MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma

Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "micro RNAs", "mi RNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis.

Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma:A systematic review

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus(HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis(PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews:(1) HCV and haematopoietic malignancies;(2) HCV and cholangiocarcinoma;(3) HCV and pancreatic cancer;(4) HCV and breast cancer;(5) HCV and kidney cancer;(6) HCV and skin or oral cancer; and(7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with:(1) a higher incidence of some B-cell Non-HodgkinLymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%;(2) an increased risk of intra-hepatic cholangiocarcinoma; and(3) a correlation between HCV prevalence and pancreatic cancer(PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are requiredto confirm or deny this association.

脊髓刺激对心脏X综合征患者自发性或应激诱发的心绞痛及“缺血样”ST段压低的影响

A significant number of patients with cardiac syndrome X(CSX) present frequent episodes of severe chest pain, refractory to maximal multi-drug therapy. A few, small, uncontrolled data suggested that spinal cord stimulation(SCS) may have favourable clinical benefits in these patients. Methods and results: We studied 10 CSX patients who were being treated by SCS for refractory angina pectoris for 17± 16 months(median 8). Patients were randomized to either continue or withdraw SCS for a period of 3 weeks and were then crossed over to the other condition for a further 3- week period. During each 3- week period patients kept a detailed diary of angina episodes occurring in the last 2 weeks of each phase. Furthermore, at the end of each 3- week period, angina status was also assessed by Seattle Angina Questionnaire(SAQ), a 0- 100 visual analogue scale(VAS), and patients underwent 24- h Holter monitoring(HM) and echocardiographic dobutamine stress test(DST). Compared with the withdrawal phase, SCS reduced the number(P=0.01), duration(P=0.022), and severity(P=0.011) of angina episodes, and nitrate consumption(P=0.042). SAQ scores(P≤ 0.013 for all) and VAS(P< 0.001) were also improved, the number of episodes of ST-segment depression on HM was decreased(P=0.014), and time to angina(P=0.045) and to 1 mm ST-segment depression(P=0.04) during DST were both prolonged by SCS. Conclusions: Our data point out that SCS may be an effective form of treatment in patients with CSX suffering from frequent angina episodes significantly impairing quality of life(QOL) and refractory to maximally tolerated drug therapy.

心脏X综合征患者的异常皮质疼痛过程

Previous studies suggested that an enhanced pain sensitivity is present in patients with cardiac syndrome X(SX). We investigated whether SX patients present abnormalities in the electrical cerebral signals generated by pain stimuli. Methods and results: Cortical laser evoked potentials(LEPs) were recorded in 16 SX patients, in 10 patients with refractory angina due to obstructive coronary artery disease(CAD) and in 13 healthy controls. LEPs were recorded during stimulation of chest and right hand dorsum. Three sequences of painful stimuli were applied at each site. Subjective pain rating was assessed by a 0- 100 mm visual analogic scale(VAS). Basal LEPs did not differ among groups and there were no differences for most LEP components across the repetitions of stimuli. However, the amplitude of the N2/P2 LEP component, specifically reflecting cortical pain processing, decreased across the three sequences of stimuli in controls and CAD patients, but not in SX patients. Compared with the first sequence, the N2/P2 amplitude during the third sequence of stimuli in the three groups was 77± 16, 56± 24, and 99± 34% , respectively, for chest(P=0.001), and 63± 31, 72± 17, and 98± 46% , respectively, for right hand(P=0.03) stimulation. The changes in VAS pain score across the three sequences paralleled those of N2/P2 amplitude. Conclusion: Our data show that in SX patients, central handling of painful stimuli is characterized by inadequate habituation, which might play a role in determining the peculiar clinical characteristics of anginal chest pain of these patients.

螺内酯可改善慢性心力衰竭患者的肺弥散功能

Aims: To evaluate whether anti- aldosteronic treatment influences lung diffusion(DLco) in chronic heart failure(HF) patients. Spironolactone improves clinical conditions and prognosis in chronic HF and reduces connective tissue matrix turnover; DLco abnormalities in chronic HF are related to increase in fibrosis and connective tissue derangement. Methods and results: Thirty stable chronic HF patients, with reduced DLco(< 80% of predicted), were randomly assigned to active treatment(25 mg spironolactone daily) or placebo in addition to conventional anti- failure treatment. They were evaluated by quality of life questionnaire, laboratory investigations, cardiopulmonary exercise test, and pulmonary function test, which included DLco and membrane diffusing capacity(DM). The evaluation was done before treatment and 6 months after. Quality of life score and standard pulmonary function tests were not significantly affected by spironolactone, while active treatment increased DLco due to an increase of DM(DLco: 18.3± 3.9 vs. 19.9± 5.5 mL/min/mmHg; DM: 28.1± 7.7 vs. 33.3± 8.6 mL/min/mmHg) and peak oxygen consumption(peak VO2 16.8± 1.9 vs. 18.6± 2.2mL/min/kg). Increments of DLco and peak VO2 were linearly related(R=0.849, P< 0.001). Conclusion: These data showa positive effect of spironolactone on gas diffusion and exercise capacity suggesting a novel mechanism by which anti- aldosteronic drugs improve HF clinical condition and prognosis.

冠状动脉成形术和搭桥术治疗无保护左冠状动脉主干狭窄的比较研究:Bologna注册研究

Although great interest exists in the relative efficacy of coronary artery bypass grafting(CABG) versus percutaneous coronary intervention(PCI) for the treatment of unprotected left main coronary artery stenosis, data comparing the 2 strategies are scant. Furthermore, no comparison has ever been performed between CABG and drug-eluting stents in this setting. From January 2002 to June 2005, 154 patients with unprotected left main coronary artery stenosis underwent CABG and 157 underwent PCI. Ninety-four patients received a drug-eluting stent in the left main artery. After a median follow-up of 430 days, the rate of mortality, acute myocardial infarction, and target lesion revascularization was 12.3%, 4.5%, and 2.6%, respectively, in the CABG group and 13.4%, 8.3%, and 25.5%, respectively, in the PCI group(death and myocardial infarction p=NS, target lesion revascularization p=0.0001). Although patients treated with drug-eluting stents had a 25%relative risk reduction in the rate of death, myocardial infarction, and target lesion revascularization compared with patients treated with bare stents, event-free survival was still better for patients treated with CABG. In the multivariate analysis, age ≥70 years, New York Heart Association classes III and IV, acute coronary syndromes, and peripheral vascular disease were the only independent predictors of mortality. In conclusion, our results have indicated that at long-term follow-up no difference exists in the rate of mortality and myocardial infarction between PCI and CABG for the treatment of unprotected left main coronary artery stenosis. However, the rate of target lesion revascularization was higher in the PCI group.

心脏再同步化治疗中的心电重构

Background: More information is required on the relationship between electrical and structural reverse remodeling in patients treated with cardiac resynchronization theraphy. Methods: QRS and JT intervals were investigated during different pacing modes before and 3 months after implantation of a device for biventricular(BiV) pacing in 20 patients with severe drug refractory heart failure(with left ventricular ejection fraction< 40% and QRS >120 ms); structural remodeling was evaluated by echocardiography. Results: QRS interval was significantly shortened by BiV pacing both acutely(p=0.002) and at 3 months(p=0.007). No significant change was found in the JT interval. The extent of QRS shortening obtained by BiV pacing showed moderate correlations with the reduction of end-systolic and end-diastolic volumes(r=0.53, p=0.016 and r=0.45, p=0.045, respectively) as well as with increase of left ventricular ejection fraction(r=0.49, p=0.028) at 3 months. The widening of QRS observed during right ventricular(RV)pacing was greater after 3 months of BiV pacing(with respect to acute assessments), suggesting accentuation of pacing-induced electrical dyssynchrony after a period of pacing-induced resynchronization. Conclusion: The extent of QRS shortening induced by BiV pacing appears to correlate with the reverse structural remodeling(in terms of reduction in end-systolic volume). The acute changes and the remodeling process occurring at mid-term in the overall population of CRT-treated patients do not appear to involve the JT interval. A period of pacing-induced resynchronization appears to accentuate the potential for RV pacing-driven electrical dyssynchrony.

不稳定型心绞痛患者中室性心律失常和心率变异性的预后价值

Objectives: To assess the prognostic value of ventricular arrhythmias(VA) and heart rate variability(HRV) in patients with unstable angina. Design: Multicentre prospective study. Setting: 17 cardiological centres in Italy. Patients: 543 consecutive patients with unstable angina and preserved left ventricular function(ejection fraction ≥40%) enrolled in the SPAI(Stratificazione Prognostica dell’Angina Instabile) study. Methods: Patients underwent 24 h ECG Holter monitoring within 24 h of hospital admission. Tested variables were frequent ventricular extrasystoles(≥10/h), complex(that is, frequent or repetitive) VA, and bottom quartile values of time-domain and frequency-domainHRV variables. Primary end points were inhospital and six-month total and cardiac deaths. Results: Eight patients died in hospital(1.5%) and 32(5.9%,29 cardiac) during follow up. Both complex VA and frequent extrasystoles were strongly predictive of death in hospital and at follow up, even after adjustment for clinical(age, sex, cardiac risk factors and history of myocardial infarction) and laboratory(troponin I, C reactive protein and transient myocardial ischaemia on Holter monitoring) variables. At univariate analysis bottom quartile values of three HRV variables(standard deviation of RR intervals index, low-frequency amplitude and low to high frequency ratio) were associated with in-hospital death, and bottom quartile values of most HRV variables predicted six-month fatal events. At multivariate Cox survival analysis reduced low-frequency amplitude was consistently found to be independently associated with fatal end points. Conclusion: In patients with unstable angina with preserved myocardial function, both VA and HRV are independent predictors of in-hospital and mediumterm mortality, suggesting that these factors should be taken into account in the risk stratification of these patients.

左主干和隐静脉移植物痉挛:一种罕见的相关病例

We present a case of leftmain spasm which was associated with spasm of a saphenous vein graft. This case emphasizes the importance of excluding an excessive vasoconstrictory response in patients treated with percutaneous coronary interventions.