(1) Background: Due to similar clinical presentation and a lack of specific biomarkers, initial differentiation between Takotsubo syndrome (TTS) and non-ST-segment elevation myocardial infarction (NSTEMI) remains challenging in daily practice. Heat Shock Protein 70 (HSP70) is a novel biomarker that is recognized for its potential in the diagnosis and differentiation of cardiovascular conditions. (2) Methods: Data from a total of 156 patients were analyzed (32.1% NSTEMI, 32.7% TTS, and 35.3% controls). Serum concentrations of HSP70 were determined using ELISA and compared between patients and controls. ROC curve analysis, logistic regression analysis and propensity-score-weighted logistic regression were conducted. (3) Results: Concentrations of HSP70 were highest in patients with TTS (median 1727 pg/mL vs. ACS: median 1545 pg/mL vs. controls: median 583 pg/mL, p < 0.0001). HSP70 was predictive for TTS in binary logistic regression analysis (B(SE) = 0.634(0.22), p = 0.004), which even remained significant after correction for possible confounders in propensity-score-weighted analysis. ROC curve analysis also revealed a significant association of HSP70 with TTS (AUC: 0.633, p = 0.008). (4) Conclusions: Based on our findings, HSP70 constitutes a promising biomarker for discrimination between TTS and NSTEMI, especially in combination with established cardiovascular biomarkers like pBNP or high-sensitivity cardiac troponin.

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This is a revision of the online November 2021 Brighton thrombosis with thrombocytopenia syndrome (TTS) case definition and a new Brighton Collaboration case definition for vaccine-induced immune thrombocytopenia and thrombosis (VITT). These case definitions are intended for use in clinical trials and post-licensure pharmacovigilance activities to facilitate safety data comparability across multiple settings. They are not intended to guide clinical management. The case definitions were developed by a group of subject matter and Brighton Collaboration process experts as part of the Coalition for Epidemic Preparedness Innovations (CEPI)-funded Safety Platform for Evaluation of vACcines (SPEAC). The case definitions, each with defined levels of diagnostic certainty, are based on relevant published evidence and expert consensus and are accompanied by specific guidelines for TTS and VITT data collection and analysis. The document underwent peer review by a reference group of vaccine safety stakeholders and haematology experts to ensure case definition useability, applicability and scientific integrity.

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UNASSIGNED: Thrombosis with thrombocytopenia syndrome (TTS) has been reported following receipt of adenoviral vector-based COVID-19 vaccines. However, no validation studies evaluating the accuracy of International Classification of Diseases-10-Clinical Modification (ICD-10-CM)-based algorithm for unusual site TTS are available in the published literature.
UNASSIGNED: The purpose of this study was to assess the performance of clinical coding to 1) leverage literature review and clinical input to develop an ICD-10-CM-based algorithm to identify unusual site TTS as a composite outcome and 2) validate the algorithm against the Brighton Collaboration\'s interim case definition using laboratory, pathology, and imaging reports in an academic health network electronic health record (EHR) within the US Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative. Validation of up to 50 cases per thrombosis site was conducted, with positive predictive values (PPV) and 95% confidence intervals (95% CI) calculated using pathology or imaging results as the gold standard.
UNASSIGNED: The algorithm identified 278 unusual site TTS cases, of which 117 (42.1%) were selected for validation. In both the algorithm-identified and validation cohorts, over 60% of patients were 56 years or older. The positive predictive value (PPV) for unusual site TTS was 76.1% (95% CI 67.2-83.2%) and at least 80% for all but one individual thrombosis diagnosis code. PPV for thrombocytopenia was 98.3% (95% CI 92.1-99.5%).
UNASSIGNED: This study represents the first report of a validated ICD-10-CM-based algorithm for unusual site TTS. A validation effort found that the algorithm performed at an intermediate-to-high PPV, suggesting that the algorithm can be used in observational studies including active surveillance of COVID-19 vaccines and other medical products.

Chloroplast and mitochondrial DNA (cpDNA and mtDNA) are apart from nuclear DNA (nuDNA) in a eukaryotic cell. The transcription system of chloroplasts differs from those of mitochondria and eukaryotes. In contrast to nuDNA and animal mtDNA, the transcription of cpDNA is still not well understood, primarily due to the unresolved identification of transcription initiation sites (TISs) and transcription termination sites (TTSs) on the genome scale. In the present study, we characterized the transcription of chloroplast (cp) genes with greater accuracy and comprehensive information using PacBio full-length transcriptome data from Arabidopsis thaliana. The major findings included the discovery of four types of artifacts, the validation and correction of cp gene annotations, the exact identification of TISs that start with G, and the discovery of polyA-like sites as TTSs. Notably, we proposed a new model to explain cp transcription initiation and termination at the whole-genome level. Four types of artifacts, degraded RNAs and splicing intermediates deserve the attention from researchers working with PacBio full-length transcriptome data, as these contaminant sequences can lead to incorrect downstream analysis. Cp transcription initiates at multiple promoters and terminates at polyA-like sites. Our study provides new insights into cp transcription and new clues to study the evolution of promoters, TISs, TTSs and polyA tails of eukaryotic genes.

The serotonin release assay (SRA) has been the gold-standard assay for detection of heparin-dependent platelet-activating antibodies and integral for the diagnosis for heparin-induced thrombotic thrombocytopenia (HIT). In 2021, a thrombotic thrombocytopenic syndrome was reported after adenoviral vector COVID-19 vaccination. This vaccine-induced thrombotic thrombocytopenic syndrome (VITT) proved to be a severe immune platelet activation syndrome manifested by unusual thrombosis, thrombocytopenia, very elevated plasma D-dimer, and a high mortality even with aggressive therapy (anticoagulation and plasma exchange). While the platelet-activating antibodies in both HIT and VITT are directed toward platelet factor 4 (PF4), important differences have been found. These differences have required modifications to the SRA to improve detection of functional VITT antibodies. Functional platelet activation assays remain essential in the diagnostic workup of HIT and VITT. Here we detail the application of SRA for the assessment of HIT and VITT antibodies.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) was first described in 2021 and represents an adverse reaction to adenoviral vector COVID-19 vaccines AstraZeneca ChAdOx1 nCoV-19 (AZD1222) and Johnson & Johnson Ad26.COV2.S vaccine. VITT is a severe immune platelet activation syndrome with an incidence of 1-2 per 100,000 vaccinations. The features of VITT include thrombocytopenia and thrombosis within 4-42 days of first dose of vaccine. Affected individuals develop platelet-activating antibodies against platelet factor 4 (PF4). The International Society on Thrombosis and Haemostasis recommends both an antigen-binding assay (enzyme-linked immunosorbent assay, ELISA) and a functional platelet activation assay for the diagnostic workup of VITT. Here, the application of multiple electrode aggregometry (Multiplate) is presented as a functional assay for VITT.

There are emerging reports of Takotsubo syndrome (TTS) in cancer patients treated with immune checkpoint inhibitors (ICIs); however, the association of the two remains uncertain.
A systematic literature review was performed in the PubMed database and web sources (Google Scholar) according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. Case reports/series or studies including cancer patients treated with ICIs and presenting with TTS were considered.
Seventeen cases were included in the systematic review. Most patients were males (59%) with median age of 70 years (30-83). Most common tumor types were lung cancer (35%) and melanoma (29%). Most patients were on first-line immunotherapy (35%) and after the first cycle (54%) of treatment. The median time on immunotherapy at the time of TTS presentation was 77 days (1-450). The most used agents were pembrolizumab and the combination of nivolumab-ipilimumab (35%, respectively). Potential stressors were recognized in 12 cases (80%). Six patients (35%) presented with concurrent cardiac complications. Corticosteroids were used in the management of eight patients (50%). Fifteen patients (88%) recovered from TTS, two patients (12%) relapsed, and one patient died. Immunotherapy was reintroduced in five cases (50%).
TTS may be associated with immunotherapy for cancer. Physicians should be alert for TTS diagnosis in any patient with myocardial infarction-like presentation under treatment with ICIs.

BACKGROUND: Spontaneous Coronary Artery Dissection (SCAD) and Takotsubo Syndrome (TTS) are two different entities with several shared risk factors, but their management is different. They can co-exist in patients with chest pain which affects their management. We present two cases of combined SCAD and TTS in patients presented with chest pain.
METHODS: Case 1: 80F admitted with typical chest pain and dynamic ECG changes on the background of known anxiety/depression and social stresses. Her coronary angiogram showed SCAD affecting distal LAD. The left ventriculogram (LV gram) showed apical ballooning consistent with Takotsubo Syndrome (TTS). Patient was discharged on aspirin as well as angiotensin receptor blocker (ARB). Case 2: 60F admitted with typical chest pain in the setting of emotional trauma on the background of known cardiovascular risk factors. She was found to have ST elevation in inferior leads with no reciprocal changes. Subsequently, coronary angiogram showed SCAD affecting mid-left anterior descending artery (LAD) with normal distal wrap around LAD. Her LV gram showed apical ballooning consistent with TTS. However, transthoracic echocardiogram showed akinetic left ventricular apex. She was discharged on aspirin as well as an ACE inhibitor and warfarin to prevent LV thrombus.
CONCLUSIONS: SCAD and TTS can co-exist in patients with chest pain. It is important to identify SCAD in patients with TTS as it may affect their short as well as long-term management.