Proteinase­3­antineutrophil cytoplasmic antibody­associated vasculitis secondary to subacute infective endocarditis: A case report.

A 58-year-old male patient was admitted to Peking University First Hospital (Beijing, China) due to recurrent hematuria, proteinuria and kidney dysfunction. The patient was positive for proteinase-3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). Pathology of the kidney showed focal proliferative necrotizing glomerulonephritis with crescent formation and immune complex-mediated glomerulonephritis. The patient was diagnosed with PR3-ANCA-associated vasculitis (AAV), received intensive immunosuppressive therapy and experienced two relapses within 1 year. After admission, aortic valve vegetation was observed via echocardiography. The patient subsequently received antibiotic treatment and valve replacement, and achieved complete remission of kidney and cardiac function. The present case emphasized the importance of identifying secondary reasons for ANCA formation, especially infective endocarditis in patients with PR3-AAV.

Esmolol increases the fecal abundance of Lactobacillus in a rat model of sepsis.

BACKGROUND: Disorders of the gut microbiome could be responsible for the progression of multiple organ dysfunction syndrome. In this study, we examined the effect of esmolol on the gut microbiome in a rat model of sepsis induced by cecal ligation and puncture (CLP). METHODS: The animals (n = 32) were randomly divided into 3 groups: Sham group (sham operation + normal saline treatment, n = 8), CLP group (cecal ligation and puncture + normal saline treatment, n = 12), and CLP + ESM group (cecal ligation and puncture + esmolol treatment, n = 12). After 24 h, feces in the colon were collected for 16S rRNA gene sequencing and nitric oxide analysis. In addition, colon was removed for immunohistochemical staining of inducible nitric oxide synthase (iNOS). RESULTS: Four rats in the CLP group and two rats in the CLP + ESM group died. The abundance of Lactobacillus in the CLP + ESM group was higher than CLP group (P = 0.048). In the linear discriminant analysis effect size analysis, Norank f Muribaculaceae, Escherichia-Shigella and Lactobacillus were the predominant bacteria in the Sham group, CLP group and CLP + ESM group, respectively. The iNOS expression in colonocytes stained by brown in the CLP group were much more than Sham group (P = 0.001). Compared to CLP group, the iNOS expression in colonocytes reduced after esmolol treatment (P = 0.013). The concentration of nitric oxide in colon feces was different in Sham group, CLP group and CLP + ESM group (1.31 ± 0.15µmmol/l vs. 1.98 ± 0.27µmmol/l vs. 1.51 ± 0.14µmmol/l, P = 0.001). In addition, the concentration of nitric oxide in CLP group was higher than Sham group (P = 0.001) or CLP + ESM group (P = 0.001). CONCLUSIONS: Esmolol increased the fecal abundance of Lactobacillus in a rat model of sepsis. Moreover, esmolol reduced the iNOS expression of colonocytes and the nitric oxide concentration of colon feces.

Cardiogenic shock caused by Takotsubo syndrome complicated with severe anxiety: A case report and literature review.

RATIONALE: Takotsubo syndrome (TTS) is characterized by transient and reversible left ventricular systolic dysfunction, which are often associated with acute physical or emotional stressors. Cancer is one of the comorbidities in TTS, and TTS is even considered as a paraneoplastic syndrome, but its mechanism remains unclear. We report a patient in whom cancer and untreated mental disorders triggered TTS. PATIENT CONCERNS: A 59-year-old man was transferred to the Department of Cardiology because of acute onset of severe chest pain and dyspnea before cystoscopy. He presented with hematuria, had been diagnosed with a high-grade urothelial bladder cancer, and underwent transurethral resection of bladder tumors 4 months previously. He had severe anxiety regarding recurrence and death from cancer, especially after the hematuria recurred. DIAGNOSIS: TTS and severe anxiety. INTERVENTIONS: The results of coronary angiography, a left ventriculogram, echocardiography, and the clinical outcome led to the diagnosis of TTS. The patient was treated with extracorporeal membrane oxygenation support, mechanical ventilation, and drugs for heart failure and anxiety. OUTCOMES: Echocardiography showed normal wall motion on day 6 of symptom onset. Six months after symptom onset, the anxiety score was reduced from 12 to 11, and the patient had no episodes of any discomfort, and no evidence of cancer recurrence was observed. LESSONS: Patients with cancer and TTS have a higher level of stress, and physicians need to pay more attention to early screening and early treatment of mental disorders in these patients. Prompt and effective multidisciplinary treatment, including psychological counseling and antianxiety drugs, can improve the prognosis in such cases.

Combining CHA2DS2-VASc score into RCRI for prediction perioperative cardiovascular outcomes in patients undergoing non-cardiac surgery: a retrospective pilot study.

BACKGROUND: Treatment decisions in patients undergoing non-cardiac surgery are based on clinical assessment. The Revised Cardiac Risk Index (RCRI) is pragmatic and widely used but has only moderate discrimination. We aimed to test the efficacy of the CHA2DS2-VASc score and the combination of CHA2DS2-VASc and RCRI to predict perioperative risks for non-cardiac surgery. METHODS: This pre-specified analysis was performed in a retrospective cohort undergoing intra-abdominal surgery in our center from July 1st, 2007 to June 30th, 2008. The possible association between the baseline characteristics (as defined by CHA2DS2-VASc and RCRI) and the primary outcome of composite perioperative cardiac complications (myocardial infarction, cardiac ischemia, heart failure, arrhythmia, stroke, and/or death) and secondary outcomes of individual endpoints were explored using multivariate Logistic regression. The area under the receiver operating characteristic curve (C-statistic) was used for RCRI, CHA2DS2-VASc, and the combined models, and the net reclassification improvement (NRI) was calculated to assess the additional discriminative ability. RESULTS: Of the 1079 patients (age 57.5 ± 17.0 years), 460 (42.6%) were women. A total of 83 patients (7.7%) reached the primary endpoint. Secondary outcomes included 52 cardiac ischemic events, 40 myocardial infarction, 20 atrial fibrillation, 18 heart failure, four strokes, and 30 deaths. The endpoint events increased with the RCRI and CHA2DS2-VASc grade elevated (P < 0.05 for trend). The RCRI showed a moderate predictive ability with a C-statistics of 0.668 (95%CI 0.610-0.725) for the composite cardiac outcome. The C-statistics for the CHA2DS2-VASc was 0.765 (95% CI 0.709-0.820), indicating better performance than the RCRI (p = 0.011). Adding the CHA2DS2-VASc to the RCRI further increased the C-statistic to 0.774(95%CI 0.719-0.829), improved sensitivity, negative predictive value, and enhanced reclassification in reference to RCRI. Similar performance of the combined scores was demonstrated in the analysis of individual secondary endpoints. The best cut-off of a total of 4 scores was suggested for the combined CHA2DS2-VASc and RCRI in the prediction of the perioperative cardiac outcomes. CONCLUSIONS: The CHA2DS2-VASc score significantly enhanced risk assessment for the composite perioperative cardiovascular outcome in comparison to traditional RCRI risk stratification. Incorporation of CHA2DS2-VASc scores into clinical-decision making to improve perioperative management in patients undergoing non-cardiac surgery warrants consideration.

Differences in perioperative cardiovascular outcomes in elderly male and female patients undergoing intra-abdominal surgery: a retrospective cohort study.

OBJECTIVE: Perioperative cardiovascular events constitute the majority of complications in noncardiac surgery. Older and female patients have been less investigated. We aimed to evaluate differences in perioperative cardiovascular outcomes by age and sex. METHODS: We enrolled 1079 patients (57.5 ± 17.0 years, 42.6% women) undergoing intra-abdominal surgery from July 2007 to June 2008 and compared occurrence of perioperative cardiac events by age (≥65 vs. <65 years) and sex. Multivariable logistic regression was used to investigate associations between age, sex, and outcomes. RESULTS: Age ≥65 years was associated with perioperative myocardial infarction (MI) (odds ratio [OR] 2.9, 95% confidence interval [CI]: 1.3-6.6) and total cardiovascular events (OR 2.4, 95% CI: 1.3-4.2). Age ≥65 years was associated with higher perioperative MI risks in men (OR 4.7, 95% CI: 1.3-17.6) than in women (OR 3.1, 95% CI: 1.2-8.3). Advanced age was associated with heart failure in women (OR 13.9, 95% CI: 1.7-110.5). Female sex was a risk factor for heart failure in elderly patients (OR 4.2, 95% CI: 1.1-15.7). CONCLUSIONS: Advanced age appeared to be associated with increased perioperative cardiac risk but differed by sex. Tailored strategies should be considered with respect to the patient's sex.

Long-term follow-up of antithrombotic management patterns in patients with acute coronary syndrome in China.

OBJECTIVE: To describe the long-term antithrombotic management patterns (AMPs) and clinical outcomes of Chinese patients with acute coronary syndrome (ACS). METHODS: This was an observational, multicenter, longitudinal cohort extension study of Chinese patients who had completed the EPICOR Asia 2-year follow-up study post-hospitalization for an ACS event. Changes in AMP and clinical outcomes for up to 5 years post-ACS event were evaluated. RESULTS: Overall, 2334 patients with ACS were enrolled at 49 sites. The mean age was 61.6 years and 76.3% were men. By study end, 2093 patients completed the 3-year follow-up. At baseline (2 years post-ACS event), 72.4% of patents received one antiplatelet (AP) medication, with aspirin being the preferred one. A small proportion of patients (21.5%) was treated with two or more APs (2+ AP), and even fewer patients (6.1%) did not receive any AP medication at baseline. Upon study completion, the proportion of patients without AP therapy increased to 13.6%, while the percentage of patients on one AP and 2+ AP decreased to 69.3% and 17.1%, respectively. Numerically, a higher incidence of clinical events (composite of all-cause mortality, myocardial infarction, stroke) was observed for the 2+ AP (13.2%) subgroup than for the no AP (10.5%) and one AP (8.6%) subgroups. Furthermore, the 2+ AP subgroup exhibited the greatest number of bleeding events, outpatient visits, and hospitalization rates. Unlike myocardial infarction or stroke, bleeding events prompted an adjustment in AMP. CONCLUSION: Most patients in China received at least one AP medication up to 5 years after an ACS event.

Catestatin in defense of oxidative-stress-induced apoptosis: A novel mechanism by activating the beta2 adrenergic receptor and PKB/Akt pathway in ischemic-reperfused myocardium.

Apoptosis induced by oxidative stress is one of the most important cardiomyocytes losses during ischemia-reperfusion (I/R). Catestatin (CST) has been demonstrated to have the anti-oxidative capacity in vitro. We hypothesized that CST intervention could reduce apoptosis of cardiomyocytes induced by oxidative stress in I/R. In Langendorff-perfused rat heart global I/R model, CST was introduced at the reperfusion stage. In comparison to the control group, CST led to preservation on activities of superoxide dismutase and glutathione peroxidase, improvement of hemodynamics, and reduced infarction area in reperfused myocardium. The protection of CST was also shown by less apoptotic cardiomyocytes in TUNEL staining, less caspase-3 activation, and increased phosphorylation of protein kinase B (PKB/Akt) in Western blot. To further demonstrate the benefits of CST and explore the possible underlying mechanism, H2O2-challenged primary-cultured neonatal rat cardiomyocytes were used to simulate the oxidative-stressed scenario. CST incubation with the H2O2-challenged cardiomyocytes led to reduction of apoptosis, which was demonstrated by less Hoechst 33342 positive staining of nuclei, less caspase-3 activation, and DNA fragmentation. The effect of CST was abrogated by pretreatment of the cardiomyocytes with the PI3K inhibitor LY294002. Furthermore, Akt activation and the anti-apoptosis effect of CST were abolished by pretreatment of the cardiomyocytes with ß2 receptor inhibitor ICI118551. Thus, the salvage of oxidative-stress-induced apoptotic cardiomyocytes in I/R by CST might involve activation ß2 receptor and regulation of PI3K/Akt signaling in reperfusion injury salvage kinase (RISK) pathway.

A CASPR1-ATP1B3 protein interaction modulates plasma membrane localization of Na+/K+-ATPase in brain microvascular endothelial cells.

Contactin-associated protein 1 (CASPR1 or CNTNAP1) was recently reported to be expressed in brain microvascular endothelial cells (BMECs), the major component of the blood-brain barrier. To investigate CASPR1's physiological role in BMECs, here we used CASPR1 as a bait in a yeast two-hybrid screen to identify CASPR1-interacting proteins and identified the ß3 subunit of Na+/K+-ATPase (ATP1B3) as a CASPR1-binding protein. Using recombinant and purified CASPR1, RNAi, GST-pulldown, immunofluorescence, immunoprecipitation, and Na+/K+-ATPase activity assays, we found that ATP1B3's core proteins, but not its glycosylated forms, interact with CASPR1, which was primarily located in the endoplasmic reticulum of BMECs. CASPR1 knockdown reduced ATP1B3 glycosylation and prevented its plasma membrane localization, phenotypes that were reversed by expression of full-length CASPR1. We also found that the CASPR1 knockdown reduces the plasma membrane distribution of the α1 subunit of Na+/K+-ATPase, which is the major component assembled with ATP1B3 in the complete Na+/K+-ATPase complex. The binding of CASPR1 with ATP1B3, but not the α1 subunit, indicated that CASPR1 binds with ATP1B3 to facilitate the assembly of Na+/K+-ATPase. Furthermore, the activity of Na+/K+-ATPase was reduced in CASPR1-silenced BMECs. Interestingly, shRNA-mediated CASPR1 silencing reduced glutamate efflux through the BMECs. These results demonstrate that CASPR1 binds with ATP1B3 and thereby contributes to the regulation of Na+/K+-ATPase maturation and trafficking to the plasma membrane in BMECs. We conclude that CASPR1-mediated regulation of Na+/K+-ATPase activity is important for glutamate transport across the blood-brain barrier.

Genetic polymorphisms of UTS2 rs2890565 Ser89Asn in coronary heart disease and myocardial infarction in Chinese population.

OBJECTIVE: Atherosclerosis plays a key role in the inducibility and persistence of coronary heart disease. Clinical evidence, in vitro and in vivo studies have implicated Urotensin II (U-II/UTS2) in the development of atherosclerosis and coronary artery disease, contributing to the (patho) physiological regulation of cardiovascular homeostasis in humans. Increased U-II plasma levels have been reported in patients with atherosclerosis and coronary heart disease. Considering these, our objective was to evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to coronary heart disease and myocardial infarction in a Chinese population. METHODS: A case-control study was designed to compare the distribution of alleles and genotypes between case group (subjects with myocardial infarction, n=409) and control group (subjects with coronary heart disease, n=830). The detection of UTS2 gene polymorphisms was achieved with PCR-RFLP technique. RESULTS: We did not identify statistically significant differences between the myocardial infarction and coronary heart disease groups, neither with regard to the frequency of genotype/variant at the Ser89Asn locus nor at the Thr21Met locus. When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn were only seen in female subjects in both additive tested inheritance model (OR=0.257, 95% CI: 0.074-0.896, P=0.033) and recessive tested inheritance model (OR=0.280, 95% CI: 0.082-0.955, P=0.042). For subjects with myocardial infarction, we identified statistically significant differences between the ST-segment elevation myocardial infarction and non ST-segment elevation myocardial infarction groups. Differences in genotype distribution of polymorphism Ser89Asn not Thr21Met were seen in both additive tested inheritance model (OR=0.202, 95% CI: 0.049-0.833, P=0.027) and recessive tested inheritance model (OR=0.208, 95% CI: 0.052-0.835, P=0.027). When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn were only seen in male subjects in both additive tested inheritance model (OR=0.208, 95% CI: 0.049-0.890, P=0.034) and recessive tested inheritance model (OR=0.197, 95% CI: 0.047-0.824, P=0.026). CONCLUSIONS: Ser89Asn (S89N) polymorphisms of the UTS2 gene were significantly associated with coronary heart disease and myocardial infarction in Chinese population. Additionally, we demonstrated that Genotype Asn89Asn may imply a potential benefit role for myocardial infarction.

Genetic polymorphisms of UTS2 rs2890565 Ser89Asn in cardiac hypertrophy in Chinese Han population.

OBJECTIVE: Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli, some of which might finally lead up to a maladaptive state. Clinical evidence, in vitro and in vivo studies have implicated urotensin II (U-II/UTS2) in the development of cardiac hypertrophy, contributing to the (patho)-physiological regulation of cardiovascular homeostasis in humans. Several genes are associated with left ventricular hypertrophy; considering these, our objective was to evaluate the possible role of UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to cardiac hypertrophy in a Chinese population. METHODS: A case-control study was designed to compare the distribution of alleles and genotypes between three groups: case group 1 (subjects with hypertension and cardiac hypertrophy, n=265), case group 2 (subjects with hypertension, without cardiac hypertrophy, n=768), and the control group (subjects neither with hypertension nor with cardiac hypertrophy, n=416). The detection of UTS2 gene polymorphisms was achieved with the PCR restriction fragment length polymorphism technique. RESULTS: We did not identify statistically significant differences between the three groups, neither with regard to the frequency of genotype/variant at the Ser89Asn locus nor at the Thr21Met locus. When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn were only seen in female subjects in both the additive tested inheritance model (OR=0.507, 95% CI 0.249 to 1.032, p=0.032) and the recessive tested inheritance model (OR=0.475, 95% CI 0.239 to 0.945, p=0.034) between case group 2 (subjects with hypertension, without cardiac hypertrophy) and the control group (subjects neither with hypertension nor with cardiac hypertrophy). When stratified by sex, for female subjects with cardiac hypertrophy, we identified statistically significant differences in left ventricular posterior wall thickness for variant genotypes at the Ser89Asn locus (AA vs GG: 1.2500 (1.2000, 1.3750) vs 1.2500 (1.2000, 1.3750), p=0.03) and (AG+AA vs GG: 1.2000 (1.2000, 1.3000) vs 1.2000 (1.1000, 1.2000), p=0.01). CONCLUSIONS: Ser89Asn (S89N) polymorphisms of the UTS2 gene were associated with hypertension in a Chinese female population. Additionally, we demonstrated that genotype Asn89Asn was associated with left ventricular posterior wall thickness for subjects with hypertension and cardiac hypertrophy in a Chinese female population.

[Analysis of perioperative cardiovascular events and related risk factors in patients undergoing intraperitoneal surgery].

OBJECTIVES: To investigate incidence of perioperative cardiovascular events, to analyze related risk factors for the patients undergoing intraperitoneal surgery. METHODS: The data of 1079 patients who underwent intraperitoneal surgery (exclude laparoscope surgery) from July 2007 to June 2008 was reviewed and analyzed. RESULTS: For the patients undergoing intraperitoneal surgery, the incidence of major cardiovascular events was 3.99% (43/1079), all-cause mortality was 1.58% (17/1079). The independent risk factors of major cardiovascular events were age ≥ 60 years, history of coronary heart disease, cardiac insufficiency, arrhythmia, chronic obstructive pulmonary disease, estimated glomerular filtration rate (eGFR) < 60 ml/(min·1.73 m(2)), emergency surgery and duration of surgery > 2.82 h (OR = 2.68 to 5.19, P = 0.001 to 0.031). CONCLUSIONS: The cardiac risk of intraperitoneal surgery is 3.99%. The risk of cardiac complications should be evaluated in elderly patients and those with ischaemic heart disease, chronic obstructive pulmonary disease, and renal disease, more specifically, when emergent or long duration major surgeries are needed.

[An analysis of clinical factors for coronary artery calcification score].

OBJECTIVE: To evaluate the correlating clinical factors of coronary artery calcification score (CACS). METHODS: 141 patients suspected of coronary artery disease were included. They underwent multi-slice row computed tomography, pulse wave velocity (PWV), UCG and blood biochemistry within a period of 3 months. The subjects were divided into three groups according to CAC score: A (CACS = 0 - 10), B (CACS = 11 - 400), C (CACS > 400). RESULTS: CACS was significantly associated with age, history of hypertension and diabetes mellitus. It was also associated with the presence of mitral annular calcification and aortic valve calcification, low ankle brachial pressure index (ABI) and high mean artery pressure (MAP) as well as high values of brachial ankle PWV (baPWV) and Upstroke time (UT). Multifactorial logistic regression analysis showed that the presence of aortic valve calcification and mitral annular calcification, the history of diabetes mellitus and high value of UT were independently correlated with severe coronary artery calcification. CONCLUSIONS: Aortic valve calcification, mitral annular calcification, history of diabetes mellitus, high value of UT were independently correlated with severe coronary artery calcification. Measurement of PWV and UCG should be performed before multi-slicerow computed tomography, because the assessment of coronary artery lumen narrowing with multi-slice row computed tomography can not be carried out accurately in the presence of severe coronary artery calcification.

[In vivo interleukin-10 gene transfer down-regulates myocardial matrix metalloproteinase and myocardial collagen expressions in rats with acute myocardial infarction].

OBJECTIVE: We investigated the in vivo effects of recombinant adenovirus-associated virus type-2 (AAV-2) mediated interleukin-10 (IL-10) gene transfer on the expression of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of metalloproteinase (TIMP)-1, collagen type I and type III in a rat acute myocardial infarction model. METHOD: Male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 6): sham operation group, MI/AAV2 group, and MI/AAV2-IL-10 group (10(10) vg/ml x 0.1 ml injection at peri-infarct regions immediately post MI). Five days later, the expressions of MMP-2 and MMP-9 were measured by RT-PCR, Western blot and zymography. The expression of TIMP-1 was measured by RT-PCR and Western blot. Collagen type I and type III were assessed by RT-PCR and immunohistochemical stain. RESULTS: The myocardial expressions of MMP-2, MMP-9 and collagen contents in MI/AAV2 group were significantly increased than those in sham operation group. Myocardial expressions of MMP-2, MMP-9 were significantly decreased and the expression of TIMP-1 significantly increased in the MI/AAV2-IL-10 group than those in MI/AAV2 group. Moreover, the expressions of collagen type I, collagen type III and the ratio of I/III collagen in border zones of infarcted myocardium were decreased by 47.6% (P < 0.01), 23.6% (P < 0.05), and 17.9% (P < 0.05) respectively, while the expression of TIMP-1 increased by 73.1%(P < 0.05) in MI/AAV2-IL-10 group compared to MI/AAV2 group. CONCLUSION: In vivo myocardial IL-10 transfer reduced myocardial MMP and collagen expression and increasing the TIMP expression.