Citations

Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org ).

AbstractTranscription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural‐derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low‐density lipoprotein receptor‐related protein 6, heat‐shock factor‐1, and repressor element 1‐silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1‐silencing transcription factor than in controls. Exosomal transcription factors were diminished 2–10 years before clinical diagnosis of Alzheimer's disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer's disease neurotoxic proteins.

Abstract Aim The objective of this meta‐analysis was to compare the effects of off‐pump and on‐pump coronary artery bypass grafting ( CABG ) on acute kidney injury ( AKI ) and the need of dialysis after surgery. Methods Comprehensive literature searches for randomized controlled trials ( RCTs ) of CABG with on‐pump and off‐pump was performed using MEDLINE , EMBASE , C ochrane D atabase of S ystematic R eviews, C ochrane C entral R egister of C ontrolled T rials S ystematic R eviews and clinicaltrials.gov from inception through S eptember 2014. Primary outcomes were the incidence of AKI and the need of dialysis. Mortality was assessed among the studies that reported renal outcomes. Pooled risk ratios ( RR s) and 95% confidence interval ( CI ) were calculated using a random‐effect, generic inverse variance method. Results Thirty‐three RCTs with 17 322 patients were enrolled in our study. Patients in the off‐pump CABG group had overall lower incidence of AKI (19.1%) compared with the on‐pump CABG group (22.2%). There was a protective effect of off‐pump CABG on the incidence of AKI compared with the on‐pump CABG group ( RR : 0.87; 95% CI : 0.77–0.98). However, there was no significant difference in the need for dialysis in the off‐pump group compared with the on‐pump group ( RR : 0.84; 95% CI 0.63–1.13). Within the selected trials, post hoc analysis assessing the mortality outcome demonstrated a pooled RR of 0.97 (95% CI , 0.77–1.23) in off‐pump versus on‐pump CABGs . Conclusions Our study demonstrates a beneficial effect of off‐pump CABG on the incidence of AKI . However, our meta‐analysis does not show benefits of the need of dialysis or survival among patients undergoing off‐pump CABG .

Abstract T-cell immunophenotype of acute lymphoblastic leukemia (T-ALL) is an uncommon aggressive leukemia that can present with leukemic and/or lymphomatous manifestations. Molecular studies are enhancing our understanding of the pathogenesis of T-ALL, and the discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation. The use of pediatric intensive combination chemotherapy regimens in adolescents and young adults has significantly improved the outcome of patients with T-ALL. The use of nelarabine for relapsed and refractory T-ALL results in responses in a substantial minority of patients. Allogeneic hematopoietic cell transplantation (HCT) still plays a key role in patients with high-risk or relapsed/refractory disease. γ-Secretase inhibitors hold promise for the treatment of patients with NOTCH1 mutations, and the results of clinical trials with these agents are eagerly awaited. It is recommended that younger patients receive a pediatric-intensive regimen. Older and unfit patients can receive suitable multiagent chemotherapy and be allocated to HCT based on their response, risk factors, and comorbidities. Although advances in the treatment of T-ALL have lagged behind those of B-cell ALL, it is hoped that the molecular revolution will enhance our understanding of the pathogenesis and treatment of this aggressive lymphoid malignancy.

Objective: To review the literature evaluating gabapentin for alcohol withdrawal and dependence. Data Sources: A literature search of MEDLINE (1966 to end of March 2015) and PubMed was performed using the terms alcohol, gabapentin, withdrawal, and dependence. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: English-language prospective studies evaluating gabapentin for alcohol withdrawal and dependence were evaluated. Data Synthesis: A total of 10 publications utilizing gabapentin in alcohol withdrawal (n = 5) and alcohol dependence (n = 5) were included in this review. Limited data suggest that gabapentin can provide benefit in managing mild alcohol withdrawal syndrome. There were 5 reported or suspected seizures in the withdrawal studies, suggesting that additional safety data are necessary before gabapentin monotherapy can be routinely considered. Sleep and mood/anxiety-related outcomes were positively influenced by gabapentin, which may result in long-term benefits if continued beyond the withdrawal period for the treatment of alcohol dependence. Studies evaluating gabapentin for alcohol dependence demonstrated dose-dependent benefits for complete abstinence, rates of no heavy drinking, and cravings. Gabapentin used to treat alcohol dependence was well tolerated with no severe adverse reactions reported in the extant literature. Conclusion: Gabapentin may have a role in the treatment of mild alcohol withdrawal, but future studies should focus on adequate dosing strategies. Gabapentin should be considered for the treatment of alcohol dependence when barriers prevent the use of traditional agents. Additional studies should be conducted to further validate findings from the research conducted to date, but the current literature is promising for gabapentin in the treatment of alcohol dependence.