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1.
Katrina L. Ellis Leopoldo Pérez de Isla Rodrigo Alonso Francisco Fuentes Gerald F. Watts Pedro Mata 《Journal of the American College of Cardiology》2019,73(9):1029-1039
Background
Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Cascade testing is recommended for FH, but there are no similar recommendations for elevated Lp(a).Objectives
This study investigated whether testing for Lp(a) was effective in detecting and risk stratifying individuals participating in an FH cascade screening program.Methods
Family members (N = 2,927) from 755 index cases enrolled in SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) were tested for genetic FH and elevated Lp(a) via an established screening program. Elevated Lp(a) was defined as levels ≥50 mg/dl. The authors compared the prevalence and yield of new cases of high Lp(a) in relatives of FH probands both with and without high Lp(a), and prospectively investigated the association between elevated Lp(a) and ASCVD events among family members.Results
Systematic screening from index cases with both FH and elevated Lp(a) identified 1 new case of elevated Lp(a) for every 2.4 screened. Opportunistic screening from index cases with FH, but without elevated Lp(a), identified 1 individual for 5.8 screened. Over 5 years’ follow-up, FH (hazard ratio [HR]: 2.47; p = 0.036) and elevated Lp(a) (HR: 3.17; p = 0.024) alone were associated with a significantly increased risk of experiencing an ASCVD event or death compared with individuals with neither disorder; the greatest risk was observed in relatives with both FH and elevated Lp(a) (HR: 4.40; p < 0.001), independent of conventional risk factors.Conclusions
Testing for elevated Lp(a) during cascade screening for FH is effective in identifying relatives with high Lp(a) and heightened risk of ASCVD, particularly when the proband has both FH and elevated Lp(a). 相似文献2.
Umut I. Onat Asli D. Yildirim Özlem Tufanli Ismail Çimen Begüm Kocatürk Zehra Veli Syed M. Hamid Kenichi Shimada Shuang Chen Jon Sin Prediman K. Shah Roberta A. Gottlieb Moshe Arditi Ebru Erbay 《Journal of the American College of Cardiology》2019,73(10):1149-1169
Background
Eukaryotic cells can respond to diverse stimuli by converging at serine-51 phosphorylation on eukaryotic initiation factor 2 alpha (eIF2α) and activate the integrated stress response (ISR). This is a key step in translational control and must be tightly regulated; however, persistent eIF2α phosphorylation is observed in mouse and human atheroma.Objectives
Potent ISR inhibitors that modulate neurodegenerative disorders have been identified. Here, the authors evaluated the potential benefits of intercepting ISR in a chronic metabolic and inflammatory disease, atherosclerosis.Methods
The authors investigated ISR’s role in lipid-induced inflammasome activation and atherogenesis by taking advantage of 3 different small molecules and the ATP-analog sensitive kinase allele technology to intercept ISR at multiple molecular nodes.Results
The results show lipid-activated eIF2α signaling induces a mitochondrial protease, Lon protease 1 (LONP1), that degrades phosphatase and tensin-induced putative kinase 1 and blocks Parkin-mediated mitophagy, resulting in greater mitochondrial oxidative stress, inflammasome activation, and interleukin-1β secretion in macrophages. Furthermore, ISR inhibitors suppress hyperlipidemia-induced inflammasome activation and inflammation, and reduce atherosclerosis.Conclusions
These results reveal endoplasmic reticulum controls mitochondrial clearance by activating eIF2α-LONP1 signaling, contributing to an amplified oxidative stress response that triggers robust inflammasome activation and interleukin-1β secretion by dietary fats. These findings underscore the intricate exchange of information and coordination of both organelles’ responses to lipids is important for metabolic health. Modulation of ISR to alleviate organelle stress can prevent inflammasome activation by dietary fats and may be a strategy to reduce lipid-induced inflammation and atherosclerosis. 相似文献3.
Hong Chee Chew Arjun Iyer Mark Connellan Sarah Scheuer Jeanette Villanueva Ling Gao Mark Hicks Michelle Harkness Claudio Soto Andrew Dinale Priya Nair Alasdair Watson Emily Granger Paul Jansz Kavitha Muthiah Andrew Jabbour Eugene Kotlyar Anne Keogh Kumud Dhital 《Journal of the American College of Cardiology》2019,73(12):1447-1459
Background
Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice.Objectives
The purpose of this study is to provide an update on the authors’ Australian clinical program and discuss lessons learned since performing the world’s first series of distantly procured DCD heart transplants.Methods
The authors report their experience of 23 DCD heart transplants from 45 DCD donor referrals since 2014. Donor details were collected using electronic donor records (Donate Life, Australia) and all recipient details were collected from clinical notes and electronic databases at St. Vincent’s Hospital.Results
Hearts were retrieved from 33 of 45 DCD donors. A total of 12 donors did not progress to circulatory arrest within the pre-specified timeframe. Eight hearts failed to meet viability criteria during normothermic machine perfusion, and 2 hearts were declined due to machine malfunction. A total of 23 hearts were transplanted between July 2014 and April 2018. All recipients had successful implantation, with mechanical circulatory support utilized in 9 cases. One case requiring extracorporeal membrane oxygenation subsequently died on the sixth post-operative day, representing a mortality of 4.4% over 4 years with a total follow-up period of 15,500 days for the entire cohort. All surviving recipients had normal cardiac function on echocardiogram and no evidence of acute rejection on discharge. All surviving patients remain in New York Heart Association functional class I with normal biventricular function.Conclusions
DCD heart transplant outcomes are excellent. Despite a higher requirement for mechanical circulatory support for delayed graft function, primarily in recipients with ventricular assist device support, overall survival and rejection episodes are comparable to outcomes from contemporary brain-dead donors. 相似文献4.
Pradeep Natarajan Tim S. Collier Zhicheng Jin Asya Lyass Yiwei Li Nasrien E. Ibrahim Renata Mukai Cian P. McCarthy Joseph M. Massaro Ralph B. D’Agostino Hanna K. Gaggin Cory Bystrom Marc S. Penn James L. Januzzi 《Journal of the American College of Cardiology》2019,73(17):2135-2145
Background
Concentrations of circulating apolipoproteins are strongly linked to risk for coronary artery disease (CAD). The relative importance of the additional knowledge of apolipoprotein concentrations within specific lipoprotein species for CAD risk prediction is limited.Objectives
This study sought to evaluate the performance of a high-density lipoprotein (HDL) apolipoproteomic score, based on targeted mass spectrometry of HDL-associated apolipoproteins, for the detection of angiographic CAD and outcomes.Methods
HDL-associated apolipoprotein (apo) A-1, apoC-1, apoC-2, apoC-3, and apoC-4 were measured in 943 participants without prevalent myocardial infarction (MI) referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study. A composite HDL apolipoproteomic score (pCAD) was associated with likelihood of obstructive CAD (≥70% lesion in ≥1 vessel) and with incident cardiovascular outcomes over 4-year follow-up.Results
There were 587 (62.2%) patients with coronary stenosis. The pCAD score was associated with the presence of obstructive CAD (odds ratio: 1.39; 95% confidence interval [CI]: 1.14 to 1.69; p < 0.001), independently of conventional cardiovascular risk factors including circulating plasma apoA-1 and apoB. The C-index for pCAD was 0.63 (95% CI: 0.59 to 0.67) for the presence of obstructive CAD. Although pCAD was not associated with cardiovascular mortality among all individuals (hazard ratio: 1.24; 95% CI: 0.93 to 1.66; p = 0.15), there was evidence of association for individuals with obstructive CAD (hazard ratio: 1.48; 95% CI: 1.07 to 2.05; p = 0.019).Conclusions
An HDL apolipoproteomic score is associated with the presence of CAD, independent of circulating apoA-1 and apoB concentrations and other conventional cardiovascular risk factors. Among individuals with CAD, this score may be independently associated cardiovascular death. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868) 相似文献5.
Julie Hallet Shiva Jayaraman Guillaume Martel Jean-François B. Ouellet Yulia Lin Stuart McCluskey Kaitlyn A. Beyfuss Paul J. Karanicolas 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2019,21(4):393-404
Background
Blood loss and transfusion remain a significant concern in liver resection (LR). Patient blood management (PBM) programs reduce use of transfusions and improve outcomes and costs, but are not standardized for LR. This study sought to create an expert consensus statement on PBM for LR using modified Delphi methodology.Methods
An expert panel representing hepato-biliary surgery, anesthesiology, and transfusion medicine was invited to participate. 28 statements addressing the 3 pillars of PBM were created. Panelists were asked to rate statements on a 7-point Likert scale. Three-rounds of iterative rating and feedback were completed anonymously, followed by an in-person meeting. Consensus was reached with at least 70% agreement.Results
The 35 experts panel recommended routine pre-operative transfusion risk assessment, and investigation and management of anemia with iron supplementation. Intra-operatively, restrictive fluid administration without routine central line insertion was recommended, along with intermittent hepatic pedicle occlusion and surgical techniques considerations. Specific criteria for restrictive intra-operative and post-operative transfusion strategy were recommended.Conclusions
PBM for LR included medical and technical interventions throughout the perioperative continuum, addressing specificities of LR. Diffusion and adoption of these recommendations can standardize PBM for LR to improve patient outcomes and resource utilization. 相似文献6.
Betulinic acid inhibits high-fat diet-induced obesity and improves energy balance by activating AMPK
K.-D. Kim H.-Y. Jung H.G. Ryu B. Kim J. Jeon H.Y. Yoo C.H. Park B.-H. Choi C.-K. Hyun K.-T. Kim S. Fang S.H. Yang J.-B. Kim 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(4):409-420
Background and aim
Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity.Methods and results
Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA.Conclusions
The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease. 相似文献7.
Yasuhiro Tomita Yuma Fukutomi Mari Irie Kazuhiro Azekawa Hiroaki Hayashi Yosuke Kamide Kiyoshi Sekiya Yoichi Nakamura Chiharu Okada Terufumi Shimoda Yoshinori Hasegawa Masami Taniguchi 《Allergology international》2019,68(2):240-246
Background
Several cross-sectional studies have suggested an association between obesity and asthma. However, few studies have investigated this relationship longitudinally, especially in middle-aged subjects. Although metabolic syndrome is a well-known risk factor for many non-communicable diseases, its contribution to asthma remains controversial.Methods
From 2008, specific health checkups for metabolic syndrome have been conducted throughout Japan. To seek relationships of obesity and metabolic syndrome with late-onset asthma in Japan, we analyzed data collected from health insurance claims and specific health checkups for metabolic syndrome at three large health insurance societies. Among subjects aged 40–64 years (n = 9888), multivariate logistic regression analyses were performed to investigate the relationships of obesity and metabolic syndrome in fiscal year 2012 (from April 2012 to March 2013) with the incidence of late-onset asthma in the following two years (from April 2013 to March 2015).Results
In women, BMI 25–29.9 kg/m2 or ≥30 kg/m2, waist circumference ≥90 cm, and waist-to-height ratio ≥0.5 were shown to be significant risk factors for asthma, with adjusted odds ratios (95% CI) of 1.92 (1.35–2.75), 2.24 (1.23–4.09), 1.89 (1.30–2.75), and 1.53 (1.15–2.03), respectively. Significance was retained even after adjustment for metabolic syndrome, and there were no significant relationships between metabolic syndrome itself and the incidence of asthma in men or women.Conclusions
Only the obesity measures, not metabolic syndrome, were shown to be significant risk factors for the incidence of late-onset asthma but only in middle-aged Japanese women, and not in men. 相似文献8.
William G. Stevenson Usha B. Tedrow Vivek Reddy Amir AbdelWahab Srinivas Dukkipati Roy M. John Akira Fujii Benjamin Schaeffer Shinichi Tanigawa Ihab Elsokkari Jacob Koruth Tomofumi Nakamura Aditi Naniwadekar Daniele Ghidoli Christine Pellegrini John L. Sapp 《Journal of the American College of Cardiology》2019,73(12):1413-1425
Background
Catheter ablation is effective for eliminating most drug-refractory ventricular arrhythmias (VA). However, a major reason for procedural failure is arrhythmia originating deep within the myocardium where it is inaccessible to conventional endocardial or epicardial approaches. Affected patients have limited therapeutic options.Objectives
The objective of this study was to assess the safety and outcome of a novel radiofrequency ablation catheter that used an extendable/retractable 27-g needle capable of targeting deep arrhythmia (intramural) substrate.Methods
Patients who failed at least one prior catheter ablation procedure for sustained ventricular tachycardia (VT) or nonsustained VA with associated left ventricular dysfunction were enrolled at 3 centers. The target was sustained monomorphic VT in 26 patients, including 8 with recent VT storm or VT requiring intravenous medication, and 5 with incessant VA associated with ventricular dysfunction.Results
Needle ablation was performed in 31 patients (median of 2 failed prior ablation procedures; 71% nonischemic heart disease). After a median of 15 needle lesions/patient, ablation abolished at least 1 inducible VT in 19 of 26 VT patients (73%), and suppressed ambient arrhythmia in 4 of 5 nonsustained arrhythmia patients. At the 6-month follow-up, 48% of patients were free of recurrent arrhythmia and another 19% were improved. Procedure-related complications included a single pericardial effusion treated with percutaneous drainage and a left ventricular pacing lead dislodgement with no deaths.Conclusions
In patients with recurrent ventricular arrhythmias refractory to medications and conventional catheter ablation, intramural needle radiofrequency ablation offers significant arrhythmia control with an acceptable procedural risk. 相似文献9.
Takehiro Nakahara Jagat Narula Jan G.P. Tijssen Sunil Agarwal Mohammed M. Chowdhury Patrick A. Coughlin Marc R. Dweck James H.F. Rudd Masahiro Jinzaki John Mulhall H. William Strauss 《Journal of the American College of Cardiology》2019,73(12):1386-1394
Background
Fluorine-18 sodium fluoride (NaF), a bone-seeking radiopharmaceutical used to detect osseous metastases, localizes in regions of microcalcification in atherosclerosis.Objectives
To determine if atherosclerosis of penile arteries plays a role in erectile dysfunction (ED), this study analyzed NaF images in prostate cancer patients.Methods
NaF positron emission tomography–computed tomography bone scans were evaluated in 437 prostate cancer patients (age 66.6 ± 8.7 years). Their urologic histories were reviewed for prevalent ED (diagnosed before the scan date) or incident ED (no ED at first scan, but developed during 1-year follow-up); patients with no ED (neither before the scan nor during follow-up) were included as a control group. A semicircular region of interest was set on the dorsal one-half of the penis (to avoid residual excreted activity in the urethra) on 5 contiguous slices at the base of the penis on positron emission tomography–computed tomography coronal reconstructions, and the average standardized uptake value (SUVmax) was described as NaF uptake.Results
Of 437 patients, 336 (76.9%) had prevalent ED, 60 incident ED (13.7%), and 41 had no ED (9.4%). SUVmax in patients with prevalent (median 1.88; interquartile range [IQR]: 1.67 to 2.16) or incident (median 1.86; IQR: 1.72 to 2.08) ED was significantly higher than no ED (median 1.42; IQR: 1.25 to 1.54) patients (p < 0.001). After adjustment for other risk factors, the odds ratio of prevalent or incident ED was 25.2 (95% confidence interval: 9.5 to 67.0) for every 0.5-U increment in SUVmax with receptor operating characteristic area of 0.91 (95% confidence interval: 0.88 to 0.94).Conclusions
NaF uptake in penile vessels suggests that atherosclerosis is associated with ED in prostate cancer patients. The importance of NaF uptake needs to be tested in noncancer subjects and cause-effect relationship needs to be established. 相似文献10.
Yusheng Jie Jiao Gong Cuicui Xiao Jun Zheng Zhiwei Zhang Xinhua Li Zhiliang Gao Bo Hu Yutian Chong 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2019,21(4):499-507
Background
Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising from the liver. Fibulin-1 has been demonstrated to be involved in various cancers, however, its role in ICC remains unclear.Methods
To study the clinical value and potential molecular mechanism of Fibulin-1 in ICC, immunohistochemistry and bioinformatic analyses were performed using data in the Gene Expression Omnibus Datasets and The Cancer Genome Atlas database.Results
Fibulin-1 expression was overexpressed in ICC tissues compared with adjacent non-cancerous tissues, and was significantly associated with unfavorable overall survival. Moreover, similar genes were identified by Gene Expression Profiling Interactive Analysis and microarray data set. Next, functional and pathway enrichment analysis demonstrated that Fibulin-1 was overrepresented in the pathways of extracellular matrix organization and angiogenesis, which are associated with tumor progression and potential for metastasis. Gene set enrichment analysis indicated that the gene sets of epithelial mesenchymal transition, TGF-beta signaling pathway and angiogenesis were enriched in tissues with high Fibulin-1 level. Furthermore, Fibulin-1 silencing suppressed the ability of ICC tumor cells to form colonies and siFibulin-1 repressed the endogenous protein level of p-AKT.Conclusion
Collectively, this study suggests that Fibulin-1 overexpression may play key roles in the carcinogenesis and progression of ICC via regulation of tumor-related pathways. 相似文献11.
Manar D. Samad Alvaro Ulloa Gregory J. Wehner Linyuan Jing Dustin Hartzel Christopher W. Good Brent A. Williams Christopher M. Haggerty Brandon K. Fornwalt 《JACC: Cardiovascular Imaging》2019,12(4):681-689
Objectives
The goal of this study was to use machine learning to more accurately predict survival after echocardiography.Background
Predicting patient outcomes (e.g., survival) following echocardiography is primarily based on ejection fraction (EF) and comorbidities. However, there may be significant predictive information within additional echocardiography-derived measurements combined with clinical electronic health record data.Methods
Mortality was studied in 171,510 unselected patients who underwent 331,317 echocardiograms in a large regional health system. The authors investigated the predictive performance of nonlinear machine learning models compared with that of linear logistic regression models using 3 different inputs: 1) clinical variables, including 90 cardiovascular-relevant International Classification of Diseases, Tenth Revision, codes, and age, sex, height, weight, heart rate, blood pressures, low-density lipoprotein, high-density lipoprotein, and smoking; 2) clinical variables plus physician-reported EF; and 3) clinical variables and EF, plus 57 additional echocardiographic measurements. Missing data were imputed with a multivariate imputation by using a chained equations algorithm (MICE). The authors compared models versus each other and baseline clinical scoring systems by using a mean area under the curve (AUC) over 10 cross-validation folds and across 10 survival durations (6 to 60 months).Results
Machine learning models achieved significantly higher prediction accuracy (all AUC >0.82) over common clinical risk scores (AUC = 0.61 to 0.79), with the nonlinear random forest models outperforming logistic regression (p < 0.01). The random forest model including all echocardiographic measurements yielded the highest prediction accuracy (p < 0.01 across all models and survival durations). Only 10 variables were needed to achieve 96% of the maximum prediction accuracy, with 6 of these variables being derived from echocardiography. Tricuspid regurgitation velocity was more predictive of survival than LVEF. In a subset of studies with complete data for the top 10 variables, multivariate imputation by chained equations yielded slightly reduced predictive accuracies (difference in AUC of 0.003) compared with the original data.Conclusions
Machine learning can fully utilize large combinations of disparate input variables to predict survival after echocardiography with superior accuracy. 相似文献12.
Zhijing Lin Renjie Chen Yixuan Jiang Yongjie Xia Yue Niu Cuiping Wang Cong Liu Chen Chen Yihui Ge Weidong Wang Guanjin Yin Jing Cai Viviane Clement Xiaohui Xu Bo Chen Honglei Chen Haidong Kan 《Journal of the American College of Cardiology》2019,73(16):2076-2085
Background
Few studies have evaluated the health benefits of omega-3 fatty acid supplementation against fine particulate matter (aerodynamic diameter <2.5 μm [PM2.5]) exposure in highly polluted areas.Objectives
The authors sought to evaluate whether dietary fish-oil supplementation protects cardiovascular health against PM2.5 exposure in China.Methods
This is a randomized, double-blinded, and placebo-controlled trial among 65 healthy college students in Shanghai, China. Participants were randomly assigned to either the placebo group or the intervention group with dietary fish-oil supplementation of 2.5 g/day from September 2017 to January 2018, and received 4 rounds of health examinations in the last 2 months of treatments. Fixed-site PM2.5 concentrations on campus were measured in real time. The authors measured blood pressure and 18 biomarkers of systematic inflammation, coagulation, endothelial function, oxidative stress, antioxidant activity, cardiometabolism, and neuroendocrine stress response. Acute effects of PM2.5 on these outcomes were evaluated within each group using linear mixed-effect models.Results
The average PM2.5 level was 38 μg/m3 during the study period. Compared with the placebo group, the fish-oil group showed relatively stable levels of most biomarkers in response to changes in PM2.5 exposure. Between-group differences associated with PM2.5 exposure varied by biomarkers and by lags of exposure. The authors observed beneficial effects of fish-oil supplementation on 5 biomarkers of blood inflammation, coagulation, endothelial function, oxidative stress, and neuroendocrine stress response in the fish-oil group at a false discovery rate of <0.05.Conclusions
This trial shows that omega-3 fatty acid supplementation is associated with short-term subclinical cardiovascular benefits against PM2.5 exposure among healthy young adults in China. (Effect of Dietary Supplemental Fish Oil in Alleviating Health Hazards Associated With Air Pollution; NCT03255187) 相似文献13.
Nina Reistad Jan H. Nilsson Magnus Bergenfeldt Pehr Rissler Christian Sturesson 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2019,21(2):175-180
Background
Liver steatosis is associated with poor outcome after liver transplantation and liver resection. There is a need for an accurate and reliable intraoperative tool to identify and quantify steatosis. This study aimed to investigate whether surface diffuse reflectance spectroscopy (DRS) measurements could detect liver steatosis on humans during liver surgery.Methods
The DRS instrumentation setup consists of a computer, a high-power tungsten halogen light source and two spectrometers, connected through a trifurcated optical fiber to a hand-held probe. Patients scheduled for open resection for liver tumors were considered for inclusion. Multiple DRS measurements were performed on the liver surface after mobilization.Results
In total, 1210 DRS spectra originated from 38 patients, were analyzed. When applying the data to an analytical model the volumetric absorption ratio factor of fat and water specified an explicit distinction between mild to moderate, and moderate to severe steatosis (p < 0.001). There were significant differences between none-to-mild and moderate-to-severe steatosis grade for the following parameters: reduced scattering coefficient (p < 0.001), Mie to total scattering fraction (p < 0.001), Mie slope (p = 0.003), lipid/(lipid + water) (p < 0.001), blood volume (p = 0.044) and bile volume (p < 0.001).Conclusion
This study shows that it is possible to evaluate steatosis grades with hepatic surface diffuse reflectance spectroscopy measurements. 相似文献14.
Swapna Kanade Gita Nataraj Preeti Mehta Daksha Shah 《The Indian journal of tuberculosis》2019,66(1):139-143
Setting
Department of Microbiology.Objective
To determine the common mutations responsible for rifampicin resistance in TB cases detected by Xpert MTB/RIF assay.Design
Results of Xpert MTB/RIF assay performed from 2013 to 2017 were analysed for missing probes in different types of specimens containing rifampicin resistant MTB.Results
Successful results were obtained in14872 of the total 15129 specimens processed by Xpert MTB/RIF assay, of which 9458 (63.6%) were sputum and 5414 (36.4%) were extrapulmonary specimens. MTB was detected in 1624 (17.17%) sputum and 1121 (20.70%) extrapulmonary specimens of which 409 (25.18%) and 277 (24.71%) were rifampicin resistant respectively.Probe E (83.82%) was the commonest probe responsible for rifampicin resistance followed by D (3.93%) and B (3.79%). Mutation in probe C (0.29%) was very rare. Combination of missing probes like AB (0.73%), DE (1.16%) and ADE (0.14%) was observed. 22 (3.2%) specimens showed presence of all five probes.Conclusion
Xpert MTB/RIF assay uses various combinations of probe to detect MTB along with rifampicin resistance and is a valuable diagnostic tool. It can become a useful epidemiological tool to identify dynamics of transmission of TB by addition of few more probes to identify mutations at specific codons. 相似文献15.
V. Provost V. Lamantia S. Bissonnette Y. Cyr M. Faraj 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(5):504-512
Background and aims
Higher fiber intake is associated with increased insulin sensitivity (IS) and reduced glucose-induced insulin secretion (GIIS) during isocaloric-diets; however, its role in hypocaloric-diets is unclear. We examined whether increased fiber intake predicts the amelioration in IS and GIIS following a hypocaloric-diet.Methods and results
This is a post-hoc analysis of 55 adult subjects (BMI > 27 kg/m2) who completed a 6-month hypocaloric-diet (?500 kcal/day). Dietary intake was assessed using 3-day food records at baseline and post-intervention. We evaluated glucose-induced insulin and C-peptide secretions as AUC of plasma insulin and C-peptide during intravenous-glucose-tolerance tests (IVGTT) and IS via hyperinsulinemic-euglycemic clamps. Data analysis employed regression models and 2-way RM ANOVAs. Post-intervention % change in fiber intake was associated positively with ISclamp (r = 0.30) and negatively with % change in total (r = ?0.37) and 2nd phase GIISIVGTT (r = ?0.44) but not C-peptide secretion. It remained associated with lower 2nd phase GIISIVGTT after adjustment for sex and % changes in BMI and energy-intake, independently of other macronutrients. Subjects who increased fiber intake (to 28.7 ± 9.0 g/day) had a greater decrease in 2nd phase GIISIVGTT, not C-peptide secretion, independently of sex or changes in adiposity or energy-intake compared to subjects who decreased intake (to 20.0 ± 6.8 g/day).Conclusion
Higher fiber intake is an independent predictor of reduced 2nd phase glucose-induced hyperinsulinemia after a hypocaloric-diet. It was not associated with plasma C-peptide, suggesting a role in faster insulin clearance rather reduced insulin secretion. Promoting high-fiber intake may increase the effectiveness of hypocaloric-diets in preventing type 2 diabetes.Registration
ISRCTN14476404, BioMedCentral.com.Clinical trial registration
This trial was registered at BioMed Central as ISRCTN14476404, on July 28th, 2017. 相似文献16.
Javed Butler Mei Yang Massimiliano Alfonzo Manzi Gregory P. Hess Mahesh J. Patel Thomas Rhodes Michael M. Givertz 《Journal of the American College of Cardiology》2019,73(8):935-944
Background
Epidemiology of patients with worsening heart failure and reduced ejection fraction (HFrEF) in the real-world setting is not well described.Objectives
The purpose of this study was to describe incidence, clinical characteristics, treatment, and outcomes of patients with HFrEF who develop worsening heart failure (HF) in the real-world setting.Methods
Data on patients with incident HFrEF from the National Cardiovascular Data Registry PINNACLE were linked to pharmacy, private practitioner, and hospital claims databases. Incidence, clinical characteristics, treatment (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist) and outcomes of patients with worsening HF, defined as ≥90 days of stable HF with subsequent worsening requiring intravenous diuretic agents, were assessed.Results
Of 11,064 HFrEF patients, 1,851 (17%) developed worsening HF on average 1.5 years following initial HF diagnosis. Patients who developed worsening HF were more likely to be African American, be octogenarians, and have higher comorbidity burden (p < 0.001). At the onset of worsening HF, 42.4% of patients were on monotherapy, 43.4% were on dual therapy, and 14.1% were on triple therapy. A total of 48%, 61%, and 98% of patients were on >50% target dose for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist, respectively. The 2-year mortality rate was 22.5%, and 56% of patients were rehospitalized within 30 days of the worsening HF event.Conclusions
In the real-world setting, 1 in 6 patients with HFrEF develop worsening HF within 18 months of HF diagnosis. These patients have a high risk for 2-year mortality and recurrent HF hospitalizations. The use of standard-of-care therapies both before and after the onset of worsening HF is low. With high unmet medical need, patients with worsening HF require novel treatment strategies as well as greater optimization of existing guideline-directed therapy. 相似文献17.
Sophie Chopinet Emilie Grégoire Emilie Bollon Jean-François Hak Anaïs Palen Vincent Vidal Jean Hardwigsen Yves-Patrice Le Treut 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2019,21(3):352-360
Background
The benefit of performing major hepatic resection (MHR) for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial because of its high risk of posthepatectomy liver failure (PHLF). This study was conducted to assess the risk of MHR for HCC in patients with cirrhosis.Methods
Patients with Child-Pugh A or B cirrhosis and HCC who underwent MHR from January 2000 to June 2014 were retrospectively identified. Risk factors for postoperative morbidity and mortality using univariate and multivariate analyses were evaluated.Results
Seventy patients with Child-Pugh A (93%) and 5 (7%) with Child-Pugh B cirrhosis underwent MHR for HCC. Thirteen (17%) had Barcelona Clinic Liver Cancer (BCLC) stage A, 39 (50%) had BCLC B, and 23 (32%) had BCLC C disease. A perioperative blood transfusion was performed in 18 patients (24%). Ninety-day postoperative mortality was 9% (n=7). Major complications occurred in 16 patients (21%), including PHLF in 9 patients (12%). A multivariate analysis showed that perioperative blood transfusion was the main independent factor associated with mortality (OR= 6.5) and major morbidity (OR=10).Conclusion
In selected patients with HCC and cirrhosis, MHR is feasible and has acceptable mortality, but careful perioperative management and limiting blood loss are required. 相似文献18.
Tomoharu Yokooji Takahiro Fukushima Koh Hamura Naoki Ninomiya Ryo Ohashi Takanori Taogoshi Hiroaki Matsuo 《Allergology international》2019,68(2):247-253
Background
Aspirin enhances food allergy symptoms by increasing absorption of ingested allergens. The objective of this study is to elucidate the role of aspirin in facilitating intestinal absorption of the wheat allergen, gliadin, in rats.Methods
Plasma concentrations of gliadin were determined after oral administration by gavage or administration into a closed intestinal loop in rats. We used an in situ intestinal re-circulating perfusion experiment to examine the effect of pepsin on aspirin-facilitated gliadin absorption. Fluorescein isothiocyanate (FITC)-labeled dextran-40 (FD-40) was used as a marker of non-specific absorption. The molecular size of gliadin and its allergenicity in plasma were examined using immunoblot analysis and intradermal reaction tests with Evans blue dye (EBD) extravasation, respectively.Results
Aspirin increased plasma concentrations of gliadin after oral administration but had no effect in the closed intestinal loop study. An in situ intestinal re-circulating perfusion study showed that FITC-labeled gliadin was absorbed similarly to FD-40. Aspirin increased absorption of both intact and pepsin-digested gliadin, with a more significant effect on absorption of pepsin-treated gliadin. Immunoblotting showed that most gliadin was absorbed in intact form. When the gliadin fraction was extracted from rat plasma after gavage and injected intradermally into gliadin-sensitized rats, EBD extravasation was observed at injection sites in a gliadin dose-dependent manner.Conclusions
Aspirin increased the absorption of intact and pepsin-digested gliadin via the paracellular pathway, maintaining their allergenicity. Moreover, the effect of aspirin on gliadin absorption was enhanced by modification and digestion of gliadin in the stomach. 相似文献19.
Behnam N. Tehrani Alexander G. Truesdell Matthew W. Sherwood Shashank Desai Henry A. Tran Kelly C. Epps Ramesh Singh Mitchell Psotka Palak Shah Lauren B. Cooper Carolyn Rosner Anika Raja Scott D. Barnett Patricia Saulino Christopher R. deFilippi Paul A. Gurbel Charles E. Murphy Christopher M. O’Connor 《Journal of the American College of Cardiology》2019,73(13):1659-1669
Background
Cardiogenic shock (CS) is a multifactorial, hemodynamically complex syndrome associated with high mortality. Despite advances in reperfusion and mechanical circulatory support, management remains highly variable and outcomes poor.Objectives
This study investigated whether a standardized team-based approach can improve outcomes in CS and whether a risk score can guide clinical decision making.Methods
A total of 204 consecutive patients with CS were identified. CS etiology, patient demographic characteristics, right heart catheterization, mechanical circulatory support use, and survival were determined. Cardiac power output (CPO) and pulmonary arterial pulsatility index (PAPi) were measured at baseline and 24 h after the CS diagnosis. Thresholds at 24 h for lactate (<3.0 mg/dl), CPO (>0.6 W), and PAPi (>1.0) were determined. Using logistic regression analysis, a validated risk stratification score was developed.Results
Compared with 30-day survival of 47% in 2016, 30-day survival in 2017 and 2018 increased to 57.9% and 76.6%, respectively (p < 0.01). Independent predictors of 30-day mortality were age ≥71 years, diabetes mellitus, dialysis, ≥36 h of vasopressor use at time of diagnosis, lactate levels ≥3.0 mg/dl, CPO <0.6 W, and PAPi <1.0 at 24 h after diagnosis and implementation of therapies. Either 1 or 2 points were assigned to each variable, and a 3-category risk score was determined: 0 to 1 (low), 2 to 4 (moderate), and ≥5 (high).Conclusions
This observational study suggests that a standardized team-based approach may improve CS outcomes. A score incorporating demographic, laboratory, and hemodynamic data may be used to quantify risk and guide clinical decision-making for all phenotypes of CS. 相似文献20.
Eleonora Avenatti G. Burkhard Mackensen Kinan Carlos El-Tallawi Mark Reisman Lara Gruye Colin M. Barker Stephen H. Little 《JACC: Cardiovascular Interventions》2019,12(6):582-591