Long-term prognosis of diabetic patients with acute myocardial infarction in the era of acute revascularization

Abstract Background The long-term prognosis of diabetic patients with acute myocardial infarction (AMI) treated by acute revascularization is uncertain, and the optimal pharmacotherapy for such cases has not been fully evaluated. Methods To elucidate the long-term prognosis and prognostic factors in diabetic patients with AMI, a prospective, cohort study involving 3021 consecutive AMI patients was conducted. All patients discharged alive from hospital were followed to monitor their prognosis every year. The primary endpoint of the study was all-cause mortality, and the secondary endpoint was the occurrence of major cardiovascular events. To elucidate the effect of various factors on the long-term prognosis of AMI patients with diabetes, the patients were divided into two groups matched by propensity scores and analyzed retrospectively. Results Diabetes was diagnosed in 1102 patients (36.5%). During the index hospitalization, coronary angioplasty and coronary thrombolysis were performed in 58.1% and 16.3% of patients, respectively. In-hospital mortality of diabetic patients with AMI was comparable to that of non-diabetic AMI patients (9.2% and 9.3%, respectively). In total, 2736 patients (90.6%) were discharged alive and followed for a median of 4.2 years (follow-up rate, 96.0%). The long-term survival rate was worse in the diabetic group than in the non-diabetic group, but not significantly different (hazard ratio, 1.20 [0.97-1.49], p = 0.09). On the other hand, AMI patients with diabetes showed a significantly higher incidence of cardiovascular events than the non-diabetic group (1.40 [1.20-1.64], p Conclusions Although diabetic patients with AMI have more frequent adverse events than non-diabetic patients with AMI, the present results suggest that acute revascularization and standard therapy with aspirin and RAS inhibitors may improve their prognosis.</p

Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle

The concept of the plasticity or transdifferentiation of adult stem cells has been challenged by the phenomenon of cell fusion. In this work, we examined whether neonatal cardiomyocytes fuse with various somatic cells including endothelial cells, cardiac fibroblasts, bone marrow cells, and endothelial progenitor cells spontaneously in vitro. When cardiomyocytes were cocultured with endothelial cells or cardiac fibroblasts, they fused and showed phenotypes of cardiomyocytes. Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes. Transplanted endothelial cells or skeletal muscle–derived cells fused with adult cardiomyocytes in vivo. In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins. These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes

Efficient RT-QuIC seeding activity for \u3b1-synuclein in olfactory mucosa samples of patients with Parkinson's disease and multiple system atrophy

Background: Parkinson's disease (PD) is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms. PD is characterized by intraneuronal accumulation of abnormal \u3b1-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of either \u3b1-synuclein, as in the case of Multiple System Atrophy (MSA) or tau, as in the case of Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), in other disease-specific brain regions. Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization of \u3b1-synuclein or tau aggregates in the brain. Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues, including receptor neurons of the olfactory mucosa (OM). Methods: We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion (RT-QuIC) assay for OM analysis. In particular, by using human recombinant \u3b1-synuclein as substrate of reaction, we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induce \u3b1-synuclein aggregation, and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP. Results: Our results showed that a significant percentage of MSA and PD samples induced \u3b1-synuclein aggregation with high efficiency, but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect. Notably, the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination. Conclusions: Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities for \u3b1-synuclein. Additional studies are required for (i) estimating sensitivity and specificity of the technique and for (ii) evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms. RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases, especially in the early stages

Excessive daytime sleepiness is associated with an increased frequency of falls and sarcopenia

Background: This cross-sectional study aimed to examine associations between excessive daytime sleepiness (EDS) with falls and falls related conditions in older adults. Methods: To assess EDS, the Epworth Sleepiness Scale was used, with a score of ≥11/24 points indicating EDS. Number of falls and fall history (at least one) in the last year were recorded. Timed Up and Go test (TUG) was used to assess fall risk. Sarcopenia was defined by SARC-F tool. A grip strength score of the dominant hand, measured with a hand-grip dynamometer, less than 16 kg in females and 27 kg in males was accepted as dynapenia. Frailty status was defined by five dimensions including shrinking, exhaustion, low levels of activity, weakness, and slowness with those scoring positive on ≥3 dimensions being categorized as frail. The relationship between EDS with outcomes including fall, number of falls, falls risk, dynapenia, sarcopenia and frailty was investigated. Results: Of the 575 outpatients (mean age 78.7 ± 7.5 years, female:70.4%), the prevalence of EDS was 19.8%. In the multivariable model adjusted for age, sex, living status, marital status, polypharmacy, osteoarthritis, Parkinson disease, depression and dementia; EDS was significantly associated with the number of falls last year (IRR = 1.94, 95% CI: 1.42–2.65) and sarcopenia (OR = 2.41, 95% CI: 1.41–4.12). EDS was not significantly associated with TUG based fall risk, frailty and dynapenia. Conclusions: EDS was observed in approximately one in every five older adults. EDS should be evaluated as part of geriatric assessment. Moreover, older patients with EDS should be further assessed for falls and sarcopenia

Mutation analysis in Bardet-Biedl syndrome by DNA pooling and massively parallel resequencing in 105 individuals

Bardet–Biedl syndrome (BBS) is a rare, primarily autosomal-recessive ciliopathy. The phenotype of this pleiotropic disease includes retinitis pigmentosa, postaxial polydactyly, truncal obesity, learning disabilities, hypogonadism and renal anomalies, among others. To date, mutations in 15 genes (BBS1–BBS14, SDCCAG8) have been described to cause BBS. The broad genetic locus heterogeneity renders mutation screening time-consuming and expensive. We applied a strategy of DNA pooling and subsequent massively parallel resequencing (MPR) to screen individuals affected with BBS from 105 families for mutations in 12 known BBS genes. DNA was pooled in 5 pools of 21 individuals each. All 132 coding exons of BBS1–BBS12 were amplified by conventional PCR. Subsequent MPR was performed on an Illumina Genome Analyzer II(™) platform. Following mutation identification, the mutation carrier was assigned by CEL I endonuclease heteroduplex screening and confirmed by Sanger sequencing. In 29 out of 105 individuals (28%), both mutated alleles were identified in 10 different BBS genes. A total of 35 different disease-causing mutations were confirmed, of which 18 mutations were novel. In 12 additional families, a total of 12 different single heterozygous changes of uncertain pathogenicity were found. Thus, DNA pooling combined with MPR offers a valuable strategy for mutation analysis of large patient cohorts, especially in genetically heterogeneous diseases such as BBS

経皮的旧バルーン動脈形成術後の再狭窄に関する5HT_2A受容体拮抗薬(塩酸サルポグレラート)の有用性

〔背景〕セロトニン受容体,特に5HT_2受容体は血管収縮および血小板凝集に大いに関与し,また,経皮的冠動脈形成術(PTCA)後の血管内皮機能障害の進行にも影響を及ぼしている. 〔目的〕5HT_2A受容体拮抗薬(塩酸サルポグレラート)が経皮的旧バルーン動脈形成術(POBA)後の再狭窄率の減少に有用であるか否かアスピリンと対比し検討する.〔方法〕1996年3月より1997年6月までに急性冠症候群の診断で入院となりPOBAを施行した56例(男性45例,女性11例;平均年齢63歳)について検討した. 56例中無作為に抽出した26例に対し5HT_2A受容体拮抗薬150mg(分3)を投与し,残りの30例に対してはアスピリン81mg(分1)を投与した.また,QCA法により計測し6ヵ月後(follow up時)の冠動脈造影上で標的血管に50%以上の狭窄を認めた場合を再狭窄と定義した.〔結果〕56例すべてにおいてfollow upを行った. POBA前後での両群間における対照血管最小血管経(MLD)に有意差は認めなかった(5HT_2A群vsアスピリン群:2.67±0.53mm vs 2.79±0.56mm; p=0.42). POBA後6ヵ月後(follow up時)のMLDは5HT_2A群の方がアスピリン群より有意に大きい結果であった(5HT_2A群vsアスピリン群: 1.64±0.69mm vs 1.06±0.91mm; p=0.03).再狭窄率は5HT_2A群7/26(27%),アスピリン群13/30(43%)であった.また, 5HT_2A群において,診断造影上右冠動脈に有意狭窄を認めた症例でPOBA後の再狭窄が少ない傾向を認めた.全経過中に明らかな合併症は認めなかった.〔結語〕5HT_2A受容体拮抗薬(塩酸サルポグレラート)はPOBA後の再狭窄率の減少に有用かつ明らかな合併症を認めない安全な薬剤であり,診断造影上右冠動脈に有意狭窄を認めた症例においては特に有用な薬剤であると思われる.Background: Serotonin receptors, especially 5HT_2 receptors, are important in vasoconstriction and platelet aggregation and are involved in the chronic progression of endothelial dysfunction after percutaneous transluminal coronary angioplasty (PTCA). Objective: To determine whether the 5HT_2A receptor antagonist, sarpogrelate hydrochloride, was more effective than aspirin in reducing the rate of restenosis after percutaneous old balloon angioplasty (POBA). Methods: Between March 1996 and June 1997, 45 men and 11 women (average age of 63 years) underwent POBA for acute coronary syndromes. Of these, 26 received the 5HT_2A receptor antagonist 50 mg three times a day and 30 received aspirin 81 mg daily in a randomized, open trial. Restenosis was defined as a narrowing of the target vessel of at least 50% at follow-up, as measured by quantitative coronary angiography (QCA). Results: The angiographic follow-up rate was 100%. The reference minimal lumen diameter (MLD) before and after POBA did not differ significantly between the two groups (post MLD: 2.67 (0.53) in the 5HT_2A group and 2.79 (0.56) in the aspirin group; p=0.42). The mean (SD) MLD at 6 months was significantly larger in the 5HT_2A group than in the aspirin group (1.64 (0.69) mm vs 1.06 (0.91) mm; p =0.03). Angiographically identified restenosis occurred in 7/26 (27%) of the patients in the 5HT_2A group and in 13/30 (43%) of those in the aspirin group. In the 5HT_2A group, restenosis rate was likely to be less frequent in patients with right coronary artery (RCA) stenosis on the initial diagnostic angiogram (p=0.040). No complications were observed during the follow-up period. Conclusions: The 5HT_2A receptor antagonist, sarpogrelate hydrochloride, reduced the rate of restenosis after POBA, especially in patients with RCA stenosis on the initial diagnostic angiogram. No adverse events were reported in this series