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Raid A Jastania,1 Muhammad Saeed,2,3 Hisham Al-Khalidi,4 Khalid AlQuthami,5 Tahani H Nageeti,6 Faisal A Al-Allaf,7,8 Kristoffer Valerie,9 Mohiuddin M Taher7,8 1Department of Pathology, Faculty of Medicine, Umm-Al-Qura University, Makkah, Saudi Arabia; 2Department of Radiology, Faculty of Medicine, Umm-Al-Qura University, Makkah, Saudi Arabia; 3Department of Radiology, Al-Noor Specialty Hospital, Makkah, Saudi Arabia; 4Department of Pathology, King Saud University, Riyadh, Saudi Arabia; 5Division of Histopathology, Department of Laboratory Medicine and Blood Bank, Al-Noor Specialty Hospital, Makkah, Saudi Arabia; 6Department of Radiation Oncology, King Abdullah Medical City, Makkah, Saudi Arabia; 7Science and Technology Unit, Umm-Al-Qura University, Makkah, Saudi Arabia; 8Department of Medical Genetics, Faculty of Medicine, Umm-Al-Qura University, Makkah, Saudi Arabia; 9Department of Radiation Oncology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USACorrespondence: Mohiuddin M Taher Email TMMohiuddin@uqu.edu.saPurpose: Several recent studies have documented CTNNB1 and BRAF mutations which are mutually exclusive for adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) tumors. This discovery is helpful in the development of novel targeted therapies in successful clinical trials with BRAF mutations in PCP cases. However, no such targeted therapy is available yet for ACP. Here, we report novel mutations, which are not previously reported, in a case of an adult ACP using NGS analysis.Results: Patient DNA was sequenced using Ion PI v3 chip on Ion Proton. A total of 16 variants were identified in this tumor by NGS analysis, out of which four were missense mutations, seven were synonymous mutations, and five were intronic variants. In CTNNB1 gene a known missense mutation in c.101G>T; in TP53 a known missense mutation in c.215C>G; and two known missense variants in PIK3CA, viz., in c.1173A>G; in exon 7, and in c.3128T>C; in exon 21, were found, respectively. Seven synonymous mutations were detected in this tumor, viz., in IDH1 (rs11554137), in FGFR3 (rs7688609), in PDGFRA (rs1873778), in APC (COSM3760869), in EGFR (rs1050171), in MET (rs35775721), and in RET (rs1800861), respectively. Three known, intronic variants were found in genes, such as PIK3CA, KDR, and JAK3, respectively. Also, a 3’-UTR and a splice site acceptor site variant in CSF1R and FLT3 genes were found in this tumor. We have shown allele coverage, allele ratio, and p-value, for all these mutations. The p-values and Phred quality score were significantly high for these variants.Conclusion: As reported in previous studies, in ACP tumors we found a CTNNB1 mutation by NGS analysis. The PIK3CA variants we detected were not known previously in ACP tumors. Finding the PIK3CA mutations in the ACP tumors may help develop targeted therapy for a subset of craniopharyngiomas with PIK3CA activating mutations. Clinical trials are in progress with specific PIK3CA inhibitors in advanced stages of many cancers.Keywords: craniopharyngioma, adamantinomatous, brain tumor, NGS, next generation DNA sequencing, CTNNB1

In the article the authors consider economic and political aspects of restoration and development of the oil industry in Iraq and make a brief historical analysis of it. It’s emphasized the role of political factors in the history of the development of the oil sector in the country. The article deals with the current situation in the oil industry of Iraq, and also the prospects and forecasts of development of it. It’s emphasized the idea that the oil export is one of the most important directions of Iraq's oil policy, which has a high degree of flexibility. It is noted that currently, the speedy recovery of Iraq and its oil industry depends on international companies. However, it is emphasized that there are established a lot of state-owned oil companies in recent decades in Iraq, which are working successfully in the global market. Authors consider the activity of one of them, a marketing company SOMO.

Abstract Background Steroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD) and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management. Our purpose was to assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) on cardiovascular magnetic resonance (CMR) derived circumferential strain (εcc). Methods We used CMR to assess effects of corticosteroids alone (Group A) or in combination with ACEI or ARB (Group B) on heart rate (HR), left ventricular ejection fraction (LVEF), mass (LVM), end diastolic volume (LVEDV) and circumferential strain (εcc) in a cohort of 171 DMD patients >5 years of age. Treatment decisions were made independently by physicians at both our institution and referral centers and not based on CMR results. Results Patients in Group A (114 studies) were younger than those in Group B (92 studies)(10 ± 2.4 vs. 12.4 ± 3.2 years, p < 0.0001), but HR, LVEF, LVEDV and LVM were not different. Although εcc magnitude was lower in Group B than Group A (-13.8 ± 1.9 vs. -12.8 ± 2.0, p = 0.0004), age correction using covariance analysis eliminated this effect. In a subset of patients who underwent serial CMR exams with an inter-study time of ~15 months, εcc worsened regardless of treatment group. Conclusions These results support the need for prospective clinical trials to identify more effective treatment regimens for DMD associated cardiac disease.

Abstract Background Cardiac dysfunction in boys with Duchenne muscular dystrophy (DMD) is a leading cause of death. Cardiac resynchronization therapy (CRT) has been shown to dramatically decrease mortality in eligible adult population with congestive heart failure. We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR) may predict CRT efficacy. Methods DMD patients (n = 236) were stratified into 4 groups based on age, diagnosis of DMD, left ventricular (LV) ejection fraction (EF), and presence of myocardial fibrosis defined as positive late gadolinum enhancement (LGE) compared to normal controls (n = 77). Dyssynchrony indices were calculated based on timing of CMR derived circumferential strain (ecc). The calculated indices included cross-correlation delay (XCD), uniformity of strain (US), regional vector of variance (RVV), time to maximum strain (TTMS) and standard deviation (SD) of TTMS. Abnormal XCD value was defined as > normal + 2SD. US, RVV, TTMS and SD were calculated for patients with abnormal XCD. Results There was overall low prevalence of circumferential dyssynchrony in the entire DMD population; it increased to 17.1% for patients with abnormal EF and to 31.2% in the most advanced stage (abnormal EF with fibrosis). All but one DMD patient with mechanical dyssynchrony exhibited normal QRS duration suggesting absence of electrical dyssynchrony. The calculated US and RVV values (0.91 ± 0.09, 1.34 ± 0.48) indicate disperse rather than clustered dyssynchrony. Conclusion Mechanical dyssynchrony is frequent in boys with end stage DMD-associated cardiac dysfunction. It is associated with normal QRS complex as well as extensive lateral fibrosis. Based on these findings, it is unlikely that this patient population will benefit from CRT.

Background: The STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure) demonstrated that coronary artery bypass grafting (CABG) reduced all-cause mortality rates out to 10 years compared with medical therapy alone (MED) in patients with ischemic cardiomyopathy and reduced left ventricular function (ejection fraction ≤35%). We examined the economic implications of these results., Methods: We used a decision-analytic patient-level simulation model to estimate the lifetime costs and benefits of CABG and MED using patient-level resource use and clinical data collected in the STICH trial. Patient-level costs were calculated by applying externally derived US cost weights to resource use counts during trial follow-up. A 3% discount rate was applied to both future costs and benefits. The primary outcome was the incremental cost-effectiveness ratio assessed from the US health care sector perspective., Results: For the CABG arm, we estimated 6.53 quality-adjusted life-years (95% CI, 5.70-7.53) and a lifetime cost of $140 059 (95% CI, $106 401 to $180 992). For the MED arm, the corresponding estimates were 5.52 (95% CI, 5.06-6.09) quality-adjusted life-years and $74 894 lifetime cost (95% CI, $58 372 to $93 541). The incremental cost-effectiveness ratio for CABG compared with MED was $63 989 per quality-adjusted life-year gained. At a societal willingness-to-pay threshold of $100 000 per quality-adjusted life-year gained, CABG was found to be economically favorable compared with MED in 87% of microsimulations., Conclusions: In the STICH trial, in patients with ischemic cardiomyopathy and reduced left ventricular function, CABG was economically attractive relative to MED at current benchmarks for value in the United States., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT00023595.

Multiple sodium glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to impart significant cardiovascular and kidney benefits, but are underused in clinical practice. Both SGLT-2i and GLP-1RA were first studied as glucose-lowering drugs, which may have impeded uptake by cardiologists in the wake of proven cardiovascular efficacy. Their significant effect on cardiovascular and kidney outcomes, which are largely independent of glucose-lowering effects, must drive a broader use of these drugs. Cardiologists are 3 times more likely than endocrinologists to see patients with both type 2 diabetes and cardiovascular disease, thus they are ideally positioned to share responsibility for SGLT-2i and GLP-1RA treatment with primary care providers. In order to increase adoption, SGLT-2i and GLP-1RA must be reframed as primarily cardiovascular and kidney disease risk-reducing agents with a side effect of glucose-lowering. Coordinated and multifaceted interventions engaging clinicians, patients, payers, professional societies, and health systems must be implemented to incentivize the adoption of these medications as part of routine cardiovascular and kidney care. Greater use of SGLT-2i and GLP-1RA will improve outcomes for patients with type 2 diabetes at high risk for cardiovascular and kidney disease.

Objective: To investigate changes in quality of life (QoL), cognition and functional status according to arrhythmia recurrence after atrial fibrillation (AF) ablation., Methods: We compared QoL, cognition and functional status in patients with recurrent atrial tachycardia (AT)/AF versus those without recurrent AT/AF in the AXAFA-AFNET 5 clinical trial. We also sought to identify factors associated with improvement in QoL and functional status following AF ablation by overall change scores with and without analysis of covariance (ANCOVA)., Results: Among 518 patients who underwent AF ablation, 154 (29.7%) experienced recurrent AT/AF at 3 months. Patients with recurrent AT/AF had higher mean CHA 2 DS 2 -VASc scores (2.8 vs 2.3, p<0.001) and more persistent forms of AF (51 vs 39%, p=0.012). Median changes in the SF-12 physical (3 (25th, 75th: -1, 8) vs 1 (-5, 8), p=0.026) and mental scores (2 (-3, 9) vs 0 (-4, 5), p=0.004), EQ-5D (0 (0,2) vs 0 (-0.1, 0.1), p=0.027) and Karnofsky functional status scores (10 (0, 10) vs 0 (0, 10), p=0.001) were more favourable in patients without recurrent AT/AF. In the overall cohort, the proportion with at least mild cognitive impairment (Montreal Cognitive Assessment <26) declined from 30.3% (n=157) at baseline to 21.8% (n=113) at follow-up. ANCOVA identified greater improvement in Karnofsky functional status (p<0.001) but not SF-12 physical (p=0.238) or mental scores (p=0.065) in those without recurrent AT/AF compared with patients with recurrent AT/AF., Conclusions: Patients without recurrent AT/AF appear to experience greater improvement in functional status but similar QoL as those with recurrent AT/AF after AF ablation., Competing Interests: Competing interests: The study was sponsored by the AF-NET with funding from BMS-Pfizer and the European Union. JPP receives grants for clinical research from Abbott, ARCA biopharma, Boston Scientific, Gilead, Janssen Pharmaceuticals and NHLBI and serves as a consultant to Abbott, Allergan, ARCA Biopharma, Bayer, Biotronik, GSK, Johnson & Johnson, Medtronic, Motif Bio, Sanofi and Phillips. DMT receives speaking honoraria from Boston Scientific, Medtronic and Abbott. KGH reports study grants by Bayer and Sanofi-Aventis, lecture fees/advisory board fees from Sanofi-Aventis, Pfizer, Bristol-Myers-Squibb, Boehringer Ingelheim, Daiichi Sankyo, Edwards Lifesciences, Biotronik and Medtronic. JV reports speaker honoraria from Abbott. PK receives research support for basic, translational and clinical research projects from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK) and German Centre for Cardiovascular Research, from several drug and device companies active in atrial fibrillation and has received honoraria from several such companies in the past. JCN is supported by a grant from the Novo Norvodisk Foundation (NNF16OC0018658). PK is listed as inventor on two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783)., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Molecular pathology and personalized medicine are still being evolved in Saudi Arabia, and genetic testing for the detection of mutations as cancer markers have not been established in the diagnostics laboratories in Saudi Arabia. The aim of the present study was to determine the prevalence of isocitrate dehydrogenase (IDH1 and IDH2) mutations and epidermal growth factor receptor variant (EGFRv)III transcript expression in Saudi Arabian patients with glioma. Out of 117 brain tumors tested by reverse transcription-quantitative PCR for EGFRvIII, 41 cases tested positive. In the glioblastoma (GBM) category, 28/55 tumors were positive, in astrocytoma tumors 5/22, and in oligodendrogliomas 4/13 cases were positive respectively. EGFRvIII transcript was sequenced by capillary electrophoresis to demonstrate the presence of EGFRvIII-specific junction where exons 2-7 were deleted. In the present study 106 tumors were sequenced for IDH1 exon-4 mutations using the capillary sequencing method. The most common substitution missense mutation c.395G>A was found in 16 tumors. In the case of adamantinomatous craniopharyngioma, a novel missense mutation in c.472C>T was detected in IDH2 gene. Using next-generation sequencing (NGS), 74 tumors were sequenced for the IDH1 gene, and a total of 8 missense variants were identified in 36 tumors in a population of Saudi Arabia. The missense mutation (c.395G>A) was detected in 29/36 of tumors. A novel intronic mutation in c.414+9T>A was found in 13 cases in the IDH1 gene. In addition, one case exhibited a novel synonymous mutation in c.369A>G. Eleven tumors were found to have compound mutations in the IDH1 gene. In IDH2 gene, out of a total of 16 variants found in 6 out of 45 tumors, nine were missense, five were synonymous and one was intronic. This is the first report from Saudi Arabian laboratories analyzing glioma tumors for EGFRvIII expression, and the first study from Saudi Arabia to analyze IDH mutations in gliomas using the capillary and NGS methods., (Copyright: © Taher et al.)

Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Arabian patients with pLGGs to identify genetic abnormalities that can inform prognostic and therapeutic decision-making. We detected genetic alterations (GAs) in 97% (36/37) of cases, averaging 2.51 single nucleotide variations (SNVs) and 0.91 gene fusions per patient. The KIAA1549-BRAF fusion was the most common alteration (21/37 patients) followed by AFAP1-NTRK2 (2/37) and TBLXR-PI3KCA (2/37) fusions that were observed at much lower frequencies. The most frequently mutated) genes were NOTCH1-3 (7/37), ATM (4/37), RAD51C (3/37), RNF43 (3/37), SLX4 (3/37) and NF1 (3/37). Interestingly, we identified a GOPC-ROS1 fusion in an 8-year-old patient whose tumor lacked BRAF alterations and histologically classified as low grade glioma. The patient underwent gross total resection (GTR). The patient is currently disease free. To our knowledge this is the first report of GOPC-ROS1 fusion in PLGG. Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG., Competing Interests: One of our authors is affiliated with Foundation Medicine Inc. The author only contributed relevant pathology consultation. This affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: This study sought to determine updated conversion factors (k-factors) that would enable accurate estimation of radiation effective dose (ED) for coronary computed tomography angiography (CTA) and calcium scoring performed on 12 contemporary scanner models and current clinical cardiac protocols and to compare these methods to the standard chest k-factor of 0.014 mSv·mGy -1 cm -1 ., Background: Accurate estimation of ED from cardiac CT scans is essential to meaningfully compare the benefits and risks of different cardiac imaging strategies and optimize test and protocol selection. Presently, ED from cardiac CT is generally estimated by multiplying a scanner-reported parameter, the dose-length product, by a k-factor which was determined for noncardiac chest CT, using single-slice scanners and a superseded definition of ED., Methods: Metal-oxide-semiconductor field-effect transistor radiation detectors were positioned in organs of anthropomorphic phantoms, which were scanned using all cardiac protocols, 120 clinical protocols in total, on 12 CT scanners representing the spectrum of scanners from 5 manufacturers (GE, Hitachi, Philips, Siemens, Toshiba). Organ doses were determined for each protocol, and ED was calculated as defined in International Commission on Radiological Protection Publication 103. Effective doses and scanner-reported dose-length products were used to determine k-factors for each scanner model and protocol., Results: k-Factors averaged 0.026 mSv·mGy -1 cm -1 (95% confidence interval: 0.0258 to 0.0266) and ranged between 0.020 and 0.035 mSv·mGy -1 cm -1 . The standard chest k-factor underestimates ED by an average of 46%, ranging from 30% to 60%, depending on scanner, mode, and tube potential. Factors were higher for prospective axial versus retrospective helical scan modes, calcium scoring versus coronary CTA, and higher (100 to 120 kV) versus lower (80 kV) tube potential and varied among scanner models (range of average k-factors: 0.0229 to 0.0277 mSv·mGy -1 cm -1 )., Conclusions: Cardiac k-factors for all scanners and protocols are considerably higher than the k-factor currently used to estimate ED of cardiac CT studies, suggesting that radiation doses from cardiac CT have been significantly and systematically underestimated. Using cardiac-specific factors can more accurately inform the benefit-risk calculus of cardiac-imaging strategies., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer tumor samples to determine whether tumor heterogeneity can predict tumor metastasis. Experimental Design: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole-exome sequencing. Tumor clonality was estimated from single-nucleotide and copy-number variations. The correlation between clinical parameters of patients and clonal heterogeneity in liver metastasis was evaluated. Results: Tumor heterogeneity across colorectal cancer samples was highly variable; however, a high degree of tumor heterogeneity was associated with a worse disease-free survival. Highly heterogeneous primary colorectal cancer was correlated with a higher rate of liver metastasis. Recurrent somatic mutations in APC, TP53 , and KRAS were frequently detected in highly heterogeneous colorectal cancer. The variant allele frequency of these mutations was high, while somatic mutations in other genes such as PIK3CA and NOTCH1 were low. The number and distribution of primary colorectal cancer subclones were preserved in metastatic tumors. Conclusions: Heterogeneity of primary colorectal cancer tumors can predict the potential for liver metastasis and thus, clinical outcome of patients. Clin Cancer Res; 23(23); 7209-16. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Left ventricular noncompaction (LVNC) is a genetically and phenotypically heterogeneous disease and, although increasingly recognized in clinical practice, there is a lack of widely accepted diagnostic criteria. We sought to identify novel genetic causes of LVNC and describe genotype-phenotype correlations., Methods and Results: A total of 190 patients from 174 families with left ventricular hypertrabeculation (LVHT) or LVNC were referred for cardiac magnetic resonance and whole-exome sequencing. A total of 425 control individuals were included to identify variants of interest (VOIs). We found an excess of 138 VOIs in 102 (59%) unrelated patients in 54 previously identified LVNC or other known cardiomyopathy genes. VOIs were found in 68 of 90 probands with LVNC and 34 of 84 probands with LVHT (76% and 40%, respectively; P <0.001). We identified 0, 1, and ≥2 VOIs in 72, 74, and 28 probands, respectively. We found increasing number of VOIs in a patient strongly correlated with several markers of disease severity, including ratio of noncompacted to compacted myocardium ( P <0.001) and left ventricular ejection fraction ( P =0.01). The presence of sarcomeric gene mutations was associated with increased occurrence of late gadolinium enhancement ( P =0.004)., Conclusions: LVHT and LVNC likely represent a continuum of genotypic disease with differences in severity and variable phenotype explained, in part, by the number of VOIs and whether mutations are present in sarcomeric or nonsarcomeric genes. Presence of VOIs is common in patients with LVHT. Our findings expand the current clinical and genetic diagnostic approaches for patients with LVHT and LVNC., (© 2017 American Heart Association, Inc.)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with obesity. Bariatric surgery has been shown to be the most effective method for weight reduction. However, no conclusive data exists on the effects of weight reduction surgery on NAFLD. This study aimed to characterize liver histology, metabolic status, and liver function changes in patients who underwent bariatric surgery, before and after the weight-reduction procedure. This is a phase 1 report of a prospective cohort study of patients who underwent bariatric surgery. Biopsies were obtained at baseline (intraoperatively) and 3 months postoperatively. Clinical characteristics, biochemical profile, and histopathological data [steatosis, NAFLD activity score (NAS), hepatocyte ballooning, lobular inflammation, and degree of fibrosis] were obtained at each time point. Twenty-seven patients were included (9 men and 18 women), and the median age was 35 ± 8 years old. At baseline, 3 patients had dyslipidemia, 4 had diabetes, and 5 patients had hypertension, which did not change at follow-up. The average body mass index decreased from 44.6 ± 7.8 to 34.2 ± 6.3 kg/m 2 at follow-up (P < 0.001). On histopathology, 12 of the 18 patients with preoperative steatosis (median score 2) had reduced steatosis scores postoperatively (P = 0.025); fibrosis (median score 1) was also reduced in 17 patients (P = 0.012), and NAS was decreased from 4 (3-5) to 2 (1-3) (P = 0.004). The changes in lobular inflammation and hepatocyte ballooning were not statistically significant on follow-up. The phase 1 results of this study described the histopathological changes following weight reduction surgery and suggested that hepatic steatosis, fibrosis, and NAFLD activity score were reduced 3 months after surgery. This clinical trial is financially supported by the National Plan for Science, Technology and Innovation Program grant number (11-MED1910-02).

Aims: Catheter ablation is the most efficacious rhythm control therapy in atrial fibrillation (AF) patients. There is growing evidence that catheter ablation procedures are best performed during continuous oral anticoagulation, but outcomes are variable depending on the anticoagulation strategy or agent chosen. Specifically, there is a need to evaluate the peri-procedural use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients undergoing catheter ablation of AF. The AXAFA-AFNET 5 trial will test whether peri-procedural anticoagulation therapy using apixaban is a safe alternative to vitamin K antagonist (VKA) therapy for patients undergoing catheter ablation of AF., Methods and Results: AXAFA-AFNET 5 is a randomized, prospective multi-centre study conducted in Europe and the USA. A total of 650 patients scheduled for AF ablation will be randomized 1:1 to undergo AF ablation on continuous treatment with the NOAC apixaban or with a VKA. Patients can undergo AF ablation after at least 30 days of continuous effective anticoagulation or after exclusion of atrial thrombi by transoesophageal echocardiogram. The trial includes a post-ablation magnetic resonance imaging substudy that will quantify silent brain lesions that can occur in neurologically asymptomatic patients after AF ablation. Patients will be followed on continuous anticoagulation for 3 months after the ablation. The primary outcome parameter of AXAFA-AFNET 5 is a composite of all-cause death, stroke, and major bleeding events., Conclusion: The results of AXAFA-AFNET 5 will provide evidence informing about the safety of apixaban in ablation patients and on its efficacy including effects on silent brain lesions. AXAFA - AFNET 5 is an investigator-initiated trial sponsored by AFNET. The trial is supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research) and by Bristol-Myers Squibb/Pfizer Alliance., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Bioabsorbable cardiac matrix (BCM) is a novel device that attenuates adverse left ventricular (LV) remodeling after large myocardial infarctions in experimental models., Objectives: This study aimed to analyze whether BCM, compared with saline control, would result in less LV dilation and fewer adverse clinical events between baseline and 6 months., Methods: In an international, randomized, double-blind, controlled trial, 303 subjects with large areas of infarction despite successful primary percutaneous coronary intervention (PCI) of ST-segment elevation myocardial infarction (STEMI) were randomized 2:1 to BCM or saline injected into the infarct-related artery 2 to 5 days after primary PCI. The primary outcome was mean change from baseline in LV end-diastolic volume index (LVEDVI) at 6 months. Secondary outcomes included change in Kansas City Cardiomyopathy Questionnaire score, 6-minute walk time, and New York Heart Association functional class at 6 months. The primary safety endpoint was a composite of cardiovascular death, recurrent MI, target-vessel revascularization, stent thrombosis, significant arrhythmia requiring therapy, or myocardial rupture through 6 months., Results: In total, 201 subjects were assigned to BCM and 102 to saline control. There was no significant difference in change in LVEDVI from baseline to 6 months between the groups (mean change ± SD: BCM 14.1 ± 28.9 ml/m(2) vs. saline 11.7 ± 26.9 ml/m(2); p = 0.49). There was also no significant difference in the secondary endpoints. The rates of the primary safety outcome were similar between the 2 groups (BCM 11.6% vs. saline 9.1%; p = 0.37)., Conclusions: Intracoronary deployment of BCM 2 to 5 days after successful reperfusion in subjects with large myocardial infarction did not reduce adverse LV remodeling or cardiac clinical events at 6 months. (IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction [PRESERVATION I]; NCT01226563)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Postinfarction left ventricular (LV) remodeling can result in chronic heart failure and functional impairment. Although pharmacological strategies for established heart failure can be beneficial, preventing remodeling remains a challenge. Injectable bioabsorbable alginate or "bioabsorbable cardiac matrix" (BCM), composed of an aqueous mixture of sodium alginate and calcium gluconate, is a sterile colorless liquid that is a polysaccharide polymer produced from brown seaweed. When exposed to excess ionized calcium present in infarcted myocardium, BCM assembles to form a flexible gel, structurally resembling extracellular matrix, which provides temporary structural support to the infarct zone through and beyond the time needed for mature fibrotic tissue to develop. The PRESERVATION I trial is an early phase randomized, double-blind, placebo-controlled trial comparing intracoronary application of 4 mL of BCM with saline control in patients who develop large infarctions after successful reperfusion of large ST-segment elevation myocardial infarction (MI). Subjects will be randomized 2:1 to either BCM or saline control and will have the study device deployed through an intracoronary microcatheter in the infarct-related artery 2 to 5 days after index ST-segment elevation MI treated with successful primary or rescue percutaneous coronary intervention. The primary effectiveness end point is the absolute change in LV diastolic volume index as measured by 3-dimensional echocardiography from baseline to 6 months after BCM deployment. Secondary effectiveness end points include clinical outcomes, patient-reported quality of life, additional echocardiographic measures, and functional status measures. In summary, the PRESERVATION I trial is a randomized double-blind trial evaluating the effectiveness and safety of the novel device BCM in preventing LV remodeling patients who have large MIs despite undergoing successful primary or rescue percutaneous coronary intervention., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban., Methods and Results: Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI., Conclusion: Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Objective: A review of published data addressing hepatic histopathological, metabolical, and functional changes following gastric banding, sleeve gastrectomy, gastric bypass surgery, and biliopancreatic with duodenal switch surgeries on nonalcoholic fatty liver disease (NAFLD). NAFLD is currently the most common chronic liver disease. Owing to the strong relationship between obesity and NAFLD, the idea of weight reduction as a method to treat NAFLD has rapidly emerged. Bariatric surgery has proved to be the most efficient method for weight reduction; hence, their beneficial effects on NAFLD have been evaluated by several studies. A literature review of published data was performed during the years 2012-2014 using PubMed with the following key words: Bariatric, NAFLD, steatosis, sleeve gastrectomy, gastric bypass, gastric banding, biliopancreatic diversion with duodenal switch, obesity, and insulin resistance (IR). Exclusion criteria were non-English articles and inherited NAFLD, pregnancy-induced NAFLD, and children. The majority of published data are in favor of indicating that bariatric surgeries improve the histologic and metabolic changes associated with NAFLD. The suggested mechanisms are: The reversal of IR, reduction of inflammatory markers, and improved histological features of NAFLD. Accordingly, bariatric surgeries are potentially one of the future methods in treating patients with morbid obesity and NAFLD. However, some questions remain unanswered, such as whether timing of surgery, type of surgery most effective, and whether bariatric surgeries are capable of curing the disease. Long-term and well-designed prospective studies are needed to address these issues.

With mobile moving range queries, there is a need to recalculate the relevant surrounding objects of interest whenever the query moves. Therefore, monitoring the moving query is very costly. The safe region is one method that has been proposed to minimise the communication and computation cost of continuously monitoring a moving range query. Inside the safe region the set of objects of interest to the query do not change; thus there is no need to update the query while it is inside its safe region. However, when the query leaves its safe region the mobile device has to reevaluate the query, necessitating communication with the server. Knowing when and where the mobile device will leave a safe region is widely known as a difficult problem. To solve this problem, we propose a novel method to monitor the position of the query over time using a linear function based on the direction of the query obtained by periodic monitoring of its position. Periodic monitoring ensures that the query is aware of its location all the time. This method reduces the costs associated with communications in client-server architecture. Computational results show that our method is successful in handling moving query patterns.

Importance: Randomized clinical trials have shown that implantable cardioverter-defibrillator (ICD) therapy saves lives. Whether the survival of patients who received an ICD in primary prevention clinical trials differs from that of trial-eligible patients receiving a primary prevention ICD in clinical practice is unknown., Objective: To determine whether trial-eligible patients who received a primary prevention ICD as documented in a large national registry have a survival rate that differs from the survival rate of similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n = 742) and SCD-HeFT (n = 829)., Design, Setting, and Patients: Retrospective analysis of data for patients enrolled in the National Cardiovascular Data Registry ICD Registry between January 1, 2006, and December 31, 2007, meeting the MADIT-II criteria (2464 propensity score-matched patients) or the SCD-HeFT criteria (3352 propensity score-matched patients). Mortality data for the registry patients were collected through December 31, 2009., Main Outcome Measures: Cox proportional hazards models were used to compare mortality from any cause., Results: The median follow-up time in MADIT-II, SCD-HeFT, and the ICD Registry was 19.5, 46.1, and 35.2 months, respectively. Compared with patients enrolled in the clinical trials, patients in the ICD Registry were significantly older and had a higher burden of comorbidities. In the matched cohorts, there was no significant difference in survival between MADIT-II-like patients in the registry and MADIT-II patients randomized to receive an ICD (2-year mortality rates: 13.9% and 15.6%, respectively; adjusted ICD Registry vs trial hazard ratio, 1.06; 95% CI, 0.85-1.31; P = .62). Likewise, the survival among SCD-HeFT-like patients in the registry was not significantly different from survival among patients randomized to receive ICD therapy in SCD-HeFT (3-year mortality rates: 17.3% and 17.4%, respectively; adjusted registry vs trial hazard ratio, 1.16; 95% CI, 0.97-1.38; P = .11)., Conclusions and Relevance: There was no significant difference in survival between clinical trial patients randomized to receive an ICD and a similar group of clinical registry patients who received a primary prevention ICD. Our findings support the continued use of primary prevention ICDs in similar patients seen in clinical practice., Trial Registration: clinicaltrials.gov Identifier: NCT00000609.

Background. Magnetic resonance imaging (MRI) strain analysis is a sensitive method to assess myocardial function. Our objective was to define the feasibility of MRI circumferential strain (ε cc) analysis in assessing subtle changes in myocardial function following stem cell therapy. Methods and Results. Patients in the Amorcyte Phase I trial were randomly assigned to treatment with either autologous bone-marrow-derived stem cells infused into the infarct-related artery 5 to 11 days following primary PCI or control. MRI studies were obtained at baseline, 3, and 6 months. ε cc was measured in the short axis views at the base, mid and apical slices of the left ventricle (LV) for each patient (13 treatments and 10 controls). Mid-anterior LV ε cc improved between baseline -18.5 ± 8.6 and 3 months -22.6 ± 7.0, P = 0.03. There were no significant changes in ε cc at 3 months and 6 months compared to baseline for other segments. There was excellent intraobserver and interobserver agreement for basal and mid circumferential strain. Conclusion. MRI segmental strain analysis is feasible in assessment of regional myocardial function following cell therapy with excellent intra- and inter-observer variability's. Using this method, a modest interval change in segmental ε cc was detected in treatment group.