Impact of gout on in-hospital outcomes of acute coronary syndrome-related hospitalizations and revascularizations: Insights from the national inpatient sample

BACKGROUND Previous studies have established a role of gout in predicting risk and prognosis of cardiovascular diseases. However, large-scale data on the impact of gout on inpatient outcomes of acute coronary syndrome (ACS)-related hospitalizations and post-revascularization is inadequate. AIM To evaluate the impact of gout on in-hospital outcomes of ACS hospitalizations, subsequent healthcare burden and predictors of post-revascularization inpatient mortality. METHODS We used the national inpatient sample (2010-2014) to identify the ACS and goutrelated hospitalizations, relevant comorbidities, revascularization and postrevascularization outcomes using the ICD-9 CM codes. A multivariable analysis was performed to evaluate the predictors of post-revascularization in-hospital mortality. RESULTS We identified 3144744 ACS-related hospitalizations, of which 105198 (3.35%) also had gout. The ACS-gout cohort were more often older white males with a higher prevalence of comorbidities. Coronary artery bypass grafting was required more often in the ACS-gout cohort. Post-revascularization complications including cardiac (3.2% vs 2.9%), respiratory (3.5% vs 2.9%), and hemorrhage (3.1% vs 2.7%) were higher whereas all-cause mortality was lower (2.2% vs 3.0%) in the ACSgout cohort (P < 0.001). An older age (OR 15.63, CI: 5.51-44.39), non-elective admissions (OR 2.00, CI: 1.44-2.79), lower household income (OR 1.44, CI: 1.17- 1.78), and comorbid conditions predicted higher mortality in ACS-gout cohort undergoing revascularization (P < 0.001). Odds of post-revascularization inhospital mortality were lower in Hispanics (OR 0.45, CI: 0.31-0.67) and Asians (OR 0.65, CI: 0.45-0.94) as compared to white (P < 0.001). However, postoperative complications significantly raised mortality odds. Mean length of stay, transfer to other facilities, and hospital charges were higher in the ACS-gout cohort. CONCLUSION Although gout was not independently associated with an increased risk of postrevascularization in-hospital mortality in ACS, it did increase postrevascularization complications.

Survival benefit with extended lymphadenectomy for advanced renal malignancy: A population-based analysis

Objective:We used population-based data to examine the possible benefit of extended lymphadenectomy for patients with renal malignancy in the setting of more advanced disease.Methods:The Surveillance,Epidemiology,and End Results(SEER)database was utilized to identify non-metastatic,T3-T4 renal cancer patients from 2004-2015 treated with removal of≥1 lymph node at the time of nephrectomy.Non-parametric bivariate statistics were used to assess associations between covariates of interest and extended lymphadenectomy(≥10 lymph nodes removed).Cancer-specific survival(CSS)and overall survival(OS)benefit was evaluated using Kaplane-Meier analysis.Results:Of the 4397 patients identified,816(18.6%)underwent extended lymphadenectomy.For patients with T3a disease,5-year CSS and OS benefit with extended lymphadenectomy did not reach statistical significance(CSS:hazard ratio[HR]0.98,95%confidence interval[CI]0.77-1.24;OS:HR 0.96,95%CI 0.77-1.20).Conversely,for those with T3b-T3c disease,extended lymphadenectomy led to statistically significant improvements in both 5-year CSS and OS compared to non-extended lymphadenectomy(CSS:HR 0.78,95%CI 0.61-0.99;OS:HR 0.72,95%CI 0.58-0.90).Finally,for those with T4 disease,use of extended lymphadenectomy had OS benefit after 5 years(OS:HR 0.51,HR 0.29-0.90,p = 0.02).Conclusion:Based on population-level data,extended lymphadenectomy was associated with improved survival in select patients with advanced renal malignancy treated with surgical nephrectomy.Understanding the basis of these real-world findings in the face of conflicting randomized trial results will be key,moving forward.

Major histocompatibility complex I upregulation in clear cell renal cell carcinoma is associated with increased survival

Objective:To examine the prognostic value of tumor major histocompatibility complex I(MHCI)expression on survival and recurrence in patients with clear cell renal cell carcinoma(RCC).Methods:Fifty-three patients that underwent nephrectomy at our institution for clear cell RCC(T1eT3)with
4 years of follow-up were queried from our nephrectomy database.Immunohistochemical staining for MHCI was performed on tumor specimens and MHCI expression was quantified with an automated image analysis technique.Patients were divided into high and low MHCI expression groups in order to study the relationship between MHCI expression and prognosis using the KaplaneMeier method and log-rank test.Results:Overall survival and recurrence free survival were increased in the high MHCI expression group compared to the low MHCI expression group(log-rank,p=0.036 and p=0.028,respectively).Patients alive at the end of the study had higher MHCI expression(mean positivity score 0.82)than those that died of disease(mean positivity score 0.76,t test,p=0.030).Patients that did not develop recurrence during the study period had higher MHCI expression(mean positivity score 0.83)than those that did develop recurrence(mean positivity score 0.78),but this difference was not significant(t test,p =0.079).

神经精神药理学治疗药物监测共识指南:2017版

治疗药物监测(Therapeutic Drug Monitoring,TDM)通过定量测定和解释血药浓度以优化药物治疗。TDM着眼于药代动力学的个体差异,使个体化药物治疗成为可能。在精神病学和神经病学领域中,有可能明显获益于TDM的主要患者群体包括少年儿童、孕妇、老年患者、智障患者、药物滥用者、涉法精神病患者、已知或怀疑药代动力学异常的患者以及合并躯体疾病影响药代动力学的患者。常规剂量下治疗无效,用药依从性难以判断,药物耐受性不佳,以及可能存在药代动力学方面的药物-药物相互作用等情况都是治疗药物监测的典型指征。然而,只有将TDM充分整合到临床治疗过程中,才能发挥其优化药物治疗的潜在优势。为了向临床医生和实验室提供有效的TDM信息,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了第一版《精神科治疗药物监测指南》。2011年进行了更新之后,现在再次更新。遵循新版指南,可能会改善神经精神药物治疗的效果,加快很多患者的康复,并降低医疗费用。

神经精神药理学治疗药物监测共识指南:2017版

2.2剂量相关参考浓度范围对于TDM结果的解释,除了治疗参考浓度范围外还有另一个浓度范围,即所谓的剂量相关参考浓度范围。治疗参考浓度范围的应用是药效动力学问题,而剂量相关参考浓度范围的运用是药代动力学问题。后者比较的是测得的药物浓度与理论预期药物浓度范围。参照药代动力学研究,优先考虑没有合并用药或药物基因组异常的患者群(“正常”患者),在日维持剂量(Daily maintenance dose,D m)、给药间隔(Dosing interval,d i)、总清除率(Total clearance,CL)和生物利用度(Bioavailability,F)已知情况下,某种药物在某个“正常”患者体内的预期平均稳态浓度(Average steady-state concentration,C av)可通过下面的公式计算。

Alcoholism and critical illness: A review

Alcohol is the most commonly used and abused drug in the world, and alcohol use disorders pose a tremendousburden to healthcare systems around the world. The lifetime prevalence of alcohol abuse in the United States is estimated to be around 18%, and the economic consequences of these disorders are staggering. Studies on hospitalized patients demonstrate that about one in four patients admitted to critical care units will have alcohol-related issues, and unhealthy alcohol consumption is responsible for numerous clinical problems encountered in intensive care unit(ICU) settings. Patients with alcohol use disorders are not only predisposed to developing withdrawal syndromes and other conditions that often require intensive care, they also experience a considerably higher rate of complications, longer ICU and hospital length of stay, greater resource utilization, and significantly increased mortality compared to similar critically ill patients who do not abuse alcohol. Specific disorders seen in the critical care setting that are impacted by alcohol abuse include delirium, pneumonia, acute respiratory distress syndrome, sepsis, gastrointestinal hemorrhage, trauma, and burn injuries. Despite the substantial burden of alcoholinduced disease in these settings, critical care providers often fail to identify individuals with alcohol use disorders, which can have significant implications for this vulnerable population and delay important clinical interventions.

精神病学临床研究——探讨机制,着眼治疗

本文对精神科的重要研究进行了回顾,提出尽管研究的热点时常变化,但基于实证的方法仍需要遵循,同时应鼓励在多个方向、多条路径上开展研究。精神障碍的异源性及病因的非特异性,使得病因的探寻往往很难,甚至一无所获,关于精神障碍候选基因的研究便是例证之一。另外,有时即使病因已知,也往往意义不大或对临床诊断治疗于事无补。作者建议应将更多的资源放到机制及新型治疗的研究,二者均可能加深对精神障碍的认识,或改善治疗。

A novel preoperative inflammatory marker prognostic score in patients with localized and metastatic renal cell carcinoma

Objective:Several inflammatory markers have been studied as potential biomarkers in renal cell carcinoma(RCC),however few reports have analyzed their prognostic value in aggregate and in non-clear cell histologies.We hypothesize that a combination of specific inflammatory markers into an RCC Inflammatory Score(RISK)could serve as a rigorous prognostic indicator of overall survival(OS)in patients with clear cell and non-clear cell RCC.Methods:Combination of preoperative C-reactive protein(CRP),albumin,erythrocyte sedimentation rate(ESR),corrected calcium,and aspartate transaminase to alanine transaminase(AST/ALT)ratio was used to develop RISK.RISK was developed using grid-search methodology,receiver-operating-characteristic(ROC)analysis,and sensitivity-specificity trade-off analysis.Prognostic value of RISK was analyzed using the KaplaneMeier method and Cox proportional regression models.Predictive accuracy was compared with RISK to Size,Size,Grade,and Necrosis(SSIGN)score,University of California-LOS Angeles(UCLA)Integrated Staging System(UISS),and Leibovich Prognosis Score(LPS).

Intracoronary brachytherapy for the treatment of recurrent drugeluting stent in-stent restenosis:A systematic review and metaanalysis

BACKGROUND We performed a meta-analysis on observational studies since randomized control trials are not available.We studied intracoronary brachytherapy(ICBT)and recurrent drug eluting stent in-stent restenosis(DES-ISR)to evaluate the procedural success,target lesion revascularization(TLR),incidence of myocardial infarction(MI)and all-cause mortality at 2 years follow-up.AIM To perform meta-analysis for patients undergoing ICBT for recurrent DES-ISR.METHODS We performed a systematic search of the PubMed/MEDLINE,Cochrane and DARE databases to identify relevant articles.Studies were excluded if intracoronary brachytherapy was used as a treatment modality for initial ISR and studies with bare metal stents.We used a random-effect model with DerSimonian&Laird method to calculate summary estimates.Heterogeneity was assessed using I2 statistics.RESULTS A total of 6 observational studies were included in the final analysis.Procedural angiographic success following intra-coronary brachytherapy was 99.8%.Incidence of MI at 1-year was 2%and 4.1%at 2-years,respectively.The incidence of TLR 14.1%at 1-year and 22.7%at 2-years,respectively.All-cause mortality at 1-and 2-year follow-up was 3%and 7.5%,respectively.CONCLUSION Given the observational nature of the studies included in the analysis,heterogeneity was significantly higher for outcomes.While there are no randomized controlled trials or definitive guidelines available for recurrent ISR associated with DES,this analysis suggests that brachytherapy might be the alternative approach for recurrent DES-ISR.Randomized controlled trials are required to confirm results from this study.

Introduction and recent progress of BRAIN Initiative in the United States

The presidential research program Brain Research through Advancing Innovative Neurotechnologies(BRAIN)Initiative was established5years ago in the United States;it has been a driving force of the United States government and private factors to promote technology development in basic and translational neuroscience research.We here summarize the research plan and recent progress in cellular neuroscience,electrical and optical engineering,chemical and systems neurobiology,and brain mapping technologies.The research plan recognizes the importance of identifying different cell populations and unknown cell types in the human brain and diseased models.Technological advances in multielectrode arrays and chemical flow measurement probes not only demonstrate the capacity of detecting neural activities in large areas,but also enable a new era of studying the neural coding information.Large-scale coordination of neuronal activity and brain mapping information will allow for the identification of therapeutic targets in neurological disorders,which is benefited by big data acquisition and analysis.Specifically,increased brain databases will expedite the dissection of thoughts,emotions,cognition,and will thereby help the development of better understanding and treatments of brain disorders.Since cell therapy demonstrates potential for regenerative medicine,the utilization of the newly advanced technologies may further improve the translational potentials and precision controls of transplanted grafts.The development of new diagnostic and therapeutic tools also requires international collaborations on science,technology,advocating,healthcare and medical ethics to advance the innovation and clinical practices.

Prepulse inhibition deficits in antipsychotic-na-ve first-episode schizophrenia:a meta-analysis

Objective:Published studies have found prepulse inhibition(PPI)in schizophrenia is impaired,suggesting PPI may be a biomarker of schizophrenia.We aim to examine whether PPI deficits exist in antipsychotic-na-ve,first-episode schizophrenia,and evaluate the effect size of PPI deficits between patients and healthy controls.Methods:The effect size of PPI deficits was evaluated for PPI%by calculating standard mean differences(SMDs)between patients with antipsychotic-na-ve,first-episode schizophrenia and healthy controls.Results:Twelve studies met the inclusion criteria,consisting390antipsychotic-na-ve,first-episode schizophrenia and406healthy controls.The effect sizes of76dB PPI in60ms and120ms interstimulus interval(ISI)were-0.19and-0.41respectively,and the76dB PPI overall effect size was-0.30.The effect sizes of85/86dB PPI in30ms,60ms and120ms ISI were-0.25,-0.42and-0.59respectively,and the85/86dB PPI overall effect size was-0.46.One study were excluded due to heterogeneity in the85/86dB,120ms ISI group,the pooled effect size of the PPI differences between patient group and health control dropped to-0.42,and the overall effect size changed to-0.39.There were no statistical differences in startle magnitude(overall effect size=-0.18)and habituation%(overall effect size=-0.17)between patients and healthy controls.Conclusions:Antipsychotic-na-ve,first-episode schizophrenia patients exhibit robust and reliable deficits in PPI,85/86dB PPI deficit was more severe than76dB PPI,and85/86dB,60-ms ISI PPI was more likely to be a biomarker for schizophrenia,it suggested that the parameters of PPI are particularly significant to affect the effect size so that should be interpreted with cautions in the future studies.

经皮冠状动脉血运重建及遵循指南强化药物治疗临床结果评估(COURAGE)试验中的经济学方法

Percutaneous coronary intervention(PCI) remains a major therapeutic option for the treatment of chronic coronary artery disease. In the COURAGE trial, 2287 patients with chronic coronary disease were randomized between PCI with medical management and medical management alone. Embedded within the COURAGE trial is a detailed economic analysis being conducted in three health care systems: the US Veterans Administration(VA), Canada, and the US non-VA. Resource use and costs are being collected for each system and overall. Survival is assessed internally in the trial with mean follow-up of 4.5 years. Long-term mean survival will be estimated by projecting survival beyond the trial period by extrapolating the in-trial hazard rates. Utility is being assessed at baseline and at 1, 3, and 6 months and annually thereafter, using a computer-administered standard gamble. Quality-adjusted life years are calculated by multiplying survival by utility. The incremental cost-effectiveness ratio of PCI will be defined as the additional cost of PCI divided by the gain in life years and quality-adjusted life years. The 95%confidence regions of efficacy and costs will be determined by bootstrap over a range of acceptability thresholds, which will then be displayed in the cost-effectiveness plane and as a cost-effectiveness acceptability curve. A multilevel regression model will assess cost-effectiveness from a net benefit perspective. These approaches should provide the most detailed assessment available of the cost-effectiveness of PCI for coronary artery disease.

M13 Bacteriophage-Polymer Nanoassemblies as Drug Delivery Vehicles

Poly (caprolactone-b-2-vinylpyridine )(PCL-P2VP ) 与叶酸结合 M13 (FA-M13 ) 涂提供能够包含象 doxorubicin (纪录影片) 那样的恐水病的 antitumor 药的一个 nanosized 交货系统。装载纪录影片的 FA-M13-PCL-P2VP 集会有约 200 nm 的一条平均直径，他们的结构用传播电子显微镜学被描绘，扫描电子显微镜学，并且动态轻散布。粒子在生理的 pH 是稳定的，但是能在更低的 pH 被降级。从在酸的条件下面的 nanoassemblies 的纪录影片的版本比在生理的 pH 观察了的被显示显著地快。另外，装载纪录影片的 FA-M13-PCL-P2VP 粒子比 folate-receptor-negative 房间对 folate-receptor-positive 癌症房间显示出显然更大的细胞的举起和 cytotoxicity，显示受体便于经由调停受体的 endocytosis 的叶酸的举起。而且，装载纪录影片的粒子也与免费纪录影片相比有显著地更高的肿瘤举起和选择。这研究因此提供一个新方法制作 nanosized 药交货车辆。