Comparison of the antianginal efficacy of isosorbide dinitrate (ISDN) 40 mg and verapamil 120 mg three times daily in the acute trial and following two-week treatment

Fourteen male patients with exertion-related angina pectorisand reproducible ST-segment depression on stress testing wereeach treated with isosorbide dinitrate (ISDN) 40 mg three timesdaily, verapamil 120 mg three times daily and placebo threetimes daily for two weeks according to a double-blind cross-overprotocol. The mean improvement of exercise-induced ST-segment depressionamounted to 73% on the first day of ISDN treatment (P < 0.001)and to 54% following acute administration of verapamil (P <0.001). On the last day of continuous treatment, the antianginalefficacy of ISDN was somewhat mitigated (reduction of ST-segmentdepression: 54%; P<0.001), while the effect of verapamilremained unchanged (55%, P<0.001). The double product (heartrate x systolic blood pressure) at the end of stress testingdecreased most pronouncedly on day 1 of ISDN treatment ( - 21%;P<0.01). On chronic testing, both drugs similarly influencedthis parameter: 10–11% (P<0.05). The mean global ejectionfraction (EF) assessed by gated blood pool scintigraphy on day13 showed a stress-induced fall from 49 to 44% (P<0.05) afterthe administration of placebo. The respective values with ISDNwere 53% at rest and 52% on exercise (n.s.), and after givingverapamil 50% and47% (n.s.). Thus, ISDN 40 mg and verapamil 120 mg displayed beneficial anti-ischaemiceffects in patients with stable exertion-related angina pectorisafter acute and chronic administration. The efficacy of ISDNdeclined somewhat in the course of the two-week treatment, whereasthat of verapamil remained unchanged. Beneficial effects ofboth drugs were also demonstrated with regard to the rate pressureproduct. Isosorbide dinitrate 40 mg and verapamil 120 mg administeredthree times daily can be recommended for the acute and chronictherapy of patients with stable angina.     

Long-Term Follow-Up in Patients With Stable Angina and Unobstructed Coronary Arteries Undergoing Intracoronary Acetylcholine Testing

ObjectivesThe aim of this study was to investigate the prognosis of a large cohort of patients with stable angina and unobstructed coronaries undergoing acetylcholine spasm testing.BackgroundCoronary artery spasm can be found in up to 60% of patients with symptoms of myocardial ischemia despite unobstructed coronary arteries.MethodsConsecutive symptomatic patients with unobstructed coronary arteries undergoing acetylcholine testing to detect epicardial or microvascular coronary spasm were prospectively enrolled. After a median follow-up period of 7.2 years (6.5 to 7.9 years), data regarding mortality, nonfatal myocardial infarction, stroke, repeat coronary angiography, recurrent symptoms, and quality of life were obtained in 736 patients (57% women, mean age 62 ± 12 years).ResultsIn total, 55 deaths (7.5%), 8 nonfatal myocardial infarctions (1.4%), and 12 strokes (2.2%) occurred during the follow-up period. Recurrent symptoms were reported by 64% of patients, and repeat coronary angiography was performed in 12% of cases. Multivariate analysis revealed epicardial spasm as a predictor of nonfatal myocardial infarction (hazard ratio: 14.469; 95% confidence interval: 1.735 to 120.646) and repeat angiography (hazard ratio: 1.703; 95% confidence interval: 1.062 to 2.732), whereas patients with microvascular spasm more often had recurrent angina at follow-up (hazard ratio: 1.311; 95% confidence interval: 1.013 to 1.697).ConclusionsIn this long-term follow-up study, the overall prognosis of patients with coronary spasm was favorable. Patients with epicardial spasm were at increased risk for myocardial infarction and repeat angiography, while microvascular spasm was associated with recurrent angina. Acetylcholine testing may help identify patients at increased risk for adverse cardiac events among this overall low-risk population.     

Randomized Comparison Between Everolimus-Eluting Bioresorbable Scaffold and Metallic Stent: Multimodality Imaging Through 3 Years

ObjectivesThe aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging.BackgroundSerial comprehensive image assessments after BVS implantation in the context of a randomized trial have not yet been reported.MethodsIn the ABSORB Japan trial, 400 patients were randomized to a BVS (n = 266) or a cobalt-chromium everolimus-eluting stent (n = 134). Through 3 years, patients underwent serial angiography and intravascular ultrasound or optical coherence tomography (OCT).ResultsLuminal dimension at 3 years was consistently smaller with the BVS than with the cobalt-chromium everolimus-eluting stent (mean angiographic minimal luminal diameter 2.04 ± 0.63 mm vs. 2.40 ± 0.56 mm, mean difference −0.37 mm [95% confidence interval: −0.50 to −0.24 mm]; p < 0.001), mainly because of smaller device area (6.13 ± 2.03 mm² vs. 7.15 ± 2.16 mm², mean difference −1.04 mm² [95% confidence interval: −1.66 to −0.42 mm²]; p < 0.001), and larger neointimal area (2.10 ± 0.61 mm² vs. 1.86 ± 0.64 mm², mean difference 0.24 mm² [95% confidence interval: 0.06 to 0.43 mm²]; p = 0.01) by OCT. BVS-treated vessels did not show previously reported favorable vessel responses, such as positive vessel remodeling, late luminal enlargement, and restoration of vasomotion, although the OCT-based healing score was on average zero (interquartile range: 0.00 to 0.00). At 3 years, intraluminal scaffold dismantling (ISD) was observed in 14% of BVS. On serial OCT, ISD was observed in 6 lesions at 2 years, where the struts had been fully apposed at post-procedure, while ISD was observed in 12 lesions at 3 years, where 8 lesions were free from ISD on 2-year OCT. In 5 cases of very late scaffold thrombosis, strut discontinuities were detected in all 4 cases with available OCT immediately before reintervention.ConclusionsIn this multimodality serial imaging study, luminal dimension at 3 years was smaller with the BVS than with the cobalt-chromium everolimus-eluting stent. ISD, suspected to be one of the mechanisms of very late BVS thrombosis, was observed in a substantial proportion of cases at 3 years, which developed between post-procedure and 2 years and even beyond 2 years. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb™ BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284)     

Patients with unstable angina pectoris show an increased frequency of the Fc gamma RIIa R131 allele

Patients with Systemic Lupus Erythematosus (SLE) carry an increased risk for the development of coronary artery disease (CAD). The R131 allele of the Fc gamma receptor IIa (FcγRIIa) is associated with SLE incidence and disease severity but also with CAD. Compared to stable angina pectoris (SAP) the unstable angina (UAP), as a manifestation of destabilizing CAD, is associated with increased risk of persistent instability, myocardial infarction, and death. Identification of clinically relevant determinants for unstable angina promises reduction of UAP-associated mortality in patients with SLE. We conducted a clinical study among 553 consecutive patients with stable angina pectoris (n = 330) and unstable angina pectoris (n = 223). All patients were genotyped for a frequent functional variant at position 131 of the mature FcγRIIa. UAP, but not SAP was significantly associated with the R/R131 genotype (P < 0.001). In troponin-negative patients with angina carrying the R/R131 genotype the odds ratio for suffering from UAP was 4.02 (95% confidence interval, 2.52–6.41) compared to those with non-R/R131 genotypes. In a multivariable analysis, the R/R131 genotype independently predicted the risk for development of UAP in a model adjusted for classical atherogenic risk factors. Our data imply that risk stratification of SLE- and other high risk patients with troponin-negative angina could be significantly improved by FcγRIIa genotyping.     

Gene-disruption of the entomopathogenic fungus Beauveria bassiana incubated with dsRNA

The species of Beauveria bassiana is widely used for the management of agricultural insect pests. In this study, we integrated egfp-double-stranded RNA (dsRNA) to a previously generated egfp-expressing B. bassiana transformant (Bb-egfp#3) using a protoplast integration method. The Bb-egfp#3 protoplast was mixed with the dsRNA under PEG/CaCl₂ conditions and liquid-cultured in Sabouraud dextrose broth for 5 days. A control culture followed the same procedure without dsRNA. Bb-egfp#3/egfp-dsRNA cultures showed very low fungal growth (OD₆₃₀ = 0.2) compared to the control culture, Bb-egfp#3 only (OD₆₃₀ = 1.1). Screening of possible transformants on Sabouraud dextrose agar revealed a transformant T3, without egfp signal. T3 was confirmed as B. bassiana through sequencing of conserved genes and insect bioassays. Interestingly, the genomic egfp fragment of T3 was disrupted, and the egfp signal was not detected over four subcultures, which was also confirmed by RNA-seq of Bb-egfp#3 and T3. This study provides an interesting observation that protoplast integration with dsRNA could possibly generate significantly reduced gene expression in B. bassiana and it is stable across several generations.     

Needle tract seeding of papillary thyroid carcinoma after fine-needle capillary biopsy: A case report

BACKGROUNDFine-needle biopsy is an accurate and cost-efficient tool for the assessment of thyroid nodules. It includes two primary methods: Fine-needle capillary biopsy (FNCB) and fine-needle aspiration biopsy. Needle tract seeding (NTS) is a rare complication of thyroid fine-needle biopsy mainly caused by fine-needle aspiration biopsy rather than FNCB. Here, we present an extremely rare case of a papillary thyroid carcinoma (PTC) patient with FNCB-derived NTS. CASE SUMMARYWe report a 32-year-old woman with PTC who showed subcutaneous NTS 1 year after FNCB and thyroidectomy. NTS was diagnosed based on clinical manifestations, biochemistry indices, and imaging (computed tomography and ultrasound). Pathological identification of PTC metastases consistent with the puncture path is the gold standard for diagnosis. Surgical resection was the main method used to treat the disease. After surgery, thyroid function tests and ultrasound scans were performed every 3-6 mo. To date, no evidence of tumor recurrence has been observed.CONCLUSIONFNCB is a safe procedure as NTS is rare, and can be easily removed surgically with no recurrence. Accordingly, NTS should not limit the usefulness of FNCB.     

沉默热休克蛋白27基因对头颈部鳞状细胞癌细胞生物学行为的影响

目的 观察长效沉默热休克蛋白（Hsp）27基因后头颈部鳞状细胞癌细胞生物学行为的改变。方法 实验分为3组：高滴度pLenti-shRNA-Hsp27慢病毒颗粒长效转染入UM-SCC-22B细胞为实验组（shHsp27组）,常规培养UM-SCC-22B细胞（ctrl组）为空白对照,UM-SCC-22B细胞转染pLenti-shRNA-ctrl慢病毒颗粒（shctrl组）为阴性对照。采用实时荧光定量聚合酶链反应和蛋白质印迹法检测各组中Hsp27的表达,采用MTS细胞增殖实验、细胞划痕实验及Matrigel侵袭实验,观察各组Hsp27表达抑制后UM-SCC-22B细胞的增殖、迁移和侵袭能力的变化。结果 shHsp27组的Hsp27表达明显降低;MTS细胞增殖实验可见,细胞培养24、48 h后,shHsp27组的细胞增殖能力与ctrl组和shctrl组无明显差异;划痕实验表明,划痕产生72 h后,ctrl组细胞迁移能力为shHsp27组的4.38倍;Matrigel侵袭实验显示,ctrl组细胞的体外侵袭能力为shHsp27组的2.03倍。结论 长效转染慢病毒颗粒pLenti-shRNA-Hsp27能够高效、特异地沉默高转移潜能头颈部鳞状细胞癌细胞系UM-SCC-22B的Hsp27基因表达,并能显著抑制其体外侵袭和转移能力。     

植入药物洗脱支架后短期与长期双联抗血小板疗效比较的Meta分析

目的 评价短期（3～6个月）与长期（12个月）双联抗血小板治疗对冠状动脉药物洗脱支架植入后的临床效果。方法 研究病例包括稳定性心绞痛、急性冠脉综合征、无症状心肌缺血,均为原位血管病变。临床观察终点为：全因死亡、心源性死亡、心肌梗死、卒中、支架内血栓形成、靶病变再血管化治疗、严重出血、净不良临床事件（net adverse clinical event）。通过检索Pubmed、中国生物医学文献等中、英文数据库及手工检索,对符合条件的随机对照研究经质量评估、数据提取,进行Meta分析。结果 共计纳入12项随机对照研究。Detsky评分均大于5分。共计25 949个病例,随访率97.9%。两组在全因死亡（OR=0.86,95%CI 0.71～1.05,P=0.14）、心源性死亡（OR=0.94,95% CI 0.70～1.25,P=0.67）、支架血栓形成（OR=1.36,95%CI 0.94～1.98,P=0.11）、卒中（OR=1.01,95%CI 0.71～1.42,P=0.98）、靶病变再血管化（OR=0.121,95%CI 0.94～1.55,P=0.14）及净不良临床事件（OR=0.98,95%CI 0.83～1.14,P=0.75）均无明显差别;短期组随访期间心肌梗死发生率高于长期组（OR=1.27,95%CI 1.02～1.59,P=0.04）,长期组严重出血的比例明显增加（OR=0.69,95%CI 0.50～0.95,P=0.02）。亚洲人群研究结果：长期治疗组全因死亡高于短期组（OR=0.72,95%CI 0.53～0.97,P=0.03）,两组严重出血无明显差别。结论 依据限定的临床观察终点,短期双联抗血小板疗效不劣于长期组;7项亚组人群研究,长期组全因死亡率高,不排除与样本量偏少产生的偏移及（或）人群的个体差异有关,结果还有待进一步验证。此结果可作为临床工作警示,依据患者出血风险及冠状动脉病变结果个体化调整双联抗血小板周期。