Circulating tumor DNA profiling reveals clonal evolution and real-time disease progression in advanced hepatocellular carcinoma.

Circulating tumor DNA (ctDNA) provides a potential non-invasive biomarker for cancer diagnosis and prognosis, but whether it could reflect tumor heterogeneity and monitor therapeutic responses in hepatocellular carcinoma (HCC) is unclear. Focusing on 574 cancer genes known to harbor actionable mutations, we identified the mutation repertoire of HCC tissues, and monitored the corresponding ctDNA features in blood samples to evaluate its clinical significance. Analysis of 3 HCC patients' mutation profiles revealed that ctDNA could overcome tumor heterogeneity and provide information of tumor burden and prognosis. Further analysis was conducted on the 4th HCC case with multiple lesion samples and sequential plasma samples. We identified 160 subclonal SNVs in tumor tissues as well as matched peritumor tissues with PBMC as control. 96.9% of this patient's tissue mutations could be also detected in plasma samples. These subclonal SNVs were grouped into 9 clusters according to their trends of cellular prevalence shift in tumor tissues. Two clusters constituted of tumor stem somatic mutations showed circulating levels relating with cancer progression. Analysis of tumor somatic mutations revealed that circulating level of such tumor stem somatic mutations could reflect tumor burden and even predict prognosis earlier than traditional strategies. Furthermore, HCK (p.V174M), identified as a recurrent/metastatic related mutation site, could promote migration and invasion of HCC cells. Taken together, study of mutation profiles in biopsy and plasma samples in HCC patients showed that ctDNA could overcome tumor heterogeneity and real-time track the therapeutic responses in the longitudinal monitoring.

Interactions of Bovine Serum Albumin with Anti-Cancer Compounds Using a ProteOn XPR36 Array Biosensor and Molecular Docking.

The aim of the work was to determine the interactions of a set of anti-cancer compounds with bovine serum albumin (BSA) using a ProteOn XPR36 array biosensor and molecular docking studies. The results revealed that a total of six anti-cancer compounds: gallic acid, doxorubicin, acteoside, salvianolic acid B, echinacoside, and vincristine were able to reversibly bind to the immobilized BSA. The sensorgrams of these six compounds were globally fit to a Langmuir 1:1 interaction model for binding kinetics analysis. There were significant differences in their affinity for BSA, with doxorubicin, the weakest binding compound having 1000-fold less affinity than salvianolic acid B, the strongest binding compound. However, compounds with a similar KD often exhibited markedly different kinetics due to the differences in ka and kd. Molecular docking experiments demonstrated that acteoside was partially located within sub-domain IIA of BSA, whereas gallic acid bound to BSA deep within its sub-domain IIIA. In addition, the interactions between these compounds and BSA were dominated by hydrophobic forces and hydrogen bonds. Understanding the detailed information of these anti-cancer compounds can provide important insights into optimizing the interactions and activity of potential compounds during drug development.

Successful percutaneous coronary intervention for acute and chronic occlusion of the left main coronary artery: report of two cases and review of the literature.

Total occlusion of the left main coronary artery (LMCA) is a rare but clinically serious event due to its poor prognosis. While coronary artery bypass grafting (CABG) is currently recommended for treatment of these patients, recent studies support the feasibility of treatment by percutaneous intervention (PCI). Here, we report the diagnoses and treatment of two cases of total occlusion of the LMCA. One patient presented with acute myocardial infarction complicated by cardiogenic shock resulting from acute occlusion of the LMCA, and the other patient presented with unstable angina pectoris resulting from chronic occlusion of the LMCA. Both cases were successfully treated with PCI. Our results in these cases suggest that PCI may be a safe and effective alternative to CABG for treatment of LMCA occlusion.

Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: A retrospective study.

Acute fulminant myocarditis (AFM) is a serious heart disease with limited treatment. This observational retrospective study aimed to investigate whether intravenous immunoglobulin (IVIG) was able to improve left ventricular function and reduce the episodes of arrhythmia in adult patients with AFM. The medical records of all patients with AFM who were admitted to the Critical Care Unit of Guangdong General Hospital (Guangzhou, China) between January 2001 and December 2010 were reviewed. A cohort of 58 patients was included in the study. Of these 58, 32 patients were treated with IVIG (400 mg/kg per day) for five days, while the remaining patients did not receive IVIG therapy. The patients who received IVIG therapy had a higher left ventricular ejection fraction (LVEF) and a reduced left ventricular end-diastolic diameter (LVDD) compared with the non-IVIG therapy patients four weeks subsequent to the treatment (PLVEF=0.011 and PLVDD=0.048). The post-treatment incidence of ventricular tachycardia/ventricular fibrillation (VT/VF) and atrioventricular block (AVB) was reduced in the patients who received IVIG therapy compared with the baseline values (PVT/VF=0.025, PAVB=0.003); however, no significant differences were observed in the non-IVIG therapy patients (PVT/VF=0.564, PAVB=0.083) following treatment. There were two mortalities in the IVIG therapy group and seven in the non-IVIG therapy group (P=0.072). This retrospective study suggested that the use of IVIG for the treatment of AFM may be associated with improved left ventricular function and reduced episodes of fulminant arrhythmias.

Combined use of hydration and alprostadil for preventing contrast-induced nephropathy following percutaneous coronary intervention in elderly patients.

Contrast-induced nephropathy (CIN) is a complex syndrome of acute kidney injury that follows exposure to intravascular contrast media. Although a series of preventive measures have been developed, CIN remains a major challenge encountered in elderly patients by interventional cardiologists. No data are currently available concerning the potential effects of the combined use of hydration and alprostadil in the prevention of CIN following percutaneous coronary intervention (PCI) in elderly patients. Therefore, the aim of the present study was to investigate the ability of a combination of hydration and alprostadil to prevent CIN following PCI in elderly patients. From June 1, 2010 to January 31, 2012, 85 elderly patients undergoing PCI were included in the present study. The included patients were randomly allocated into three groups: the control (22 cases), hydration (28 cases) and hydration + alprostadil (35 cases) group. Serum creatinine (SCr) levels were measured prior to PCI and then daily for 3 days following PCI. Creatinine clearance (Ccr) was also calculated. Following investigation of the incidence of CIN, a significant decline in Ccr was observed in the control group but not in the hydration + alprostadil group after PCI. The reduction in the level of Ccr from baseline in the hydration + alprostadil group was the smallest among the three groups. Moreover, the highest incidence of CIN was in the control group (6 cases, 27.27%), followed by the hydration group (3 cases, 10.71%) and the hydration + alprostadil group (1 case, 2.86%). Therefore, the combined use of hydration and alprostadil significantly reduces the incidence of CIN in elderly patients undergoing PCI. Hydration and alprostadil are suggested to act synergistically to protect renal function. In conclusion, the combined use of hydration and alprostadil is more effective in the prevention of CIN in elderly patients undergoing PCI compared with hydration alone.

[Treatment of lactic acidosis with early continuous blood purification].

OBJECTIVE: To observe the therapeutic effect of early continuous blood purification (CBP) on lactic acidosis patients. METHODS: Using prospective randomized study method, 41 patients with lactic acidosis in intensive care unit (ICU) from January 2010 to April 2012 were randomly divided into CBP group (n=21) and control group (n=20). Among them, blood gas analysis, lactic acid, blood biochemistry were prospectively monitored at the time before treatment, 12, 24 and 72 hours after treatment. They were also evaluated with acute physiology and chronic health evaluation II (APACHEII) score, and length of stay in ICU and mortality in 28 days were recorded. RESULTS: Lactic acid level and APACHEII score were gradually decreased after treatment in both groups. Compared with control group, lactic acid at 12, 24 and 72 hours in CBP group was obviously lowered (12 hours: 8.23±3.94 mmol/L vs. 12.47±4.62 mmol/L, 24 hours: 4.46±1.57 mmol/L vs. 10.54±3.48 mmol/L, 72 hours: 2.69±1.03 mmol/L vs. 5.74±1.56 mmol/L, all P<0.01), while the APACHEII score at 12, 24 and 72 hours in CBP group was also significantly lowered (12 hours: 18.23±5.85 vs. 21.64±5.38, 24 hours: 16.49±4.62 vs. 20.61±5.71, 72 hours: 11.54±3.67 vs. 16.02±4.34, all P<0.05). Compared with control group, length of stay in ICU was also significantly shorter in CBP group (6.58±3.45 days vs. 11.65±4.94 days, P<0.05), and 28-day mortality was significantly lower in CBP group (23.8% vs. 45.0%, P<0.05). CONCLUSION: Early correction of lactic acidosis with CBP could reduce the mortality of lactic acidosis.

Takotsubo cardiomyopathy in a 90-year-old Chinese man.

A 90-year-old Chinese man was transferred to the Emergency Department of the Affiliated Shantou Hospital of Sun Yat-sen University for treatment of an acute myocardial infarction. He suffered chest pain with three days of cough, dyspnea and fever. A diagnosis of Takotsubo cardiomyopathy was made in normal coronary arteries from urgent coronary angiography and characteristic apical dyskinesis and basal hyper contractility in left ventriculography. The patient died from severe multi-organ failure on the second day of hospitalization.

[Clinical value of plasma N-terminal pro-brain natriuretic peptide in diagnosis of diastolic heart dysfunction].

OBJECTIVE: To explore the clinical value of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) detection in the diagnosis of diastolic heart dysfunction. METHODS: Ninety patients with diastolic heart dysfunction and left ventricular ejection fraction (LVEF)>or=45% were divided into 3 groups according to the findings by conventional echocardiography and/or tissue Doppler imaging, namely impaired relaxation pattern group (n=58), pseudonormal pattern group (n=22) and restrictive filling pattern group (n=10). Ten patients with normal heart function served as the control group. Plasma NT-proBNP level was determined in all the subjects and its correlation to diastolic heart dysfunction was analyzed. RESULTS: Compared with the control group, all the 3 case groups had significantly higher plasma NT-proBNP level (P<0.01). Plasma NT-proBNP level increased gradually with the severity of diastolic dysfunction. Spearman rank correlation analysis indicated that lg(NT-proBNP) was positively correlated to the severity of diastolic dysfunction. Simple linear regression showed that 52.7% of the total variation of lg(NT-proBNP) was correlated to the severity of the condition. The ROC curve demonstrated a sensitivity of 80%, specificity of 90%, positive predictive value of 84.2% and the negative predictive value of 87.1% for NT-proBNP level of 133 ng/L in predicting diastolic heart dysfunction regardless of the clinical manifestations, and the sensitivity was 81.7% and specificity was 75% for NT-proBNP level at 280.25 ng/L in predicting symptomatic diastolic heart dysfunction; the sensitivity was 81.2% and the specificity was 92.6% for NT-proBNP at 655 ng/L in predicting moderate to severe diastolic heart dysfunction. CONCLUSION: Plasma NT-proBNP level increases gradually with the severity of diastolic dysfunction and has a high clinical value in severity rating and assisting the diagnosis of diastolic dysfunction.

[Correlation between pressure-derived coronary collateral flow and Rentrop grade after primary percutaneous intervention of acute myocardial infarction].

OBJECTIVE: To analyze the correlation between pressure-derived collateral coronary flow (PDCF) and Rentrop grade of patients with acute myocardial infarction (AMI). METHODS: PDCF, determined by the ratio of P(w)/P(a), was measured in 29 patients with AMI of the first onset who received primary percutaneous coronary intervention (PCI) within 12 h after the onset. Sufficient collateral flow (group A, n=19) was defined as PDCF>0.24 and insufficient collateral flow (group B, n=10) as PDCF< or =0.24. Rentrop grade of the collateral flow was evaluated by coronary angiography. Echocardiography was performed on the 3rd and 30th day after PCI. The left ventricular ejection fraction, end-systolic and end-diastolic volumes, and the related indexes were obtained. RESULT: Rentrop grade was significantly related to PDCF (r=0.75, P<0.01), but a wide range of PDCF was observed in patients with Rentrop grade< or =1. CONCLUSION: PDCF measurement allows quantitative evaluation of the collateral flow in patients with AMI.