Updated Electrocardiographic Classification of Acute Coronary Syndromes

The electrocardiogram (ECG) findings in acute coronary syndrome should always be interpreted in the context of the clinical findings and symptoms of the patient, when these data are available. It is important to acknowledge the dynamic nature of ECG changes in acute coronary syndrome. The ECG pattern changes over time and may be different if recorded when the patient is symptomatic or after symptoms have resolved. Temporal changes are most striking in cases of ST-elevation myocardial infarction. With the emerging concept of acute reperfusion therapy, the concept ST-elevation/non-ST elevation has replaced the traditional division into Q-wave/non-Q wave in the classification of acute coronary syndrome in the acute phase.

Keypoints:

In acute coronary syndrome, in addition to the traditional electrocardiographic risk markers, such as ST depression, the 12-lead ECG contains additional, important diagnostic and prognostic information. Clinical guidelines need to acknowledge certain high-risk ECG patterns to improve patient care.     

Molecular architecture of the αβ T cell receptor–CD3 complex

αβ T-cell receptor (TCR) activation plays a crucial role for T-cell function. However, the TCR itself does not possess signaling domains. Instead, the TCR is noncovalently coupled to a conserved multisubunit signaling apparatus, the CD3 complex, that comprises the CD3εγ, CD3εδ, and CD3ζζ dimers. How antigen ligation by the TCR triggers CD3 activation and what structural role the CD3 extracellular domains (ECDs) play in the assembled TCR–CD3 complex remain unclear. Here, we use two complementary structural approaches to gain insight into the overall organization of the TCR–CD3 complex. Small-angle X-ray scattering of the soluble TCR–CD3εδ complex reveals the CD3εδ ECDs to sit underneath the TCR α-chain. The observed arrangement is consistent with EM images of the entire TCR–CD3 integral membrane complex, in which the CD3εδ and CD3εγ subunits were situated underneath the TCR α-chain and TCR β-chain, respectively. Interestingly, the TCR–CD3 transmembrane complex bound to peptide–MHC is a dimer in which two TCRs project outward from a central core composed of the CD3 ECDs and the TCR and CD3 transmembrane domains. This arrangement suggests a potential ligand-dependent dimerization mechanism for TCR signaling. Collectively, our data advance our understanding of the molecular organization of the TCR–CD3 complex, and provides a conceptual framework for the TCR activation mechanism.T cells are key mediators of the adaptive immune response. Each αβ T cell contains a unique αβ T-cell receptor (TCR), which binds antigens (Ags) displayed by major histocompatibility complexes (MHCs) and MHC-like molecules (1). The TCR serves as a remarkably sensitive driver of cellular function: although TCR ligands typically bind quite weakly (1–200 μM), even a handful of TCR ligands are sufficient to fully activate a T cell (2, 3). The TCR does not possess intracellular signaling domains, uncoupling Ag recognition from T-cell signaling. The TCR is instead noncovalently associated with a multisubunit signaling apparatus, consisting of the CD3εγ and CD3εδ heterodimers and the CD3ζζ homodimer, which collectively form the TCR–CD3 complex (4, 5). The CD3γ/δ/ε subunits each consist of a single extracellular Ig domain and a single immunoreceptor tyrosine-based activation motif (ITAM), whereas CD3ζ has a short extracellular domain (ECD) and three ITAMs (6–11). The TCR–CD3 complex exists in 1:1:1:1 stoichiometry for the αβTCR:CD3εγ:CD3εδ:CD3ζζ dimers (12). Phosphorylation of the intracellular CD3 ITAMs and recruitment of the adaptor Nck lead to T-cell activation, proliferation, and survival (13, 14). Understanding the underlying principles of TCR–CD3 architecture and T-cell signaling is of therapeutic interest. For example, TCR–CD3 is the target of therapeutic antibodies such as the immunosuppressant OKT3 (15), and there is increasing interest in manipulating T cells in an Ag-dependent manner by using naturally occurring and engineered TCRs (16).Assembly of the TCR–CD3 complex is primarily driven by each protein’s transmembrane (TM) region, enforced through the interaction of evolutionarily conserved, charged, residues in each TM region (4, 5, 12). What, if any, role interactions between TCR and CD3 ECDs play in the assembly and function of the complex remains controversial (5): there are several plausible proposed models of activation, which are not necessarily mutually exclusive (5, 17–19). Although structures of TCR–peptide–MHC (pMHC) complexes (2), TCR–MHC-I–like complexes (1), and the CD3 dimers (6–10) have been separately determined, how the αβ TCR associates with the CD3 complex is largely unknown. Here, we use two independent structural approaches to gain an understanding of the TCR–CD3 complex organization and structure.     

Outcomes of preoperative Angiotensin-converting enzyme inhibitor therapy in patients undergoing isolated coronary artery bypass grafting

The association between preoperative use of angiotensin-converting enzyme (ACE) inhibitors and outcomes after coronary artery bypass grafting (CABG) remain controversial. Our aim was to study in-hospital outcomes after isolated CABG in patients on preoperative ACE inhibitors. A retrospective analysis of 8,889 patients who underwent isolated CABG from 2000 through 2011 was conducted. The primary outcome of interest was the incidence of major adverse events (MAEs) defined as a composite of mortality, postoperative renal dysfunction, myocardial infarction, stroke, and atrial fibrillation during index hospitalization. The secondary outcome was the incidence of individual outcomes included in MAEs. Logistic regression analyses were performed. Of 8,889 patients, 3,983 (45%) were on preoperative ACE inhibitors and 4,906 (55%) were not. Overall incidence of MAEs was 38.1% (n = 1,518) in the ACE inhibitor group compared to 33.6% (n = 1,649) in the no-ACE inhibitor group. Preoperative use of ACE inhibitors was independently associated with MAEs (odds ratio 1.13, 95% confidence interval 1.03 to 1.24), most of which was driven by a statistically significant increase in postoperative renal dysfunction (odds ratio 1.18, 95% confidence interval 1.03 to 1.36) and atrial fibrillation (odds ratio 1.15, 95% confidence interval 1.05 to 1.27). In-hospital mortality, postoperative myocardial infarction, and stroke were not significantly associated with preoperative ACE inhibitor use. Analyses performed after excluding patients with low ejection fractions yielded similar results. In conclusion, preoperative ACE inhibitor use was associated with an increased risk of MAEs after CABG, in particular postoperative renal dysfunction and atrial fibrillation.     

Pharmacoepidemiology of Antipsychotic Use in Youth with ADHD: Trends and Clinical Implications

Although concern has been raised about antipsychotic prescribing to youth with attention-deficit/hyperactivity disorder (ADHD), the available database is limited to individual studies. Therefore, in order to provide a synthesis of prevalence and time trends, we conducted a systematic review and pooled analysis of pharmaco-epidemiologic data on antipsychotic use in ADHD youth. Of 1806 hits, 21 studies (N) were retained that reported analyzable data for three separate populations: 1) antipsychotic-treated youth (N?=?15, n?=?341,586); 2) ADHD youth (N?=?9, n?=?6,192,368), and 3) general population youth (N?=?5, n?=?14,284,916). Altogether, 30.5?±?18.5 % of antipsychotic-treated youth had ADHD. In longitudinal studies, this percentage increased over time (1998–2007) from 21.7?±?7.1 % to 27.7?±?7.7 %, ratio?=?1.3?±?0.4. Furthermore, 11.5?±?17.5 % of ADHD youth received antipsychotics. In longitudinal studies, this percentage also increased (1998–2006) from 5.5?±?2.6 % to 11.4?±?6.7 %, ratio?=?2.1?±?0.6. Finally, 0.12?±?0.07 % of youth in the general population were diagnosed with ADHD and received antipsychotics. Again, in longitudinal studies, this percentage increased over time (1993–2007): 0.13?±?0.09 % to 0.44?±?0.49 %, ratio?=?3.1?±?2.2. Taken together, these data indicate that antipsychotics are used by a clinically relevant and increasing number of youth with ADHD. Reasons for and risk/benefit ratios of this practice with little evidence base require further investigation.     

Tegillarca granosa extract Haishengsu (HSS) suppresses expression of mdr1, BCR/ABL and sorcin in drug-resistant K562/ADM tumors in mice

PurposeTo evaluate the effect of Haishengsu (HSS), a protein extract from Tegillarca granosa, on multidrug-resistance genes mdr1, BCR/ABL and sorcin in transplanted tumors.Material/MethodsMice were inoculated subcutaneously with a drug resistant leukemia cell line K562/ADM. Tumor-bearing animals were divided into control, adriamycin, HSS and combination therapy (adriamycin plus HSS) groups. Flow cytometry was used to detect apoptosis of tumor cells, and RT-PCR was used to evaluate the expression of mdr1, BCR/ABL and sorcin.ResultsThe apoptosis rate in the high (71.8%), medium (72.3%) and low doses HSS group (72.4%) was higher than in control (1.2%, p<0.01), adriamycin (34.4%, p<0.05) or combination therapy group (46.4%, p<0.05). The mean optical density of mdr1, BCR/ABL and sorcin in HSS groups was lower than in control, adriamycin and combination therapy group (p<0.01). The optical density of the three genes in high HSS group was lower than in medium and low HSS group (p<0.01).ConclusionsHaishengsu promotes apoptosis of drug-resistant K562/ADM tumors in mice in a dose-dependent manner. The pro-apoptotic effect of Haishengsu may be related to a reduced expression of multidrug-resistance genes mdr1, BCR/ABL and sorcin.     

Thermometry during coblation and radiofrequency ablation of vertebral metastases: a cadaver study

Purpose

To evaluate safety of coblation of simulated lytic metastases in human cadaveric vertebral bodies by measuring heat distribution during thermal tissue ablation and comparing it to radiofrequency ablation (RFA).

Materials and methods

Three devices were compared: a 10 mm single-needle RFA electrode, a 20 mm array RFA electrode and the coblation device. To simulate bone metastases, a spinal tumor model was used stuffing a created lytic cavity with muscle tissue. Measuring of heat distribution was performed during thermal therapy within the vertebral body, in the epidural space and at the ipsilateral neural foramen. Eight vertebral bodies were used for each device.

Results

Temperatures at heat-sensitive neural structures during coblation were significantly lower than using RFA. Maximum temperatures measured at the end of the procedure at the neural foramen: 46.4 °C (±2.51; RFA 10 mm), 52.2 °C (±5.62; RFA 20 mm) and 42.5 °C (±2.88; coblation). Maximum temperatures in the epidural space: 46.8 °C (±4.7; RFA 10 mm), 49.5 °C (±6.48; RFA 20 mm) and 42.1 °C (±2.5; coblation). Maximum temperatures measured within the vertebral body: 50.6 °C (±10.48; RFA 10 mm), 61.9 °C (±15.39; RFA 20 mm) and 54.4 °C (±15.77; coblation).

Conclusion

In addition to RFA, the application of coblation is a safe method to ablate vertebral lesions with regards to heat distribution at heat-sensitive neural spots. The measured temperatures did not harbor danger of thermal damage to the spinal cord or the spinal nerves.     

Associations of motor abilities with biological,sociodemographic, and behavioural factors in children: results from the ToyBox study

Sport Sciences for Health - In this cross-sectional study, we examined the association of selected basic motor abilities with biological (sex, age, and BMI), sociodemographic [socio-economic status...     

Survey on practice of venom immunotherapy in France

Introduction

Venom immunotherapy (VIT) is the only efficient prevention for sting-induced anaphylaxis, but its application is not without risks and needs precautions and standardization. European guidelines were proposed in 2005, but recent practice surveys and more recent knowledge raise the need for an update. The aim of this study was to analyze VIT practices in France, based on previous surveys in Europe but also extended to outcome event management.

Material and methods

A paper questionnaire was sent widely to persons involved in venom treatment.

Results

Eighty-six responses could be included from physicians actively involved in VIT induction evenly distributed in France. The survey shows that VIT was engaged from grade III down to grade I reactions, starting preferentially with the ultra-rush protocol. Premedication was used by 42% only and risks induced by co-treatment with β-blockers were well known but not with angiotensin-converting enzyme inhibitors. However, side effects were very variably managed from arrest to enhancement in doses, time-delay or duration. Similarly, we observed a large discrepancy in treatment evaluation (skin tests, biology, timing and interpretation), decision making for treatment termination (when and how long to be prolonged) and post-treatment follow-up (adrenaline kit, event record) as well as procedures in case of late relapse (new induction, different doses).

Conclusions

Our study shows that most recommendations were fully or partially followed and may need reminding, but many points need to be completed or updated with new tools and knowledge acquired during the last 10 years.