Documents published in 2017 : Scipedia

Is HATCH score a reliable predictor of atrial fibrillation after cavotricuspid isthmus ablation for typical atrial flutter?
. Javier García-Seara, F. Sampedro, J. Sande, X. López, M. Mañero, L. Melchor, B. Alvarez, D. Alvarez, J. Juanatey

IJC Heart & Vasculature (2016). Vol. 12 pp. 88-94

Abstract
We determined the effectiveness of the HATCH score in patients with typical atrial flutter (AFl) undergoing cavotricuspid isthmus (CTI) ablation to predict long-term atrial fibrillation (AF). We conducted an observational retrospective single-center cohort study including all patients admitted to our hospital for a CTI ablation between 1998 and 2010. The patients were divided into four categories: 1) new-onset AF (no prior AF and AF during follow-up (FU)), 2) old AF (prior AF and no AF during FU), 3) prior and post AF (AF prior and post CTI ablation), and 4) no AF. Four hundred and eight patients were included. In patients without prior AF, the hazard ratio (HR) for new-onset AF during FU was 0.98 (CI 95%: 0.65–1.50, p = 0.95) and 1.00 (CI 95%: 0.57–1.77, p = 0.98) for HATCH ≥ 2 and HATCH ≥ 3, respectively. In patients with prior AF, the HR for AF was 1.41 (CI 95%: 0.87–2.28, p = 0.17) and 1.79 (CI 95%: 0.96–3.35, p = 0.06), for HATCH ≥ 2 and HATCH ≥ 3, respectively. Left atrial enlargement was positively correlated with the occurrence of AF during FU, especially in the subgroup without prior AF, which had a HR of 2.44 (CI 95%: 1.35–4.40, p = 0.003), a HR of 2.88 (CI 95%: 1.36–6.10, p = 0.006) and a HR of 3.68 (CI 95%: 1.71–7.94, p = 0.001), for slight, moderate and severely dilated left atrial dimension, respectively, compared with a normal value. HATCH score did not predict AF in patients with typical AFl who underwent CTI ablation. Basal left atrium dimension could help predict new-onset AF.
Abstract
We determined the effectiveness of the HATCH score in patients with typical atrial flutter (AFl) undergoing cavotricuspid isthmus (CTI) ablation to predict long-term atrial [...]
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A new circular mapping-guided approach for endoscopic laser balloon pulmonary vein isolation
. Pim Gal, J. J. Smit, . Ahmet Adiyaman, A. Misier, P. Delnoy, . Arif Elvan

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 68-72

Abstract
Pulmonary vein isolation (PVI) for atrial fibrillation (AF) is performed with the endoscopically assisted laser balloon ablation system (EAS). We hypothesized that placement of a circular mapping catheter (CMC) in the pulmonary vein (PV) distal to the laser balloon during ablation is feasible and safe. Out of 58 included patients, 37 underwent mapping-guided EAS PVI, with the CMC inside the PV during laser ablation, and 21 patients underwent standard EAS PVI, with the CMC outside the PV during laser ablation. Mean age was 56 years and 81% had paroxysmal AF. In the mapping-guided ablation group, 91% of PVs were isolated with the CMC in the PV during EAS ablation, isolation was completed in 9% of PVs after the CMC was removed from the PV. After passing a learning curve in 18 patients, a significant drop in unsuccessfully isolated PVs was observed in the mapping guided EAS PVI group (15% to 4%, P = 0.020). No major complications were seen in the mapping-guided EAS PVI group. However, in the standard EAS PVI group, laser ablation was complicated by a temporary phrenic nerve palsy in 1 patient. After a median follow-up of 16.7 months, there was no statistical difference in AF free survival among treatment groups (mapping-guided: 56% vs. 52%, P = 0.875). Mapping guided EAS PVI with a distal CMC in the PV during laser ablation is feasible and seems safe as the standard EAS PVI approach.
Abstract
Pulmonary vein isolation (PVI) for atrial fibrillation (AF) is performed with the endoscopically assisted laser balloon ablation system (EAS). We hypothesized that placement [...]
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Pulmonary vein orientation assessment: Is it necessary in patients undergoing contact force sensing guided radiofrequency catheter ablation of atrial fibrillation
P. Gal, J. F.W. Ooms, J. Paul Ottervanger, J. J. Smit, . Ahmet Adiyaman, A. Misier, P. Delnoy, P. L. Jager, . Arif Elvan

IJC Heart & Vasculature (2015).

Abstract
We hypothesized that pulmonary vein (PV) orientation influences tissue contact of the contact force (CF) sensing radiofrequency ablation catheter (CFC) and therefore atrial fibrillation (AF) free survival after pulmonary vein isolation (PVI). The aim of this study was to determine the association between PV orientation, CF and AF free survival in patients undergoing CFC PVI. Sixty consecutive patients undergoing CFC PVI were included. ECG-triggered cardiac CT scans were obtained in all patients before PVI, and the PV orientation was measured at the insertion in the LA for all PVs in both the transverse and frontal plane. PVs were assigned to 1 of 4 orientation groups: ventral–caudal, dorsal–caudal, ventral–cranial and dorsal–cranial. Mean age was 59 years, 88% had paroxysmal AF. AF free survival off anti-arrhythmic drugs after a median follow-up of 12 months was 58% after a single PVI procedure. No association was found between PV orientation and CF. Furthermore, no association was found between PV orientation and AF free survival. In univariate analysis, the number of lesions with a mean CF of 10 g was associated with AF free survival. However, in multivariate analysis, only the AF duration was significantly associated with AF free survival. This study shows that in patients undergoing PVI with the CFC ablation system, PV orientation does not affect CF and is not associated with AF free survival. PV orientation assessment does not appear to be necessary in patients undergoing CFC PVI.
Abstract
We hypothesized that pulmonary vein (PV) orientation influences tissue contact of the contact force (CF) sensing radiofrequency ablation catheter (CFC) and therefore atrial [...]
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Effectiveness of renal sympathetic denervation in renal function and blood pressure in CKD and non-CKD patients with controlled vs. uncontrolled hypertension
M. Kiuchi, S. Chen

IJC Heart & Vasculature (2016). Vol. 13 pp. 3-5
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Late gadolinium enhancement does occur in Tako-tsubo cardiomyopathy — A quantitative cardiac magnetic resonance and speckle tracking strain study
. Niranjan Gaikwad, T. Butler, R. Maxwell, E. Shaw, W. E. Strugnell, J. Chan, G. A. Figtree, R. E. Slaughter, C. Hamilton-Craig

IJC Heart & Vasculature (2016).

Abstract
Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) has been recommended to distinguish Tako-tsubo cardiomyopathy (TTC) from either acute myocardial infarction or myocarditis. 44 consecutive patients with confirmed Mayo Clinic criteria for TTC underwent CMR imaging at 1.5 Tesla during the acute phase. 10 patients who had CMRI to exclude scar related ventricular tachycardia, and had negative studies, were used as negative controls. LGE was quantitated at two signal intensity thresholds (CircleCVi software) at > 2 and > 5 standard-deviations (SD) above reference myocardium, and compared to biomarkers. Mean door-to-CMR time was 57 hours. 18 patients (41%) had LGE > 2 SD localized to the area of abnormal wall motion, representing 28.9 ± 11.2% LV mass. In 16 of these 18 patients (89%) LGE signal intensity was > 5 SD above normal myocardium, representing 12.1 ± 10% LV mass. LGE signal intensity was significantly greater in TTC than in matched controls (p < 0.05) but lower than in STEMI patients (p < 0.05). Mean troponin was significantly higher in LGE positive patients (2.5 ± 1.8 vs 4.4 ± 6.9, p = 0.001). Mean ejection fraction (EF) by CMR was 45% ± 8.7 in LGE-negative, and 40% ± 7.1 in LGE-positive patients (p = 0.37). Recovery of segmental function was confirmed at follow-up, mean EF was 59% in both groups. LGE was present in 41% of cases of TTC, 89% of which had intense enhancement > 5 SD above normal myocardium. Presence of LGE was associated with worse myocardial injury in the acute setting, with no difference in recovery of function.
Abstract
Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) has been recommended to distinguish Tako-tsubo cardiomyopathy (TTC) from either acute myocardial [...]
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The experimental model of transition from compensated cardiac hypertrophy to failure created by transverse aortic constriction in mice
. Takaaki Furihata, . Shintaro Kinugawa, . Shingo Takada, . Arata Fukushima, . Masashige Takahashi, . Tsuneaki Homma, . Yoshihiro Masaki, . Masaya Tsuda, . Junichi Matsumoto, . Wataru Mizushima, . Shouji Matsushima, . Takashi Yokota, . Hiroyuki Tsutsui

IJC Heart & Vasculature (2016). Vol. 11 pp. 24-28

Abstract
Transverse aortic constriction (TAC) operation is used as an experimental model of left ventricular (LV) hypertrophy and LV failure in mice. The severity of LV remodeling or failure may depend on the degree of TAC, but is variable among operated animals. Therefore, we tried to identify the optimal diameter of TAC to create this model with ease and high reproducibility. To produce TAC in C57BL/6J mice (7–9 weeks, body weight 19–26 g, n = 109), a 7–0 nylon suture ligature was tightly tied around the transverse aorta against needles with 3 different diameters (mm), 0.40, 0.385 and 0.375. LV wall thickness, end-diastolic dimension, fractional shortening were measured by echocardiography. At 4 weeks after TAC, no mouse with the 0.400 mm gauge progressed in LV failure. The 0.385 mm pin gauge mouse kept a more survival rate compared with the 0.375 mm (59% vs 48%), representing same efficient in LV failure. With the 0.385 mm pin gauge, hearts of mice remained LV hypertrophy at 1 week after TAC, followed by LV failure at 4 weeks. TAC with the diameter of 0.385 mm can effectively induce the transition from LV hypertrophy to failure in mice with relatively preserved survival.
Abstract
Transverse aortic constriction (TAC) operation is used as an experimental model of left ventricular (LV) hypertrophy and LV failure in mice. The severity of LV remodeling [...]
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Relationship between electrocardiographic findings and Cardiac Magnetic Resonance phenotypes in patients with Hypertrophic Cardiomyopathy
. Matteo Fronza, . Claudia Raineri, . Adele Valentini, E. Maria Bassi, . Laura Scelsi, M. Laura Buscemi, . Annalisa Turco, . Grazia Castelli, . Stefano Ghio, L. Visconti

IJC Heart & Vasculature (2016). Vol. 11 pp. 7-11

Abstract
Q waves and negative T waves are common electrocardiographic (ECG) abnormalities in patients with Hypertrophic Cardiomyopathy (HCM). Several studies correlated ECG findings with presence and extent of fibrosis and hypertrophy, however, their significance remains incompletely clarified. Our study aimed to explain the mechanism behind Q and negative T waves by comparing their positions on a 12-lead ECG with phenotypes observed at Late Gadolinium Enhancement (LGE) Cardiac Magnetic Resonance (CMR). 12-lead ECG and LGE-CMR were performed in 88 consecutive patients with HCM (42 SD 16 years, 65 males). Using Delta Thickness ratio (DT ratio), and “global” and “parietal” LGE at CMR, the extent and distribution of myocardial hypertrophy and fibrosis were studied in correlation with ECG abnormalities. Q waves in different leads were not associated with “parietal” LGE score. Lateral Q waves correlated with an increased DT ratio Inferior Septum/Lateral wall (p = 0.01). A similar correlation between inferior Q waves and an increased DT Ratio Anterior wall/Inferior wall was of borderline statistical significance (p = 0.06). As expected, ECG signs of LV hypertrophy related to a raised Left Ventricular Mass Index (LVMI) (p < 0.0001) and mean wall thickness (p = 0.01). Depolarization disturbances, including negative T waves in lateral (p = 0.044) and anterior (p = 0.031) leads correlated with “parietal” LGE scores while QT dispersion (p = 0.0001) was associated with “global” LGE score. In HCM patients, Q waves are generated by asymmetric hypertrophy rather than by myocardial fibrosis, while negative T waves result from local LGE distribution at CMR.
Abstract
Q waves and negative T waves are common electrocardiographic (ECG) abnormalities in patients with Hypertrophic Cardiomyopathy (HCM). Several studies correlated ECG findings [...]
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I-1-deficiency negatively impacts survival in a cardiomyopathy mouse model
F. W. Friedrich, . Hannieh Sotoud, . Birgit Geertz, . Silvio Weber, . Frederik Flenner, . Silke Reischmann, . Thomas Eschenhagen, . Lucie Carrier, . Ali El-Armouche

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 87-94

Abstract
Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis. Current treatment is based on beta-adrenoceptor (AR) and calcium channel blockers. Since mice deficient of protein phosphatase-1 inhibitor-1 (I-1), an amplifier in beta-AR signalling, were protected from pathological adrenergic stimulation in vivo, we hypothesized that I-1 ablation could result in an improved outcome in a HCM mouse model. We crossed mice deficient of I-1 with homozygous myosin-binding protein C knock-out (Mybpc3 KO) mice exhibiting cardiac dilatation and reduced survival. Unexpectedly, survival time was shorter in double I-1/Mybpc3 KO than in single Mybpc3 KO mice. Longitudinal echocardiographic assessment revealed lower fractional area change, and higher diastolic left ventricular inner dimensions and end-diastolic volumes in Mybpc3 KO than in WT mice. In comparison to Mybpc3 KO, double I-1/Mybpc3 KO presented higher left ventricular end-diastolic volumes, inner dimensions and ventricular surface areas with increasing differences over time. Phosphorylation levels of PKA-downstream targets and mRNA levels of hypertrophic markers did not differ between I-1/Mybpc3 KO and single Mybpc3 KO mice, except a trend towards higher beta-myosin heavy chain levels in double I-1/Mybpc3 KO. The data indicate that interference with beta-AR signalling has no long-term benefit in this severe MYBPC3-related cardiomyopathy mouse model.
Abstract
Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis. Current treatment is based on [...]
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Etiology-specific assessment of predictors of long-term survival in chronic systolic heart failure
. Jennifer Franke, . Christian Zugck, . Matthias Hochadel, . Anna Hack, . Lutz Frankenstein, J. Zhao, . Philipp Ehlermann, . Manfred Nelles, . Uwe Zeymer, . Ralph Winkler, . Ralf Zahn, H. A. Katus, . Jochen Senges

IJC Heart & Vasculature (2015). Vol. 7(1) pp. 61-68

Abstract
We sought to identify prognostic factors of long-term mortality, specific for the underlying etiology of chronic systolic heart failure (CHF). Between 1995 and 2009 baseline characteristics, treatment and follow-up data from 2318 CHF-patients due to ischemic (ICM, 1100 patients) or dilated cardiomyopathy (DCM, 1218 patients) were prospectively compared. To calculate hazard ratios with 95%-confidence intervals cox regression was used. We respectively established etiology-specific multivariable models of independent prognostic factors. During the follow-up period of up to 14.8 years (mean = 53.1 ± 43.5 months, 10, 264 patient-years) 991 deaths (42.8%) occurred. In the ICM-cohort, 5-year-survival was 53.4% (95% CI: 49.9–56.7%), whereas in DCM-patients it was higher (68.1% (95% CI: 65.1–71.0%)). Age, ejection fraction, or hyponatremia were independent predictors for mortality in both cohorts, whereas diabetes, COPD, atrial fibrillation and a heart rate of ≥ 80/min carried independent predictive power only in ICM-patients. This study demonstrates the disparity of prognostic value of clinically derived risk factors between the two main causes of CHF. The effects of covariables in DCM-patients were lower, suggesting a less modifiable disease through risk factors considering mortality risk. An etiology-specific prognostic model may improve accuracy of survival estimations in CHF.
Abstract
We sought to identify prognostic factors of long-term mortality, specific for the underlying etiology of chronic systolic heart failure (CHF). Between 1995 and 2009 baseline [...]
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Percutaneous interventions in Fontan circulation
. Eduardo Franco, E. Domingo, V. Val, L. Silva, M. Marín, A. Ruiz, . Fernando Villagrá, F. Aguado

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 138-146

Abstract
Different percutaneous interventional procedures are needed to reach and maintain adequate anatomical and physiological conditions for the Fontan circulation. We aim to describe the experience gained at a childrens hospital in such interventions, and to analyze the clinical outcomes. Retrospective study of all patients with Fontan circulation completed between 1995 and 2013. We analyzed the clinical characteristics and the different types of percutaneous interventions performed, considering three different periods of time: before Glenn surgery, between Glenn and Fontan surgeries, and after Fontan was completed. Survival and time to indication of percutaneous interventions in each period were analyzed, as well as the clinical situation at last follow-up. Of the 91 patients analyzed, 46 (50.5%) required percutaneous interventions. The most frequent procedures were pulmonary artery angioplasty and angioplasty of the Fontan conduit. Estimated survival at 10, 20 and 30 years of age was 96.2%, 94.7% and 89.4%, respectively. There were no significant differences in survival of patients undergoing percutaneous interventions or not. Overall survival and time to indication of percutaneous interventions were significantly lower in the group of patients with right morphology systemic ventricle. Patients with fenestrated Fontan required interventions more frequently. At the end of follow-up, 66 patients (72.5%) were asymptomatic, without significant differences between patients who underwent or did not undergo percutaneous interventions. Interventional catheterization procedures are often necessary to reach and maintain the fragile Fontan circulation, mainly in patients with right morphology systemic ventricles and fenestrated Fontan conduits.
Abstract
Different percutaneous interventional procedures are needed to reach and maintain adequate anatomical and physiological conditions for the Fontan circulation. We aim to describe [...]
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Third CoreValve™ insertion for treatment of a severe paravalvular leak after a failed valve-in-valve procedure
R. Estévez-Loureiro, . Carlos Cuellas, . Javier Gualis, A. Prado, . Mario Castaño, . Carlos Soria, . David Alonso, . Carmen Garrote, M. Rodríguez, F. Fernández-Vázquez

IJC Heart & Vasculature (2015). Vol. 7(1) pp. 58-60

Abstract
An 83-year-old high-risk gentleman diagnosed with severe symptomatic aortic stenosis was scheduled for TAVR. A 31 mm CoreValve was implanted but severe paravalvular leak was noted. A valve-in-valve procedure was performed. However, the valve frame was partially dislodged into de ascending aorta. We report our strategy to solve this severe leak after a failed valve-in-valve procedure.
Abstract
An 83-year-old high-risk gentleman diagnosed with severe symptomatic aortic stenosis was scheduled for TAVR. A 31 mm CoreValve was implanted but severe paravalvular leak was [...]
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Early use of beta blockers in patients with cocaine associated chest pain
C. Schmidt, . Luciano Pastori, . Gerald Pekler, . Ferdinand Visco, . Savi Mushiyev

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 167-169

Abstract
The most common symptom of cocaine abuse is chest pain. Cocaine induced chest pain (CICP) shares patho-physiological pathways with the acute coronary syndromes (ACS). A key event is the increase of activity of the adrenergic system. Beta blockers (BBs), a cornerstone in the treatment of ACS, are felt to be contraindicated in the patient with CICP due to a potential of an “unopposed alpha adrenergic effect (UAE)”. Identify signs of UAE and in-hospital complications in patients who received BB while having cocaine induced chest pain. We performed a retrospective review of 378 patients admitted to a medical unit because of CICP. Twenty six of these were given a BB at the time of admission while having CICP. We compared these patients to a control group paired by age, sex, race and history of hypertension who did not received a BB while having CICP. Blood pressure, heart rate, length of stay and in-hospital cardiovascular complications were compared. No statistically significant differences were found between the two groups except for a longer length of stay in the case group. This was felt to be due to unrelated causes. This study does not support the presence of an UAE in patients with continuing CICP and treated early with BB. There were no in-hospital cardiovascular complications in the group of patients who had an early dose of BB while having CICP. BB appeared safe when given early on admission to patients with CICP.
Abstract
The most common symptom of cocaine abuse is chest pain. Cocaine induced chest pain (CICP) shares patho-physiological pathways with the acute coronary syndromes (ACS). A key [...]
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The histology of human right atrial tissue in patients with high-risk Obstructive Sleep Apnea and underlying cardiovascular disease: A pilot study
E. van Oosten, A. H. Boag, . Kris Cunningham, . John Veinot, . Andrew Hamilton, . Dimitri Petsikas, . Darrin Payne, W. M. Hopman, D. P. Redfearn, . WonJu Song, . Shawn Lamothe, . Shetuan Zhang, . Adrián Baranchuk

IJC Heart & Vasculature (2015).

Abstract
Obstructive Sleep Apnea (OSA) results in intermittent hypoxia leading to atrial remodeling, which, among other things, facilitates development of atrial fibrillation. While much data exists on the macrostructural changes in cardiac physiology induced by OSA, there is a lack of studies looking for histologic changes in human atrial tissue induced by OSA which might lead to the observed macrostructural changes. A case control study was performed. Patients undergoing coronary artery bypass grafting (CABG) were evaluated for OSA and categorized as high-risk or low-risk. The right atrial tissue samples were obtained during CABG and both microscopic histological analysis and Sirius Red staining were performed. 18 patients undergoing CABG were included, 10 high-risk OSA and 8 low-risk OSA in evenly matched populations. No statistically significant difference between the two groups was observed in amount of myocytolysis (p = 0.181), nuclear hypertrophy (p = 0.671), myocardial inflammation (p = n/a), amyloid deposition (p = n/a), or presence of thrombi (p = n/a), as measured through routine H&E staining. As well, no statistically significant difference in interstitial and epicardial collagen was observed, as measured by Sirius Red staining (for total tissue: p = 0.619: for myocardium: p = 0.776). In this pilot study there were no observable histological differences in human right atrial tissue from individuals at high- and low-risk for OSA. Further investigation would be required for more definitive results.
Abstract
Obstructive Sleep Apnea (OSA) results in intermittent hypoxia leading to atrial remodeling, which, among other things, facilitates development of atrial fibrillation. While [...]
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Repeat remote ischaemic pre-conditioning for improved cardiovascular function in humans: A systematic review
J. Epps, G. Dieberg, . N.A. Smart

IJC Heart & Vasculature (2016). Vol. 11 pp. 55-58

Abstract
Single exposure to remote ischaemic pre-conditioning (RIPC) has been shown to be effective in reducing major adverse events during cardiac surgery. We evaluated the efficacy of repeated exposure RIPC to elicit improvements in cardiovascular function. A systematic search was conducted up until May 1st, 2015, using the following databases: EMBASE, PubMed (Medline), Web of Science and the Cochrane Central Registry of Controlled Trials (CENTRAL). Data was extracted and synthesized from published studies of repeat RIPC. Data from seven studies showed evidence of improvements in vascular function and anti-hypertensive effects of systolic, diastolic and mean arterial blood pressure following repeat RIPC. Currently existing work justifies a systematic review but not data pooling of individual study data. Repeat RIPC has also produced evidence of improvements in endothelial dependent vasodilation, but not non-endothelial dependent vasodilation, cutaneous vascular conductance or cardiorespiratory fitness. Repeated RIPC exposure has produced evidence of improvements in endothelial dependent vasodilation, ulcer healing and blood pressure but no benefit in non-endothelial dependent vasodilation, cutaneous vascular conductance or cardiorespiratory fitness. The optimal delivery of RIPC remains unclear, but at least 3 or preferably 4, 5 min exposures appears to be most beneficial, at least for reducing blood pressure. Aside from those undertaking cardiac surgery, other study populations with endothelial dysfunction may benefit from repeat exposure to RIPC.
Abstract
Single exposure to remote ischaemic pre-conditioning (RIPC) has been shown to be effective in reducing major adverse events during cardiac surgery. We evaluated the efficacy [...]
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Resistance to renal denervation therapy — Identification of underlying mechanisms by analysis of differential DNA methylation
. Frederic Emschermann, C. S. Zuern, . Johannes Patzelt, K. Rizas, . Günter Jäger, . Christian Eick, S. G. Meuth, . Meinrad Gawaz, . Axel Bauer, H. F. Langer

IJC Heart & Vasculature (2016).

Abstract
Factors causing resistance to renal denervation (RDN) for treatment of arterial hypertension are not known. In the current study, we sought to determine mechanisms involved in responsiveness to renal denervation therapy in patients with difficult-to-control and resistant hypertension. We evaluated the differential CpG methylation of genes in blood samples isolated from patients of a recently described cohort of responders or non-responders to renal denervation using microarray technique and measured protein levels of identified downstream effectors in blood samples of these patients by ELISA. Our analysis revealed up to 6103 methylation sites differing significantly between non-responders and responders to renal denervation therapy. Software based analysis showed several of these loci to be relevant for arterial hypertension and sympathetic nervous activity. Particularly, genes involved in glutamate synthesis, degradation and glutamate signaling pathways were differently methylated between both groups. For instance, genes for glutamate dehydrogenase 1 and 2 central to glutamate metabolism, genes for ionotropic (AMPA, NMDA) and metabotropic glutamate receptors as well as glutamate transporters revealed significant differences in methylation correlating with responsiveness to RDN. To underline their potential relevance for responsiveness to RDN, we measured plasma protein levels of norepinephrine, a downstream effector of the glutamate receptor pathway, which were significantly lower in non-responders to RDN. The present study describes novel molecular targets potentially contributing to reduction of blood pressure after RDN in some patients. Identifying patients with a high responsiveness to RDN could contribute to an individualized therapy in drug resistant hypertension.
Abstract
Factors causing resistance to renal denervation (RDN) for treatment of arterial hypertension are not known. In the current study, we sought to determine mechanisms involved [...]
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Non-invasive imaging in detecting myocardial viability: Myocardial function versus perfusion
I. A. Elfigih, M. Y. Henein

IJC Heart & Vasculature (2014). Vol. 5 pp. 51-56

Abstract
Coronary artery disease (CAD) is the most prevalent and single most common cause of morbidity and mortality [1] with the resulting left ventricular (LV) dysfunction an important complication. The distinction between viable and non-viable myocardium in patients with LV dysfunction is a clinically important issue among possible candidates for myocardial revascularization. Several available non-invasive techniques are used to detect and assess ischemia and myocardial viability. These techniques include echocardiography, radionuclide images, cardiac magnetic resonance imaging and recently myocardial computed tomography perfusion imaging. This review aims to distinguish between the available non-invasive imaging techniques in detecting signs of functional and perfusion viability and identify those which have the most clinical relevance in detecting myocardial viability in patients with CAD and chronic ischemic LV dysfunction. The most current available studies showed that both myocardial perfusion and function based on non-invasive imaging have high sensitivity with however wide range of specificity for detecting myocardial viability. Both perfusion and function imaging modalities provide complementary information about myocardial viability and no optimum single imaging technique exists that can provide very accurate diagnostic and prognostic viability assessment. The weight of the body of evidence suggested that non-invasive imaging can help in guiding therapeutic decision making in patients with LV dysfunction.
Abstract
Coronary artery disease (CAD) is the most prevalent and single most common cause of morbidity and mortality [1] with the resulting left ventricular (LV) dysfunction an important [...]
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Impact of combination therapy with statin and ezetimibe on secondary prevention for post-acute myocardial infarction patients in the statin era
S. Ebisawa, . Atsushi Izawa, . Yasushi Ueki, . Hirofumi Hioki, . Masatoshi Minamisawa, . Naoto Hashizume, . Naoyuki Abe, . Yuichiro Kashima, . Takashi Miura, . Takahiro Takeuchi, . Hirohiko Motoki, . Ayako Okada, . Yusuke Miyashita, . Jun Koyama, . Uichi Ikeda

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 154-160

Abstract
Little is known concerning the effect of ezetimibe for secondary prevention in post-myocardial infarction (MI) patients. In this study, we investigated the secondary prevention effect of ezetimibe for post-MI patients. This study is a retrospective analysis of Assessing Lipophilic vs. hydrophilic Statin therapy for Acute MI (ALPS-AMI study). The patients were divided into two groups: those administered a statin to control low density lipoprotein-cholesterol (LDL-C), the ezetimibe(−) group, and those administered ezetimibe in addition to a statin to control LDL-C, the ezetimibe(+) group. The endpoints were Major Adverse Cardiac and Cerebrovascular Event (MACCE), including all-cause death, recurrence of MI, stroke, and heart failure requiring hospitalization, and MACCE with revascularization. The ezetimibe(+) and ezetimibe(−) groups contained 113 and 337 patients, respectively. Incidences of MACCE and MACCE with revascularization were lower in the ezetimibe(+) group than in the ezetimibe(−) group (2.6% vs. 11.5%, p = 0.002, 23.0% vs. 36.7%, p = 0.014, respectively). Moreover, logistic regression analysis revealed ezetimibe(+) was a significant negative predictor of MACCE (OR 0.208, 95% CI 0.048 to 0.903, p = 0.047) and MACCE with revascularization (OR 0.463, 95% CI 0.258 to 0.831, p = 0.008). The preventive effect of ezetimibe against MACCE was observed in both moderate- and high-intensity lipid lowering treatment groups (0% vs. 17%, p = 0.077, 3.1% vs. 9.4%, p = 0.033). In lipid-lowering therapy post-MI, ezetimibe and statin combination therapy improved MACCE with or without revascularization compared with statin monotherapy. These findings suggest that post-MI secondary prevention should be more intensive.
Abstract
Little is known concerning the effect of ezetimibe for secondary prevention in post-myocardial infarction (MI) patients. In this study, we investigated the secondary prevention [...]
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Acute contractile recovery extent during biventricular pacing is not associated with follow-up in patients undergoing resynchronization
. Federica DeVecchi, . Emanuela Facchini, . Anna Degiovanni, . Chiara Sartori, . Chiara Cavallino, . Matteo Santagostino, V. Di Ruocco, . Andrea Magnani, . Eraldo Occhetta, P. Marino

IJC Heart & Vasculature (2016). Vol. 11 pp. 66-73

Abstract
It has been reported that contractility, as assessed using dobutamine infusion, is independently associated with reverse remodeling after CRT. Controversy, however, exists about the capacity of this approach to predict a long-term clinical response. This studys purpose was to assess whether long-term CRT clinical effects can be predicted according to acute inotropic response induced by biventricular stimulation (CRT on), as compared with AAI–VVI right stimulation pacing mode (CRT off), quantified at the time of implantation. In 98 patients (ejection fraction 29 ± 10%), acute changes in left ventricular (LV) elastance (Ees), arterial elastance (Ea), and Ees/Ea, as assessed from slope changes of the force–frequency relation obtained when the heart rate increased, and also assessed while measuring triplane LV volumes and continuous noninvasive blood pressure, were related to death or rehospitalization during a 3-year follow-up. Other covariances tested were age, gender, disease etiology, QRS duration, amount of mitral regurgitation, LV diastolic volume, ejection fraction, and the degree of asynchrony and longitudinal strain at baseline. There was a marked increment in the Ees slope with CRT (interaction P = 0.004), no Ea change, and modest Ees/Ea increase (interaction P < 0.05). In Cox analysis, however, neither slope changes nor baseline values of Ees, Ea, and Ees/Ea were associated with long-term follow-up. Only ventricular diastolic volume (direct relation P = 0.002) and QRS duration (inverse relation P = 0.009) predicted death/rehospitalization. Acute contractile recovery in CRT patients is not associated with 3 years prognosis. Instead, death or rehospitalization can be predicted from QRS duration and LV diastolic volume at baseline.
Abstract
It has been reported that contractility, as assessed using dobutamine infusion, is independently associated with reverse remodeling after CRT. Controversy, however, exists [...]
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Effect of respiration on cardiac filling at rest and during exercise in Fontan patients: A clinical and computational modeling study
A. Bruaene, . Guido Claessen, A. La Gerche, . Ethan Kung, . Alison Marsden, P. De Meester, . Sarah Devroe, . Jan Bogaert, . Piet Claus, . Hein Heidbuchel, . Werner Budts, . Marc Gewillig

IJC Heart & Vasculature (2015). Vol. 9(7) pp. 100-108

Abstract
Due to the absence of a sub-pulmonary ventricle, the Fontan circulation is sensitive to respiration-induced changes in intrathoracic pressure. However, the importance of a ‘respiratory pump’ in creating forward flow remains controversial. We aimed at evaluating the effect of respiration on ventricular filling during exercise using clinical data and computational modeling predictions. Ten Fontan patients (6 male, 20 ± 4 years) underwent ungated cardiac magnetic resonance (CMR) imaging at rest and during supine bicycle exercise to evaluate systemic ventricular volumes (end-diastolic volume index (EDVi), end-systolic volume index (ESVi) and stroke volume index (SVi)) during normal respiration and a Valsalva maneuver. Respiratory-dependent SV was calculated. Clinical results were compared to predictions made by a closed-loop lumped-parameter (LPN) computational model of Fontan circulation. Inspiration resulted in increased EDVi (98 ± 16 to 103 ± 15 mL, P = 0.001), SVi (55 ± 9 to 59 ± 9 mL, P = 0.001) and cardiac index (3.9 ± 0.7 to 4.2 ± 0.8 L/min, P = 0.002), whereas ESVi (P = 0.096) remained unchanged. The effect of inspiration on EDVi (mean effect + 6 ± 1 mL, P < 0.0001) and SVi (+ 4 ± 1 mL, P < 0.0001) was maintained during exercise. Respiratory-dependent SVi tended to increase during exercise (3 ± 2% to 5 ± 3%, P = 0.084). Valsalva resulted in decreased EDVi (P = 0.001), ESVi (P = 0.003) and SVi (P = 0.005). Computational modeling indicated higher EDV and SV at end-inspiration and expiration, showing a phased time delay between peak caval vein flow and peak SV. In Fontan patients, inspiration resulted in increased ventricular filling at rest and during exercise. Results were confirmed using a computational model indicating a phased time delay between peak SV and peak caval vein flow.
Abstract
Due to the absence of a sub-pulmonary ventricle, the Fontan circulation is sensitive to respiration-induced changes in intrathoracic pressure. However, the importance of a [...]
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Risk stratification in non-ST elevation acute coronary syndromes: Risk scores, biomarkers and clinical judgment
. David Corcoran, . Patrick Grant, . Colin Berry

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 131-137

Abstract
Undifferentiated chest pain is one of the most common reasons for emergency department attendance and admission to hospitals. Non-ST elevation acute coronary syndrome (NSTE-ACS) is an important cause of chest pain, and accurate diagnosis and risk stratification in the emergency department must be a clinical priority. In the future, the incidence of NSTE-ACS will rise further as higher sensitivity troponin assays are implemented in clinical practice. In this article, we review contemporary approaches for the diagnosis and risk stratification of NSTE-ACS during emergency care. We consider the limitations of current practices and potential improvements. Clinical guidelines recommend an early invasive strategy in higher risk NSTE-ACS. The Global Registry of Acute Coronary Events (GRACE) risk score is a validated risk stratification tool which has incremental prognostic value for risk stratification compared with clinical assessment or troponin testing alone. In emergency medicine, there has been a limited adoption of the GRACE score in some countries (e.g. United Kingdom), in part related to a delay in obtaining timely blood biochemistry results. Age makes an exponential contribution to the GRACE score, and on an individual patient basis, the risk of younger patients with a flow-limiting culprit coronary artery lesion may be underestimated. The future incorporation of novel cardiac biomarkers into this diagnostic pathway may allow for earlier treatment stratification. The cost-effectiveness of the new diagnostic pathways based on high-sensitivity troponin and copeptin must also be established. Finally, diagnostic tests and risk scores may optimize patient care but they cannot replace patient-focused good clinical judgment.
Abstract
Undifferentiated chest pain is one of the most common reasons for emergency department attendance and admission to hospitals. Non-ST elevation acute coronary syndrome (NSTE-ACS) [...]
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Medium term follow-up after percutaneous pulmonary valve replacement with the Melody® valve
B. Cools, . Werner Budts, . Ruth Heying, . Derize Boshoff, . Benedicte Eyskens, . Stefan Frerich, . Els Troost, . Marc Gewillig

IJC Heart & Vasculature (2015). Vol. 7(1) pp. 92-97

Abstract
Data on long term function of the Melody valve are scarce. Patients and methods: single institution, results of percutaneous pulmonary valve implantation (PPVI) from 2006 to 2014. The function of the valved conduit was analyzed by Doppler echocardiography. Annual Chest X-ray after implant and permanent screening for events (e.g. Endocarditis). 112 Melody valves were implanted in 111 patients, mean age 19.3 years (4.5–81.6). No pre-stenting of the RVOT was performed (n = 4) at first. In the next 107 patients pre-stenting was always performed. In 82 patients 1 pre-stent, 18 patients 2, in 6 patients 3 stents and 1 patient 4 stents were used. The Melody stent was dilated up to 24 mm (n = 4), 22 mm (n = 72), 20 mm (n = 28) and 18 mm (n = 6). When stenotic, the Doppler gradient reduced from 67.0 mm Hg (SD 13.9) to 18.9 mm Hg (SD 10.4) (p < 0.001), pulmonary regurgitation (PR) was reduced from median 3.5/4 (range 0–4/4) to none or trivial (p < 0.001). There was no significant change in RVOT peak velocity at 5 years (p = 0.122) nor PR (p = 0.835). Type 1 stent fractures were observed in 1/4 non-pre-stented patients and in 5/107 pre-stented (p < 0.05). Endocarditis occurred in 8/112 valves, freedom of endocarditis was 85% at 5 years. In 2 patients early surgical replacement was necessary. Six were sterilized with antibiotic treatment, 2 patients required re-stenting and re-PPVI due to residual gradient. Adequate pre-stenting of the RVOT before PPVI nearly abolishes or delays stent fracture. Cusp function is well preserved in mid-term follow-up, endocarditis is a threat.
Abstract
Data on long term function of the Melody valve are scarce. Patients and methods: single institution, results of percutaneous pulmonary valve implantation (PPVI) from 2006 [...]
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Cardiovascular changes in patients with non-severe Plasmodium vivax malaria
A. Alencar-Filho, J. Ferreira, J. Luis Salinas, . Camila Fabbri, W. Monteiro, A. Siqueira, . Katashi Okoshi, M. Lacerda, M. Okoshi

IJC Heart & Vasculature (2016). Vol. 11 pp. 12-16

Abstract
Cardiovascular system involvement in patients with Plasmodium vivax malaria has been poorly addressed. The aim of this study was to evaluate cardiac structures and function, and serum markers of cardiovascular injury in patients with the non-severe form of vivax malaria in Manaus, Amazonas State, Brazil. We prospectively evaluated 26 patients with vivax malaria in an outpatient referral hospital and compared results with a control group of 25 gender- and age-matched healthy individuals. Patients underwent clinical evaluation, laboratory tests, and transthoracic echocardiography at first evaluation (day zero, D0) and seven days (D7) after malaria diagnosis. At D0 echocardiography showed higher left ventricular (LV) systolic diameter (28.8 ± 2.82 vs 30.9 ± 4.03 mm, p = 0.037) and LV diastolic volume (82.4 ± 12.3 vs 93.8 ± 25.9 ml, p = 0.05), and lower LV ejection fraction (Teicholz method: 73.2 ± 6.59 vs 68.4 ± 4.87%, p = 0.004) in patients compared to controls. Right ventricle (RV) fractional area change (54.7 ± 5.11 vs 50.5 ± 6.71%, p = 0.014) was lower, and RV myocardial performance index (0.21 ± 0.07 vs 0.33 ± 0.19, p = 0.007), and pulmonary vascular resistance (1.13 ± 0.25 vs 1.32 ± 0.26 Woods unit, p = 0.012) were higher in patients than controls. Patients presented higher serum levels of unconjugated bilirubin (0.24 ± 0.15 vs 1.30 ± 0.89 mg/dL, p < 0.001), soluble vascular cell adhesion molecule–1 (sVCAM-1, 453 ± 143 vs 1983 ± 880 ng/mL, p < 0.001), N-terminal prohormone brain natriuretic peptide (0.59 ± 0.86 vs 1.08 ± 0.81 pg/mL, p = 0.045), and troponin T (861 ± 338 vs 1037 ± 264 pg/mL, p = 0.045), and lower levels of plasma nitrite (13.42 ± 8.15 vs 8.98 ± 3.97 μM, p = 0.016) than controls. Most alterations had reversed by D7. Patients with non-severe Plasmodium vivax malaria present subclinical reversible cardiovascular changes.
Abstract
Cardiovascular system involvement in patients with Plasmodium vivax malaria has been poorly addressed. The aim of this study was to evaluate cardiac structures and function, [...]
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Compensatory enlargement of Ossabaw miniature swine coronary arteries in diffuse atherosclerosis
J. S. Choy, T. Luo, . Yunlong Huo, . Thomas Wischgoll, . Kyle Schultz, S. D. Teague, . Michael Sturek, G. S. Kassab

IJC Heart & Vasculature (2015).

Abstract
Studies in human and non-human primates have confirmed the compensatory enlargement or positive remodeling (Glagov phenomenon) of coronary vessels in the presence of focal stenosis. To our knowledge, this is the first study to document arterial enlargement in a metabolic syndrome animal model with diffuse coronary artery disease (DCAD) in the absence of severe focal stenosis. Two different groups of Ossabaw miniature pigs were fed a high fat atherogenic diet for 4 months (Group I) and 12 months (Group II), respectively. Group I (6 pigs) underwent contrast enhanced computed tomographic angiography (CCTA) and intravascular ultrasound (IVUS) at baseline and after 4 months of high fat diet, whereas Group II (7 pigs) underwent only IVUS at 12 months of high fat diet. IVUS measurements of the left anterior descending (LAD), left circumflex (LCX) and right coronary (RCA) arteries in Group I showed an average increase in their lumen cross-sectional areas (CSA) of 25.8%, 11.4%, and 43.4%, respectively, as compared to baseline. The lumen CSA values of LAD in Group II were found to be between the baseline and 4 month values in Group I. IVUS and CCTA measurements showed a similar trend and positive correlation. Fractional flow reserve (FFR) was 0.91 ± 0.07 at baseline and 0.93 ± 0.05 at 4 months with only 2.2%, 1.6% and 1% stenosis in the LAD, LCX and RCA, respectively. The relation between percent stenosis and lumen CSA shows a classical Glagov phenomenon in this animal model of DCAD.
Abstract
Studies in human and non-human primates have confirmed the compensatory enlargement or positive remodeling (Glagov phenomenon) of coronary vessels in the presence of focal [...]
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Gender differences in the prevalence of coronary artery tortuosity and its association with coronary artery disease
. Joseph Chiha, . Paul Mitchell, . Bamini Gopinath, . George Burlutsky, . Pramesh Kovoor, . Aravinda Thiagalingam

IJC Heart & Vasculature (2017). Vol. 14 pp. 23-27

Abstract
Little is known about the significance of severe coronary tortuosity (SCT) despite it being a relatively common finding on coronary angiography. We examined whether the presence of tortuosity was influenced by gender or cardiac risk factors. We examined 870 patients (Men = 589, Women = 281) who presented to Westmead Hospital, Sydney, Australia for invasive coronary angiography for the assessment of chest pain due to suspected CAD. Female gender and age were significantly associated with SCT (p < 0.001 for age) with 45.2% of women having SCT as opposed to 19.7% of men (p < 0.001). Men with SCT had lower Extent scores only compared than those without tortuosity (22.4 vs. 32.4, p = 0.003). However, women with SCT had less severe coronary artery disease than those with no SCT as measured by both the Extent score (12.4 vs. 19.1, p = 0.03) and Gensini score (10.4 vs. 15.5, p = 0.02). There is a significant relationship between coronary artery tortuosity and gender. Women with severe tortuosity are more likely to have normal coronary arteries or less severe disease than men despite presenting with chest pain.
Abstract
Little is known about the significance of severe coronary tortuosity (SCT) despite it being a relatively common finding on coronary angiography. We examined whether the presence [...]
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Gender differences in the severity and extent of coronary artery disease
. Joseph Chiha, . Paul Mitchell, . Bamini Gopinath, A. J.H. Plant, . Pramesh Kovoor, . Aravinda Thiagalingam

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 161-166

Abstract
To investigate whether women presenting with suspected angina would show less severe coronary artery disease in than men as determined by the extent score. We examined 994 participants of the Australian Heart Eye Study presenting for coronary angiography in the investigation of chest pain from June 2009 to February 2012. People were excluded if there was a history of coronary artery bypass surgery, previous stenting procedure or incomplete angiogram scoring. An extent and vessel score was calculated using invasive coronary angiography. Normal coronary arteries were defined as having no luminal irregularity (Extent score = 0). Obstructive coronary artery disease was defined as a luminal narrowing of greater than 50%. Women compared to men without infarction had a lower burden of CAD with up to 50% having normal coronary arteries in the 30–44 year group and 40% in the 45–59 year group. Compared to men, women with chest pain had lower mean extent scores (19.6 vs 36.8, P < 0.0001) and lower vessel scores (0.7 v 1.3, P < 0.0001). Although the mean extent score was lower in women than men with myocardial infarction, this was not statistically significant (34.8 vs 41.6 respectively, P = 0.18). There is a marked difference in coronary artery disease severity and burden between females and males presenting for the investigation of suspected angina. Women are more likely to have normal coronary arteries or less severe disease than age-matched men, particularly if they do not present with myocardial infarction.
Abstract
To investigate whether women presenting with suspected angina would show less severe coronary artery disease in than men as determined by the extent score. We examined 994 [...]
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Risk factors responsible for atrial fibrillation development between symptomatic patients with concealed or manifest atrioventricular accessory pathways
M. Chen, . Xiangfei Feng, J. Sun, . Qunshan Wang, . Pengpai Zhang, J. Wang, . Yi-Gang Li

IJC Heart & Vasculature (2015). Vol. 7(1) pp. 69-75

Abstract
Patients with manifest atrioventricular accessory pathways (mAPs) have a greater tendency to develop atrial fibrillation (AF) compared with patients with concealed atrioventricular accessory pathways (cAPs). However, the risk factors of developing AF in patients with various atrioventricular accessory pathways (APs) are not clear. This retrospective study included 460 symptomatic patients with either cAPs (n = 246) or mAPs (n = 214) who underwent electrophysiological study and successful radiofrequency catheter ablation of APs. Clinical and electrophysiological characteristics were compared between cAPs and mAPs and between AF and non-AF groups with cAPs or mAPs. Independent risk factors of AF were analyzed using multivariate logistic regression. AF was more frequent in mAPs group than in cAPs group (23.4% vs 9.8%, p < 0.01). Clinical features were similar between cAPs and mAPs. Anterograde conduction properties served as the major electrophysiological feature of mAPs. Multivariate analysis indicated that mAPs, hypertension, post-ablation P wave dispersion (Pd), N-terminal proB-type natriuretic peptide (NT-proBNP) and creatinine were independent risk factors of AF in the complete cohort. Hypertension, post-ablation Pd and high-sensitivity C-reactive protein (hsCRP) were independent risk factors of AF in cAPs group. Post-ablation Pd, NT-proBNP, creatinine and shorter effective refractory period of anterograde accessory pathways (AAP ERP) were independent risk factors of AF in mAPs group. Results from this study demonstrate that the risk factors of AF are not homogenous between concealed and manifest APs, which might suggest heterogeneous pathogenesis of AF in these two types of APs.
Abstract
Patients with manifest atrioventricular accessory pathways (mAPs) have a greater tendency to develop atrial fibrillation (AF) compared with patients with concealed atrioventricular [...]
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The association among age, early mitral leaflet closure, cardiac structure, diastolic indices and NT-proBNP in an asymptomatic Taiwanese population
C. Chen, . Yung-Tzi Chen, . Kuang-Te Wang, . Shou-Chuan Shih, . Chuan-Chuan Liu, . Jen-Yuan Kuo, C. Hou, . Yih-Jer Wu, . Chung-Lieh Hung, . Hung-I Yeh

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 114-121

Abstract
Advanced age is associated with left ventricular (LV) remodeling and impaired diastole. The association among aging, mitral leaflet closure (EF slope), cardiac structures, and diastolic indices in an asymptomatic Taiwanese population is largely unknown. We studied 8103 asymptomatic participants (49.5 ± 11.6 years, 38.2% women) from a health evaluation cohort (2004–2012) in a tertiary center in Taiwan. Echo-derived LV structure/function, and M-mode based EF slope (mm/s) and serum NT-proBNP level were obtained. The association between EF slope and the other clinical or echo-based parameters was investigated. Average values for EF slope among various age groups in the Taiwanese population were determined for both genders. Advanced age was associated with reductions in EF slope (adjusted estimate: − 0.35/per decade). Reduced EF slope was associated with older age, higher blood pressure and greater body mass index in multivariate models (all p < 0.05). Reduced EF slope was correlated with greater cardiac concentricity, abnormal E′ and E/E′ (AUROC: 0.74 and 0.77, respectively, both p < 0.05) and elevated NT-proBNP (Coef: 5.98 pg/mL, per − 10 mm/s EF slope, 95% CI: 7.82 to 4.17, p < 0.001). EF-slope also clearly discriminated individuals with abnormal estimated LV filling (E/E′ categorized by < 8, ≥ 8 & < 15, ≥ 15, ANOVA p < 0.001). EF-slope reduction in the asymptomatic Taiwanese population was correlated with age, several unfavorable LV remodeling, and impaired diastolic function parameters, and EF-slope can be an effective clinical diagnostic tool for identifying poor E′ and elevated LV filling pressure. In addition, our data provided reference values for EF-slope in various age groups.
Abstract
Advanced age is associated with left ventricular (LV) remodeling and impaired diastole. The association among aging, mitral leaflet closure (EF slope), cardiac structures, [...]
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Transradial percutaneous coronary intervention for chronic total occlusion of coronary artery disease using sheathless standard guiding catheters
. Huang-Chung Chen, . Wei-Chieh Lee, . Shu-Kai Hsueh, . Cheng-I Cheng, . Chien-Jen Chen, . Cheng-Hsu Yang, . Chih-Yuan Fang, . Chi-Ling Hang, . Hon-Kan Yip, . Chiung-Jen Wu, . Hsiu-Yu Fang

IJC Heart & Vasculature (2015). Vol. 6(1) pp. 35-41

Abstract
Our aim was to evaluate the feasibility and safety of routine transradial approach (TRA) percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions using the sheathless technique with standard guiding catheters. Transradial approach PCI was applied for CTO lesions. A major limitation of TRA CTO PCI is the inability to use large guiding catheters because of the relatively small size of the radial artery. Therefore, the sheathless technique for TRA PCI has been recently developed. However, reports on TRA CTO PCI using the sheathless technique are still lacking. Sixty-eight patients with CTO lesions were enrolled for TRA PCI using the sheathless technique with standard guiding catheters. The baseline characteristics, coronary angiographic characteristics and major procedure or access site related complications were compared between procedure success and procedure failure group to determine the predictors of success in sheathless CTO PCI. In-hospital and 30-day clinical outcomes were also evaluated in this study. Routine assessments of radial artery occlusion via Doppler ultrasound and pulse oximeter were recorded during one-year clinical follow-up. The mean duration of CTO by history was 31.8 ± 42.3 months. The 7 Fr standard guiding catheter was used with the sheathless technique in 91.2%, and bilateral sheathless approach in 42.6% of the study patients. The procedure-related complications included coronary perforation needing covered stent deployment (2.9%), cardiac tamponade (2.9%), collateral perforation needing coil deployment (4.4%), and contrast induced nephropathy (2.9%). Only 2 patients (2.9%) experienced forearm ecchymosis at the radial artery access sites. In-hospital mortality and 30-day all-cause mortality were 2.9%, and 30-day MACEs were 1.5%. The rate of radial artery occlusion during one-year clinical follow-up was only 3.0%. It is feasible and safe to routinely use the sheathless technique with standard guiding catheters for TRA CTO PCI, with a low incidence of procedure-related complications and long-term radial artery occlusion.
Abstract
Our aim was to evaluate the feasibility and safety of routine transradial approach (TRA) percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions [...]
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Ischemic postconditioning of the isolated human myocardium: Role of the applied protocol
. Kelly Casós, . María-Llanos Pérez, . Arnau Blasco-Lucas, . Gemma Ferrer-Curriu, J. Gracia-Baena, . Carlos Sureda, . Eduard Permanyer, . Alberto Igual, . Manuel Galiñanes

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 55-61

Abstract
Ischemic postconditioning (IPostC), has been proposed as a useful approach to reduce infarct size in all species, but its clinical utility remains unclear. To investigate the role played by the protocol used on the efficacy of IPostC in protecting the diseased human myocardium. Myocardial atrial samples from patients were subjected to a 90 min ischemia/120 min reoxygenation followed by different IPostC protocols to investigate the role of the time of ischemia (30, 60, 90 and 120 s) and the number of cycles (1, 2, 3 and 4) with 60 and 120 s of total ischemic time. Muscles were also subjected to ischemic preconditioning (IPreC). The release of lactate dehydrogenase (LDH) and the measurement of tetrazolium bromide (MTT) were determined. IPostC increased the LDH and decreased the MTT values from those of control, independently of the duration of the conditioning ischemia. LDH and MTT values also worsened by augmenting the number of IPostC cycles whereas they were significantly improved by IPreC. However, analysis of individual results indicated that in approximately 1/3 of the cases IPostC exhibited some degree of protection especially in the presence of increased ischemic injury. The present findings show that IPostC of the human myocardium may be influenced by the protocol used and also by the degree of the preceding ischemic injury. IPostC was beneficial in approximately 1/3 of the cases, however in the remaining cases it increased ischemic damage and, therefore, these results raise a word of caution on its broad clinical use.
Abstract
Ischemic postconditioning (IPostC), has been proposed as a useful approach to reduce infarct size in all species, but its clinical utility remains unclear. To investigate [...]
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Acute and spontaneous coronary thrombosis in non-culprit artery during percutaneous coronary intervention in myocardial infarction with ST-segment elevation: A “shocking” case
. Dario Buccheri, . Patrizia Carità, . Michele Carella, . Davide Piraino, P. Rosa Chirco, . Giuseppe Andolina

IJC Heart & Vasculature (2015).
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Clinical evaluation of R860Q semi-conservative amino acid substitution in CACNA1C gene in association with long QT syndrome
. Usama Boles, . Chris Simpson, E. E. Gul, . Cortney Kiss, . Andres Enriquez, . Zongchao Jia, . Adrián Baranchuk, J. S. Walia

IJC Heart & Vasculature (2017). Vol. 15 pp. 21-23
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A review of the safety aspects of radio frequency ablation
. Abhishek Bhaskaran, . William Chik, . Stuart Thomas, . Pramesh Kovoor, . Aravinda Thiagalingam

IJC Heart & Vasculature (2015). Vol. 8(1) pp. 147-153

Abstract
In light of recent reports showing high incidence of silent cerebral infarcts and organized atrial arrhythmias following radiofrequency (RF) atrial fibrillation (AF) ablation, a review of its safety aspects is timely. Serious complications do occur during supraventricular tachycardia (SVT) ablations and knowledge of their incidence is important when deciding whether to proceed with ablation. Evidence is emerging for the probable role of prophylactic ischemic scar ablation to prevent VT. This might increase the number of procedures performed. Here we look at the various complications of RF ablation and also the methods to minimize them. Electronic database was searched for relevant articles from 1990 to 2015. With better awareness and technological advancements in RF ablation the incidence of complications has improved considerably. In AF ablation it has decreased from 6% to less than 4% comprising of vascular complications, cardiac tamponade, stroke, phrenic nerve injury, pulmonary vein stenosis, atrio-esophageal fistula (AEF) and death. Safety of SVT ablation has also improved with less than 1% incidence of AV node injury in AVNRT ablation. In VT ablation the incidence of major complications was 5–11%, up to 3.4%, up to 1.8% and 4.1–8.8% in patients with structural heart disease, without structural heart disease, prophylactic ablations and epicardial ablations respectively. Vascular and pericardial complications dominated endocardial and epicardial VT ablations respectively. Up to 3% mortality and similar rates of tamponade were reported in endocardial VT ablation. Recent reports about the high incidence of asymptomatic cerebral embolism during AF ablation are concerning, warranting more research into its etiology and prevention.
Abstract
In light of recent reports showing high incidence of silent cerebral infarcts and organized atrial arrhythmias following radiofrequency (RF) atrial fibrillation (AF) ablation, [...]
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Alpha2A-adrenergic receptor and eNOS genetic polymorphisms are associated with exercise muscle vasodilatation in apparently healthy individuals
R. Nunes, L. Barroso, A. Pereira, M. Rondon, C. Negrão, J. Krieger, A. Mansur

IJC Heart & Vasculature (2016). Vol. 13 pp. 14-18

Abstract
Muscle vasodilatation during exercise has been associated with cardiovascular health and may be influenced by genetic variability. The purpose of this study was to evaluate functional genetic polymorphisms of physiologic pathways related to the regulation of the cardiovascular function (alpha-adrenergic receptors, endothelial nitric oxide synthase and bradykinin B2 receptor) and exercise muscle vasodilatation in apparently healthy men and women. We enrolled 689 individuals without established cardiovascular disease that had attended a check-up program. The vasodilatation was studied with venous occlusion plethysmography and determined by the increase of vascular conductance during handgrip exercise. Genotypes for ADRA1A Arg347Cys (rs1048101), ADRA2A 1780 C > T (rs553668), ADRA2B Del 301–303 (rs28365031), eNOS 786 T > C (rs2070744), eNOS Glu298Asp (rs1799983) and BDKRB2 (rs5810761) polymorphisms were assessed by polymerase chain reaction followed by high resolution melting analysis. The eNOS rs2070744 polymorphism was significantly associated with forearm vascular conductance during exercise in women. Women with CC genotype showed higher vasodilatation than carriers of TC and TT genotypes (p = 0.043). The ADRA2A rs553668 polymorphism was significantly associated with forearm vascular conductance during exercise in men. Men with TT genotype had higher vasodilatation than carriers of CT and CC genotypes (p = 0.025). eNOS rs207074 polymorphism in women and ADRA2A rs553668 polymorphism in men were associated with the increase of forearm vascular conductance during handgrip exercise. These findings suggest that eNOS and ADRA2A genetic polymorphisms may be potential markers of exercise muscle vasodilatation.
Abstract
Muscle vasodilatation during exercise has been associated with cardiovascular health and may be influenced by genetic variability. The purpose of this study was to evaluate [...]
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Novel linkage of LMNA Single Nucleotide Polymorphism with Dilated Cardiomyopathy in an Indian case study
A. Banerjee, P. K. Ghoshal, . Kaushik Sengupta

IJC Heart & Vasculature (2015). Vol. 7(1) pp. 99-105

Abstract
Dilated Cardiomyopathy (DCM) is one of the most commonly encountered heart diseases reported globally. It is characterized by enlarged ventricles with impaired systolic and diastolic functions. Mutations in LMNA gene are one of the causative factors to precipitate the disease. However, association of SNPs of LMNA with DCM in particular has not been well documented. Here we present a limited and restricted case study of patients from south eastern part of India afflicted with idiopathic DCM and conduction defects. By using next generation sequencing we have sequenced the exons of LMNA gene from genomic DNA isolated from patients. We have identified the linkage of 8 different LMNA SNPs with idiopathic DCM viz. rs121117552, rs538089, rs505058, rs4641, rs646840, rs534807, rs80356803 and rs7339. These SNPs are scattered throughout the gene with prevalence for the region encoding the central rod domain of lamin A/C. Most of these SNPs in LMNA were previously reported to be involved in various disorders other than DCM. We conclude that, variation in LMNA is one of the major underlying genetic causes for the pathogenesis of DCM, as observed in few Indian populations.
Abstract
Dilated Cardiomyopathy (DCM) is one of the most commonly encountered heart diseases reported globally. It is characterized by enlarged ventricles with impaired systolic and [...]
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Postinfarction posterior ventricular septal rupture mimicking a biventricular free wall rupture with extracardiac left-to-right shunt
. Kattih Badder, . Jens Vogel-Claussen, . Udo Bavendiek, . Akin Muharrem, . Christian Kühn, . Johann Bauersachs, . Michael Brehm

IJC Heart & Vasculature (2015). Vol. 9(7) pp. 32-36
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The renin–angiotensin–aldosterone-system and right heart failure in congenital heart disease
. Stine Andersen, A. Andersen, J. Nielsen-Kudsk

IJC Heart & Vasculature (2016). Vol. 11 pp. 59-65

Abstract
Adults with congenital heart disease represent a rapidly growing patient group. Dysfunction of the right ventricle is often present, and right heart failure constitutes the main cause of death. Heart failure therapies used in acquired left heart failure are often initiated in adults with right heart failure due to congenital heart disease, but the right ventricle differs substantially from the left ventricle, and the clinical evidence for this treatment strategy is lacking. In this review, we identified existing clinical studies evaluating the effects of ACE inhibitors, angiotensin II receptor blockers and aldosterone antagonists in adults with congenital heart disease by a systematic literature search. From 13 identified studies no clear evidence of beneficial effects was found, but the design of the studies limits the validity of the results. The studies in general include low numbers of patients, have short follow-up periods and evaluate surrogate endpoints instead of hard clinical endpoints. Specific evaluation of symptomatic patients with a systemic right ventricle indicates that these patients may benefit from RAAS inhibitory treatments, but this requires further investigation. To conclude, existing studies do not support the use of RAAS inhibitory treatments in right heart failure due to congenital heart disease but contain important limitations. Hence, there is a need for new well-designed trials including higher numbers of patients and validated endpoints to optimize and guide future treatment of this patient group.
Abstract
Adults with congenital heart disease represent a rapidly growing patient group. Dysfunction of the right ventricle is often present, and right heart failure constitutes the [...]
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Fragmented QRS and ejection fraction in heart failure patients admitted to the hospital
. Fadi Alattar, . Nashat Imran, . Fayez Shamoon

IJC Heart & Vasculature (2015). Vol. 9(7) pp. 11-14

Abstract
Fragmented QRS (FQRS) in 12 lead ECG was recently correlated with various outcomes in ischemic and non-ischemic heart disease. We studied the relationship between FQRS and ejection fraction (EF) in heart failure patients with QRS < 120 ms. Medical records and echocardiograms of 339 patients admitted with CHF were reviewed. ECGs were read twice by a reader blinded to all data. 70 patients with wide QRS were excluded, 63 patients had FQRS and 206 patients did not have FQRS. FQRS group were more likely to be black (OR = 2.17, p = 0.0093), and diabetic (OR = 1.79, p = 0.0451). ROC curve analysis revealed a significant relationship between EF and FQRS (p = 0.002). At EF of 48%, OR for FQRS was 4.36 (95% CI: 2.1–9.05, p < .0001). Adjustment for race and diabetes did not change the OR, or confidence intervals (Adjusted OR for race: 4.08 (95% CI: 1.06–15.67, p = 0.04), for diabetes: 4.13 (95% CI: 1.46–11.69, p = 0.008)). There was a significant difference in EF between patients with FQRS involving ≥ 2 ECG areas and non-FQRS group (p < 0.05), but not between patients with ≥ 2 vs. one area, or 1 area vs. non-FQRS. In heart failure patients with QRS < 120 ms, FQRS was observed more frequently in persons of black race and in diabetics and was associated with lower EF. This was mainly seen in patients with FQRS involving ≥ 2 ECG areas.
Abstract
Fragmented QRS (FQRS) in 12 lead ECG was recently correlated with various outcomes in ischemic and non-ischemic heart disease. We studied the relationship between FQRS and [...]
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Corrigendum to “Regional variations in baseline characteristics of cardiac rhythm device recipients: The PANORAMA observational cohort study” [Int. J. Cardiol. Heart Vessels (2014) 90–96]
F. Al Kandari, . Andrejs Erglis, . Raed Sweidan, . Ingrid Dannheimer, . Milan Sepsi, . Juan Bénézet, . Michal Padour, . Ajay Naik, . Jaime Escudero, . Teena West, . Reece Holbrook, . Faizel Lorgat

IJC Heart & Vasculature (2014).
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CYP2C19 variants and epoxyeicosatrienoic acids in patients with microvascular angina
. Tomonori Akasaka, . Daisuke Sueta, . Yuichiro Arima, . Noriaki Tabata, . Seiji Takashio, . Yasuhiro Izumiya, . Eiichiro Yamamoto, . Kenichi Tsujita, . Sunao Kojima, . Koichi Kaikita, . Ayami Kajiwara, . Kazunori Morita, . Kentaro Oniki, . Junji Saruwatari, . Kazuko Nakagawa, . Seiji Hokimoto

IJC Heart & Vasculature (2017). Vol. 15 pp. 15-20

Abstract
Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the impact of CYP2C19 polymorphisms and EETs on the patients with microvascular angina (MVA) caused by coronary microvascular dysfunction. We examined CYP2C19 genotypes in patients with MVA (n = 81). MVA was defined as absence of coronary artery stenosis and epicardial spasms, and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. In MVA, the patients with CYP2C19 PM were 34.6% and high sense C-reactive protein (hs-CRP) levels in CYP2C19 PM were significantly higher than that of non-PM group (0.165 ± 0.116 vs. 0.097 ± 0.113 mg/dL, P = 0.026). Moreover, DHET levels in CYP2C19 PM were significantly lower than that of non-PM (10.4 ± 4.58 vs. 15.6 ± 11.1 ng/mL, P = 0.003 (11, 12-DHET), 12.1 ± 3.79 vs. 17.3 ± 6.49 ng/mL, P = 0.019 (14, 15-DHET)). The decline of EET owing to CYP2C19 variants may affects coronary microvascular dysfunction via chronic inflammation.
Abstract
Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) [...]
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Comparison of circadian, weekly, and seasonal variations of electrical storms and single events of ventricular fibrillation in patients with Brugada syndrome
. Yoshiyasu Aizawa, . Seiji Takatsuki, . Yoshiaki Kaneko, . Takashi Noda, . Yoshinori Katsumata, . Takahiko Nishiyama, . Takehiro Kimura, . Nobuhiro Nishiyama, . Kotaro Fukumoto, . Shinichi Niwano, . Takashi Kurita, . Takeshi Mitsuhashi, . Shiro Kamakura, . Akihiko Shimizu, . Minoru Horie, . Yoshifusa Aizawa, . Keiichi Fukuda

IJC Heart & Vasculature (2016). Vol. 11 pp. 104-110

Abstract
In patients with Brugada syndrome (BS), VF occurred predominantly during the nocturnal period. Some patients also developed ESs. In addition to the circadian rhythm, patients showed weekly and seasonal patterns. The patients with ESs had peak episodes of VF on Saturday and in the winter and spring, while episodes of VF in patients with single VF events occurred most often on Monday with smaller seasonal variation. Except for age, there was no difference in the clinical or ECG characteristics between the patients with ESs and those with single VF episodes.
Abstract
In patients with Brugada syndrome (BS), VF occurred predominantly during the nocturnal period. Some patients also developed ESs. In addition to the circadian rhythm, patients [...]
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Pulmonary hypertension: prevalence and risk factors
S. Ait Faqih, . Béfa Noto-Kadou-Kaza, L. Abouamrane, . Naoufal Mtiou, S. El Khayat, . Mohamed Zamd, . Ghislaine Medkouri, M. Benghanem, . Benyounes Ramdani

IJC Heart & Vasculature (2016). Vol. 11 pp. 87-89

Abstract
Pulmonary arterial hypertension (PAH), defined as a systolic pulmonary artery pressure above 35 mm Hg, is another vascular disease entity recently described in patients receiving hemodialysis. It is a major problem due to its high prevalence and morbidity and mortality. Its pathophysiological mechanism is just known and the strategies for its supported not yet defined. To determine the prevalence of PAH in our hemodialysis patients and its risk factors. Single center descriptive and analytical cross-sectional study, including 111 hemodialysis patients who had benefit from a trans-thoracic cardiac Doppler ultrasound during 2014. A value greater than or equal to 35 mm Hg is considered PAH and classified as follows: mild PAH (35 50 mm Hg), moderate PAH (50 70 mm Hg), and severe pulmonary hypertension (> 70 mm Hg). Patients with a high probability of secondary PAH, especially those with the following history: chronic obstructive pulmonary disease, pulmonary embolism, were not included. The mean age was 44.3 ± 14.2 years. Among the 111 patients, 18 had pulmonary arterial pressure above 35 mm Hg corresponding to 16.22% of PAH prevalence. The average pressure was 45 mm Hg. Of these 18 patients, 11.8% had mild PAH, 3.4% moderate PAH and 0.8% severe PAH. The average hemodialysis duration was significantly associated with PAH (p = 0.003), as well as valvular calcification (p = 0.000), mitral regurgitation (p = 0.001) and tricuspid regurgitation (p = 0.002). Primary pulmonary hypertension is a major problem among our hemodialysis because of its high prevalence and its risk factors.
Abstract
Pulmonary arterial hypertension (PAH), defined as a systolic pulmonary artery pressure above 35 mm Hg, is another vascular disease entity recently described in patients receiving [...]
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Left atrial geometry and pump function in ischemic cardiomyopathy
M. Abdelzaher, W. Atteia

IJC Heart & Vasculature (2014). Vol. 5 pp. 45-50

Abstract
Many of the factors that are known to alter left atrial (LA) contractility are present in patients with ischemic cardiomyopathy (ICM). Nevertheless, preservation of LA contractile function in this group of patients was reported in previous studies. The aim of this study was to assess the changes in LA size, geometry and contractile function in ICM. 60 subjects (age: 49 ± 12 years, 53% males) in sinus rhythm undergoing coronary angiography (CA), were enrolled in this study, 15 subjects as a control group, 30 patients with reduced ejection fraction (EF) and significant coronary artery disease, as the ICM group, and 15 with reduced EF and normal CA, as the dilated cardiomyopathy (DCM) group. LA dimensions, volume, active emptying fraction (ACTEF) and eccentricity index (LAEi) as well as late diastolic velocities of the mitral annulus (a′) and LA free wall (A3) were measured. Compared with the control group, ICM patients had larger LA volume and reduced ACTEF, a′ and A3, with no significant difference between patients with ICM and DCM in any of these parameters. LA eccentricity was, non-significantly, higher in both cardiomyopathy groups than in the control group. Patients with ICM have increased LA volume and reduced LA contractile function in comparison with normal controls. LA enlargement, LA contractile dysfunction and LA geometric changes in ICM are similar to that occurring in DCM. LA size, contractile function and eccentricity may not be reliable in differentiating ischemic from idiopathic dilated cardiomyopathy.
Abstract
Many of the factors that are known to alter left atrial (LA) contractility are present in patients with ischemic cardiomyopathy (ICM). Nevertheless, preservation of LA contractile [...]
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Identification of nonlinear kinematic hardening parameters for sheet metal from biaxial loading tests
B. Söhngen

Presentations to the XIV International Conference on Computational Plasticity (COMPLAS 2017).

Abstract
In this work an anisotropic material model at finite strains with nonlinear mixed (isotropic and kinematic) hardening is used for the identification of the hardening parameters of sheet steel. The algorithmic system is thereby reduced to a single equation return mapping. For the identification, a cruciform specimen is loaded biaxially in an alternating shear test to provoke the kinematic hardening behavior and prevent the sheet from buckling. The material parameters are found through an optimization strategy by comparing the deformation field from the experiment to that from a finite element (FE) simulation. The resulting cost function is minimized by means of a gradient-based method.
Abstract
In this work an anisotropic material model at finite strains with nonlinear mixed (isotropic and kinematic) hardening is used for the identification of the hardening parameters [...]
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Time domain simulation of coupled sloshing-seakeeping problems by coupling PFEM-2 and SeaFEM
J. Colom Cobb, B. Servan Camas, P. Becker, J. García-Espinosa, S. Idelsohn

Presentations to the VII International Conference on Computational Methods in Marine Engineering (Marine 2017).

Abstract
The aim of this work is to be able to cope with complex sloshing-seakeeping problems in an effective manner. For this purpose, two different solvers will be integrated into one coupled tool to take advantage of their characteristics. The Particle Finite Element Method is a versatile framework for the analysis of fluid-structure interaction problems. The latest development within the framework of the PFEM is the X-IVAS (eXplicit Integration along the Velocity and Acceleration Streamlines) scheme. It is a semi-implicit scheme built over a Semi-Lagrangian (SL) formulation. This new scheme was named PFEM-2 and will be used in this work to solve the fluid dynamics (sloshing) inside the tanks. The PFEM-2 will be coupled in the time domain with SeaFEM, a solver developed for seakeeping problems. SeaFEM solves the second-order diffraction-radiation equations by using the Finite Element Method (FEM) and will be used in this work to simulate the interaction between waves and a floating body. The coupling of the two tools will be accomplished by using an effective coupling algorithm and a communication technique that allows simulations to be computed without affecting the global compute time and the accuracy of the solvers. This new tool has been validated against experimental benchmarks carried out in a model basin at model scale.
Abstract
The aim of this work is to be able to cope with complex sloshing-seakeeping problems in an effective manner. For this purpose, two different solvers will be integrated into [...]
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Hydrodynamic analysis of fishing farms.
J. Gutiérrez Romero, J. García-Espinosa, B. Zamora-Parra, J. Pérez

Presentations to the VII International Conference on Computational Methods in Marine Engineering (Marine 2017).

Abstract
There is no question about the relevancy of the blue growth concept, as a long term strategy to support sustainable growth in the marine sector. One of the sectors that has a higher potential for sustainable growth in this field is the aquaculture. This work is focused on the development of a time domain hydrodynamic solver for analysis and assessment of floating fishing farms. The paper also presents a demonstration case based on typical configuration of fishing farms used in the Mediterranean Sea. It is composed by a set of individual circular fishing cages. Several arrangements of fishing cages are also analysed subject to wind waves and currents. Different fishing cages are used in the performed simulations: circular, square and hexagonal. The influence of several configurations on fishing farm mooring behaviour in different sea states is studied. The analysis is focused in the dynamic behaviour of fishing cages. In particular mean drift and slow drift motions, including the second order-effects, will be studied, since they have important role on the behaviour of fishing farm in seaway. The results lead to final discussion about the best performance in fishing farm layout.
Abstract
There is no question about the relevancy of the blue growth concept, as a long term strategy to support sustainable growth in the marine sector. One of the sectors that has [...]
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Regulatory challenges for preventing firearms smuggling into Mexico
E. Vargas, S. González

Mexican Law Review (2015). Vol. 7

Abstract
The recent surge in illegal firearms trafficking from the U.S. into Mexico has helped empower Mexican criminal groups to adopt highly confrontational strategies, contributing to a surge of violence throughout the country. This article addresses the regulatory asymmetries between Mexico and the U.S. with respect to the production, import, export, sales and possession of firearms. It reviews several important gun laws and explores why this asymmetry limits bilateral cooperation and encourages gray market activity. It also examines the autonomy of U.S. states to regulate firearms, as this creates a diverse regulatory map that complicates any effort to stem smuggling. The results are flourishing gray markets on one side of the border and violent criminal activity on the other.
Abstract
The recent surge in illegal firearms trafficking from the U.S. into Mexico has helped empower Mexican criminal groups to adopt highly confrontational strategies, contributing [...]
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Regulating Mexican biobanks for human biomedical research: What can be learned from the european experience?
L. Gómez

Mexican Law Review (2014). Vol. 7

Abstract
Biobanking presents significant governance challenges. This is especially evident in Mexico, where the legal framework has not kept up with significant industry expansion. Twenty years ago, Europe was in a similar position. More recently, Europe has developed a comprehensive framework for addressing biobank expansion within ever-growing scientific and biomedical research communities. Based on this experience, we can draw many lessons, including those involving the implementation of laws, procedures and stakeholders’ consensus to ethically maximize the potential of samples. Mexican biobanking raises many issues, requiring solutions that are sensitive to its own particular needs. This article analyses the flaws of current biobanking regulations in Mexico by drawing comparisons with Europe. It pays special attention to informed consent, sample/data sharing systems, ethical tissue treatment and classification, governance models, best practices and the role of ethics committees. It argues that several European provisions regarding data protection and sharing can serve as guidelines for international research collaboration currently taking place between Mexico and Europe.
Abstract
Biobanking presents significant governance challenges. This is especially evident in Mexico, where the legal framework has not kept up with significant industry expansion. [...]
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How Mexican principals deal with teacher underperformance: A study of how public middle school principals in Mexico City manage underperforming teachers
J. Méndez

Mexican Law Review (2013). Vol. 5

Abstract
This study, based on thirty-eight interviews of principals from public middle schools in Mexico City, analyzes the criteria and methods used by these school officials to identify underperforming teachers, as well as how they wield discretionary authority. The study also proposes several measures that can be implemented by educational authorities to improve how these cases are handled. These measures include improving both principals’ training and the mechanisms used to evaluate teacher performance in the classroom.
Abstract
This study, based on thirty-eight interviews of principals from public middle schools in Mexico City, analyzes the criteria and methods used by these school officials to identify [...]
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THE EXCESSIVE USE OF FORCE BY MEXICO CITY LAW ENFORCEMENT AGENCIES: CORRUPTION, NORMAL ABUSE AND OTHER MOTIVES
C. Forné

Mexican Law Review (2016). Vol. 9
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Mexican-American studies in tucson, arizona and the acosta v. huppenthal decision
M. Schiffer, S. Nuño

Mexican Law Review (2014). Vol. 6

Abstract
This note examines the political context surrounding the banning of the Mexican American Studies program in Tucson, Arizona and the Acosta v. Huppenthal decision, which leaves the ban largely intact. The convergence of economic crisis and partisan politics contributed to the rise in anxiety over the demographic shifts of the state of Arizona, for which Mexican American Studies became a symbolic target for Republicans. Mexican American Studies was declared in violation of a new law passed by the Republican dominated legislature, A.R.S. § 15-112, by Arizona Superintendent John Huppenthal, despite the conclusion by an independent audit he ordered which concluded otherwise. This left leaders within the Mexican American community and civil rights organizations with the conclusion that the ban on Mexican American Studies was politically motivated. This note explores the motivations by individual political actors, such as the current Attorney General of Arizona Tom Horne, and how he rose to power on a platform centered on the ban against Mexican American Studies.
Abstract
This note examines the political context surrounding the banning of the Mexican American Studies program in Tucson, Arizona and the Acosta v. Huppenthal decision, which leaves [...]
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ASSESSING ATTITUDES TOWARD MUNICIPAL POLICE IN MEXICO DURING DEMOCRATIC TIMES: A CASE STUDYING
S. Perea

Mexican Law Review (2016). Vol. 8
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The objective international responsibility of states in the Inter-American human rights system
G. Tagle

Mexican Law Review (2015). Vol. 7

Abstract
The international responsibility of States is based on two legal precepts: first, a State must be subject to international obligations, and second, a State must be responsible for noncompliance with such obligations. Specific and concrete damages are not required for the allocation of international responsibility to a State. Given these elements, the Inter-American Human Rights System, through the Inter-American Court, will not hear disputes involving a State’s international responsibility without the existence of a specific and concrete human rights violation. While this seems appropriate, rulings by the Inter-American Court have subsequently opened the door to States’ objective in ternational responsibility, i.e., responsibility under the American Convention on Human Rights that require no showing of a specific violation. In the author’s view, the international responsibility of States, similar to Public International Law, should be based on noncompliance without the need for a victim –especially in human rights cases. For this reason, the Inter-American Court is correct in holding States responsible for domestic laws that contravene its own human rights commitments under international treaties– regardless of whether or not these norms have been enforced.
Abstract
The international responsibility of States is based on two legal precepts: first, a State must be subject to international obligations, and second, a State must be responsible [...]
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THE NULL-VOTE: A DESPERATE CRY FOR DEMOCRACY IN MEXICO
P. Cámara

Mexican Law Review (2016). Vol. 9
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Investor-state tribunals and constitutional courts: The Mexican sweeteners saga
S. Puig

Mexican Law Review (2013). Vol. 5

Abstract
This article tackles the complex question of the relationship between international and domestic adjudicatory bodies. It does so by analyzing the debate between liberals and developmentalists over the effects of investor-state arbitration tribunals on domestic courts. For liberals, investor-state tribunals are a positive complement to domestic judicial institutions for their ability to “de-politicize” investment disputes, leading to economic policy stability that encourages foreign investment. For developmentalists, the same international alternatives reduce institutional quality by allowing powerful actors such as powerful corporations to skirt local judicial institutions. Through a comprehensive analysis of the negotiations of Chapter Eleven of NAFTA and the recent cases in the sweeteners conflict between Mexico and the United States, this article attempts to address how investor-state arbitration tribunals and constitutional courts interact and affect each other. The case study reveals two important lessons to this debate: i) scholars arguing against investor-state arbitration on the grounds of “circumvention” of domestic courts may do well to calibrate the debate of the use of remedies as one of added remedial possibilities in complex litigation, ii) those defending investor-state arbitration on the grounds of “de-politicization” of investment disputes may do well to consider the veto power wielded by international adjudicatory bodies that impact the judiciary and political systems of the host country.
Abstract
This article tackles the complex question of the relationship between international and domestic adjudicatory bodies. It does so by analyzing the debate between liberals and [...]
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WHAT IS “CONSTITUTIONAL EFFICACY”?: CONCEPTUAL OBSTACLES FOR RESEARCH ON THE EFFECTS OF CONSTITUTIONS
A. Loyo

Mexican Law Review (2016). Vol. 9
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International support for justice reform: Is it worthwhile?
L. Pásara

Mexican Law Review (2013). Vol. 6

Abstract
Over the last twenty-five years, a number of justice reform projects funded by international actors have been implemented in Latin America. No less than 2 billion US dollars were disbursed for this purpose. Several questions on this issue are addressed in this article: How does international aid work in the field of justice and what is the rationale used? What is the relationship between and the dynamics of the actors who participate in international aid? What are the results of the funded projects and what limits have been encountered? Has international support for justice reform been worthwhile? The author elaborates on the central argument that international actors underperform their role mainly for two reasons. One, the approach used in the recipient country seriously restricts the proper comprehension of the root causes of the problems country faces. Two, international actors lack serious interest in learning. In the predominant approach, bureaucratic criteria prevail: projects are designed and promoted according to the aid agency’s blueprint, evaluation is usually poor and money is readily available. If in a given country there are no strong national actors, international agencies establish asymmetrical relationships with their counterparts, tend to import recipes that hardly suit the conditions in the country, and impose paths to reform that are difficult for local actors to appropriate. Cooperation agencies have disseminated an ideological construct based on a non-proven causal relationship between justice systems and economic growth as the driving force for reform. International actors could do better were they to develop a capacity for learning, but this goal seems difficult for them to reach.
Abstract
Over the last twenty-five years, a number of justice reform projects funded by international actors have been implemented in Latin America. No less than 2 billion US dollars [...]
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ANTITRUST IN THE NEW ECONOMY CASE GOOGLE INC. AGAINST ECONOMIC COMPETITION ON WEB
D. Mendoza

Mexican Law Review (2016). Vol. 8
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The role of China and the brics project
A. García

Mexican Law Review (2014). Vol. 7

Abstract
BRICS is an exogenous invention that was institutionalized as a convenient geopolitical market strategy, which favored each of the five BRICS countries to a greater or a lesser degree. As such, it is now a political group without deep roots and its future will be conditioned by any dividends it might yield over the coming years as a result of political, economic and social correlations and divergences.
Abstract
BRICS is an exogenous invention that was institutionalized as a convenient geopolitical market strategy, which favored each of the five BRICS countries to a greater or a lesser [...]
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THE BECOMING-OTHER OF LAW: PRELIMINARIES FOR A CITIZEN'S CONCEPTUALIZATION OF LAW
R. Miranda

Mexican Law Review (2016). Vol. 8
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THE DIGITAL DIVIDE IN MEXICO: A MIRROR OF POVERTY
J. Montiel

Mexican Law Review (2016). Vol. 9
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CRIMINALS AND ENEMIES? THE DRUG TRAFFICKER IN MEXICO'S POLITICAL IMAGINARY
A. Lajous

Mexican Law Review (2016). Vol. 8
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A Comparative-Empirical analysis of administrative courts in Mexico
S. López-Ayllón, A. García, A. Fierro

Mexican Law Review (2015). Vol. 7

Abstract
The main function of administrative courts in Mexico is to resolve disputes between administrative agencies and citizens. Mexico is a federal system with 31 states and a Federal District. Twenty-nine states and the Federal District have administrative courts of this type. Most of these courts follow the French model of reviewing administrative actions in bodies that do not form part of the regular justice system. However, almost half of the states have deviated from this model and ascribed these administrative courts to the judicial branch. How does this change in the institutional framework influence the way administrative court judges review administrative action disputes? In order to answer this question we analyzed the rulings of judges from the different types of courts empirically. The Mexican federal court structure made this experiment possible because there are both administrative courts incorporated into the judiciary and autonomous courts. We used a database of more than 4, 000 cases from over twenty local administrative courts. We analyzed the influence of the branch to which the court belongs, the procedures of appointment for judges, the length of a judge’s term in office, and the protection of judges’ salaries over their actual decisions. We classified decisions into two broad categories: pro-government decisions and case dismissals. The results point toward evidence that the branch to which the court belongs, the length of a judge’s term in office and governor intervention in the appointment of judges affect judges’ decisions.
Abstract
The main function of administrative courts in Mexico is to resolve disputes between administrative agencies and citizens. Mexico is a federal system with 31 states and a Federal [...]
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Mexicos attempt to extend its continental shelf beyond 200 nautical miles serves as a model for the international community
S. Jr

Mexican Law Review (2013). Vol. 5

Abstract
In June 2000, the United States and Mexico signed a treaty for the delimitation of the continental shelf in the western Gulf of Mexico beyond 200 nautical miles. When the treaty was signed, both countries realized that the interpretation and implementation of the treaty depended on the scientific and legal certainty of determinations regarding how far their respective submarine continental shelves extended. On 13 December 2007, Mexico submitted information to the Commission on the Limits of the Continental Shelf regarding the limits of the continental shelf beyond 200 nautical miles from the baselines from which the breadth of the territorial sea is measured in relation to the Western Polygon in the Gulf of Mexico. Mexico sought an extension of its continental shelf in the Western Polygon based on international law, UNCLOS, and bilateral treaties with the United States, in accordance with Mexicos domestic legislation. Peaceful delimitation of maritime borders is essential to maintaining world order. Mexico is a country of peace, and has attempted to use international law as a tool to represent its interests. Mexico has meticulously adhered to a series of international precedents and treaties to support its claim. Moreover, Mexico has gathered significant scientific evidence to verify its sovereign authority over its maritime areas. In the authors opinion, the United States should recognize these claims and show the world that the U.S. stands for fairness, equity and the rule of law.
Abstract
In June 2000, the United States and Mexico signed a treaty for the delimitation of the continental shelf in the western Gulf of Mexico beyond 200 nautical miles. When the [...]
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Migration of responsibility: The trust doctrine and the tohono o’odham nation
K. Gurbacki

Mexican Law Review (2014). Vol. 6

Abstract
This article discusses the impact of the influx of migrants from Mexico and Central America on the American Southwest. Specifically, it discusses how Native American tribes of the Southwest, especially the Tohono O’odham Nation, have become a magnet for illegal border crossings due to lax enforcement policies on tribal land. As a result, the tribe has encountered a surge in drug-trafficking, violence, and environmental destruction on its reservation. The article first analyzes the trust doctrine between the Native American tribes and the United States federal government. It concludes with a discussion of the monetary and equitable relief available to the Tohono O’odham Nation in the form of damage awards and increased border protection.
Abstract
This article discusses the impact of the influx of migrants from Mexico and Central America on the American Southwest. Specifically, it discusses how Native American tribes [...]
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The role of shocks and social pressures in the development of citizenship rights: Great britain and Mexico’s divergent paths
F. González

Mexican Law Review (2015). Vol. 7

Abstract
Drawing on T.H. Marshall’s classic analysis of how civil, political and social rights evolved in Great Britain, this article follows authors, like Rose and Shin, who used a “social pyramid” to illustrate how the inverted development of such citizenship rights in other nations may weaken liberal democracy. In contrast, I argue that this sequence varies depending on a society’s own unique history, and that no one single path can define the development of liberal democracy. In Mexico, the development of citizenship rights (mainly social, political and civil, following T.H. Marshall’s categorization) was catalyzed by a series of economic and security-related crises that impacted a broad cross-section of Mexican society. The result of these pressures —both from above (organized elites) and below (organized popular groups)— has been greater enforcement of already existing political rights. This major change eventually led to competitive ballot elections (since the late 1990s) which in turn has forced politicians to focus on reshaping social rights (e.g., making their application universal rather than selective). Since President Felipe Calderon’s (2006-2012) “war on drugs, ” there has also been notable legislation —backed by widespread public support— to strengthen civil rights (e.g., 2008 criminal justice reform, 2011 reforms to the amparo and human rights).
Abstract
Drawing on T.H. Marshall’s classic analysis of how civil, political and social rights evolved in Great Britain, this article follows authors, like Rose and Shin, who used [...]
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Global politics
J. Santillán

Mexican Law Review (2013).

Abstract
This article is about the great changes that have happened in recent years in international politics as well as the challenges that these thorough transformations imply. Some examples of great significance are the fall of the Berlin Wall (1989), the attack on the New York World Trade Centers twin towers and the Pentagon (2001), and the crash of Wall Street (2008). These are historical events that have had practical and theoretical repercussions for different humanistic disciplines like political science, law and international studies. The authors purpose is to analyze both practically and theoretically the new paradigms of global politics. The impact of globalization on Latin America is given special attention. The author concludes by presenting some alternatives in order to resolve the dilemmas posed by globalization.
Abstract
This article is about the great changes that have happened in recent years in international politics as well as the challenges that these thorough transformations imply. Some [...]
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Legal challenges of biometric immigration control systems
V. Díaz

Mexican Law Review (2014). Vol. 7

Abstract
This article analyzes the deployment of biometric systems in immigration control. It argues that public policy for biometric data collection and processing must be based on legal principles and involve the participation of diverse actors, including civil society organizations, industry associations, special privacy advocates and government officials. Such deployments must also involve control mechanisms that help ensure transparency and accountability. Based on a comparative study of biometric immigration control system deployment in four countries (Australia, Mexico, New Zealand and Spain), two types of asymmetries stand out: first, notable differences in the types of information collected, stored, processed, retrieved, updated, analyzed and exchanged, Second, the purposes for which biometric systems are currently used. In the latter case, wide divergence exists in areas for which these systems are employed, such as border control strategies and the use of travel documents, revealing that each nation chooses to use these systems at different points in the immigration process. These asymmetries pose both short and long-term challenges for international cooperation.
Abstract
This article analyzes the deployment of biometric systems in immigration control. It argues that public policy for biometric data collection and processing must be based on [...]
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Transitional justice, human rights and the restoration of credibility: Reconstructing Mexico’s social fabric
H. Rivera

Mexican Law Review (2014). Vol. 7

Abstract
Mexico is entering a phase of transitional justice. This can be observed in the numerous reforms and measures that are being taken to adapt the legal system to international standards, particularly those related to human rights and criminal justice. Some examples show an increased tendency to adhere to and enforce the rule of law and human rights, to recognize the official truth of authorized misconduct that took place in the past, to punish perpetrators, and above all, to ensure victims’ rights to truth and reparation. If these tendencies continue, it could potentially lead to the restoration of public trust in the authorities and pave the way for reconciliation between society and the State. While many experiences of traditional transitional justice have taken place in post-authoritarian contexts, the convergence of the main elements used in those traditional cases lead us to suggest that these models could also apply to societies in transition, not from a particular form of government to another, but from a developing democracy into a law-abiding society. In this sense, a bottom-up approach that aims at attaining truth, reform and change will be necessary to break a cycle of impunity and develop social and government institutions that respect and enforce the rule of law and human rights.
Abstract
Mexico is entering a phase of transitional justice. This can be observed in the numerous reforms and measures that are being taken to adapt the legal system to international [...]
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The development of the media and the public sphere in Mexico
F. Higareda

Mexican Law Review (2013). Vol. 5

Abstract
This article reviews the development of the Mexican media, both broadcast and print, through an analysis of their current legal framework, culture, ownership structure and common practices. It is based on archival research, interviews and a review of the available literature. Its analytical framework is based on concepts of the theory of deliberative democracy developed by contemporary philosophers such as Jürgen Habermas, James Bohman, Jane Mans-bridge and Joshua Cohen. Within this framework, it argues that the major obstacles to democracy in Mexico, which include social and economic inequalities, patronage and a weak rule of law, also constitute obstacles to the deliberative development of the Mexican media.
Abstract
This article reviews the development of the Mexican media, both broadcast and print, through an analysis of their current legal framework, culture, ownership structure and [...]
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ONE NORM, TWO MODELS. LEGAL ENFORCEMENT OF HUMAN RIGHTS IN MEXICO AND THE UNITED STATES
K. Ansolabehere

Mexican Law Review (2016).
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Why has the transition to democracy led the Mexican presidential system to political instability? A proposal to enhance institutional arrangements
J. Tovar

Mexican Law Review (2013). Vol. 5

Abstract
Over the past two decades, Mexico has gone from an authoritarian regime to an electoral democracy. Although this change is undoubtedly positive, the institutional engineering in place and the balance of power among institutions has led to increased political instability and a latent risk of political paralysis. There is substantial literature asserting that these problems may be connected to the core characteristics of presidential systems, however, I demonstrate that in the Mexican case, it is also due to the electoral rules derived from the reforms of the 1990s and the subsequent electoral results. To substantiate this claim, I present the historical conformation of the presidential, political and electoral systems, as well as the balance of power derived from later system structures and the problems that can trigger instability. Finally, in response to the vast amount of literature that asserts that presidential systems generally shift to a parliamentary or semi-presidential system to perform better, I present an original formula based on relatively simple and feasible political reforms that can enhance the Mexican presidential system and prevent political paralysis.
Abstract
Over the past two decades, Mexico has gone from an authoritarian regime to an electoral democracy. Although this change is undoubtedly positive, the institutional engineering [...]
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Massive post-polypectomy hemorrhage: Successful tulip-bundle technique with endoloop for hemostasis
H. Yen, C. Yang, S. Wu, M. Soon

Advances in Digestive Medicine (2016). Vol. 3

Abstract
Colonoscopic polypectomy is a common procedure for removing colonic polyps to prevent subsequent development of colon cancer. Hemorrhage is the most common complication following polypectomy, with a reported rate of 0.3% to 6.0%. The risk increases to 12.5% when the size of the polyp stalk exceeds 1 cm. The most commonly used endoscopic preventive techniques, such as injection therapy, prophylactic use of endoclip, or endoloop, were found to decrease the rate of post-polypectomy hemorrhage, and repeated use of these techniques is useful for controlling bleeding. Here, we reported a case of a 65-year-old man with refractory post-polypectomy hemorrhage for a 2-cm adenomatous polyp. Application of an endoloop using the tulip-bundle technique achieved successful hemostasis. To our knowledge, this is the first report of this technique being used to treat refractory acute post-polypectomy hemorrhage.
Abstract
Colonoscopic polypectomy is a common procedure for removing colonic polyps to prevent subsequent development of colon cancer. Hemorrhage is the most common complication following [...]
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Medical utilization by liver cancer patients under the National Health Insurance program in Taiwan: A population-based cross-sectional study
C. Yeh, Y. Lin, C. Yu, C. Hsu

Advances in Digestive Medicine (2015). Vol. 2

Abstract
Taiwan implemented a comprehensive and universal National Health Insurance (NHI) program to cover all inhabitants. This study aimed to assess the medical utilization by liver cancer patients under the NHI. This retrospective cross-sectional study used a sampled NHI research database, which contained 1 million beneficiaries. The claims of liver cancer patients in 2009 were analyzed. The other beneficiaries without liver cancer who used medical services in 2009 served as the control patients. Among the 2335 identified liver cancer patients, 2178 (93.3%) patients used outpatient services and 1193 (51.1%) patients used inpatient services. Liver cancer accounted for 1.8% of the NHI’s total cost. The cost per visit was United States dollars (US$)59.30 for outpatient care and US$2070.30 for inpatient care. The annual cost per patient was US$4746.60, US$1951.00 were for outpatient care and US$2795.60 for inpatient care. Patients who were female, in their 60s, had a lower income, and lived in southern Taiwan had a higher cost per patient (p < 0.0001). Fees for consultation, treatment, and medical supplies (57.3%) accounted for the highest portion of outpatient costs, followed by drug fees (30.0%) and diagnosis fees (11.2%). Ward fees accounted for the highest portion of inpatient costs (19.0%), followed by drug fees (18.7%) and X-ray fees (14.9%). Private hospitals were visited more frequently than public hospitals. The cost per visit and cost per patient with liver cancer were 206.0% and 666.8%, respectively, of the cost of the control patients. The cost of liver cancer care is substantial and varies by sex, age, income, and geographic distribution. It is critical to reduce the incidence of liver cancer and identify cost-effective treatment strategies.
Abstract
Taiwan implemented a comprehensive and universal National Health Insurance (NHI) program to cover all inhabitants. This study aimed to assess the medical utilization by liver [...]
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Pravastatin inhibits tumor growth through elevating the levels of apolipoprotein A1
C. Yeh, C. Cheng, H. Lin, T. Luo, J. Chang, A. Ho

Advances in Digestive Medicine (2016). Vol. 3

Abstract
Statins are a class of drugs used to lower cholesterol levels, accompanying increased high-density lipoprotein (HDL) levels. Previous studies have suggested that statins can inhibit inflammation, and also reduce tumor proliferation. We therefore hypothesized that pravastatin, a member of the statins, mediating the inhibitory functions in tumor growth may be associated with the upregulated HDL constituent, apolipoprotein A1 (ApoA1). Pravastatin-induced inhibition in tumor proliferation in vitro and in xenografts was investigated. Reduced ApoA1 expressions were detected in the tumor regions in specimens from tumor patients as well in xenografts using Western Blotting. Moreover, ApoA1 was administered to inhibit tumor proliferation, and pravastatin was given to enhance the chemotherapeutic efficacy of doxorubicin (DOX). We found a significant statistical reduction of ApoA1 in the tumor regions of specimens from gastric cancer and colorectal cancer patients. MKN45 cells proliferation was inhibited by 18% under the growing medium containing pravastatin. ApoA1 levels were elevated in liver Clone 9 cells administered pravastatin, but not in MKN45 cells. In vitro studies revealed that ApoA1 can reduce MKN45 tumor proliferation. Moreover, the tumor volume was significantly reduced in in vivo xenografts after the administration of pravastatin. Combined treatments of pravastatin with DOX significantly minimized the size of tumors, leading to a better therapeutic efficacy. This study demonstrated that pravastatin elevated ApoA1, an HDL major constituent with anti-inflammatory characteristics, which displayed strong adversary associations with tumor developments and growth. Increasing the amounts of ApoA1 by pravastatin coupled with DOX may improve the therapeutic efficacy for cancer treatment.
Abstract
Statins are a class of drugs used to lower cholesterol levels, accompanying increased high-density lipoprotein (HDL) levels. Previous studies have suggested that statins can [...]
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Reticulocyte production index as a predictor of clinically significant anemia in chronic hepatitis C patients receiving pegylated interferon combination therapy
S. Yan, C. Chang, C. Chen, Y. Yeh, C. Tsai

Advances in Digestive Medicine (2016). Vol. 3

Abstract
This work was conducted to study the relationship of reticulocyte production index to clinically significant anemia in chronic hepatitis C patients receiving pegylated interferon combination therapy. A total of 69 chronic hepatitis C patients receiving pegylated interferon combination therapy were included. Clinically significant anemia was defined as a hemoglobin level of < 10 g/dL. Reticulocyte count values were determined at the baseline and during treatment (4 weeks, 12 weeks, and 24 weeks). Reticulocyte production indices were calculated according to formulae. Clinical variables were analyzed using univariate analysis. Variables that were found to be significant on univariate analysis were included in multivariate analysis. A p value < 0.05 was regarded as statistically significant. Clinically significant anemia was observed in 30 patients (43.5%), and 39 patients (56.5%) never developed clinically significant anemia during the whole treatment course. On multivariate analysis, age > 60 years [odds ratio (OR), 2.94, 95% confidence interval (CI), 1.09–7.93], pretreatment hemoglobin level < 14 g/dL (OR, 5.76, 95% CI, 2.01–16.48), and reticulocyte production index < 0.9% (OR, 5.50, 95% CI, 1.78–16.97) at Week 4 were significantly associated with clinically significant anemia. Besides old age and low pretreatment hemoglobin level, our study showed that a reticulocyte production index < 0.9% at Week 4 was a significant factor associated with clinically significant anemia during pegylated interferon combination treatment.
Abstract
This work was conducted to study the relationship of reticulocyte production index to clinically significant anemia in chronic hepatitis C patients receiving pegylated interferon [...]
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Unexpected and unintentional fish bone ingestion causing acute abdomen and uncommon small intestinal perforation
T. Yang, C. Lu

Advances in Digestive Medicine (2016). Vol. 3

Abstract
Perforation of the mesenteric small bowel is an uncommon cause of acute abdomen in the emergency department. Early diagnosis is difficult owing to unspecific clinical presentations. The most common causes of perforation are tumor, trauma, Crohns disease, ischemia, and foreign body ingestion. Currently, computed tomography (CT) is often the initial modality used to assess patients with acute abdomen, and the excellent anatomic details it provides, including segmental bowel wall thickening, mesenteric air bubbles, and fatty infiltration, may help the clinician to diagnose earlier and with greater ease. Here, we present a case of acute abdomen diagnosed as small bowel perforation due to unintentional fish bone ingestion using multidetector CT. The multiplanar reconstruction images from multidetector CT helped locate the perforation site before surgical intervention.
Abstract
Perforation of the mesenteric small bowel is an uncommon cause of acute abdomen in the emergency department. Early diagnosis is difficult owing to unspecific clinical presentations. [...]
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The clinical efficacy and safety of EUS-FNA for diagnosis of mediastinal and abdominal solid tumors – A single center experience
S. Yang, S. Liao, C. Ko, C. Tung, Y. Peng, H. Lien, H. Yeh, C. Chang, J. Wang

Advances in Digestive Medicine (2015).

Abstract
Many tumors are small and located around the gastrointestinal (GI) tract, and they are difficult to obtain tissue from for pathological diagnosis by the guidance of conventional methods (sonography or computed tomography. The aim of this study was to analyze the efficacy and benefit of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the clinical diagnosis of solid tumors in the mediastinum and abdomen. Data from 233 patients with solid tumors on or around the GI tract were reviewed. They had received successful EUS-FNA without on-site cytopathology study. The lesions were classified according to the anatomic location as pancreatic tumors (Group A, n = 91), mediastinal tumors (including lymph nodes) (Group B, n = 38), abdominal tumors (including lymph nodes) (Group C, n = 49), focal transmural thickening of the GI tract (Group D, n = 6), and submucosal tumors of the GI tract (Group E, n = 49). The accuracies of pathological diagnosis of malignancy were 79.2%, 76.9%, 93.2%, and 80% for Groups A–D, respectively. The overall accuracy for malignancy was 82.9%. For the submucosal tumors of the GI tract in Group E, FNA cytopathology provided evidence of specific diagnosis all were GI stromal tumor in 47% of the cases, 14% were diagnosed as suspicious (most were of a spindle cell tumor nature), and 39% were considered negative of tumor or non-diagnostic. There were three episodes (1.3%) of complication (GI bleeding, n = 1, septic fever, n = 1, gallbladder puncture, n = 1) which occurred among all patients in this study, and all of them were treated appropriately, with no occurrence of life-threatening events. EUS-FNA appears to be a very useful tool for obtaining tissue diagnosis for lesions that are inaccessible by the conventional methods and was shown to be a safe and effective technique in the hands of experienced operators. Pathological diagnosis can be obtained for the guidance of clinical management to avoid the more invasive ways, such as surgery or mediastinal scope.
Abstract
Many tumors are small and located around the gastrointestinal (GI) tract, and they are difficult to obtain tissue from for pathological diagnosis by the guidance of conventional [...]
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Young man with chronic anemia
K. Yang, S. Shih, H. Wang, W. Chang, K. Hu

Advances in Digestive Medicine (2015). Vol. 2
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Advanced hepatocellular carcinoma treated by a combination of sorafenib and radiotherapy
B. Yang, C. Yeh, C. Hsu, T. Chang, C. Wang

Advances in Digestive Medicine (2014). Vol. 1

Abstract
Advanced hepatocellular carcinoma has a poor therapeutic outcome and treatment options are limited. Sorafenib, an orally active multikinase inhibitor, is the only systemic drug that has been shown to provide survival benefits in randomized control studies. However, the gains in survival are modest and new treatment strategies are needed. We report here the case of a patient with advanced hepatocellular carcinoma who had an impressive response to a combination of sorafenib and radiotherapy. The treatment was well tolerated with no unexpected toxicities. Post-treatment imaging showed a satisfactory partial response with regression of the tumor by more than 50%.
Abstract
Advanced hepatocellular carcinoma has a poor therapeutic outcome and treatment options are limited. Sorafenib, an orally active multikinase inhibitor, is the only systemic [...]
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Early endoscopic finding of esophageal thermal injury after having spicy hot pot
C. Wu, M. Bair, I. Lin, Y. Lee, H. Chen

Advances in Digestive Medicine (2015). Vol. 2

Abstract
We herein present the case of a woman who had esophageal thermal injury after having a spicy hot pot. The patient came to us with complaints of odynophagia, dysphagia, and burning sensation at the throat and upper chest while eating or drinking for 1 day. An upper endoscopy was conducted 1 day after the onset of symptoms, which showed a linear, disrupted bullae-like lesion with a thin detached membrane. Our report depicts the early endoscopic finding of esophageal thermal injury following the ingestion of hot food. The finding is different from what has been often reported as the “candy-cane” appearance of esophageal injury, which results from the ingestion of hot liquid.
Abstract
We herein present the case of a woman who had esophageal thermal injury after having a spicy hot pot. The patient came to us with complaints of odynophagia, dysphagia, and [...]
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Analysis of ascitic fluid lactoferrin levels in the diagnosis of spontaneous bacterial peritonitis after systemic antibiotic treatment
C. Wu, T. Chen, C. Lin, C. Chiu, M. Su, C. Chiu

Advances in Digestive Medicine (2015). Vol. 2

Abstract
Spontaneous bacterial peritonitis (SBP) is one of the most frequent complications of liver cirrhosis. Ascitic fluid lactoferrin has been proved to be a good diagnostic tool for SBP. However, lactoferrin in ascites may be checked after antibiotic treatment in these patients. Our study aims to assess the utility of ascitic fluid lactoferrin levels for the diagnosis of SBP after antibiotic treatment. Twenty-two ascites samples were collected from patients with cirrhosis. Samples were examined for bacterial culture, lactoferrin concentration, and polymorphonuclear leukocyte count. Clinical symptoms and indications for ascitic paracentesis were obtained from medical records. The diagnosis of SBP was based on an elevated ascitic fluid polymorphonuclear leukocyte count of ≥250 cells/mm3 . Four (18.1%) samples fulfilled the diagnostic criteria for SBP. Three ascites samples showed a positive result for bacterial culture. Patients who received antibiotics for treatment of SBP constituted Group B (n = 9), whereas those who did not receive any antibiotics comprised Group A (n = 9). Lactoferrin concentration was significantly elevated (mean: 261.69 ± 145.5 ng/mL) in the three cases with a positive bacterial culture compared to those without SBP, in both Group A (mean: 19.64 ± 6.32 ng/mL, p = 0.002) and Group B (mean: 23.64 ± 9.53 ng/mL, p = 0.001). After systemic antibiotic treatment, elevated lactoferrin levels in the ascites of cirrhotic patients appear to be a promising predictor for the presence of SBP having positive ascitic bacterial culture.
Abstract
Spontaneous bacterial peritonitis (SBP) is one of the most frequent complications of liver cirrhosis. Ascitic fluid lactoferrin has been proved to be a good diagnostic tool [...]
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Multipolar radiofrequency ablation with non-touch technique for hepatocellular carcinoma ≤ 3 cm: A preliminary report
L. Wu, C. Chen, C. Liu, M. Chen, P. Liu, P. Liu, O. Seror, I. Lee, S. Lin

Advances in Digestive Medicine (2014). Vol. 1

Abstract
Conventional monopolar radiofrequency ablation (RFA) bears the risks of incomplete ablation and tumor seeding. This study aimed to evaluate the effectiveness and safety of multipolar RFA with non-touch technique for hepatocellular carcinoma (HCC) ≤ 3 cm. Fifteen cirrhotic patients (9 men, 6 women, age 51–83 years, mean 64.4 years, Child-Pugh score: A = 10 and B = 5) with 17 HCCs of ≤ 3 cm (mean: 26 mm), which were diagnosed based on typical radiologic findings were enrolled. Two or three Celon Prosurge Bipolar electrodes with 3-cm active tip were deployed with non-touch technique via percutaneous approach under ultrasound guidance. Complete ablation was achieved in all 17 lesions. This is defined as no enhanced part around the ablated index tumors according to dynamic computed tomography or magnetic resonance imaging at least 1 month after ablation. No local tumor progression was detected at follow-up (range, 3–21.5 months, mean, 10 months). No track seeding was observed. There was one distant recurrence 15.4 months after ablation. One patient had procedure-related biliary stricture and died of pneumonia 3.5 months after tumor ablation. Multipolar RFA with non-touch technique is an effective method to achieve complete tumor ablation and an adequate safety margin. This method has low complication rate and bears minimal risk of tumor seeding.
Abstract
Conventional monopolar radiofrequency ablation (RFA) bears the risks of incomplete ablation and tumor seeding. This study aimed to evaluate the effectiveness and safety of [...]
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Delayed healing of gastric ulcer is associated with downregulation of connexin 32 in the gastric mucosa
S. Wang, H. Wang, T. Wang, H. Wang, W. Chang, C. Chu, S. Lin, H. Yeh, S. Shih

Advances in Digestive Medicine (2015). Vol. 2

Abstract
Most benign gastric ulcers are healed through suppression of gastric acid by a proton pump inhibitor (PPI). Despite prolonged use of a PPI, some gastric ulcers still do not heal. The primary goal of this study is to investigate the relationship between the expression of connexin 32 (Cx32), a major gap junction protein expressed in the gastric mucosa, and the healing response of gastric ulcers. Patients with endoscopically verified gastric ulcer were treated with a standard dose of PPI for 12 weeks. Histological studies were performed to exclude malignancy. In total, 10 patients having endoscopically verified gastric ulcers with delayed healing at the end of the PPI course were included in this study. The control group consisted of 11 patients with gastric ulcers that healed normally. The expression of Cx32 in the gastric mucosa of the ulcer margin was analyzed by immunoblotting. Patients with gastric ulcer showing delayed healing had significantly reduced Cx32 expression in the gastric mucosa compared with the patients in whom the ulcers healed normally (i.e., controls). Age, sex, presence of duodenal ulcers, location and size of gastric ulcer, ulcer staging, Helicobacter pylori infection, use of nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, smoking, and alcohol consumption were similar in both the control and delayed healing groups. H. pylori infection, use of NSAIDs, smoking, and alcohol consumption all had no significant impacts on the expression of Cx32. Age and expression of Cx32 were not correlated. Downregulation of Cx32 in the gastric mucosa of the ulcer margin may predict delayed healing in patients with gastric ulcer following acid-suppression therapy.
Abstract
Most benign gastric ulcers are healed through suppression of gastric acid by a proton pump inhibitor (PPI). Despite prolonged use of a PPI, some gastric ulcers still do not [...]
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Barretts esophagus and risk of esophageal adenocarcinoma: A retrospective analysis
H. Wang, C. Kuo, W. Lin, C. Hsu, Y. Ho, C. Lin, K. Chen, M. Su, C. Chiu

Advances in Digestive Medicine (2015). Vol. 2

Abstract
Barretts esophagus (BE) is the most common cause or precursor of esophageal adenocarcinoma (EAC), a condition with a poor prognosis. This study aimed to investigate the clinical characteristics and risk of EAC in patients with BE. From January 2001 to December 2012, a total of 425 patients with histologically proven BE were identified and analyzed retrospectively. Patients' personal data (smoking, alcohol consumption), underlying systemic disease data (diabetes mellitus and hypertension), endoscopic findings (hiatal hernia, peptic ulcer, endoscopically suspected esophageal metaplasia, severity of reflux esophagitis, rapid urease test), and pathological findings (degree of dysplasia, Helicobacter pylori infection) were collected for further analysis. In this retrospective study, 15 patients were diagnosed with EAC. Only one patient was found to have EAC during endoscopic surveillance for BE. The majority of patients (14/15 patients) suffered alarm symptoms and were diagnosed to have BE and EAC concurrently. Meanwhile, EAC is already relatively at an advanced stage. The mean age for diagnosis of EAC in a patient with BE was 67.67 ± 9.92 years old. All patients were male. From a total of 15 patients, 33.3% (5 patients) demonstrated erosive esophagitis under endoscopy and 60% (3 of 5 patients) of these were classified as Los Angeles grade C or D disease. Our study found that BE-associated EAC mostly occurred in older men. In the group with BE-associated EAC, the majority of patients were discovered due to alarm symptoms, at the same time as esophageal adenocarcinoma had already developed. Further prospective study is needed to stratify the risk of disease progression in BE patients.
Abstract
Barretts esophagus (BE) is the most common cause or precursor of esophageal adenocarcinoma (EAC), a condition with a poor prognosis. This study aimed to investigate the clinical [...]
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Evolution of esophageal function testing in achalasia: Linking new technology to treatment outcome
P. Tseng, M. Wu

Advances in Digestive Medicine (2014). Vol. 1
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A rare presentation of clinically intractable hypertension: Pancreatic paraganglioma
C. Tseng, J. Tsai, C. Tai, C. Chang, T. Tang, H. Wang

Advances in Digestive Medicine (2016). Vol. 3

Abstract
Paraganglioma is a rare extra-adrenal pheochromocytoma which originates from chromaffin cells within the ganglia of the sympathetic trunk and of the celiac, renal, suprarenal, and hypogastric plexuses. Pancreatic paragangliomas are rarer still. And even then, paragangliomas are mostly reported to be nonfunctional. We report a case of a 64-year-old woman with underlying disease of hypertension who presented with biliary colic. Contrast-enhanced computer tomography showed an enhancing mass in the uncinate process of the pancreas. Pylorus-sparing Whipple procedure was performed for complete tumor excision. Hypertensive crisis developed after Whipple, which improved after continuous intravenous nicardipine infusion. Pathology revealed a paraganglioma. A 24-h catecholamine urine test showed increased norepinephrine and vanillylmandelic acid level. Functional paraganglioma was diagnosed.
Abstract
Paraganglioma is a rare extra-adrenal pheochromocytoma which originates from chromaffin cells within the ganglia of the sympathetic trunk and of the celiac, renal, suprarenal, [...]
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Recurrent abdominal pain after an episode of acute diverticulitis
C. Tseng, Y. Chen

Advances in Digestive Medicine (2015). Vol. 2
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Endoscopic balloon-based radiofrequency ablation for long-segment early esophageal squamous cell neoplasia
Y. Tsai, C. Lee, T. Tang, I. Chang, C. Chang, L. Mo, W. Wang

Advances in Digestive Medicine (2016). Vol. 3

Abstract
Esophageal cancer is a common and highly lethal disease. In the Asia-Pacific region, esophageal squamous cell neoplasias are the major forms of the disease. Recent advances in endoscopic therapy enable curative treatment of early esophageal squamous cell neoplasias, however, the technique is complicated and requires a high level of expertise, especially for those with long-segment lesions. Endoscopic radiofrequency ablation is a rapidly evolving treatment modality and has been shown to have good efficacy and safety for the treatment of dysplasia in cases of Barrett’s esophagus. Theoretically, it can also be used to treat squamous dysplasia. We report a case of a 48-year-old man with an 8-cm-long circumferential squamous high-grade dysplasia over the esophagus (from 21 cm to 29 cm below the incisor) that was treated successfully and safely with balloon-based radiofrequency ablation. The procedure took only around 30 minutes to complete. There were no major adverse events during and after the procedure. In addition, we examined the histology of the esophageal coagulum, which showed an extensive cauterization effect with focal dysplasia within the ablated epithelium. Follow-up endoscopy at 1 month, 3 months, and 6 months showed no residual lesion, and biopsies also confirmed complete remission.
Abstract
Esophageal cancer is a common and highly lethal disease. In the Asia-Pacific region, esophageal squamous cell neoplasias are the major forms of the disease. Recent advances [...]
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Analgesic effect of premedication with meperidine in patients undergoing colonoscopy without sedation
M. Tsai, T. Chen, H. Lai, T. Chen, M. Chang, C. Lin

Advances in Digestive Medicine (2014). Vol. 1

Abstract
Colonoscopy is a standard and useful examination in the diagnosis of colorectal diseases, however, it usually causes pain to patients. Some patients receive narcotic drugs, e.g., meperidine, for pain relief if a colonoscopy is carried out without sedation. Whether the administration of such analgesic drugs to patients without sedation facilitates the performance of the colonoscopy or reduces pain remains to be elucidated. The aim of this study was to evaluate the analgesic effect of meperidine as premedication for patients undergoing a colonoscopy without sedation. A total of 217 patients (109 men, 108 women) undergoing a diagnostic colonoscopy without sedation were analyzed prospectively. The procedures were carried out by three experienced endoscopists in a medical center. The patients could opt to receive analgesic drugs, with 25 mg of meperidine being given intramuscularly prior to the procedure if requested by either the doctor or patient. The colonoscopic examination was performed by one person using the short-axis method. Questionnaires to evaluate abdominal pain during or after colonoscopy without sedation were collected and analyzed for patients who used meperidine as premedication (Group A) and for those who did not receive meperidine (Group B). Abdominal pain was evaluated using a visual analog scale from 0 to 10. The cecal intubation rate, total insertion time, and the patients willingness to receive another colonoscopy in the future if needed were also analyzed. In both groups, the cecal intubation rate was more than 99% with no significant difference between groups. The mean ± standard deviation insertion time was 7.14 ± 5.45 minutes in Group A and 6.24 ± 4.24 minutes in Group B (p = 0.309). The visual analog pain score was 3.54 ± 3.13 in Group A and 2.46 ± 2.75 in Group B (p = 0.009). After adjusting for age and sex, the pain score was 3.51 ± 3.21 in Group A (p = 0.055). Multivariate analysis showed that female sex and the individual endoscopist performing the colonoscopy were associated with abdominal pain during the examination. In our study, premedication with meperidine or no premedication was not associated with a reduction in abdominal pain during colonoscopy without sedation. The insertion time and cecal intubation rate showed no difference between patients with or without additional analgesic drugs prior to the procedure. However, as self-selection bias could not be ruled out, further randomized, placebo-controlled trials are needed to confirm our findings.
Abstract
Colonoscopy is a standard and useful examination in the diagnosis of colorectal diseases, however, it usually causes pain to patients. Some patients receive narcotic drugs, [...]
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Clinical factors associated with the survival of patients with intrahepatic cholangiocarcinoma
C. Ting, W. Huang, C. Feng, C. Yu, C. Peng, W. Su, H. Lai, K. Cheng, P. Chuang, J. Kao

Advances in Digestive Medicine (2016). Vol. 3

Abstract
Intrahepatic cholangiocellular carcinoma (ICC) is an uncommon but lethal cancer. The aim of this study is to assess the factors affecting the survival of ICC patients and to evaluate the benefit of these factors when various therapeutic modalities are used. Between October 2007 and June 2012, 66 ICC cases among 2255 liver cancer patients were identified by pathology and divided into two groups: Group I (surgery group, n = 17) and Group II (nonsurgery group, n = 49). Group II was further divided into Group IIa (those receiving palliative treatment, n = 19) and Group IIb (no treatment received, n = 30). Factors affecting patient survival over the study period were assessed (3- and 6-month results were reported) and therapeutic benefits identified within each of the groups were evaluated. Of the 66 patients identified (male/female = 36/30), 10.6% (7/66) were in the early stages of illness. Overall, the mean patient survival duration was 3.50 ± 0.92 months (1.69–5.31 months). The mean survival duration of Group I patients was 10.50 ± 2.84 months (4.94–16.06 months). The mean survival duration of Group II patients was 3.50 ± 0.65 months (2.24–4.76 months) with Group IIa patients surviving on average 9.50 ± 3.27 months (3.10–15.90 months) and Group IIb patients surviving on average 1.50 ± 0.12 months (1.26–1.74 months). Better survival outcomes were observed in the groups receiving treatment, Group I and Group IIa, than in Group Iib, which did not receive treatment [9.50 ± 1.73 months (6.12–12.89 months) vs. 1.50 ± 0.12 months (1.26–1.74 months), p < 0.001]. Lower albumin, higher bilirubin, higher CA19-9, advanced tumor stage, and no treatment were identified as important predictors of patient mortality at the 3- and 6-month time-points. These factors remained relevant throughout the entire study period (p = 0.002, 0.029, 0.027, 0.028, < 0.001, respectively). This study identified surgery as the treatment that provided the best survival prognosis for patients with ICC. Treatment involving either chemotherapy or radiotherapy could also prolong ICC patient survival. Better liver preservation, lower CA19-9, and less aggressive tumor conditions were identified as factors which play crucial roles in enhancing patient survival.
Abstract
Intrahepatic cholangiocellular carcinoma (ICC) is an uncommon but lethal cancer. The aim of this study is to assess the factors affecting the survival of ICC patients and [...]
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IL28B polymorphism and early anemia predict the rapid null response in genotype-1 chronic hepatitis C with dual therapy
W. Teng, T. Chang, C. Huang, W. Jeng, W. Chen, C. Huang, Y. Ho, C. Lin, I. Sheen

Advances in Digestive Medicine (2015). Vol. 2

Abstract
Rapid null response (rNR), defined as less than one log decline of Hepatitis C virus (HCV-RNA) at Week 4 of treatment with pegylated interferon-α and ribavirin (PegIFN/RBV), is highly correlated with treatment failure in patients with chronic hepatitis C (CHC), genotype-1 (GT-1). In this study, we investigate the possible predictors of rNR. We retrospectively analyzed a cohort of 199 GT-1 CHC naive patients who had been treated with a dual therapy of PegIFN/RBV. Clinical parameters and genotypes of rs12979860, the single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B ) were analyzed for their relationship with rNR. Of the patients analyzed, 41.7% did not exhibit a rapid virological response (RVR). Only 13.1% of patients who experienced a rNR showed an RVR. The treatment failure rate was 36.2%. High baseline viral load (OR: 5.74, p = 0.028), nonrapid virological response (non-RVR, OR: 4.32, p = 0.004) and rNR (OR: 51.82, p < 0.001) were the predictors of treatment failure. In addition, both the non-CC allele of rs12979860 (OR: 13.8, p < 0.001) and the Hb (hemoglobin) decline to < 3 g/dL within 4 weeks of treatment (no early anemia, OR: 4.6, p = 0.024) were predictors of rNR. rNR predicted treatment failure early in GT-1 CHC patients treated with PegIFN/RBV. Non-CC genotype of rs12979860 and no early anemia were significant predictors of rNR.
Abstract
Rapid null response (rNR), defined as less than one log decline of Hepatitis C virus (HCV-RNA) at Week 4 of treatment with pegylated interferon-α and ribavirin (PegIFN/RBV), [...]
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An unusual polynodular liver disease: Multiple biliary hamartoma
S. Teng, J. Shin, J. Huang

Advances in Digestive Medicine (2015). Vol. 2

Abstract
We report a 73-year-old male patient who suffered from right upper abdominal dull pain, fever, and chills for 2 days. Gall bladder stones and acute cholecystitis were diagnosed, and parenteral antibiotics were used. The abdominal ultrasonography showed multiple tiny hyperechoic nodules over both lobes of the liver. His computed tomography scan revealed low-density lesions without contrast enhancement. Magnetic resonance imaging and magnetic resonance cholangiopancreatography further revealed lesions that were hypointense on T1-weighted images and hyperintense on T2-weighted images. Laparoscopic cholecystectomy and liver biopsy were performed, and biliary hamartoma was diagnosed based on the pathology. This report describes an unusual case of multiple biliary hamartomas and reviews the literature regarding the incidence, pathogenesis, and diagnosis of this disease.
Abstract
We report a 73-year-old male patient who suffered from right upper abdominal dull pain, fever, and chills for 2 days. Gall bladder stones and acute cholecystitis were diagnosed, [...]
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Younger age and female sex predict a better therapeutic response in HBeAg-positive chronic hepatitis B patients to entecavir therapy
W. Su, T. Hsieh, T. Hsieh, K. Tseng, C. Peng, C. Lin, T. Su, T. Hsiao, T. Tseng, H. Lin, C. Wang, J. Kao

Advances in Digestive Medicine (2014). Vol. 1

Abstract
Clinical trials and real-world data confirm the efficacy of entecavir treatment for chronic hepatitis B (CHB), however, the factors associated with a favorable response remain unknown. In a retrospective multicenter study, 132 treatment-naïve hepatitis B e antigen (HBeAg)-positive CHB patients (71% male, median age, 40.2 years) received entecavir therapy for >2 years. At baseline, 15% of these patients had cirrhosis. The primary endpoint was HBeAg loss at 2 years of entecavir treatment. The rates of serum alanine aminotransferase (ALT) normalization at treatment Year 1 and Year 2 were 86% and 88%, respectively. The cumulative rate of HBeAg loss at treatment Year 1 and Year 2 were 17% and 33.3%, respectively. The rates of undetectable levels of serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) at treatment Year 1 and Year 2 were 64% and 80.8%, respectively. In univariate analysis, HBeAg loss at 2 years was associated with a young age (≤35 years, p = 0.007) and a high baseline ALT level (p < 0.001). Multivariate analysis after adjusting for age, sex, and ALT level [>5 times the upper limit of normal (ULN)] showed that a young age (odds ratio, 2.66, 95% confidence interval, 1.2–5.92) and male sex (odds ratio, 0.36, 95% confidence interval, 0.16–0.83) were independent factors associated with HBeAg loss at 2 years of therapy. Two-year entecavir therapy has good biochemical and virologic responses, however, the rate of HBeAg loss is modest in HBeAg-positive CHB patients. A young age (i.e., ≤35 years) and female sex were also associated with a better serologic response.
Abstract
Clinical trials and real-world data confirm the efficacy of entecavir treatment for chronic hepatitis B (CHB), however, the factors associated with a favorable response remain [...]
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Pseudomelanosis duodeni in a female adult with chronic renal failure
W. Sun, F. Tsay, K. Lai, P. Hsu, C. Shih

Advances in Digestive Medicine (2014). Vol. 1

Abstract
Pseudomelanosis duodeni is a rare endoscopic finding that manifests as dark speckled spots in the duodenum. It is considered a benign condition and is associated with certain diseases and the use of certain medications. This study reports a case of a 74-year-old woman, with end-stage renal disease under maintenance hemodialysis, hypertension under regular medical control, iron deficiency anemia under oral iron supplement, and progressive anemia with suspicious occult gastrointestinal bleeding. Upper gastrointestinal endoscopy revealed multiple tiny brownish-black pigmentation throughout the proximal second portion of the duodenum. The histopathological examination showed pigment-laden macrophages with positive iron stain and negative melanin stain in the lamina propria of the mucosal villi.
Abstract
Pseudomelanosis duodeni is a rare endoscopic finding that manifests as dark speckled spots in the duodenum. It is considered a benign condition and is associated with certain [...]
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Ileal ulcers in a patient with Henoch-Schönlein purpura
Y. Shih, C. Liang, C. Lin, W. Hsu, C. Wu, C. Chung

Advances in Digestive Medicine (2015). Vol. 2

Abstract
Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by a classic tetrad of nonthrombocytopenic palpable purpura, arthritis, gastrointestinal, and renal involvement. The most common gastrointestinal complaint is abdominal pain. The characteristic endoscopic findings are ulcers seen in the second portion of the duodenum. We present the case of a 45-year-old man suffering from abdominal pain. Erythematous purpura over bilateral lower extremities and soreness of the joints developed 3 days before abdominal pain. An abdominal computed tomography showed an edematous change of the intestinal wall and the distal part of the ileum. A retrograde single balloon enteroscopy revealed several discrete ulcers and hyperemic mucosa in the distal ileum. The middle, proximal, and terminal ileum and ileocecal valve to the rectum were not affected. Under the impression of HSP, nonsteroidal anti-inflammatory drugs and prednisolone were administered. We concluded that balloon-assisted enteroscopy is helpful for differential diagnosis of small bowel lesions in adult patients with HSP.
Abstract
Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by a classic tetrad of nonthrombocytopenic palpable purpura, arthritis, gastrointestinal, and renal [...]
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Intraobserver and interobserver agreement for identifying extraluminal manifestations of Crohns disease with magnetic resonance enterography
I. Shih, T. Lee, C. Tu, C. Chang, Y. Wang, Y. Tseng, H. Chiu, M. Wu, H. Wang, T. Shih, K. Liu

Advances in Digestive Medicine (2016). Vol. 3

Abstract
Magnetic resonance (MR) enterography has emerged as a new imaging modality in evaluating patients with Crohns disease. However, whether interpretations of MR enterography findings are consistent among radiologists has not yet been fully investigated. The purpose of this study is to evaluate the intraobserver and interobserver agreement for identifying extraluminal manifestations of Crohns disease with MR enterography. MR enterography was performed with a 3-tesla system. We retrospectively enrolled patients with Crohns disease that had MR enterography between November 2011 and March 2013. Three radiologists reviewed the images independently. Extraluminal findings of these patients were recorded and described. Intraobserver and interobserver agreement were calculated using the kappa statistic. A total of 22 sessions of MR enterography were performed on 15 patients (12 men and 3 women) with Crohns disease. The mean age was 38.7 ± 11.4 years. We identified extraluminal manifestations such as engorged vasa recta, enlarged mesenteric lymph nodes, fibrofatty proliferation, fistulas, and abscesses. In addition, avascular necrosis of the femoral head as a complication of long-term steroid treatment was also depicted. The intraobserver agreement was almost perfect (κ = 0.83, p < 0.001), and the interobserver agreement was substantial (κ = 0.65, p < 0.001). MR enterography is a clinically useful tool for evaluating extraluminal manifestations of Crohns disease with good intraobserver and interobserver agreement.
Abstract
Magnetic resonance (MR) enterography has emerged as a new imaging modality in evaluating patients with Crohns disease. However, whether interpretations of MR enterography [...]
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Gastroprotective effect of bezafibrate, a peroxisome proliferator activated receptor α agonist and its mechanism in a rat model of aspirin-induced gastric ulcer
L. Saha, A. Bhatia, A. Chakrabarti

Advances in Digestive Medicine (2016). Vol. 3

Abstract
The aim of the present study was to demonstrate the antiulcer activity and mechanism of bezafibrate in a rat model of aspirin-induced gastric ulcer. We used an aspirin-induced gastric ulcer model. Bezafibrate was administered orally in graded doses (10 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg) to detect the best effective antiulcer dose of bezafibrate. The parameters measured were: ulcer index, histopathological scoring of gastric ulcer, gastric juice analysis, gastric mucosal lipid peroxidation parameters, estimation of NO metabolite in blood, mRNA expression of inducible NO synthase iNOS and constitutive NO synthase (cNOS) in gastric mucosa, and gastric mucosal DNA fragmentation. The dose-dependent antiulcer activity of bezafibrate was shown by the ulcer index and histopathological score. Bezafibrate (100 mg/kg) significantly reduced total acidity, free acidity, and pepsin activity, and increased total hexoses and total proteins. Bezafibrate (100 mg/kg) also significantly reduced lipid peroxidation, inhibited iNOS expression, preserved cNOS expression, and inhibited DNA fragmentation. Bezafibrate can decrease aspirin-induced gastric mucosal injury via reducing lipid peroxidation, inhibiting iNOS expression, preserving cNOS expression, and decreasing DNA fragmentation.
Abstract
The aim of the present study was to demonstrate the antiulcer activity and mechanism of bezafibrate in a rat model of aspirin-induced gastric ulcer. We used an aspirin-induced [...]
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Liver cirrhosis as a predisposing factor for esophageal candidiasis
T. Ou, H. Huang, T. Hsieh, W. Chang, H. Chu, C. Hsu, Y. Shih, T. Huang, P. Chen, H. Lin

Advances in Digestive Medicine (2014). Vol. 1

Abstract
Esophageal candidiasis (EC) often occurs in human immunodeficiency virus (HIV)-infected patients, but is uncommon in non-HIV-infected patients. It is known that malignancy, diabetes mellitus, previous gastric surgery, and medications (antibiotics, proton pump inhibitors, and steroids) are risk factors for esophageal candidiasis in non-HIV-infected patients. However, the relationship between liver cirrhosis and esophageal candidiasis was unclear. This study aimed to elucidate the role of liver cirrhosis in esophageal candidiasis. A retrospective chart review study was conducted on non-HIV-infected patients with esophageal candidiasis who presented to Tri-Service General Hospital from January 2009 to December 2012. The diagnosis of EC was primarily based on endoscopic findings. The incidence of EC in cirrhotic and noncirrhotic patients was compared. Furthermore, differences in baseline characteristics, clinical variables, and mortality after antifungal treatment between the two groups were analyzed. In this study, 43, 217 non-HIV-infected patients were enrolled, 3017 of whom had liver cirrhosis. The incidence of EC in cirrhotic patients was higher than that in noncirrhotic patients (0.8% vs. 0.36%, relative risk = 2.2, p < 0.001). Multivariate logistic regression analysis identified liver cirrhosis as an independent risk factor for EC (odds ratio, 1.74, 95% confidence interval, 1.06–2.87, p = 0.029). Moreover, cirrhotic patients tended to be asymptomatic compared with noncirrhotic patients (45.8% vs. 9%, p < 0.01). The most common coexisting endoscopic finding was reflux esophagitis (83.9%). However, antifungal treatment did not decrease the mortality of patients with EC during hospitalization. Liver cirrhosis is an independent risk factor for EC. EC may be asymptomatic in cirrhotic patients. Although antifungal treatment did not improve the outcome in this study, a prospective study is still required to investigate this issue.
Abstract
Esophageal candidiasis (EC) often occurs in human immunodeficiency virus (HIV)-infected patients, but is uncommon in non-HIV-infected patients. It is known that malignancy, [...]
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Immunoglobulin G4-related disease presenting with obstructive jaundice
Y. Li, C. Pan, H. Chan, K. Lai, P. Hsu

Advances in Digestive Medicine (2014). Vol. 1

Abstract
A 48-year-old male presented with diffuse abdominal fullness for 1 month and tea-colored urine for 10 days. Abdominal computed tomography/magnetic resonance cholangiopancreatography revealed diffuse enlargement of the pancreas and unusual soft tissue density around the left ureter. Endoscopic retrograde cholangiopancreatography demonstrated lumen narrowing of the distal common bile duct and irregularity of the pancreatic duct. Markedly elevated serum immunoglobulin G4 (IgG4) was also noted. Biopsy of soft tissue from the area surrounding the left ureter identified lymphoplasmacytic infiltration with high concentrations of IgG4-positive plasma cells accompanied by obliterative phlebitis, compatible with IgG4-related disease. The patient was administered steroid therapy and his symptoms improved. Clinicians should be aware of possible IgG4-related disease in a patient presenting with obstructive jaundice and diffuse pancreatic enlargement because glucocorticoid administration can achieve good response.
Abstract
A 48-year-old male presented with diffuse abdominal fullness for 1 month and tea-colored urine for 10 days. Abdominal computed tomography/magnetic resonance cholangiopancreatography [...]
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Bile aspiration enhances the diagnostic accuracy of Clonorchis sinensis : A case report
T. Lin, H. Chan, P. Hsu, T. Tsai, E. Wang, K. Lai, J. Cheng, H. Wang

Advances in Digestive Medicine (2016). Vol. 3

Abstract
Clonorchis sinensis is endemic to Southeast Asia, Japan, China, and Taiwan. Those infected often have a history of consumption of raw fresh fish. Its manifestations can be asymptomatic of cholangitis, biliary stones, or cholangiocarcinoma. A 69-year-old male living in Chishan, Taiwan visited our hospital with obstructive jaundice. Noninvasive analyses, such as stool examination, abdominal ultrasound, and an abdominal computed tomography scan did not reveal clues of clonorchiasis. As the obstructive jaundice was unexplained, endoscopic retrograde cholangiopancreatography (ERCP) was then performed and a hepatic fluke was seen via aspiration of bile. Subsequently, the ova of C. sinensis were detected via microscopic examination of bile samples. Bile aspiration is not routine during an ERCP procedure, however, we suggest the bile aspiration can be diagnostically accurate for clonorchiasis, especially for patients with a suspicious infection.
Abstract
Clonorchis sinensis is endemic to Southeast Asia, Japan, China, and Taiwan. Those infected often have a history of consumption of raw fresh fish. Its manifestations can be [...]
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