUND: Patch testing is an important diagnostic tool for suspected allergic contact dermatitis (ACD) in occupational settings. OBJECTIVE: Provide an overview of occupational skin disease (OSD) and an analysis of occupational ACD in North American patients undergoing patch testing between 2001and 2016. METHODS: Patients with OSD were analyzed for frequency of allergic reactions to a screening series of allergens, occupational relevance, location of skin disease, and exposure sources. Demographic, occupation, and industry information were recorded. RESULTS: Of 38,614 patients evaluated, 4471 (11.6%) had OSD, of whom 3150 (70.5%) had ACD. The most common occupationally related allergens included rubber accelerators, preservatives, and bisphenol A epoxy resin. Hands (75.8%), arms (30.0%), and face (15.9%) were common sites of dermatitis. The occupations most affected were service workers and machine operators. LIMITATIONS: Our cohort may not reflect the general working population. CONCLUSION: This study identified common occupational allergens, exposure sources, and occupations/industries at risk. This information may help the clinician evaluate and manage patients with occupational contact dermatitis.

The differential diagnostic value of selected cardiovascular biomarkers in Takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is clinically indistinguishable from an acute coronary syndrome (ACS). In the absence of valid markers for differential diagnosis, coronary angiography has been indispensable. METHODS: In our study, we evaluated the serum levels of sST-2, GDF-15, suPAR and H-FABP in 92 patients with the suspicion of TTS (51 TTS and 41 ACS patients) and 40 gender matched controls (no coronary artery disease or signs of heart failure) at baseline. RESULTS: H-FABP was significantly higher in ACS patients compared to TTS patients. Even in in propensity score matching for left ventricular ejection fraction, sex and cardiovascular risk factors, differences in the plasma levels of H-FABP in the matched cohort of TTS vs ACS remained statistically significant. Whereas, sST-2 was significantly elevated in TTS patients. H-FABP was superior for prediction of an ACS with even higher accuracy than hs troponin in differential diagnosis (AUC 0.797, p ≤ 0.0001); the optimal cut off for discrimination towards a TTS was calculated as 2.93 ng/ml (sensitivity 70.0%, specificity 82.4%, PPV 75.7%, NPV 77.4%). sST-2 seemed most appropriate for identification of a TTS (AUC 0.653, p = 0.012). The optimal cut off for differential diagnosis was 11018.06 pg/ml (sensitivity 82.0%, specificity 51.2%, PPV 69.4%, NPV 71.9 %). CONCLUSION: H-FABP and sST-2 are the most promising markers with better accuracy than preexisting biomarkers in differential diagnosis in our study and therefore, could be crucial for the guidance of treatment in patients with high bleeding risk, advanced renal failure or multimorbidity.

The externalizing and internalizing pathways to marijuana use initiation: Examining the synergistic effects of impulsiveness and sensation seeking.

Adolescent marijuana use has become increasingly more problematic compared with the past; thus, understanding developmental processes that increase the liability of marijuana use is essential. Two developmental pathways to adolescent substance use have been proposed: an externalizing pathway that emphasizes the expression of aggressive and delinquent behavior, and an internalizing pathway that emphasizes the role of depressive symptoms and negative affect. In this study, we aimed to examine the synergistic role of impulsiveness and sensation seeking in the two risk pathways to determine whether both high and low levels of the traits are risk factors for marijuana use. Our study included 343 adolescents (52% were girls, 78% identified as Hispanic) that oversampled high-risk youth (78% had a family history of substance use disorder), assessed biannually between the ages of 13-16 years old. Moderated mediation analyses revealed that high levels of sensation seeking indirectly predicted marijuana use through higher mean levels of externalizing behavior. The positive relationship between sensation seeking and externalizing behavior was only significant at high levels of impulsiveness. Conversely, low levels of sensation seeking indirectly predicted marijuana use through higher mean levels of internalizing behavior. The negative relationship between sensation seeking and internalizing behavior was only significant at low levels of impulsiveness. Collectively, these results demonstrate that high and low levels of both impulsiveness and sensation seeking confer increased risk of marijuana use, albeit through different mechanisms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

CoxBase: an Online Platform for Epidemiological Surveillance, Visualization, Analysis, and Typing of Coxiella burnetii Genomic Sequences.

Q (query) fever is an infectious zoonotic disease caused by the Gram-negative bacterium Coxiella burnetii. Although the disease has been studied for decades, it still represents a threat due to sporadic outbreaks across farms in Europe. The absence of a central platform for Coxiella typing data management is an important epidemiological gap that is relevant in the case of an outbreak. To fill this gap, we have designed and implemented an online, open-source, web-based platform called CoxBase (https://coxbase.q-gaps.de). This platform includes a database that holds genotyping information on more than 400 Coxiella isolates alongside metadata that annotate them. We have also implemented features for in silico genotyping of completely or minimally assembled Coxiella sequences using five different typing methods, querying of existing isolates, visualization of isolate geodata via aggregation on a world map, and submission of new isolates. We tested our in silico typing method on 50 Coxiella genomes downloaded from the RefSeq database, and we successfully genotyped all genomes except for cases where the sequence quality was poor. We identified new spacer sequences using our implementation of the multispacer sequence typing (MST) in silico typing method and established adaA gene phenotypes for all 50 genomes as well as their plasmid types. IMPORTANCE Q fever is a zoonotic disease that is a source of active epidemiological concern due to its persistent threat to public health. In this project, we have identified areas in the field of Coxiella research, especially regarding public health and genomic analysis, where there is an inadequacy of resources to monitor, organize, and analyze genomic data from C. burnetii. Subsequently, we have created an open, web-based platform that contains epidemiological information, genome typing functions comprising all the available Coxiella typing methods, and tools for isolate data discovery and visualization that could help address the above-mentioned challenges. This is the first platform to combine all disparate genotyping systems for Coxiella burnetii as well as metadata assets with tools for genomic comparison and analyses. This platform is a valuable resource for laboratory researchers as well as research epidemiologists interested in investigating the relatedness or dissimilarity among C. burnetii strains.

Ultrasensitive Detection of Bacillus anthracis by Real-Time PCR Targeting a Polymorphism in Multi-Copy 16S rRNA Genes and Their Transcripts.

The anthrax pathogen Bacillus anthracis poses a significant threat to human health. Identification of B. anthracis is challenging because of the bacterium's close genetic relationship to other Bacillus cereus group species. Thus, molecular detection is founded on species-specific PCR targeting single-copy genes. Here, we validated a previously recognized multi-copy target, a species-specific single nucleotide polymorphism (SNP) present in 2-5 copies in every B. anthracis genome analyzed. For this, a hydrolysis probe-based real-time PCR assay was developed and rigorously tested. The assay was specific as only B. anthracis DNA yielded positive results, was linear over 9 log10 units, and was sensitive with a limit of detection (LoD) of 2.9 copies/reaction. Though not exhibiting a lower LoD than established single-copy PCR targets (dhp61 or PL3), the higher copy number of the B. anthracis-specific 16S rRNA gene alleles afforded ≤2 unit lower threshold (Ct) values. To push the detection limit even further, the assay was adapted for reverse transcription PCR on 16S rRNA transcripts. This RT-PCR assay was also linear over 9 log10 units and was sensitive with an LoD of 6.3 copies/reaction. In a dilution series of experiments, the 16S RT-PCR assay achieved a thousand-fold higher sensitivity than the DNA-targeting assays. For molecular diagnostics, we recommend a real-time RT-PCR assay variant in which both DNA and RNA serve as templates (thus, no requirement for DNase treatment). This can at least provide results equaling the DNA-based implementation if no RNA is present but is superior even at the lowest residual rRNA concentrations.

On the Annotation of Health Care Pathways to Allow the Application of Care-Plans That Generate Data for Multiple Purposes.

Objectives: Procedural interoperability in health care requires information support and monitoring of a common work practice. Our aim was to devise an information model for a complete annotation of actions in clinical pathways that allow use of multiple plans concomitantly as several partial processes underlie any composite clinical process. Materials and Methods: The development of the information model was based on the integration of a defined protocol for clinical interoperability in the care of patients with chronic obstructive pulmonary disease and an observational study protocol for cohort characterization at the group level. In the clinical process patient reported outcome measures were included. Results: The clinical protocol and the observation study protocol were developed on the clinical level and a single plan definition was developed by merging of the protocols. The information model and a common data model that had been developed for care pathways was successfully implemented and data for the medical records and the observational study could be extracted independently. The interprofessional process support improved the communication between the stakeholders (health care professionals, clinical scientists and providers). Discussion: We successfully merged the processes and had a functionally successful pilot demonstrating a seamless appearance for the health care professionals, while at the same time it was possible to generate data that could serve quality registries and clinical research. The adopted data model was initially tested and hereby published to the public domain. Conclusion: The use of a patient centered information model and data annotation focused on the care pathway simplifies the annotation of data for different purposes and supports sharing of knowledge along the patient care path.

FlexTaxD: flexible modification of taxonomy databases for improved sequence classification.

SUMMARY: The Flexible Taxonomy Database framework provides a method for modification and merging official and custom taxonomic databases to create improved databases. Using such databases will increase accuracy and precision of existing methods to classify sequence reads. AVAILABILITY AND IMPLEMENTATION: Source code is freely available at https://github.com/FOI-Bioinformatics/flextaxd and installable through Bioconda.

Catching SARS-CoV-2 by Sequence Hybridization: a Comparative Analysis.

Controlling and monitoring the still ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic regarding geographical distribution, evolution, and emergence of new mutations of the SARS-CoV-2 virus is only possible due to continuous next-generation sequencing (NGS) and sharing sequence data worldwide. Efficient sequencing strategies enable the retrieval of increasing numbers of high-quality, full-length genomes and are, hence, indispensable. Two opposed enrichment methods, tiling multiplex PCR and sequence hybridization by bait capture, have been established for SARS-CoV-2 sequencing and are both frequently used, depending on the quality of the patient sample and the question at hand. Here, we focused on the evaluation of the sequence hybridization method by studying five commercially available sequence capture bait panels with regard to sensitivity and capture efficiency. We discovered the SARS-CoV-2-specific panel of Twist Bioscience to be the most efficient panel, followed by two respiratory panels from Twist Bioscience and Illumina, respectively. Our results provide on the one hand a decision basis for the sequencing community including a computation for using the full capacity of the flow cell and on the other hand potential improvements for the manufacturers. IMPORTANCE Sequencing the genomes of the circulating SARS-CoV-2 strains is the only way to monitor the viral spread and evolution of the virus. Two different approaches, namely, tiling multiplex PCR and sequence hybridization by bait capture, are commonly used to fulfill this task. This study describes for the first time a combined approach of droplet digital PCR (ddPCR) and NGS to evaluate five commercially available sequence capture panels targeting SARS-CoV-2. In doing so, we were able to determine the most sensitive and efficient capture panel, distinguish the mode of action of the various bait panels, and compute the number of read pairs needed to recover a high-quality full-length genome. By calculating the minimum number of read pairs needed, we are providing optimized flow cell loading conditions for all sequencing laboratories worldwide that are striving for maximizing sequencing output and simultaneously minimizing time, costs, and sequencing resources.