[Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study].

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 µg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

[The current status of early use of oral ß-blockers in patients with acute coronary syndrome and the association with the in-hospital outcomes].

Objective: To analyze the status of early use of oral ß-blocker and its relationship with in-hospital outcomes in eligible patients with acute coronary syndrome (ACS). Methods: The study was based on the Improving Care for Cardiovascular Disease in China (CCC)-ACS project. The data of ACS patients that collected during 2014 to 2019 from 230 collaborating hospitals across China were analyzed. Propensity score matching method and Cox multivariate regression analysis were used to analyze the association between early use of oral ß-blocker and in-hospital outcomes within 15 days. Results: A total of 38 663 eligible ACS patients were included in this study. The mean age was (57.0±9.0), and 78.8% of the ACS patients (30 470/38 663) were male. The proportion of early use of oral ß-blockers was 64.9% (25 112/38 663), but varied substantially, in the 230 hospitals with a range from 0 to 100%. Compared with the patients no early use of oral ß-blocker, the patients receiving early oral ß-blocker had significantly lower incidence of major cardiovascular adverse events (MACEs) (3.4% (395/11 536) vs. 2.9%(339/11 536), P=0.036)and less occurrences of heart failure (2.7% (316/11 536) vs. 2.1% (248/11 536), P=0.004). Multivariate Cox regression analyses showed the patients receiving early oral ß-blocker had 15.5%, 23.1%, and 35.3% lower risks of MACEs, heart failure and cardiogenic shock respectively than the patients no early oral ß-blocker. Conclusions: Compared with the patients no early oral ß-blocker, the patients receiving early oral ß-blocker had lower risks of MACEs events, heart failure and cardiogenic shock. However, the early use of oral ß-blocker in ACS patients was generally insufficient with huge differences among different hospitals in China.

[Current status of thromboembolism risk assessment in patients hospitalized with non-valvular atrial fibrillation in tertiary hospitals in China].

Objective: To analyze the current status, trend and predictors of thromboembolism risk assessment in patients hospitalized with non-valvular atrial fibrillation (NVAF) in tertiary hospitals in China. Methods: The study was based on data from the Improving Care for Cardiovascular disease in China (CCC)-Atrial Fibrillation (AF) project. About 10% of the tertiary hospitals in each geographic-economic stratum were recruited. Participating hospitals reported the first 10 to 20 patients with a discharge diagnosis of atrial fibrillation monthly. From February 2015 to December 2019, a total of 49 104 NVAF patients from 151 tertiary hospitals in 30 provinces, municipalities and autonomous regions were enrolled. Clinical data of the patients was collected. The proportion of NVAF patients receiving thromboembolism risk assessment, variations in the proportion between different hospitals, the time trend of the application of thromboembolism risk assessment, and the predictors of the application of thromboembolism risk assessment were analyzed. Results: The age of the NVAF patients was (68.7±12.1) years, 27 709 patients (56.4%) were male. Only 17 251 patients (35.1%) received thromboembolism risk assessment. The proportion varied substantially between hospitals with the lowest value of 0 and the highest value of 100%. Among the hospitals, which enrolled more than 30 patients, no patients received thromboembolism risk assessment in 18.4% (26/141) of the hospitals, more than 50% of the patients received thromboembolism risk assessment in 21.3% (30/141) of the hospitals, and all the patients received thromboembolism risk assessment in only 1 hospital. The proportion of NVAF patients receiving thromboembolism risk assessment was 16.2% (220/1 362) in the first quarter of 2015, and significantly increased to 67.1% (1 054/1 572) in the last quarter of 2019 (P<0.001). Patients' characteristics were associated with the application of thromboembolism risk assessment. The odds of receiving thromboembolism risk assessment was lower in male patients compared to female patients(OR=0.94,95%CI 0.89-0.99), lower in patients with acute coronary syndrome or other cardiovascular diseases compared to those with AF as the primary admission reason (OR=0.59, 95%CI 0.55-0.63, OR=0.52, 95%CI 0.45-0.61, respectively), and lower in patients with paroxysmal, persistent and long-standing/permanent AF compared to those with first detected AF (OR=0.62, 95%CI 0.57-0.67, OR=0.72, 95%CI 0.66-0.79, OR=0.57, 95%CI 0.52-0.64, respectively). The odds was higher in patients with a history of hypertension, heart failure, stroke/TIA, and previous anticoagulant therapy compared to those without the above conditions (OR=1.17, 95%CI 1.11-1.23, OR=1.18, 95%CI 1.07-1.30, OR=1.17, 95%CI 1.08-1.27, OR=1.28, 95%CI 1.19-1.37, respectively) (P all<0.05). Conclusion: Thromboembolism risk assessment was underused in patients hospitalized with NVAF in tertiary hospitals in China, and there were substantial variations between hospitals in the application of thromboembolism risk assessment. The application of thromboembolism risk assessment in tertiary hospitals has been improved in recent years, but there is still plenty of room for future improvement. Patients' characteristics could affect the application of thromboembolism risk assessment in China.

[The expanding needs on lipid-lowering treatment in patients with acute coronary syndrome by applying newly issued definition of extreme high-risk by Chinese Society of Cardiology].

Objective: To assess the expanding needs on lipid-lowering treatment in patients with acute coronary syndrome (ACS) by applying newly issued definition of extreme high-risk, which is proposed by Chinese expert consensus on lipid management of extreme high-risk atherosclerotic cardiovascular disease (ASCVD) patients of Chinese Society of Cardiology (CSC). Methods: Data of this study was derived from the Improving Care for Cardiovascular Disease in China (CCC) project, which was a case-based nationwide registry study and launched as a collaborative initiative by the American Heart Association and the CSC. The project consecutively recruited ACS patients from158 tertiary hospitals and 82 second hospitals across China, and detailed clinical information of patients was collected. This study enrolled ACS inpatients in CCC project from November 2014 to July 2019. The proportion of extreme high-risk patients, their characteristics, mean LDL-C levels at admission, the gap between measured LDL-C level and the new target, and lipid-lowering therapy at discharge were assessed. Results: Among 104 516 ACS inpatients enrolled in this study, 75.1% (78 527/104 516) met the criteria of extreme high-risk and were expected to achieve the new LDL-C goal. Among patients at extreme high-risk, 21.2% (16 651/78 527) had multiple severe ASCVD events and 78.8% (61 876/78 527) had 1 severe ASCVD event and at least two high-risk factors. For the extreme high-risk patients, the mean level of LDL-C at admission was (2.8±1.0) mmol/L, prevalence of LDL-C ≥1.4 mmol/L was 93.4% (73 307/78 527) and the median gap between LDL-C level at admission and the target of 1.4 mmol/L was 1.3 (0.8, 2.0) mmol/L. If LDL-C could be further reduced to 50% of the admission level, we estimated that 55.6% (43 632/78 527) of the extreme high-risk patients would achieve the new LDL-C goal. Among 40 875 patients with information about discharge statin dosage, 93.5% (28 004/29 947) of the extreme high-risk patients were prescribed with statins at discharge, and among them 95.1% (26 632/28 004) received statin monotherapy and 91.1% (25 501/28 004) were at moderate doses of statins. Conclusion: About three fourth of inpatients with ACS were categorized as extreme high-risk based on the new definition of CSC expert consensuses, nine out of ten patients at extreme high-risk didn't achieve the new LDL-C target at admission, and the intensity of lipid-lowering therapy was insufficient in clinical practice. There are substantially expanding needs for implementing more intensive and effective lipid-lowering strategies.

[Association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome].

Objective: To investigate the association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome (ACS). Methods: Data of this study were derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a collaborative study of the Chinese Society of Cardiology and the American Heart Association. Since 2014, the CCC-ACS project consecutively enrolled inpatients with ACS, systematically collected their clinical data and evaluated medical quality of these patients from 158 tertiary hospitals and 82 secondary hospitals across China. This study enrolled female patients less than 60 years old with initial ACS, who received coronary angiography in CCC-ACS project. Patients were divided into two groups according to smoking status. A multivariate logistic regression analysis was used to analyze the association between smoking and the severity of coronary lesions among young and middle-aged female patients with ACS. Results: A total of 2 863 female patients younger than 60 years old with initial ACS, who received coronary angiography, were enrolled. Among them, 12% (340 cases) was smokers. Proportion of patients younger than 45 years old was higher (13.2% (45/340) vs. 8.5% (215/2 523), P<0.01) and prevalence of hypertension (59.4% (202/340) vs. 66.7% (1 683/2 523), P<0.01) and diabetes (39.4% (134/340) vs. 44.2% (1 116/2 523), P=0.09) was lower in smoker group than in non-smoker group. However, prevalence of ST-elevation myocardial infarction (66.8% (227/340) vs. 53.7% (1 354/2 523), P<0.01), coronary multi-vessel lesions (39.1% (133/340) vs. 32.6% (822/2 523), P<0.01) and severe stenosis in either single-vessel (56.2% (109/194) vs. 46.1% (706/1 530), P<0.01) or multi-vessel (63.2% (84/133) vs. 58.2% (478/822), P=0.29) was significantly higher in smoker group than in non-smoker group. Multivariate logistic regression analyses showed that after adjusting for age, hypertension, diabetes, elevated low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, elevated triglyceride, renal insufficiency, family history of coronary heart disease and types of ACS, smokers faced a higher risk of coronary multi-vessel lesions, coronary multi-vessel severe lesions and coronary severe lesions with the odds ratios and 95% confidence interval of 1.41 (1.11-1.79), 1.40 (1.10-1.78) and 1.78 (1.11-2.87), compared with non-smokers. Conclusions: Smoking is significantly associated with an increased risk of extensive and severe coronary lesions among young and middle-aged female patients with ACS. This study provides crucial evidence for further understanding the harms of smoking and the need to strengthen the tobacco control education and smoking cessation guidance for young and middle-aged women.

Impact of postoperative infective complications on long-term survival after liver resection for hepatocellular carcinoma.

BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection. RESULTS: Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021). CONCLUSION: Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.

Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. I. Studies with fluoride.

Fluoride (F-), a known stimulator of G-proteins, was used to examine the relationship between G-proteins and calcium channels (CaC) in rat vascular smooth muscle (VSM). Treatment of isolated rat tail artery helical strips with F- (2.5-20 microM) produced a Ca++-dependent contraction. In the absence of added AlCl3, subthreshold NaF shifted the KCl, as well as the arginine vasopressin and norepinephrine concentration-related tension curves to the left. Nifedipine and verapamil, known CaC blockers, inhibited the NaF-related contraction. AlCl3 (20 microM), which is required for G-protein stimulation by F-, strikingly potentiated the contractile response to F-. The NaF-induced contraction was relaxed by 3-isobutyl-1-methylxanthine as well as by forskolin and by dibutyryladenosine-cyclic AMP, and the effect therefore may be independent of cAMP. 45Ca-uptake was elevated by NaF, and partially blocked by nifedipine and verapamil. NaF also inhibited the basal and forskolin-stimulated cAMP production, suggesting that F- stimulated the putative Gi in the intact VSM cells. NaF stimulated accumulation of IP in a concentration-dependent manner, indicating that F- stimulated the putative G-protein Gp which couples various receptors to hydrolysis of phosphoinositides and mobilization of Ca++. These results indicate that NaF-induced vasoconstriction is related to the opening of the CaC in the plasma membrane and perhaps a subsequent entry of the extracellular Ca++ into the cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. II. Studies with guanosine 5'-(gamma)triphosphate.

Our previous studies with fluoride have indicated that G-proteins may mediate the gating of Ca++ channels in vascular smooth muscle (VSM). We now present further studies on the relationship between G-proteins and Ca++ channels in VSM using guanosine-5'-(gamma-thio)triphosphate (GTP gamma S), a hydrolysis-resistant analog of GTP. Rat tail artery helical strips pretreated with GTP gamma S in a cytosol-like solution contracted in a Ca++-dependent manner in the absence of a depolarizing concentration of K+, hormones or any other Ca++ agonists. Contraction was dependent on the concentrations of applied GTP gamma S. The ability of strips pretreated with GTP gamma S to contract in response to Ca++ was not reversed by repeated washing. Incubation with 1 mM GTP applied extracellularly did not induce tension development. Treatment with a subthreshold concentration of GTP gamma S shifted the K+ concentration-related tension curve to the left but did not alter the maximum response. The contractions induced by GTP gamma S pretreatment and by submaximal (60 mM) KCI were additive at all levels of Ca++ tested. Extra tension development could be evoked from tissue maximally contracted with GTP gamma S by adding maximal K+ and norepinephrine. The relaxing sensitivity of the GTP gamma S-related contraction to reversal by nifedipine was between those for K+ depolarization and norepinephrine, and the GTP gamma S-induced rise in tension was partially inhibited by the Ca++ channel blocker nifedipine. Ca++-elicited contraction of the GTP gamma S-pretreated strips was relaxed by forskolin, an adenylate cyclase activator, 3-isobutyl-l-methyl-xanthanine, a cyclic nucleotide phosphodiesterase inhibitor, and dibutyryl cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid hormone-like immunoreactivity in fish plasma and tissues.

Although fish lack parathyroid glands, parathyroid hormone (PTH)-like substances, reacting with guinea pig antibodies raised against bovine PTH1(-84), were detected in the circulation of trout (Salmo gairdneri) and goldfish (Carassius auratus). The immunoreactive (IR) PTH concentration in plasma (0.5-1.5 ng/ml) was less than that measured in heat-treated and dialyzed 0.6% NaCl extracts of brain tissue (4.0-5.0 ng/g wet wt brain) and much less than that present in pituitary extracts (20-40 ng/g pituitary gland). Heat-treated saline extracts of hake (Urophycis tenuis) and coho salmon (Oncorhynchus kisutch) pituitary glands also had PTH-like immunoreactivity in radioimmunoassays for C-terminal and N-terminal PTH, in which serial dilutions of the extracts were parallel to the respective standards. The IR PTH material present in the pituitary glands was absorbed on Sep Pak columns and was eluted in the same buffer (90% methanol, 4% acetic acid) and same volume as authentic bovine PTH1(-84). IR PTH was not detected in extracts of muscle, liver, or kidney tissue, but was present in the corpuscles of Stannius (CS), at levels comparable to those in the pituitary glands. While heating the CS extracts had no effect on the IR C-terminal PTH content, it completely destroyed that of the N-terminal PTH. These results suggest that the brain, pituitary, and CS all produce a peptide which shows immunoreactive cross-reactivity with mammalian PTH but that the peptide produced by the CS is not identical to that produced by the brain or pituitary. The brain, pituitary, and CS may be the source of plasma IR PTH in fish.