Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting

Aims

Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of–function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting.

Methods and Results

137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y₁₂ inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient’s informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y₁₂ inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS.

Conclusion

The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y₁₂ receptor inhibition.     

Kidney dysfunction and deterioration of ejection fraction pose independent risk factors for mortality in implantable cardioverter-defibrillator recipients for primary prevention

Background:

A growing number of patients with advanced heart failure fulfill a primary‐prevention indication for an implantable cardioverter‐defibrillator (ICD). This study seeks to identify new predictors of overall mortality in a Sudden Cardiac Death in Heart Failure Trial (SCD‐HeFT)‐like collective to enhance risk stratification.

Hypothesis:

An impaired renal function and severely depressed left ventricular ejection fraction pose relevant risk factors for mortality in primary prevention ICD recipients.

Methods:

Ninety‐four consecutive ICD patients with New York Heart Association class II–III heart failure and depressed left ventricular function (left ventricular ejection fraction [LVEF] ≤35%) with no history of malignant ventricular arrhythmias were followed for 34 ± 20 months.

Results:

During this period, 30 patients died (32%). Deceased patients revealed a significantly worse renal function before ICD implantation (1.55 ± 0.7 mg/dL vs 1.1 ± 0.4 mg/dL; P = 0.007), suffered more often from coronary artery disease (53 vs 29; P = 0.006), and were older (69.5 ± 8 y vs 67 ± 12 y; P = 0.0002) than surviving patients. Furthermore, increased serum creatinine at baseline (2 mg/dL vs 1 mg/dL; odds ratio [OR]: 3.96, 95% confidence interval [CI]: 1.2–13.04, P = 0.02), presence of coronary artery disease (OR: 8.6, 95% CI: 1.1–65, P = 0.036), and low LVEF (OR per 5% baseline LVEF deterioration: 1.4, 95% CI: 1–1.8, P = 0.034) represented strong and independent predictors for overall mortality.

Conclusions:

Impaired renal function, the presence of coronary artery disease, and reduced LVEF before implantation represent independent predictors for mortality in a cohort of patients with advanced systolic heart failure. These conditions still bear a high mortality risk, even if ICD implantation effectively prevents sudden arrhythmic death. Indeed, in patients suffering from several of the identified “high‐risk” comorbidities, primary‐prevention ICD implantation might have a limited survival benefit. The possible adverse effects of these comorbidities should be openly discussed with the potential ICD recipient and his or her close relatives. Clin. Cardiol. 2012 doi: 10.1002/clc.22018 The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Clinical markers of early nigrostriatal neurodegeneration in idiopathic rapid eye movement sleep behavior disorder

Background

Rapid eye movement sleep behavior disorder (RBD) is an early feature in α synucleinopathies and may precede other clinical manifestations of disease for several years. Olfactory dysfunction and mild motor abnormalities (MMAs) are highly prevalent in prodromal α synucleinopathies such as RBD and are suspected to be predictive neurodegenerative markers. Because both markers also are highly prevalent in the healthy elderly population, the discriminative value to detect an early neurodegenerative process is unclear.

Methods

We examined 28 patients with idiopathic RBD (iRBD) without manifest neurodegenerative disease to determine diagnostic accuracy of MMAs and olfactory dysfunction in identifying patients with early nigrostriatal degeneration in transcranial sonography (TCS) and ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single-photon emission computed tomography (¹²³I-FP-CIT-SPECT).

Results

Sixty-three percent of our participants showed MMAs which were strongly associated with abnormal TCS and ¹²³I-FP-CIT-SPECT findings. The discriminative value in detecting participants with early nigrostriatal degeneration was excellent (area under the receiver operating characteristic [ROC] curve, 0.84 [P ? .003] for TCS and 0.79 [P ? .066] for ¹²³I-FP-CIT-SPECT). Olfactory dysfunction was present in 78% of iRBD participants, but it was not linked with neuroimaging abnormalities or MMAs. Olfactory dysfunction did not discriminate participants with early nigrostriatal degeneration (area under the ROC curve, 0.54 [P ? .747] for TCS and 0.31 [P ? .225] for ¹²³I-FP-CIT-SPECT). Early RBD manifestation but no demographic (e.g., age, gender) or clinical characteristics of RBD (e.g., duration, severity of RBD) were associated with neuroimaging abnormalities in TCS and ¹²³I-FP-CIT-SPECT.

Conclusions

Unlike olfactory dysfunction, MMAs discriminate patients with early nigrostriatal degeneration in iRBD. Early RBD manifestation seems to be an additional risk factor which aggravates neurodegenerative risk.     

A Case of an Arachnoid Cyst Masquerading as Corticobasal Degeneration

We present an individual, “JD”, a 69-year-old Caucasian, married female with symptoms that included progressive right arm stiffness, tremor, and clumsiness; increasing gait and balance disturbance; increased fatigue and emotionality. Neuropsychological evaluation revealed compromised semantics and language-associated functions; impaired visual constructional ability; markedly reduced cognitive and visuomotor processing speed; low average to average working memory; variable praxis performance; variable abstract reasoning, problem solving, and set shifting; and lower overall intellectual functioning compared to premorbid estimates. Overall, her neuropsychological profile indicated marked compromise of the frontal and left parietal regions. The data coupled with her symptom pattern and demographics partially fit corticobasal degeneration diagnostic criteria. Neuroimaging, however, performed 2 years prior to the assessment and again during the current workup revealed an enlarging arachnoid cyst compressing the left parietal and posterior frontal lobe and a small portion of the right medial frontal-parietal region. We discuss the neuroanatomical substrates involved in her cognitive presentation and how two very distinct pathological processes (corticobasal degeneration, arachnoid cyst) can result in two similar symptom presentations. We summarize how multidisciplinary assessment assists with differential diagnosis and treatment planning.     

Evaluation des sagittalen Profils nach operativer Therapie der thorakalen adoleszenten idiopathischen Skoliose Lenke Typ 1

Introduction

The principle philosophy of posterior spinal instrumentation and fusion (PSIF) for the treatment of adolescent idiopathic scoliosis (AIS) has changed during recent decades. In the past the treatment of AIS mainly focused on correction of the major curve in the frontal plane while the sagittal profile and balancing were only of inferior interest in treatment planning. Various long-term outcome studies have demonstrated that many AIS patients developed a flatback syndrome (decrease of thoracic kyphosis and lumbar lordosis) associated with pain. It was concluded that treatment of AIS should consider the sagittal profile and balance; however, there are only few studies addressing additional procedures, which include the correction of the sagittal profile.

Material and methods

The purpose of this study was to evaluate the effects of different posterior correction techniques on sagittal profile and balance. A total of 36 consecutive patients with thoracic AIS, who were treated with selective thoracic posterior correction were included in this retrospective study. The patients were further assigned to three different subgroups according to different surgical strategies: A: pedicle screws, B: long-head pedicle screws and C: additional Ponte osteotomy. Standardized radiographs in the standing position of the whole spine in two planes were evaluated before and at least 2 years after correction for all patients and a subgroup analysis was done to identify differences between the three groups.

Results

A significant correction of the major curve was achieved in all three groups (p?<?0.001). There was a significant difference between the groups with groups B and C showing significantly higher levels of major curve correction in comparison to group A (p?<?0.001). Concerning the sagittal profile, there was a significant difference in the development of thoracic kyphosis (TK) and lumbar lordosis (LL). While a significant reduction of TK and LL was found in groups A and B after surgery, a significant increase of TK and LL was noted in group C which was associated with a decrease of pelvic tilt and an increase of sacral slope. The 2-year follow-up showed the lowest ODI-% value only in group C which was positively correlated with reduction in pelvic tilt.

Conclusions

The results of this study underline that the PSIF technique alone using pedicle screws leads to a satisfactory correction in the frontal plane but is associated with adverse effects on the sagittal profile (flat back syndrome), corroborating previous studies. It was further shown that significant improvements of sagittal parameters were achieved by adding techniques for the lengthening of the dorsal thoracic column. This approach can therefore be recommended for the treatment of AIS Lenke type 1.     

《英国非酒精性脂肪性肝炎肝移植指南》导读

非酒精性脂肪性肝炎（non—alcoholicsteatohepatitis,NASH）现已成为肝移植愈来愈重要的基础肝病。鉴于晚期NASH患者常并存多种影响肝移植转归的临床问题,而至今尚无针对NASH患者进行肝移植的评估和治疗指南,为此英国移植学会（British Transplant Society,BTS）邀请相关专家制定了指南,以指导肝移植前后NASH患者的处理。