CHADS2 and CHA2DS2-VASc scores as predictors of platelet reactivity in acute coronary syndrome

BackgroundPlatelet function testing (PFT) in patients treated with P2Y₁₂ inhibitors has been widely evaluated for the prediction of stent thrombosis, myocardial infarction, and bleeding events following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). Thus, PFT-guided treatment could positively affect patient outcomes. Data regarding clinical parameters for predicting platelet reactivity in ACS patients are limited. Therefore, our study aims to evaluate CHADS2 and CHA2DS2-VASc scores as predictors for platelet reactivity in ACS patients.MethodsTwo hundred and ninety-one consecutive patients who underwent PCI and were treated with aspirin and clopidogrel due to ACS were tested for their CHADS2, CHA2DS2-VASc scores and platelet reactivity using adenosine diphosphate (ADP)-induced aggregation (conventional aggregometry). Patients were classified into groups according to their CHADS2 and CHA2DS2-VASc scores. Low-risk group (0–1 score) for CHADS2 and CHA2DS2-VASc scores and high-risk group (2–6, 2–9) for CHADS2 and CHA2DS2-VASc scores, respectively. Furthermore, platelet reactivity in each group were compared (low CHADS2 group vs high CHADS2 group, and low CHA2DS2-VASc vs high CHA2DS2-VASc). Platelet reactivity was defined as low platelet reactivity (<19 U), optimal platelet reactivity [(OPR); 19–46 U], and high on-treatment platelet reactivity [(HPR); >46 U]. Thereafter receiver operating characteristic curve analysis was conducted to verify whether CHADS2 and CHA2DS2-VASc scores could predict platelet reactivity.ResultsLow CHADS2 and CHA2DS2-VASc scores were significantly correlated with lower mean platelet ADP-induced aggregation as compared with high CHADS2 and CHA2DS2-VASc scores [45.5 U (± 16) vs. 54.8 U (±15) and 44.2 U (±16) vs. 51.0 U (±17), respectively, p = 0.01 for both].ConclusionIn ACS patients treated with clopidogrel following PCI, high CHADS2 and CHA2DS2-VASc scores correlated with HPR and lower scores correlated with OPR. Further studies are needed to evaluate our findings’ clinical implications.     

Staphylococcus aureus: the search for novel targets

In the UK, 20,000 cases of Staphylococcus aureus bacteraemia are reported each year, half of which are antibiotic resistant and approximately 4% are fatal, exemplifying a worldwide phenomenon of tremendous economic and human impact. Novel treatments and prophylaxis are urgently required to combat such a serious threat. A common goal in the postgenomic era is to identify new targets for drug intervention (using small molecules) and immunologicals. Several promising cellular targets are now being developed in the quest to control such a life-threatening pathogen.     

Synaptic release of zinc from brain slices: factors governing release, imaging, and accurate calculation of concentration

Cerebrocortical neurons that store and release zinc synaptically are widely recognized as critical in maintenance of cortical excitability and in certain forms of brain injury and disease. Through the last 20 years, this synaptic release has been observed directly or indirectly and reported in more than a score of publications from over a dozen laboratories in eight countries. However, the concentration of zinc released synaptically has not been established with final certainty. In the present work we have considered six aspects of the methods for studying release that can affect the magnitude of zinc release, the imaging of the release, and the calculated concentration of released zinc. We present original data on four of the issues and review published data on two others. We show that common errors can cause up to a 3000-fold underestimation of the concentration of released zinc. The results should help bring consistency to the study of synaptic release of zinc.     

Psychodynamic psychotherapy as applied in an arab village clinic

The Arab-Palestinian sector in Israel is undergoing significant transition in all social and cultural domains, including mental health. Throughout the past decade, mental health professionals have witnessed a substantial increase in the number of Arab individuals and families seeking psychotherapeutic treatment. The vast majority of the professional literature that deals with the use of Western psychotherapy with non-Western patients urges the therapist to accommodate the patient's cultural sensitivities, even to the point of modifying therapeutic theory and technique in order to meet the patient's needs. This article, supported by a decade of psychotherapeutic experience with Arab patients, argues against this approach. A case study illustrates the effective application of psychodynamic psychotherapy to an Arab-Palestinian patient, where the standard concepts and techniques of psychotherapy were retained.     

Concentrations of extracellular free zinc (pZn)e in the central nervous system during simple anesthetization, ischemia and reperfusion

"Free Zn2+" (rapidly exchangeable Zn2+) is stored along with glutamate in the presynaptic terminals of specific specialized (gluzinergic) cerebrocortical neurons. This synaptically releasable Zn2+ has been recognized as a potent modulator of glutamatergic transmission and as a key toxin in excitotoxic neuronal injury. Surprisingly (despite abundant work on bound zinc), neither the baseline concentration of free Zn2+ in the brain nor the presumed co-release of free Zn2+ and glutamate has ever been directly observed in the intact brain in vivo. Here, we show for the first time in dialysates of rat and rabbit brain and human CSF samples from lumbar punctures that: (i) the resting or "tonic" level of free Zn2+ signal in the extracellular fluid of the rat, rabbit and human being is approximately 19 nM (95% range: 5-25 nM). This concentration is 15,000-fold lower than the "300 microM" concentration which is often used as the "physiological" concentration of free zinc for stimulating neural tissue. (ii) During ischemia and reperfusion in the rabbit, free zinc and glutamate are (as has often been presumed) released together into the extracellular fluid. (iii) Unexpectedly, Zn2+ is also released alone (without glutamate) at a variable concentration for several hours during the reperfusion aftermath following ischemia. The source(s) of this latter prolonged release of Zn2+ is/are presumed to be non-synaptic and is/are now under investigation. We conclude that both Zn2+ and glutamate signaling occur in excitotoxicity, perhaps by two (or more) different release mechanisms.     

One decade of glioblastoma multiforme surgery in 342 elderly patients: what have we learned?

To assess the utilization and outcomes of adjuvant monotherapy with hypofractionated radiation (RT) among elderly patients not receiving traditional adjuvant chemoradiotherapy (cRT) for glioblastoma multiforme (GBM). A retrospective analysis using the National Cancer Data Base with GBM patients aged 65 years or older treated between 2005 and 2012 was conducted. Patients who underwent hypofractionated RT (40 Gy), conventional RT (60 Gy), chemotherapy, or best supportive care alone were included. Statistical methods included logistic regression for utilization and Cox regression for survival analysis. A total of 9556 patients were analyzed. On multivariate analysis (compared to those receiving conventional RT), patients more likely to be treated with hypofractionated RT were older (75–84 years old OR 2.05; p?<?0.01 and ≥?85 years old OR 3.32; p?<?0.01), with a Charlson/Deyo score of 2 or higher (OR 1.80; p?=?0.05), from communities?>?50 miles from their treatment facility (50–100 miles OR 8.03; p?<?0.01 and >?100 miles OR 7.16; p?<?0.01), treated at an Academic/Research facility (OR 2.85; p?=?0.04), and diagnosed between 2011 and 2012 (OR 4.15; p?<?0.01). On Cox regression, hypofractionated RT (HR 0.65; p?<?0.01), conventional RT (HR 0.60; p?<?0.01), and chemotherapy alone (HR 0.69; p?<?0.01) were all associated with decreased risk of death compared to no adjuvant therapy. Among patients receiving adjuvant treatment, utilization of hypofractionated RT increased from 7 to 19% during the study period. Among elderly patients with GBM not receiving cRT, the utilization of adjuvant monotherapy with hypofractionated RT has increased over time. Retrospective evidence suggests it may be better than best supportive care alone and as good as conventionally fractionated RT alone.     

Coping strategies used by parents of children with traumatic brain injury: A cross-sectional study of Palestinians and Israelis

This study examined the use and helpfulness of coping strategies and patterns among parents of children with traumatic brain injury (TBI). Participants were 122 Arab-Israeli, Jewish-Israeli, and Palestinian parents of 65 children with TBI following their discharge from pediatric rehabilitation hospital. Family-focused strategies were highly prevalent and most helpful among both mothers and fathers. Jewish mothers reported that support coping pattern (but not medical or family) was more helpful than did Arab-Israeli and Palestinian mothers. The findings highlight the need to promote effective coping among mothers of children with TBI with low levels of income and education and underscore the need for continuous long-term professional support to parents of children with TBI after hospital discharge.