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1.
Ziad A Audat Mahmoud H. Hajyousef Mohammad D. Fawareh Khaldoon M. Alawneh Mohannad A. Odat Mohammad M. Barbarawi Ali A. Alomari Rami A. Jahmani Mohammad A. Khatatbeh Mohammed A. Assmairan 《Scoliosis》2016,11(1):47
Background
This was a prospective study to evaluate the effect of multilevel vertebral augmentation in addition to conventional therapy in multiple myeloma patients.Methods
We treated 27 patients, whom were recently diagnosed to have multiple myeloma by two ways of treatment. Thirteen patients (group I) were treated with conventional therapy and 14 patients (group II) with adding vertebroplasty and kyphoplasty. Patients were evaluated pre-treatment and at half, one, two and 3-years post-treatment by using Oswestry Disability Index (ODI), the Stanford Score (SS) and the Spinal Instability Neoplastic Score (SINS).Results
Mean values of ODI, SS and SINS were 31.9 (63.8%), 4.3 and 13.8 for group I and 33.2 (66.4%), 4.6 and 12.8 for group II before starting treatment. Group II showed improvement better than group I at all follow-up intervals with best results at first 6 months. P-values at the end of the study were ODI?=?0.047, SS?=?0.180 and SINS?=?0.002. Mortality rates were equal of both groups (four patients of each group).Conclusion
Adding vertebral augmentation to conventional therapy improves multiple myeloma patients’ quality of life, but didn’t affect the mortality rate.2.
Background
To determine the correlation of cyclin-dependent kinase inhibitor 1B (p27) expression with clinicopathologic features in nasopharyngeal carcinoma (NPC), including patient prognosis.Methods
Real-time PCR and immunohistochemistry were used to examine the mRNA and protein expressions of p27 in NPC and nasopharyngeal tissues. The relationship of p27 expression levels with clinical features and prognosis of NPC patients was analyzed.Results
The expression level of p27 mRNA was markedly lower in NPC tissues than that in the nasopharyngeal tissues (P?=?0.0006). Specific p27 protein staining by immunohistochemistry was found in the nuclei and cytoplasm of nasopharyngeal and malignant epithelial cells but decreased expression was observed in NPC samples compared to normal epithelium samples (P?=?0.002). In addition, low levels of p27 protein were inversely correlated with the status of T classification (p?=?0.002) and clinical stage (p?=?0.019) of NPC patients. Patients with lower p27 expression had a significantly shorter overall survival time than did patients with high p27 expression. Multivariate analysis suggested that the level of p27 expression was not an independent prognostic indicator (p?=?0.682) for NPC survival.Conclusion
Low level of p27 expression is a potential unfavorable prognostic factor for patients with NPC.Virtual slides
The virtual slide (s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1915282782109343.3.
Kai Yang Fan Zhang Peng Han Zhuo-zhong Wang Kui Deng Yuan-yuan Zhang Wei-wei Zhao Wei Song Yu-qing Cai Kang Li Bin-bin Cui Zheng-Jiang Zhu 《Metabolomics : Official journal of the Metabolomic Society》2018,14(9):110
Introduction
Colorectal cancer (CRC) is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. Only some CRC patients will benefit from neoadjuvant chemotherapy (NACT).Objectives
An accurate prediction of response to NACT in CRC patients would greatly facilitate optimal personalized management, which could improve their long-term survival and clinical outcomes.Methods
In this study, plasma metabolite profiling was performed to identify potential biomarker candidates that can predict response to NACT for CRC. Metabolic profiles of plasma from non-response (n?=?30) and response (n?=?27) patients to NACT were studied using UHPLC–quadruple time-of-flight)/mass spectrometry analyses and statistical analysis methods.Results
The concentrations of nine metabolites were significantly different when comparing response to NACT. The area under the receiver operating characteristic curve value of the potential biomarkers was up to 0.83 discriminating the non-response and response group to NACT, superior to the clinical parameters (carcinoembryonic antigen and carbohydrate antigen 199).Conclusion
These results show promise for larger studies that could result in more personalized treatment protocols for CRC patients.4.
Hailong Zhang Longzhen Cui Wen Liu Zhenfeng Wang Yang Ye Xue Li Huijuan Wang 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):47
Introduction
Gastric cancer (GC) is a malignant tumor worldwide. As primary pathway for metastasis, the lymphatic system is an important prognostic factor for GC patients. Although the metabolic changes of gastric cancer have been investigated in extensive studies, little effort focused on the metabolic profiling of lymph node metastasis (LNM)-positive or negative GC patients.Objectives
We performed 1H NMR spectrum of GC tissue samples with and without LNM to identify novel potential metabolic biomarkers in the process of LNM of GC.Methods
1H NMR-based untargeted metabolomics approach combined with multivariate statistical analyses were used to study the metabolic profiling of tissue samples from LNM-positive GC patients (n?=?40), LNM-negative GC patients (n?=?40) and normal controls (n?=?40).Results
There was a clear separation between GC patients and normal controls, and 33 differential metabolites were identified in the study. Moreover, GC patients were also well-classified according to LNM-positive or negative. Totally eight distinguishing metabolites were selected in the metabolic profiling of GC patients with LNM-positive or negative, suggesting the metabolic dysfunction in the process of LNM. According to further validation and analysis, especially BCAAs metabolism (leucine, isoleucine, valine), GSH and betaine may be as potential factors of diagnose and prognosis of GC patients with or without LNM.Conclusion
To our knowledge, this is the first metabolomics study focusing on LNM of GC. The identified distinguishing metabolites showed a promising application on clinical diagnose and therapy prediction, and understanding the mechanism underlying the carcinogenesis, invasion and metastasis of GC.5.
Jing Wen Yong Li Xia Yang Bright Eric Ohene Yu Jie Zhou Zhi Jian Wang 《BMC cardiovascular disorders》2017,17(1):295
Background
Periprocedural heparin bridging therapy aims to reduce the risk of thromboembolic events in patients requiring an interruption in their anticoagulation therapy for the purpose of an elective procedure. The efficacy and safety of heparin bridging therapy has not been well established.Objectives
To compare through meta-analysis the effects of heparin bridging therapy on the risk of major bleeding and thromboembolic events of clinical significance among patients taking oral anticoagulants.Methods
We searched PubMed, EMBASE and the Cochrane library from January 2005 to July 2016. Studies were included if they reported clinical outcomes of patients receiving heparin bridging therapy during interruption of oral anticoagulant for operations. Data were pooled using random-effects modeling.Results
A total of 25 studies, including 6 randomized controlled trials and 19 observational studies, were finally included in this analysis. Among all the 35,944 patients, 10,313 patients were assigned as heparin bridging group, and the other 25,631 patients were non-heparin bridging group. Overall, compared with patients without bridging therapy, heparin bridging therapy increased the risk of major bleeding (OR?=?3.23, 95%CI: 2.06–5.05), minor bleeding (OR?=?1.52, 95%CI: 1.06–2.18) and overall bleeding (OR?=?2.83, 95%CI: 1.86–4.30).While there was no significant difference in thromboembolic events (OR?=?0.99,95%CI: 0.49–2.00), stroke or transient ischemic attack(OR?=?1.45, 95%CI: 0.93–2.26,) or all-cause mortality (OR?=?0.71, 95%CI: 0.31–1.65).Conclusions
Heparin-bridging therapy increased the risk of major and minor bleeding without decreasing the risk of thromboembolic events and all cause death compared to non-heparin bridging.6.
Nwora Lance Okeke Damian M. Craig Michael J. Muehlbauer Olga Ilkayeva Meredith E. Clement Susanna Naggie Svati H. Shah 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):23
Introduction
Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking.Methods
Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis.Results
Factors derived from short-chain dicarboxylacylcarnitines (SCDA) (p?=?0.08) and glutamine/valine (p?=?0.003) were elevated in CAD cases compared to controls.Conclusion
SCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.7.
Background
The course of self-reported symptoms during medium- versus long-term psychodynamic psychotherapy has rarely been documented for outpatient settings. This observational study describes routine practice of ambulatory treatment in Germany and explores self-reported symptoms of a broad patient sample undergoing one (medium-term) versus two years (long-term) of psychodynamic psychotherapy.Methods
Over four and a half years, longitudinal self-report symptom data were collected from 342 outpatients as part of a standardized documentation system. Self-report data were compared between patients receiving either medium-term or long-term psychodynamic psychotherapy.Results
Routine care significantly decreased disease burden as reported by patients by small to medium effect sizes (ES) for depression (ES?=?0.58), anxiety (ES?=?0.49), obsessive-compulsive disorder (ES?=?0.54), somatoform disorder (ES?=?0.32), eating disorder (ES?=?0.38). The majority of patients completed treatment after one year and showed medium-size changes. For a subgroup of patients with depressive and/or obsessive-compulsive disorder symptoms for whom two years of therapy were deemed necessary, additional benefits were reported during the second year of treatment (ES?=?0.61 and ES??0.47, respectively).Conclusions
Our findings suggest that both medium- and long-term psychodynamic psychotherapy decrease self-reported disease burden of patients with depression, anxiety, obsessive-compulsive, somatoform and/or eating disorders. For a subgroup of patients, additional benefits were gained in the second year of treatment.8.
Chen Chen G. A. Nagana Gowda Jiangjiang Zhu Lingli Deng Haiwei Gu E. Gabriela Chiorean Mohammad Abu Zaid Marietta Harrison Dabao Zhang Min Zhang Daniel Raftery 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):125
Introduction
Metabolomics technologies enable the identification of putative biomarkers for numerous diseases; however, the influence of confounding factors on metabolite levels poses a major challenge in moving forward with such metabolites for pre-clinical or clinical applications.Objectives
To address this challenge, we analyzed metabolomics data from a colorectal cancer (CRC) study, and used seemingly unrelated regression (SUR) to account for the effects of confounding factors including gender, BMI, age, alcohol use, and smoking.Methods
A SUR model based on 113 serum metabolites quantified using targeted mass spectrometry, identified 20 metabolites that differentiated CRC patients (n?=?36), patients with polyp (n?=?39), and healthy subjects (n?=?83). Models built using different groups of biologically related metabolites achieved improved differentiation and were significant for 26 out of 29 groups. Furthermore, the networks of correlated metabolites constructed for all groups of metabolites using the ParCorA algorithm, before or after application of the SUR model, showed significant alterations for CRC and polyp patients relative to healthy controls.Results
The results showed that demographic covariates, such as gender, BMI, BMI2, and smoking status, exhibit significant confounding effects on metabolite levels, which can be modeled effectively.Conclusion
These results not only provide new insights into addressing the major issue of confounding effects in metabolomics analysis, but also shed light on issues related to establishing reliable biomarkers and the biological connections between them in a complex disease.9.
Fernanda Bertuccez Cordeiro Thaís Regiani Cataldi Beatriz Zappellini de Souza Raquel Cellin Rochetti Renato Fraietta Carlos Alberto Labate Edson Guimarães Lo Turco 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):51
Introduction
During in vitro fertilization (IVF), the hyper response to controlled ovarian stimulation (COS) is a common characteristic among patients diagnosed with polycystic ovary syndrome (PCOS), although non-diagnosed patients may also demonstrate this response.Objectives
In an effort to investigate follicular metabolic characteristics associated with hyper response to COS, the present study analyzed follicular fluid (FF) samples from patients undergoing IVF.Methods
FF samples were obtained from patients with PCOS and hyper response during IVF (PCOS group, N?=?15), patients without PCOS but with hyper response during IVF (HR group, N?=?44), and normo-responder patients receiving IVF (control group, N?=?22). FF samples underwent Bligh and Dyer extraction, followed by metabolomic analysis by ultra-performance liquid chromatography mass spectrometry, considering two technical replicates. Clinical data was analyzed by ANOVA and chi-square tests. The metabolomic dataset was analyzed by multivariate statistics, and the significance of biomarkers was confirmed by ANOVA.Results
Clinical data showed differences regarding follicles production, oocyte and embryo quality. From the 15 proposed biomarkers, 14 were of increased abundance in the control group and attributed as fatty acids, diacylglycerol, triacylglycerol, ceramide, ceramide-phosphate, phosphatidylcholine, and sphingomyelin. The PCOS patients showed increased abundance of a metabolite of m/z 144.0023 that was not attributed to a class.Conclusion
The clinical and metabolic similarities observed in the FF of hyper responders with and without PCOS diagnosis indicate common biomarkers that could assist on the development of accessory tools for assessment of IVF parameters.10.
Xiaomeng Yang Shuya Li Xingquan Zhao Liping Liu Yong Jiang Zixiao Li Yilong Wang Yongjun Wang 《BMC neurology》2017,17(1):207
Background
Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF.Methods
Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis.Results
Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR?=?4.70, 95%CI, 1.64–13.5), advanced age (OR?=?1.06, 95%CI, 1.04–1.09), NIHSS at admission (OR?=?1.06, 95%CI, 1.02–1.10), blood high density lipoprotein (HDL) (OR?=?1.52, 95%CI, 1.09–2.13), together with blood triglycerides (OR?=?0.64, 95%CI, 0.45–0.91) were independently associated with newly-detected AF.Conclusions
Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF.Trial registration
NCT02156765 (June 5, 2014).11.
Mahmoud Delphan Tengda Lin David B. Liesenfeld Johanna Nattenmüller Jürgen T. Böhm Biljana Gigic Nina Habermann Lin Zielske Petra Schrotz-King Martin Schneider Alexis Ulrich Hans-Ulrich Kauczor Cornelia M. Ulrich Jennifer Ose 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):22
Background
Branched-chain amino acids (BCAA) have been previously linked to survival in colorectal cancer (CRC) patients. It is unclear whether BCAAs are prognostic biomarkers or surrogate markers for energy balance.Objectives
We aimed to determine correlations of BCAAs with markers of energy balance over time and to investigate prognostic significance of BCAAs in CRC.Methods
We used urinary samples from newly diagnosed CRC patients [n?=?163; (stage I–IV)] from the ColoCare study in Heidelberg, Germany, collected at surgery (n?=?163), 6 (n?=?83) and 12 months follow-up (n?=?54). Isoleucine, leucine, valine, (2Z)-3-methylglutaconic acid (3HM), 2-ethylhydracrylic acid (2EA), 2-methyl-3-hydroxybutyrate (2M3H) were detected using gas-chromatography mass-spectrometry and proton-nuclear-magnetic-resonance spectroscopy. Partial correlation coefficients between BCAAs with body mass index, physical activity (metabolic equivalent) and muscle area were computed and adjusted for sex and age at diagnosis. We used Cox proportional hazard models to investigate overall survival (OS) after 24 months of follow-up.Results
We did not observe significant correlations between BCAAs and parameters of energy balance at all time points (correlation ranges: BMI: r?=???0.13 to ??0.01; METs: r?=???0.14 to 0.02; dorsal muscle: r?=???0.03 to 0.10). BCAAs were not associated with risk of death in stage I–III (e.g., valine: HRlog2?=?1.62, p?=?0.25) or in stage IV tumors. Elevated concentrations of 2EA and 2M3H were significantly associated with OS, independent of stage (2EA: stage I–III: HRlog2?=?0.42, p?=?0.04; stage IV: HRlog2?=?0.51, p?=?0.01).Conclusion
Our study suggests that BCAAs in colorectal cancer patients do not reflect parameters of energy balance and may be independently associated with overall survival.12.
Benjamin H Natelson Roxann Intriligator Neil S Cherniack Helena K Chandler Julian M Stewart 《Dynamic medicine : DM》2007,6(1):2
Context
Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.Objective
To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.Design
Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.Setting
Referral practice and research center.Participants
60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.Main outcome measures
Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.Results
CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.Conclusion
A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.13.
Yuka Torii Yoshihiko Kawano Hajime Sato Tamaki Fujimori Kazunori Sasaki Jun-ichi Kawada Osamu Takikawa Chai K. Lim Gilles J. Guillemin Yoshiaki Ohashi Yoshinori Ito 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):126
Introduction
Human herpesvirus 6 (HHV-6) is the second most common causative pathogen of acute encephalopathy in immunocompetent children in Japan. Identification of biomarkers associated the pathophysiology is desirable to monitor disease severity, progression, and prognosis.Objectives
To investigate potential biomarkers for HHV-6 encephalopathy, serum metabolome profiling was analyzed and candidate metabolites were investigated the function in the diseases.Methods
Pediatric patients with HHV-6 encephalopathy (n?=?8), febrile seizure (n?=?20), and febrile infection without febrile seizure (n?=?7) were enrolled in this study, and serum metabolites were identified and quantified. For further analysis, serum samples of HHV-6 infected patients were analyzed by absolute quantification assay for kynurenine (KYN) and quinolinic acid (QUIN) in a total of 38 patients with or without encephalopathy. An in vitro blood–brain barrier (BBB) model was used to evaluate the effect of KYN and QUIN on BBB integrity because BBB damage induces brain edema.Results
Metabolome profiling identified 159 metabolites in serum samples. The levels of KYN and QUIN, which belong to the tryptophan-KYN pathway, were significantly higher in the HHV-6 encephalopathy group than the other two groups. When quantified in the larger patient group, remarkably high levels of KYN and QUIN were observed exclusively in the encephalopathy group. Trans-endothelial electrical resistance of the BBB model was significantly decreased after QUIN treatment in culture.Conclusion
Metabolome analysis revealed that KYN and QUIN may be associated with the pathophysiology of HHV-6 encephalopathy. In particular, QUIN may damage BBB integrity.14.
Zhengling Liu Zengyan Wang Changhong Hao Yonghui Tian Jingjing Fu 《Reproductive biology and endocrinology : RB&E》2018,16(1):120
Background
Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.Methods
Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Results
Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.Conclusions
Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.15.
Ruifang Li-Gao Renée de Mutsert Patrick C. N. Rensen Jan Bert van Klinken Cornelia Prehn Jerzy Adamski Astrid van Hylckama Vlieg Martin den Heijer Saskia le Cessie Frits R. Rosendaal Ko Willems van Dijk Dennis O. Mook-Kanamori 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):13
Introduction
Fasting metabolite profiles have been shown to distinguish type 2 diabetes (T2D) patients from normal glucose tolerance (NGT) individuals.Objectives
We investigated whether, besides fasting metabolite profiles, postprandial metabolite profiles associated with T2D can stratify individuals with impaired fasting glucose (IFG) by their similarities to T2D.Methods
Three groups of individuals (age 45–65 years) without any history of IFG or T2D were selected from the Netherlands Epidemiology of Obesity study and stratified by baseline fasting glucose concentrations (NGT (n?=?176), IFG (n?=?186), T2D (n?=?171)). 163 metabolites were measured under fasting and postprandial states (150 min after a meal challenge). Metabolite profiles specific for a high risk of T2D were identified by LASSO regression for fasting and postprandial states. The selected profiles were utilised to stratify IFG group into high (T2D probability?≥?0.7) and low (T2D probability?≤?0.5) risk subgroups. The stratification performances were compared with clinically relevant metabolic traits.Results
Two metabolite profiles specific for T2D (nfasting = 12 metabolites, npostprandial = 4 metabolites) were identified, with all four postprandial metabolites also being identified in the fasting state. Stratified by the postprandial profile, the high-risk subgroup of IFG individuals (n?=?72) showed similar glucose concentrations to the low-risk subgroup (n?=?57), yet a higher BMI (difference: 3.3 kg/m2 (95% CI 1.7–5.0)) and postprandial insulin concentrations (21.5 mU/L (95% CI 1.8–41.2)).Conclusion
Postprandial metabolites identified T2D patients as good as fasting metabolites and exhibited enhanced signals for IFG stratification, which offers a proof of concept that metabolomics research should not focus on the fasting state alone.16.
Run Du Rui Yan Zhang Lin Lu Ying Shen Li Jin Pu Zheng Bin Zhu Qi Zhang Jian Hu Zhen Kun Yang Feng Hua Ding Jian Sheng Zhang Wei Feng Shen 《Cardiovascular diabetology》2018,17(1):149
Background
Negative coronary artery remodeling is frequent in patients with diabetes, but its mechanism remains unclear. We here evaluated the association of serum levels of glycated albumin (GA) and endogenous secretory receptor for advanced glycation end products (esRAGE) with coronary artery remodeling in type 2 diabetic patients.Methods
Serum levels of GA and esRAGE were measured and intravascular ultrasound was performed in 136 consecutive diabetic patients with 143 coronary intermediate lesions. The remodeling index (RI) was calculated as the ratio between external elastic membrane (EEM) area at the lesion site and EEM area at the reference segment. Negative remodeling (NR) was defined as an RI?<?0.95 and intermediate or positive remodeling as an RI?≥?0.95.Results
Mean plaque burden at the lesion site was 70.96?±?9.98%, and RI was 0.96?±?0.18. Negative coronary arterial remodeling existed in 81 (56.6%) lesions. RI correlated closely with serum esRAGE level (r?=?0.236, P?=?0.005) and was inversely related to serum GA level (r?=???0.240, P?=?0.004) and plasma low-density lipoprotein cholesterol (LDL-C) (r?=???0.206, P?=?0.014) and total cholesterol levels (r?=???0.183, P?=?0.028). Generalized estimating equations logistic regression analysis identified esRAGE (OR 0.037; 95% CI 0.012–0.564, P?=?0.021), GA (OR 1.093; 95% CI 1.013–1.179, P?=?0.018) and LDL-C (OR 1.479; 95% CI 1.072–2.835, P?=?0.023) as independent predictors for negative remodeling.Conclusions
In diabetic patients, negative coronary artery remodeling is associated with increased GA and decreased esRAGE levels in serum.17.
Anna Lindahl Rainer Heuchel Jenny Forshed Janne Lehtiö Matthias Löhr Anders Nordström 《Metabolomics : Official journal of the Metabolomic Society》2017,13(5):61
Introduction
Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer-related death in Europe with a 5-year survival rate of <5%. Chronic pancreatitis (CP) is a risk factor for PDAC development, but in the majority of cases malignancy is discovered too late for curative treatment. There is at present no reliable diagnostic marker for PDAC available.Objectives
The aim of the study was to identify single blood-based metabolites or a panel of metabolites discriminating PDAC and CP using liquid chromatography-mass spectrometry (LC-MS).Methods
A discovery cohort comprising PDAC (n?=?44) and CP (n?=?23) samples was analyzed by LC-MS followed by univariate (Student’s t test) and multivariate (orthogonal partial least squares-discriminant analysis (OPLS-DA)) statistics. Discriminative metabolite features were subject to raw data examination and identification to ensure high feature quality. Their discriminatory power was then confirmed in an independent validation cohort including PDAC (n?=?20) and CP (n?=?31) samples.Results
Glycocholic acid, N-palmitoyl glutamic acid and hexanoylcarnitine were identified as single markers discriminating PDAC and CP by univariate analysis. OPLS-DA resulted in a panel of five metabolites including the aforementioned three metabolites as well as phenylacetylglutamine (PAGN) and chenodeoxyglycocholate.Conclusion
Using LC-MS-based metabolomics we identified three single metabolites and a five-metabolite panel discriminating PDAC and CP in two independent cohorts. Although further study is needed in larger cohorts, the metabolites identified are potentially of use in PDAC diagnostics.18.
19.
Matthew F. Buas Haiwei Gu Danijel Djukovic Jiangjiang Zhu Lynn Onstad Brian J. Reid Daniel Raftery Thomas L. Vaughan 《Metabolomics : Official journal of the Metabolomic Society》2017,13(3):23
Introduction/objectives
Incidence of esophageal adenocarcinoma (EA), an often fatal cancer, has increased sharply over recent decades. Several important risk factors (reflux, obesity, smoking) have been identified for EA and its precursor, Barrett’s esophagus (BE), but a key challenge remains in identifying individuals at highest risk, since most with reflux do not develop BE, and most with BE do not progress to cancer. Metabolomics represents an emerging approach for identifying novel biomarkers associated with cancer development.Methods
We used targeted liquid chromatography-mass spectrometry (LC-MS) to profile 57 metabolites in 322 serum specimens derived from individuals with gastroesophageal reflux disease (GERD), BE, high-grade dysplasia (HGD), or EA, drawn from two well-annotated epidemiologic parent studies.Results
Multiple metabolites differed significantly (P?<?0.05) between BE versus GERD (n?=?9), and between HGD/EA versus BE (n?=?4). Several top candidates (FDR q?≤?0.15), including urate, homocysteine, and 3-nitrotyrosine, are linked to inflammatory processes, which may contribute to BE/EA pathogenesis. Multivariate modeling achieved moderate discrimination between HGD/EA and BE (AUC?=?0.75), with less pronounced separation for BE versus GERD (AUC?=?0.64).Conclusion
Serum metabolite differences can be detected between individuals with GERD versus BE, and between those with BE versus HGD/EA, and may help differentiate patients at different stages of progression to EA.20.
Celestino Sardu Michelangela Barbieri Maria Luisa Balestrieri Mario Siniscalchi Pasquale Paolisso Paolo Calabrò Fabio Minicucci Giuseppe Signoriello Michele Portoghese Pasquale Mone Davide D’Andrea Felice Gragnano Alessandro Bellis Ciro Mauro Giuseppe Paolisso Maria Rosaria Rizzo Raffaele Marfella 《Cardiovascular diabetology》2018,17(1):152