蒙特利尔认知评估量表筛查轻度认知功能障碍分界值的研究

目的研究蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA)在筛查轻度认知功能障碍(MCI)中的应用价值,初步探讨MoCA筛查MCI的最佳界值。方法分别采用简易智能状态检查量表(MMSE)及MoCA评估入组的男性患者153例,根据诊断标准分为对照组69例、MCI组60例、AD组24例。进行2种量表得分的相关性分析,并且计算MoCA筛查MCI患者的敏感性、特异性、Kappa值、约登指数等,并选取最佳分界值。结果与对照组比较,MCI组和AD组MMSE评分和MoCA评分明显降低(P<0.05)。MMSE评分与MoCA评分呈正相关(r=0.847,P<0.01);以26分为分界值,MoCA诊断MCI的敏感性为98.3%,特异性为85.5%,Kappa值=0.830;绘制ROC曲线得到MoCA筛查MCI的最佳分界值为25分,敏感性为93.3%,特异性为97.1%,Kappa值=0.906。结论本研究人群MMSE评分与MoCA评分有很好的相关性,并且与临床诊断一致性好,推荐25分为该类人群MCI的分界值。     

Contemporary clinical outcomes of primary percutaneous coronary intervention in elderly versus younger patients presenting with acute ST-segment elevation myocardial infarction

Background: Primary percutaneous coronary intervention (PPCI) is the choice reperfusion strategy for acute ST‐segment elevation myocardial infarction (STEMI). However, data on PPCI in elderly patients are sparse. This study determined clinical outcome post‐PPCI in elderly versus younger patients with STEMI. Methods and Results: A cohort of 790 consecutive STEMI patients was studied for survival and major adverse cardiovascular events (MACE) after PPCI using a precise cardiac catheterization protocol. Patients were divided into two groups: those ≥75 years (elderly) and those <75 years. Median door‐to‐balloon time (DBT) was 82 minutes in the elderly versus 66 minutes in the younger group (P = 0.002). In‐hospital all‐cause mortality was higher in the elderly group (15.5% vs. 2.7%, P < 0.001). In elderly patients, MACE were found to be higher (32.3% vs. 16.1%, P < 0.001). Using a multivariate logistic regression analysis, age (odds ratio [OR]= 1.04, 95% confidence interval [CI]= 1.02–1.05, P < 0.001), diabetes (OR = 2.17, 95% CI = 1.33–3.53, P = 0.002), renal failure (OR = 3.75, 95% CI = 1.30–10.79, P = 0.014) and coronary artery disease (OR = 1.61, 95% CI = 1.00–2.59, P = 0.050) were associated with higher in‐hospital MACE, while age (OR = 1.05, 95% CI = 1.02–1.08, P = 0.001), diabetes (OR = 2.18, 95% CI = 1.06–4.47, P = 0.034) and renal failure (OR = 6.65, 95% CI = 2.01–22.09, P = 0.002) were associated with higher in‐hospital mortality. Kaplan–Meier 1‐year survival rate was lower in the elderly. Conclusions: In a contemporary population of STEMI patients treated with PPCI, overall in‐hospital MACE and mortality remain higher in elderly compared to younger patients. Although partly due to higher burden of preexisting comorbidities, a higher DBT may also be responsible. (J Interven Cardiol 2011;24:357–365)     

The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment

OBJECTIVES: To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. DESIGN: Validation study. SETTING: A community clinic and an academic center. PARTICIPANTS: Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). MEASUREMENTS: The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. RESULTS: Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). CONCLUSION: MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.     

The impact of E‐cadherin expression on the prognosis of esophageal cancer: a meta‐analysis

E‐cadherin is a 120‐KD transmembrane calcium‐dependent cell adhesion protein that has been demonstrated drownregulated in a large amount of invasive tumors. However, its effect on the prognosis of esophageal cancer (EC) remains controversial. All the relevant English articles that reported survival data or clinicopathological parameters were enrolled in this meta‐analysis. A total of 24 studies, including 2691 cases, were included in this study. Twelve studies containing 1669 cases were enrolled to synthesize with hazard ratio (HR) and its 95% confidence interval (CI). The pooled HR for all 12 studies enrolled in this meta‐analysis was 1.33 (95% CI 1.16–1.52; z = 3.99, P = 0.00). When the study measured by enzyme‐linked immunosorbent assay is excluded, the pooled HR‐evaluated E‐cadherin to reduce the expression in EC, and in esophageal squamous cell carcinoma was 1.39 (95% CI 1.22–1.58; z = 5.08, P = 0.00) and 1.38 (95% CI 1.21–1.56; z = 4.87, P = 0.00), respectively. The risk of reduced E‐cadherin expression on poor differentiation degree was 1.636 (95% CI 1.33–2.02). The pooled odds ratio of reduced E‐cadherin expression on deeper tumor invasion, lymph node metastasis, and higher clinical stage were 2.63 (95% CI 1.75–3.94), 1.77 (95% CI 1.06 ?2.97), and 3.39 (95% CI 1.85–6.23). Reduced E‐cadherin expression detected by immunohistochemistry could be a valid prognostic marker in patients with EC, especially in patients with esophageal squamous cell carcinoma. Reduced E‐cadherin expression is significantly associated with poorer differentiation degree.     

Impact of intravascular ultrasound‐guided percutaneous coronary intervention on long‐term clinical outcomes in a real world population

Objectives : To compare long‐term clinical outcomes between intravascular ultrasound (IVUS)‐guided and angiography‐guided percutaneous coronary intervention (PCI) in a large “real world” registry. Background : The impact of IVUS‐guided PCI on clinical outcomes remains unclear. Methods : Between January 1998 and February 2006, 8,371 patients who underwent IVUS‐ (n = 4,627) or angiography‐ (n = 3,744) guided PCI were consecutively enrolled. Three‐year clinical outcomes were compared after adjustment for inverse‐probability‐of‐treatment weighting (IPTW) in the overall population and in separate populations according to stent type. Results : A crude analysis of the overall population showed that the 3‐year mortality rate was significantly lower in the IVUS‐guided group than in the angiography‐guided group (96.4% ± 0.3% vs. 93.6% ± 0.4%, log‐rank P < 0.001). When adjusted by IPTW, patients undergoing IVUS‐guided PCI remained at lower risk of mortality (hazard ratio [HR] 0.627; 95% CI 0.50–0.79, P < 0.001). Similarly, in the drug‐eluting stent (DES) population, the 3‐year risk of mortality was significantly lower in patients undergoing IVUS‐guided PCI (HR 0.46; 95% CI 0.33–0.66, P < 0.001). In contrast, IVUS‐guided PCI did not reduce the risk of mortality in the bare metal stent population (HR 0.82; 95% CI 0.60–1.10, P = 0.185). However, the risks of myocardial infarction (HR 0.95; 95% CI 0.63–1.44, P = 0.810), target vessel revascularization (HR 1.00; 95% CI 0.86–1.15, P = 0.944), and stent thrombosis (HR 0.82; 95% CI 0.53–1.07, P = 0.109) were not associated with IVUS guidance. Conclusions : IVUS‐guided PCI may reduce long‐term mortality when compared with conventional angiography‐guided PCI. This may encourage the routine use of IVUS for PCI in patients undergoing DES implantation. © 2012 Wiley Periodicals, Inc.     

海南版简易智能状态检查量表和蒙特利尔认知评估量表界值划分的初步研究

目的初步探讨中文海南版(琼北闽语版)简易智能状态检查量表(MMSE)和蒙特利尔认知评估量表(MoCA)评分在本地人群认知筛查中的可行性及界值的划分。方法选取2019年1~9月海口市养老院和海南省人民医院门诊及住院的本地被试者217例,根据临床诊断分为正常组45例,轻度认知功能障碍(MCI)组54例,轻度痴呆组62例,中度以上痴呆组56例,同时进行MMSE及MoCA评分评估,进行两种量表评分相关性及界值。结果与正常组比较,MCI组、轻度痴呆组和中度以上痴呆组MMSE及MoCA评分明显降低,差异有统计学意义(P<0.05)。正常组、MCI组、轻度痴呆组和中度以上痴呆组MMSE评分明显高于MoCA评分(P<0.01)。Person相关分析显示,MMSE评分与MoCA评分呈正相关(r=0.940,P<0.01)。MCI组、轻度痴呆组和中度以上痴呆组ROC曲线界值为:MCI组MMSE评分低于27分,MoCA评分低于22分;轻度痴呆组MMSE评分低于23分,MoCA评分低于16分;中度以上痴呆组MMSE评分低于15分,MoCA评分低于11分。结论海南版(琼北闽语版)MMSE与MoCA评分有较好的一致性,联合应用对认知障碍及痴呆患者有较好的筛查应用价值。     

北京地区蒙特利尔认知量表的应用研究

目的研究蒙特利尔认知量表（MoCA）测试结果的分布特征,为制定适合我国国情的筛查分界值标准提供科学的依据。方法通过随机抽样,以北京市≥50岁215例正常人群和66例轻度认知功能障碍（MCI）人群为样本。总结其MoCA测试结果的百分位数值和均值的年龄、性别和受教育程度分布,比较MoCA和简易精神状态量表（MMSE）检测MCI的效度。按MoCA和MMSE建立多元线性回归方程,分析影响测试结果的因素。结果MoCA的分界值≥26分,年龄和受教育程度诸因素均对MoCA得分有显著影响（P〈0．001）。检测MCI的敏感度MoCA为92．4％,显著优于MMSE的24．2％。结论MoCA用于筛查MCI病例优于MMSE。调整的分界值标准有助于早期发现MCI和痴呆病人,减少漏诊。MoCA得分是判断认知功能是否正常的非特异性指标,不能取代临床诊断。     

Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73–0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66–0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55–0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00–2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72–1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68–1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86–2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70–1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.     

p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case‐control study

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case‐control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real‐time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85–1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02–2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92–1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15–2.74) for EC overall. In never‐smokers and ever‐smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37–0.95) and 1.39 (95% CI = 1.00–1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case‐control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.     

Validation of the Finnish ISAAC questionnaire on asthma against anti-asthmatic medication reimbursement database in 5-year-old children

Background: Valid identification of childhood asthma at the population level for epidemiological purposes remains a challenge. We aimed at validating the Finnish version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire based on parental‐reported childhood asthma. Materials and Methods: The ISAAC questionnaire has been validated against anti‐asthmatic medication reimbursement data of the Finnish Social Insurance Institution, being the gold standard, among 2236 5‐year‐old consecutively born children (1996–2004) carrying human leukocyte antigen (HLA)‐conferred susceptibility to type 1 diabetes. Two combined questionnaire questions (any wheezing symptom or use of asthma medication during the preceding 12 months plus ever asthma; any wheezing symptom or use of asthma medication during the preceding 12 months plus ever doctor‐diagnosed asthma) were validated against valid reimbursement with purchase of at least one anti‐asthmatic medication during a 12‐month period. The validity of the questionnaire was estimated as the sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index. Results: The sensitivity 0.98 [95% confidence interval (CI) = 0.92–0.99]; specificity 0.98 (95% CI = 0.97–0.98); negative predictive value 1.00 (95% CI = 1.00–1.00); and Youden's index 0.96 (95% CI = 0.96–0.96) were the same for each of the two sets of combined questions. The positive predictive value for the first combined question was 0.63 (95% CI = 0.55–0.71), while it was 0.64 (95% CI = 0.57–0.72) for the second combined question. Conclusion: The Finnish ISAAC questionnaire was highly valid and is an acceptable instrument for the survey of the prevalence of parental‐reported childhood asthma for epidemiological purposes. Please cite this paper as: Nwaru BI, Lumia M, Kaila M, Luukkainen P, Tapanainen H, Erkkola M, Ahonen S, Pekkanen J, Klaukka T, Veijola R, Simell O, Knip M and Virtanen SM. Validation of the Finnish ISAAC questionnaire on asthma against anti‐asthmatic medication reimbursement database in 5‐year‐old children. Clin Respir J 2011; 5: 211–218.     

Heart failure with mid‐range ejection fraction in CHARM: characteristics,outcomes and effect of candesartan across the entire ejection fraction spectrum

Aims

We tested the hypothesis that candesartan improves outcomes in heart failure (HF) with mid‐range ejection fraction [HFmrEF; ejection fraction (EF) 40–49%].

Methods and results

In 7598 patients enrolled in the CHARM Programme (HF across the spectrum of EF), we assessed characteristics, outcomes and treatment effect of candesartan according to EF. Patients with HFmrEF (n = 1322, 17%) were similar to those with HF with reduced EF (HFrEF; n = 4323, 57%) with respect to some characteristics, and intermediate between HFrEF and HF with preserved EF (HFpEF; n = 1953, 26%) with respect to others. Over a mean follow‐up of 2.9 years, the incidence rates for the primary outcome of cardiovascular death or HF hospitalization were 15.9, 8.5 and 8.9 per 100 patient‐years in HFrEF, HFmrEF and HFpEF. In adjusted analyses, the rates of the primary outcome declined with increasing EF up to 50%. For treatment effect, the incidence rates for the primary outcome for candesartan vs. placebo were 14.4 vs. 17.5 per 100 patient‐years in HFrEF [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75–0.91; P < 0.001], 7.4 vs. 9.7 per 100 patient‐years in HFmrEF (HR 0.76, 95% CI 0.61–0.96; P = 0.02), and 8.6 vs. 9.1 per 100 patient‐years in HFpEF (HR 0.95, 95% CI 0.79–1.14; P = 0.57). For recurrent HF hospitalization, the incidence rate ratios were 0.68 in HFrEF (95% CI 0.58–0.80; P < 0.001), 0.48 in HFmrEF (95% CI 0.33–0.70; P < 0.001), and 0.78 in HFpEF (95% CI 0.59–1.03; P = 0.08). With EF as a continuous spline variable, candesartan significantly reduced the primary outcome until EF well over 50% and recurrent HF hospitalizations until EF well over 60%.

Conclusion

Candesartan improved outcomes in HFmrEF to a similar degree as in HFrEF. ClinicalTrials.gov : CHARM Alternative NCT00634400, CHARM Added NCT00634309, CHARM Preserved NCT00634712     

Reduced intensity conditioned allograft yields favorable survival for older adults with B‐cell acute lymphoblastic leukemia

Older adults with B‐cell acute lymphoblastic leukemia (B‐ALL) have poor survival. We examined the effectiveness of reduced intensity conditioning (RIC) hematopoietic cell transplant (HCT) in adults with B‐ALL age 55 years and older and explored prognostic factors associated with long‐term outcomes. Using CIBMTR registry data, we evaluated 273 patients (median age 61, range 55–72) with B‐ALL with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure (PIF)/Relapse (11%), who underwent RIC HCT between 2001 and 2012 using mostly unrelated donor (59%) or HLA‐matched sibling (32%). Among patients with available cytogenetic data, the Philadelphia chromosome (Ph+) was present in 50%. The 3‐year cumulative incidences of nonrelapse mortality (NRM) and relapse were 25% (95% confidence intervals (CI): 20–31%) and 47% (95% CI: 41–53%), respectively. Three‐year overall survival (OS) was 38% (95% CI: 33–44%). Relapse remained the leading cause of death accounting for 49% of all deaths. In univariate analysis, 3 year risk of NRM was significantly higher with reduced Karnofsky performance status (KPS <90: 34% (95% CI: 25–43%) versus KPS ≥90 (18%; 95% CI: 12–24%, P = 0.006). Mortality was increased in older adults (66+ vs. 55–60: Relative Risk [RR] 1.51 95% CI: 1.00–2.29, P = 0.05) and those with advanced disease (RR 2.13; 95% CI: 1.36–3.34, P = 0.001). Survival of patients in CR1 yields 45% (95% CI: 38–52%) at 3 years and no relapse occurred after 2 years. We report promising OS and acceptable NRM using RIC HCT in older patients with B‐ALL. Disease status in CR1 and good performance status are associated with improved outcomes. Am. J. Hematol. 92:42–49, 2017. © 2016 Wiley Periodicals, Inc.     

蒙特利尔认知评估量表用于轻度认知功能障碍患者评估的初步研究

目的探讨中文版蒙特利尔认知评估量表(Montreal cognitive assessment scale,MoCA)用于轻度认知功能障碍(mild cognitive impairment,MCI)评估的可行性。方法选择MCI患者128例(MCI组),另选同期健康体检者101例(对照组)。分别给予MoCA和简易智能状态检查量表(MMSE)评估,并分析评估结果。结果对照组和MCI组MoCA总分与MMSE总分呈正相关(r=0.352,P<0.05;r=0.765,P<0.01);MoCA评分明显低于MMSE评分(P<0.01)。与对照组比较,MCI组MoCA总分及各亚项得分明显降低(P<0.01)。MoCA筛查MCI敏感性为97.66%,特异性为95.05%,MMSE筛查MCI敏感性为32.03%,特异性为100%。结论 MCI患者及健康体检人群MoCA总分与MMSE总分相关;MoCA用于MCI筛查时敏感性优于MMSE。     

Sleep-disordered breathing and cognition in older women

OBJECTIVES: To investigate the association between objectively measured sleep‐disordered breathing (SDB) and cognitive impairment in community‐dwelling older women and to determine whether the apolipoprotein E (APOE) ?4 allele modifies this association. DESIGN: Cross‐sectional. SETTING: Participants' homes and two sites of the Study of Osteoporotic Fractures (SOF). PARTICIPANTS: Four hundred forty‐eight women with a mean age±standard deviation (SD) of 82.8±3.4. MEASUREMENTS: Participants completed the Mini‐Mental State Examination (MMSE), Trail Making Test Part B (Trails B), and polysomnography (PSG). SDB indices were the apnea–hypopnea index (AHI), the central apnea index (CAI), and oxygen saturation (SaO₂) nadir less than 80%. APOE ?4 was determined for a subset of 242 women. Cognitive impairment was defined as 1.5 SDs or more from the sample mean on either cognitive test (MMSE or Trails B). RESULTS: All SDB indices were associated with cognitive impairment according to the MMSE (AHI (per SD, odds ratio (OR)=1.4, 95% confidence interval (CI)=1.03–1.9), AHI of ≥30 (OR=3.4, 95% CI=1.4–8.1), SaO₂ nadir <80% (OR=2.7, 95% CI=1.1–6.6), and CAI (per SD, OR=1.4, 95% CI=1.1–1.7)). Weaker, nonsignificant associations emerged between SDB and Trails B. In women who completed genotyping, each SD increase in AHI was associated with 70% greater odds of cognitive impairment according to the MMSE (OR=1.7, 95% CI=1.2–2.6). Women with the ?4 allele had a nearly five times greater odds of impairment (per SD, OR=4.6, 95% CI‐1.0–20.7); the association was smaller and nonsignificant in women without the ?4 allele (per SD, OR=1.5, 95% CI‐0.9–2.4; P for interaction=.08). CONCLUSION: SDB is an important risk factor for cognitive impairment in older women, especially those with the APOE ?4 allele. Mechanisms linking these disorders need to be identified.     

蒙特利尔认知评估量表在帕金森病认知功能损害筛查中的应用

目的探讨蒙特利尔认知评估量表(MoCA)和简易智能状态检查量表(MMSE)在帕金森病(PD)患者认知功能损害筛查中的应用。方法选取1 29例年龄≥60岁的PD患者,根据认知功能将其分为正常组(60例)、轻度认知功能障碍(MCI,37例)组和PD痴呆(PDD,32例)组,采用MoCA和MMSE对患者进行评估和分析。结果 3组MoCA得分差异有统计学意义(P<0.01)。与正常组比较,MCI组和PDD组患者在画立方体、复述、1 mm动物数、抽象能力、延迟回忆得分较低(P<0.01);与PDD组比较,正常组和MCI组患者在命名、数字广度和定向力得分较高(P<0.05)。此外,受试者ROC曲线结果显示,MMSE诊断MCI的曲线下面积为0.803;MoCA诊断MCI的曲线下面积为0.947。MMSE诊断PDD的曲线下面积为0.952;MoCA诊断PDD的曲线下面积为0.990。结论 MoCA可作为有效的PD患者认知功能损害的筛查工具,且随着PD患者病情的进展,MoCA得分逐渐降低。MoCA筛查MCI的最佳界值为≤23分,且MoCA在筛查PD患者MCI方面的敏感性较MMSE高。     

Prospective study of alcohol consumption in the United States: quantity, frequency, and cause-specific mortality

Background: Alcohol average volume (quantity multiplied by frequency) has been associated with mortality in drinkers. However, average volume may mask associations due to quantity or frequency alone. Methods: We prospectively assessed relationships between alcohol quantity and frequency, and mortality from all‐causes, cardiovascular disease, cancer, and other‐causes in a cohort created by linking the 1988 National Health Interview Survey (response rate 87%) to the National Death Index through 2002. Participants were 20,765 current drinkers age ≥ 18 years. At 14‐year follow‐up 2,547 had died. Results: For quantity, among men who consumed ≥5 drinks (compared to 1 drink) on drinking days, adjusted relative risks (RR) of mortality were: for cardiovascular disease, 1.30 [95% confidence interval (CI) 0.96–1.75; p for linear trend (p‐trend) = 0.0295], for cancer, 1.53 (95% CI 1.11–2.09; p‐trend = 0.0026), and for other‐causes, 1.42 (95% CI 1.08–1.87; p‐trend = 0.0029); among women for other‐causes, 2.88 (95% CI 1.61–5.12; p‐trend = 0.0010). For frequency, among men in the highest frequency quartile (compared to the lowest), RR were: for cardiovascular disease, 0.79 (95% CI 0.63–0.99; p‐trend = 0.0330), for cancer, 1.23 (95% CI 0.95–1.59; p‐trend = 0.0461), and for other‐causes, 1.30 (95% CI 1.01–1.67; p‐trend = 0.0070); among women, for cancer, 1.65 (95% CI 1.12–2.45, p‐trend = 0.0031). Average volume obscured effects of quantity alone and frequency alone, particularly for cardiovascular disease in men where quantity and frequency trended in opposite directions. Conclusions: Alcohol quantity and frequency were independently associated with cause‐specific mortality. Accumulating evidence of their differential effects may, in the future, be useful for clinical and public health recommendations.     

Monocytic and promyelocytic myeloid‐derived suppressor cells may contribute to G‐CSF‐induced immune tolerance in haplo‐identical allogeneic hematopoietic stem cell transplantation

We investigated the effects of granulocyte colony‐stimulating factor (G‐CSF) on monocytic (M), promyelocytic (P), and granulocytic (G) myeloid‐derived suppressor cells (MDSCs) both in bone marrow and peripheral blood of 20 healthy donors and the association of MDSCs subgroups with acute and chronic graft‐versus‐host disease (aGvHD/cGvHD) in 62 patients who underwent haplo‐identical allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Patients who received a higher absolute counts of M‐MDSCs or P‐MDSCs exhibited lower incidence of grade II–IV aGvHD (P = 0.001; P = 0.031) and extensive cGvHD (P = 0.011; P = 0.021). In the multivariate analysis, absolute counts of MDSCs in allografts emerged as independent factors that reduced the occurrence of grade II–IV aGvHD (M‐MDSCs: HR = 0.087, 95% CI = 0.020–0.381, P = 0.001; P‐MDSCs: HR = 0.357, 95% CI = 0.139–0.922, P = 0.033) and extensive cGvHD (M‐MDSCs: HR = 0.196, 95% CI = 0.043–0.894, P = 0.035; P‐MDSCs: HR = 0.257, 95% CI = 0.070–0.942, P = 0.04). Delayed M‐MDSC reconstitution was associated with aGvHD onset. The 3‐year cumulative incidence of transplant related mortality and relapse, 3‐year probability of disease‐free survival, and overall survival did not differ significantly between these subgroups. Our results suggested that G‐CSF‐induced immune tolerance may be mediated by M/P‐MDSCs in allo‐HSCT. Am. J. Hematol. 90:E9–E16, 2015. © 2014 Wiley Periodicals, Inc.     

Glucosylsphingosine is a key biomarker of Gaucher disease

Gaucher disease (GD) involves the accumulation of glucosylceramide (GL1) and its deacylated lysolipid, glucosylsphingosine (lyso‐GL1) which is implicated in mediating immune dysregulation and skeletal disease. The aim of our study was to assess plasma Lyso‐GL1 as a biomarker of GD and its response to therapy. Plasma lyso‐GL1 in 169 patients with GD type 1 (GD1) was measured by LC‐MS/MS. Significant predictors of plasma LGL1 were assessed by Pearson's correlation coefficient, Wilcoxon Mann Whitney test and multiple linear regression. Propensity scores were used to match patients on treatment mode: Enzyme Replacement Therapy (ERT) vs. Eliglustat Tartrate SRT (ELI‐SRT). Plasma Lyso‐GL1 levels in healthy controls averaged 1.5 ng/ml (1.3–1.7; 95% CI). In untreated GD patients, the levels were massively elevated (180.9 ng/ml: 95% CI, 145.4–216.5) and imiglucerase ERT resulted in marked reduction (89 ng/ml: 95% CI, 69.2–129.4) (P < 0.001). Lyso‐GL1 correlated with chitotriosidase (r = 0.59 P < 0.001), CCL18 (r = 0.62 P <0.001), hepatomegaly (r = 0.28 P < 0.001), splenomegaly (r = 0.27 P = 0.003), splenectomy (P = 0.01) and treatment mode (P < 0.001). By multiple linear regression, the strongest predictors of lyso‐GL1 were age (P < 0.001), splenectomy (P = 0.02), Chitotriosidase (P < 0.001) and CCL18 levels (P = 0.001). After propensity score matching to obtain comparable groups of patients on ERT vs ELI‐SRT, lyso‐GL1 levels were lower among patients receiving ELI‐SRT by 113 ng/ml (95% CI: 136–90.3 ng/ml P < 0.001). Plasma lyso‐GL1 is a key biomarker of GD. ERT reduced lyso‐GL1 levels. By propensity scoring, ELI‐SRT resulted in greater reduction of lyso‐GL1 than ERT. Am. J. Hematol. 91:1082–1089, 2016. © 2016 Wiley Periodicals, Inc.     

Comparison of exergames versus conventional exercises on the cognitive skills of older adults: a systematic review with meta-analysis

PurposeTo compare the effects of exergames versus conventional physical training on the cognitive skills of older adults.Materials and MethodsScientific studies published in PubMed, Web of Science, and Cochrane Library databases were searched. Individual studies were assessed using the Cochrane Risk-of-bias tool for randomized trials (RoB 2). The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE Pro). The cognitive outcomes were Trail Making Test (TMT)-A, TMT-B, Stroop Word-Color test, Mini Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA).ResultsWe identified 256 studies, in which 13 studies were included in the systematic review and 11 in the meta-analysis. The majority of the exergame interventions were based on the Xbox 360′s Kinect, followed by the Impact Dance Platform, Nintendo Wii, and the Bike Labyrinth. We observed heterogeneity in the conventional exercise group and in the duration of training, which ranged from 12 to 52 sessions. There was no statistically significant difference between groups in TMT-A (p=0.083), TMT-B (p=0.122), and Stroop (p=0.191). There were differences in favor of exergames in MMSE (raw mean difference=-1.58, 95% CI: -2.87 to -0.28, p<0.001) and MoCA (raw mean difference=-1.22, 95% CI: -2.24 to -0.20, p=0.019).ConclusionsDespite statistical differences in MMSE and MoCA, these results should be interpreted with caution due to methodological heterogeneity. Some studies reported possible neurophysiological benefits induced by exergames, which should be explored in future investigations.