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1. Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study

Author

de Braud, Filippo, Dooms, Christophe, Heist, Rebecca S, Lebbe, Celeste, Wermke, Martin, Gazzah, Anas, Schadendorf, Dirk, Rutkowski, Piotr, Wolf, Jürgen, Ascierto, Paolo A, Gil-Bazo, Ignacio, Kato, Shumei, Wolodarski, Maria, McKean, Meredith, Couselo, Eva Muñoz, Sebastian, Martin, Santoro, Armando, Cooke, Vesselina, Manganelli, Luca, Wan, Kitty, Gaur, Anil, Kim, Jaeyeon, Caponigro, Giordano, Couillebault, Xuân-Mai, Evans, Helen, Campbell, Catarina D, Basu, Sumit, Moschetta, Michele, and Daud, Adil

Subjects
Cancer, Genetics, Clinical Trials and Supportive Activities, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Humans, Proto-Oncogene Proteins B-raf, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Melanoma, Pyridones, Pyrimidinones, Exanthema, Antineoplastic Combined Chemotherapy Protocols, Mutation, Membrane Proteins, GTP Phosphohydrolases, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeNo approved targeted therapy for the treatment of patients with neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS)-mutant melanoma is currently available.Patients and methodsIn this phase Ib escalation/expansion study (ClinicalTrials.gov identifier: NCT02974725), the safety, tolerability, and preliminary antitumor activity of naporafenib (LXH254), a BRAF/CRAF protein kinases inhibitor, were explored in combination with trametinib in patients with advanced/metastatic KRAS- or BRAF-mutant non-small-cell lung cancer (escalation arm) or NRAS-mutant melanoma (escalation and expansion arms).ResultsThirty-six and 30 patients were enrolled in escalation and expansion, respectively. During escalation, six patients reported grade ≥3 dose-limiting toxicities, including dermatitis acneiform (n = 2), maculopapular rash (n = 2), increased lipase (n = 1), and Stevens-Johnson syndrome (n = 1). The recommended doses for expansion were naporafenib 200 mg twice a day plus trametinib 1 mg once daily and naporafenib 400 mg twice a day plus trametinib 0.5 mg once daily. During expansion, all 30 patients experienced a treatment-related adverse event, the most common being rash (80%, n = 24), blood creatine phosphokinase increased, diarrhea, and nausea (30%, n = 9 each). In expansion, the objective response rate, median duration of response, and median progression-free survival were 46.7% (95% CI, 21.3 to 73.4; 7 of 15 patients), 3.75 (95% CI, 1.97 to not estimable [NE]) months, and 5.52 months, respectively, in patients treated with naporafenib 200 mg twice a day plus trametinib 1 mg once daily, and 13.3% (95% CI, 1.7 to 40.5; 2 of 15 patients), 3.75 (95% CI, 2.04 to NE) months, and 4.21 months, respectively, in patients treated with naporafenib 400 mg twice a day plus trametinib 0.5 mg once daily.ConclusionNaporafenib plus trametinib showed promising preliminary antitumor activity in patients with NRAS-mutant melanoma. Prophylactic strategies aimed to lower the incidence of skin-related events are under investigation.

Published
2023

2. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial.

Author

Subbiah, Vivek, Kreitman, Robert J, Wainberg, Zev A, Gazzah, Anas, Lassen, Ulrik, Stein, Alexander, Wen, Patrick Y, Dietrich, Sascha, de Jonge, Maja JA, Blay, Jean-Yves, Italiano, Antoine, Yonemori, Kan, Cho, Daniel C, de Vos, Filip YFL, Moreau, Philippe, Fernandez, Elena Elez, Schellens, Jan HM, Zielinski, Christoph C, Redhu, Suman, Boran, Aislyn, Passos, Vanessa Q, Ilankumaran, Palanichamy, and Bang, Yung-Jue

Subjects
Humans, Glioma, Adenocarcinoma, Imidazoles, Pyridones, Pyrimidinones, Proto-Oncogene Proteins B-raf, Antineoplastic Combined Chemotherapy Protocols, Mutation, Clinical Research, Cancer, Hematology, Brain Cancer, Brain Disorders, Rare Diseases, Digestive Diseases, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Medical and Health Sciences, Immunology
Abstract

BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 .

Published
2023

3. Three-Year Interval for the Multi-Target Stool DNA Test for Colorectal Cancer Screening: A Longitudinal Study

Author

Imperiale, Thomas F, Lavin, Philip T, Marti, Tara N, Jakubowski, Debbie, Itzkowitz, Steven H, May, Folasade P, Limburg, Paul J, Sweetser, Seth, Daghestani, Anas, and Berger, Barry M

Subjects
Cancer, Digestive Diseases, Colo-Rectal Cancer, Aging, Clinical Research, Genetics, Prevention, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Humans, Longitudinal Studies, Early Detection of Cancer, DNA, Colonoscopy, Colorectal Neoplasms, Feces, Precancerous Conditions, Mass Screening, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings.Prevention relevanceUnderstanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

Published
2023

4. Baseline characteristics and outcomes of end-stage renal disease patients after in-hospital sudden cardiac arrest: a national perspective

Author

Khan, Muhammad Zia, Syed, Moinuddin, Agrawal, Pratik, Osman, Mohammed, Khan, Muhammad U, Alharbi, Anas, Benjamin, Mina M, Khan, Safi U, Balla, Sudarshan, and Munir, Muhammad Bilal

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Kidney Disease, Good Health and Well Being, Comorbidity, Death, Sudden, Cardiac, Hospitals, Humans, Kidney Failure, Chronic, Propensity Score, Risk Factors, End-stage renal disease, In-hospital cardiac arrest, Outcome, Trends, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

PurposeEnd-stage renal disease (ESRD) is a well-recognized risk factor for the development of sudden cardiac arrest (SCA). There is limited data on baseline characteristics and outcomes after an in-hospital SCA event in ESRD patients.MethodsFor the purpose of this study, data were obtained from the National Inpatient Sample from January 2007 to December 2017. In-hospital SCA was identified using the International Classification of Disease, 9th Revision, Clinical Modification and International Classification of Disease, 10th Revision, Clinical Modification codes of 99.60, 99.63, and 5A12012. ESRD patients were subsequently identified using codes of 585.6 and N18.6. Baseline characteristics and outcomes were compared among ESRD and non-ESRD patients in crude and propensity score (PS)-matched cohorts. Predictors of mortality in ESRD patients after an in-hospital SCA event were analyzed using a multivariate logistic regression model.ResultsA total of 1,412,985 patients sustained in-hospital SCA during our study period. ESRD patients with in-hospital SCA were younger and had a higher burden of key co-morbidities. Mortality was similar in ESRD and non-ESRD patients in PS-matched cohort (70.4% vs. 70.7%, p = 0.45) with an overall downward trend over our study years. Advanced age, Black race, and key co-morbidities independently predicted increased mortality while prior implantable defibrillator was associated with decreased mortality in ESRD patients after an in-hospital SCA event.ConclusionsIn the context of in-hospital SCA, mortality is similar in ESRD and non-ESRD patients in adjusted analysis. Adequate risk factor modification could further mitigate the risk of in-hospital SCA among ESRD patients.

Published
2022

5. Federated learning for predicting clinical outcomes in patients with COVID-19

Author

Dayan, Ittai, Roth, Holger R, Zhong, Aoxiao, Harouni, Ahmed, Gentili, Amilcare, Abidin, Anas Z, Liu, Andrew, Costa, Anthony Beardsworth, Wood, Bradford J, Tsai, Chien-Sung, Wang, Chih-Hung, Hsu, Chun-Nan, Lee, CK, Ruan, Peiying, Xu, Daguang, Wu, Dufan, Huang, Eddie, Kitamura, Felipe Campos, Lacey, Griffin, de Antônio Corradi, Gustavo César, Nino, Gustavo, Shin, Hao-Hsin, Obinata, Hirofumi, Ren, Hui, Crane, Jason C, Tetreault, Jesse, Guan, Jiahui, Garrett, John W, Kaggie, Joshua D, Park, Jung Gil, Dreyer, Keith, Juluru, Krishna, Kersten, Kristopher, Rockenbach, Marcio Aloisio Bezerra Cavalcanti, Linguraru, Marius George, Haider, Masoom A, AbdelMaseeh, Meena, Rieke, Nicola, Damasceno, Pablo F, e Silva, Pedro Mario Cruz, Wang, Pochuan, Xu, Sheng, Kawano, Shuichi, Sriswasdi, Sira, Park, Soo Young, Grist, Thomas M, Buch, Varun, Jantarabenjakul, Watsamon, Wang, Weichung, Tak, Won Young, Li, Xiang, Lin, Xihong, Kwon, Young Joon, Quraini, Abood, Feng, Andrew, Priest, Andrew N, Turkbey, Baris, Glicksberg, Benjamin, Bizzo, Bernardo, Kim, Byung Seok, Tor-Díez, Carlos, Lee, Chia-Cheng, Hsu, Chia-Jung, Lin, Chin, Lai, Chiu-Ling, Hess, Christopher P, Compas, Colin, Bhatia, Deepeksha, Oermann, Eric K, Leibovitz, Evan, Sasaki, Hisashi, Mori, Hitoshi, Yang, Isaac, Sohn, Jae Ho, Murthy, Krishna Nand Keshava, Fu, Li-Chen, de Mendonça, Matheus Ribeiro Furtado, Fralick, Mike, Kang, Min Kyu, Adil, Mohammad, Gangai, Natalie, Vateekul, Peerapon, Elnajjar, Pierre, Hickman, Sarah, Majumdar, Sharmila, McLeod, Shelley L, Reed, Sheridan, Gräf, Stefan, Harmon, Stephanie, Kodama, Tatsuya, Puthanakit, Thanyawee, Mazzulli, Tony, de Lavor, Vitor Lima, Rakvongthai, Yothin, Lee, Yu Rim, Wen, Yuhong, Gilbert, Fiona J, Flores, Mona G, and Li, Quanzheng

Subjects
Patient Safety, Good Health and Well Being, COVID-19, Electronic Health Records, Humans, Machine Learning, Outcome Assessment, Health Care, Prognosis, SARS-CoV-2, Medical and Health Sciences, Immunology
Abstract

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site's data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare.

Published
2021

6. Descriptive characteristics of occupational exposures and medical follow-up in the cohort of workers of the Siberian Group of Chemical Enterprises in Seversk, Russia

Author

Karpov, Andrey B, Takhauov, Ravil M, Zerenkov, Andrey G, Semenova, Yulia V, Bogdanov, Igor M, Kazantceva, Svetlana B, Blinov, Aleksey P, Kalinkin, Dmitriy E, Gorina, Galina V, Litvinova, Olesya V, Ermolaev, Yuriy D, Mironova, Elena B, Plaksin, Mikhail B, Takhauov, Anas R, and Zablotska, Lydia B

Subjects
Biochemistry and Cell Biology, Medicinal and Biomolecular Chemistry, Chemical Sciences, Biological Sciences, Cancer, 2.4 Surveillance and distribution, 2.2 Factors relating to the physical environment, Aetiology, Generic health relevance, Adult, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Neoplasms, Radiation-Induced, Occupational Exposure, Radiation Exposure, Risk Factors, Russia, Uranium, ionizing radiation, gamma radiation, occupational exposures, uranium processing workers, Engineering, Medical and Health Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Medicinal and biomolecular chemistry
Abstract

PurposeTo date, only a few studies have examined long-term health risks of exposures in the uranium processing industry and reported contradictory results, necessitating further research in this area. This is the first description of a cohort of ∼65,000 uranium processing workers (20.6% women) of the Siberian Group of Chemical Enterprises (SGCE) in Seversk, Russia, first employed during 1950-2010.MethodsSGCE is one of the largest and oldest uranium processing complexes in the world. SGCE workers at the Radiochemical, Plutonium, Sublimate and Enrichment plants were exposed to a combination of internal and external radiation, while workers at the Support Facility were primarily exposed to non-radiation factors.ResultsMean cumulative gamma-ray dose based on individual external dosimetry was 28.3 millisievert. About 4,000 workers have individual biophysical survey data that could be used for estimation of organ doses from uranium. SGCE workers were followed up for mortality and cancer incidence during 1950-2013 (vital status known for 80.8% of workers). The SGCE computerized database contains information on the results of regular medical examinations, and on smoking, alcohol and other individual characteristics.ConclusionsThe SGCE cohort is uniquely suited to examine long-term health risks of exposures to gamma-radiation and long-lived radionuclides in uranium processing workers.

Published
2021

7. Genomic characterization of the adolescent idiopathic scoliosis-associated transcriptome and regulome.

Author

Makki, Nadja, Zhao, Jingjing, Liu, Zhaoyang, Eckalbar, Walter L, Ushiki, Aki, Khanshour, Anas M, Wu, Joe, Rios, Jonathan, Gray, Ryan S, Wise, Carol A, and Ahituv, Nadav

Subjects
Muscle, Skeletal, Spine, Humans, Scoliosis, Genetic Predisposition to Disease, Lysine, DNA-Binding Proteins, Receptors, G-Protein-Coupled, Histones, Genomics, Acetylation, Adolescent, Child, Female, Male, Genome-Wide Association Study, Transcriptome, RNA-Seq, Pediatric, Human Genome, Genetics, 2.1 Biological and endogenous factors, Musculoskeletal, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Adolescent idiopathic scoliosis (AIS), a sideways curvature of the spine, is the most common pediatric musculoskeletal disorder, affecting ~3% of the population worldwide. However, its genetic bases and tissues of origin remain largely unknown. Several genome-wide association studies (GWAS) have implicated nucleotide variants in non-coding sequences that control genes with important roles in cartilage, muscle, bone, connective tissue and intervertebral disks (IVDs) as drivers of AIS susceptibility. Here, we set out to define the expression of AIS-associated genes and active regulatory elements by performing RNA-seq and chromatin immunoprecipitation-sequencing against H3 lysine 27 acetylation in these tissues in mouse and human. Our study highlights genetic pathways involving AIS-associated loci that regulate chondrogenesis, IVD development and connective tissue maintenance and homeostasis. In addition, we identify thousands of putative AIS-associated regulatory elements which may orchestrate tissue-specific expression in musculoskeletal tissues of the spine. Quantification of enhancer activity of several candidate regulatory elements from our study identifies three functional enhancers carrying AIS-associated GWAS SNPs at the ADGRG6 and BNC2 loci. Our findings provide a novel genome-wide catalog of AIS-relevant genes and regulatory elements and aid in the identification of novel targets for AIS causality and treatment.

Published
2021

8. Transcatheter Aortic Valve Replacement vs Surgical Replacement in Patients With Pure Aortic Insufficiency

Author

Alharbi, Anas A, Khan, Muhammad Z, Osman, Mohammed, Khan, Muhammad U, Munir, Muhammad B, Syed, Moinuddin, Khan, Safi U, and Balla, Sudarshan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Transplantation, Rare Diseases, Clinical Research, Patient Safety, Cardiovascular, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Good Health and Well Being, Age Factors, Aged, Aortic Valve Insufficiency, Female, Heart Valve Prosthesis Implantation, Hospital Costs, Hospital Mortality, Humans, Length of Stay, Male, Middle Aged, Outcome and Process Assessment, Health Care, Postoperative Complications, Risk Assessment, Transcatheter Aortic Valve Replacement, United States, Medical and Health Sciences, Biomedical and clinical sciences
Abstract

ObjectiveTo compare the outcomes of transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in patients with pure aortic insufficiency (PAI).BackgroundThe treatment of choice for patients with severe symptomatic PAI is SAVR. However, not all patients are candidates for surgery because of comorbidities or are deemed high risk for surgery. As a result, TAVR is being used as an off-label procedure in some patients with PAI.Patients and methodsWe analyzed the National Inpatient Sample database from January 1, 2016, to December 31, 2017, using the International Classification of Diseases, 10th Revision. Inclusion criteria were patients with aortic valve insufficiency undergoing either TAVR or SAVR. Patients with concomitant aortic stenosis, or history of infective endocarditis, and those below the age of 18 years were excluded.ResultsA total of 14,720 patients with PAI underwent valve replacement. Of those, 6.2% underwent TAVR. The TAVR group was significantly older (median age 78 years vs 64 years; P

Published
2020

9. Contemporary Trends and Outcomes in Patients With ST-Segment Elevation Myocardial Infarction and End-Stage Renal Disease on Dialysis: Insight from the National Inpatient Sample

Author

Khan, Muhammad Zia, Syed, Moinuddin, Osman, Mohammed, Faisaluddin, Mohammed, Sulaiman, Samian, Farjo, Peter D, Khan, Muhammad U, Agrawal, Pratik, Alharbi, Anas, Khan, Safi U, Munir, Muhammad Bilal, and Balla, Sudarshan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Heart Disease, Clinical Research, Cardiovascular, Aging, Heart Disease - Coronary Heart Disease, Renal and urogenital, Good Health and Well Being, Aged, Female, Hospital Mortality, Humans, Inpatients, Kidney Failure, Chronic, Male, Myocardial Infarction, Percutaneous Coronary Intervention, Renal Dialysis, Risk Factors, ST Elevation Myocardial Infarction, Treatment Outcome, End stage renal disease, ST elevation myocardial infarction, National in-patient sample database, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundCardiovascular disease is the major cause of mortality in end stage renal disease (ESRD) patients on dialysis and myocardial infarction constitutes almost 20% of such deaths. We assessed the trends, characteristics and in-hospital outcomes in patients with ESRD.MethodsWe used national inpatient sample (NIS) to identify patients with ESRD presenting with ST-segment elevation myocardial infarction (STEMI) for calendar years 2012-2016. Multiple logistic regression analysis and propensity matched data was used to compare outcomes for the purpose of our study.ResultsPatients on dialysis who presented with STEMI were less likely to be treated with emergent reperfusion therapies including percutaneous coronary intervention, bypass graft surgery and thrombolytics with in first 24 h. In propensity-matched cohort, the mortality was nearly double in patients who have ESRD compared to patients without ESRD (29.7% vs. 15.9%, p

Published
2020

10. Comparison of Outcomes in Patients With Takotsubo Syndrome With-vs-Without Cardiogenic Shock

Author

Syed, Moinuddin, Khan, Muhammad Zia, Osman, Mohammed, Alharbi, Anas, Khan, Muhammad Usman, Munir, Muhammad Bilal, and Balla, Sudarshan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Cardiovascular, Heart Disease, Clinical Research, Good Health and Well Being, Aged, Female, Hospital Mortality, Hospitalization, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Shock, Cardiogenic, Takotsubo Cardiomyopathy, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

There is limited data on the in-hospital outcomes of cardiogenic shock (CS) secondary to takotsubo syndrome (TS). We aimed to assess the incidence, predictors, and outcomes of CS in hospitalized patients with TS. All patients with TS were identified from the National Inpatient Sample database from September 2006 to December 2017. The cohort was divided into those with versus without CS and logistic regression analysis was used to identify predictors of CS and mortality in patients admitted with TS. A total of 260,144 patients with TS were included in our study, of whom 14,703 (6%) were diagnosed with CS. In-hospital mortality in patients with CS was approximately six-fold higher compared with those without CS (23% vs 4%, p

Published
2020

11. Progression of valvular calcification and risk of incident stroke: The Multi-Ethnic Study of Atherosclerosis (MESA)

Author

Fashanu, Oluwaseun E, Bizanti, Anas, Al-Abdouh, Ahmad, Zhao, Di, Budoff, Matthew J, Thomas, Isac C, Longstreth, WT, and Michos, Erin D

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Atherosclerosis, Heart Disease, Cardiovascular, Heart Disease - Coronary Heart Disease, Brain Disorders, Clinical Research, Stroke, Aging, Prevention, Good Health and Well Being, Aged, Aortic Valve Stenosis, Calcinosis, Ethnicity, Female, Heart Valve Diseases, Humans, Male, Middle Aged, Risk Factors, Valvular calcification, Epidemiology, Aortic valvular calcification, Mitral annular calcification, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Background and aimsPrevalent valvular calcification (VC) is associated with stroke but little is known about associations of VC progression with stroke.MethodsProgression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors.ResultsWe studied 5,539 MESA participants free of baseline CVD and atrial fibrillation. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 83% had no progression of VC; 15%, progression at one site (AVC or MAC), and 3%, progression at both sites. Over a median of 12 years, 211 total and 167 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p > 0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratio (95% CI) 1.59 (1.11, 2.28)] and ischemic stroke [1.64 (1.10, 2.45)]. Results remained significant after further adjustment for baseline coronary artery calcification. After excluding participants with interim atrial fibrillation and coronary heart disease, findings were no longer statistically significant in fully-adjusted models. There was no interaction by age, sex, or race/ethnicity. There was no association with AVC progression and stroke.ConclusionsProgression of MAC but not AVC over 2.4 years is associated with increased risk of total and ischemic stroke.

Published
2020

12. Trends, Outcomes, and Predictors of Revascularization in Cardiogenic Shock

Author

Khan, Muhammad Zia, Munir, Muhammad Bilal, Khan, Muhammad U, Osman, Mohammed, Agrawal, Pratik, Syed, Moinuddin, Ghaffar, Yasir Abdul, Alharbi, Anas, Khan, Safi U, and Balla, Sudarshan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Good Health and Well Being, Aged, Dual Anti-Platelet Therapy, Female, Follow-Up Studies, Hospital Mortality, Humans, Male, Myocardial Infarction, Myocardial Revascularization, Prognosis, Retrospective Studies, Shock, Cardiogenic, Survival Rate, Time Factors, United States, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Cardiogenic shock (CS) carries high mortality and morbidity. Early revascularization is an important strategy in management of these patients. We sought to determine the outcomes and predictors of revascularization among patients with CS. Patients with CS and acute myocardial infarction were identified using the National Inpatient Sample (NIS) data from January 2002 to December 2014 using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Subsequently, patients who underwent revascularization were then selected. A total of 118,618 patients with CS were identified. Out of these, about 55,735 (47%) patients underwent revascularization. Mean age of patients who underwent revascularization was lower when compared with patients not who underwent revascularization (66.40 vs 72.24 years, p < 0.01). Patients who underwent revascularization had lower mortality when compared with patients not who underwent revascularization (25.1% vs 52.2%, p < 0.01). Extracorporeal membrane oxygenation and mechanical circulatory support devices were often utilized more in patients who underwent revascularization. Overall, we found modest increased trend of revascularization over our study years with decline in mortality. Female gender, weekend admission, drug abuse, pulmonary hypertension, anemia, renal failure, neurological disorders, malignancy were associated with lower odds of revascularization. In conclusion, in this large nationally represented US population sample of CS patients, we found revascularization rate of about 47% with improvement in overall mortality over our study years.

Published
2020

13. Novel measurement tool and model for aberrant urinary stream in 3D printed urethras derived from human tissue

Author

Cohen, Andrew J, Patino, German, Mirramezani, Mehran, Srirangapatanam, Sudarshan, Tresh, Anas, Cheema, Bhagat, Tai, Jenny, Romero, Dylan, Enriquez, Anthony, Baskin, Laurence S, Shadden, Shawn C, and Breyer, Benjamin N

Subjects
Engineering, Chemical Sciences, Biomedical Engineering, Bioengineering, Urologic Diseases, Cadaver, Humans, Hydrodynamics, Models, Biological, Printing, Three-Dimensional, Urethra, Urination, General Science & Technology
Abstract

BackgroundAn estimated 10% of male adults have split or dribbled stream leading to poor hygiene, embarrassment, and inconvenience. There is no current metric that measures male stream deviation.ObjectiveTo develop a novel method to measure spray in normal and abnormal anatomical conformations.Design, setting, and participantsWe developed a novel platform to reliably describe spray. We used cadaveric tissues and 3D Printed models to study the impact of meatal shape on the urinary stream. Cadaveric penile tissue and 3D printed models were affixed to a fluid pump and used to simulate micturition. Dye captured on fabric allowed for spray detection.Outcome measurements and statistical analysisSpray pattern area, deviation from normal location, and flowrates were recorded. Computational fluid dynamic models were created to study fluid vorticity.Results and limitationsObstructions at the penile tip worsened spray dynamics and reduced flow. Ventral meatotomy improved flowrate (p

Published
2020

14. Perspectives From Authors and Editors in the Biomedical Disciplines on Predatory Journals: Survey Study.

Author

Cohen, Andrew J, Patino, German, Kamal, Puneet, Ndoye, Medina, Tresh, Anas, Mena, Jorge, Butler, Christi, Washington, Samuel, and Breyer, Benjamin N

Subjects
Humans, Authorship, Libraries, Medical, Editorial Policies, Surveys and Questionnaires, citation, global, literature, open access publication, predatory journals, Libraries, Medical, Information and Computing Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Medical Informatics
Abstract

BackgroundPredatory journals fail to fulfill the tenets of biomedical publication: peer review, circulation, and access in perpetuity. Despite increasing attention in the lay and scientific press, no studies have directly assessed the perceptions of the authors or editors involved.ObjectiveOur objective was to understand the motivation of authors in sending their work to potentially predatory journals. Moreover, we aimed to understand the perspective of journal editors at journals cited as potentially predatory.MethodsPotential online predatory journals were randomly selected among 350 publishers and their 2204 biomedical journals. Author and editor email information was valid for 2227 total potential participants. A survey for authors and editors was created in an iterative fashion and distributed. Surveys assessed attitudes and knowledge about predatory publishing. Narrative comments were invited.ResultsA total of 249 complete survey responses were analyzed. A total of 40% of editors (17/43) surveyed were not aware that they were listed as an editor for the particular journal in question. A total of 21.8% of authors (45/206) confirmed a lack of peer review. Whereas 77% (33/43) of all surveyed editors were at least somewhat familiar with predatory journals, only 33.0% of authors (68/206) were somewhat familiar with them (P

Published
2019

15. Does routine repeat imaging change management in high-grade renal trauma? Results from three level 1 trauma centers.

Author

Bayne, David B, Tresh, Anas, Baradaran, Nima, Murphy, Gregory, Osterberg, E Charles, Ogawa, Shellee, Wenzel, Jessica, Hampson, Lindsay, McAninch, Jack, and Breyer, Benjamin

Subjects
Kidney, Kidney Tubules, Humans, Abdominal Injuries, Wounds, Penetrating, Hemorrhage, Tomography, X-Ray Computed, Embolization, Therapeutic, Trauma Severity Indices, Retrospective Studies, Adult, Trauma Centers, Female, Male, Urinoma, Vascular System Injuries, Asymptomatic Diseases, Conservative Treatment, Collecting system injury, High-grade renal trauma, Renal trauma grade, Repeat imaging, Vascular injury, Prevention, Kidney Disease, Injury (total) Accidents/Adverse Effects, Biomedical Imaging, Clinical Research, Injuries and accidents, Clinical Sciences, Urology & Nephrology
Abstract

PurposeGuidelines call for routine reimaging of Grade 4-5 renal injuries at 48-72 h. The aim of the current study is to evaluate the clinical utility of computed tomography (CT) reimaging in high-grade renal injuries.Materials and methodsWe assembled data on 216 trauma patients with high-grade renal trauma at three level 1 trauma centers over a 19-year span between 1999 and 2017 in retrospectively collected trauma database. Demographic, radiographic, and clinical characteristics of patients were retrospectively reviewed.ResultsIn total, 151 cases were Grade 4 renal injuries, and 65 were Grade 5 renal injuries. 53.6% (81) Grade 4 and 15.4% (10) Grade 5 renal injuries were initially managed conservatively. Of the 6 asymptomatic cases where repeat imaging resulted in intervention, 100% had collecting system injuries at initial imaging. Collecting system injuries were only present in 42.9% of cases where routine repeat imaging did not trigger surgical intervention. Collecting system injury at the time of initial imaging was a statistically significant predictor of routine repeat imaging triggering surgical intervention (p = 0.022). Trauma grade and the presence of vascular injury were not significant predictors of intervention after repeat imaging in asymptomatic patients.ConclusionIn asymptomatic patients with high-grade renal trauma, the number needed to image is approximately one in eight (12.5%) to identify need for surgical intervention. There is potentially room to improve criteria for routine renal imaging in high-grade renal trauma based on the more predictive imaging finding of collecting system injury.

Published
2019

16. STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial

Author

Reilley, Matthew J, McCoon, Patricia, Cook, Carl, Lyne, Paul, Kurzrock, Razelle, Kim, Youngsoo, Woessner, Richard, Younes, Anas, Nemunaitis, John, Fowler, Nathan, Curran, Michael, Liu, Qinying, Zhou, Tianyuan, Schmidt, Joanna, Jo, Minji, Lee, Samantha J, Yamashita, Mason, Hughes, Steven G, Fayad, Luis, Piha-Paul, Sarina, Nadella, Murali VP, Xiao, Xiaokun, Hsu, Jeff, Revenko, Alexey, Monia, Brett P, MacLeod, A Robert, and Hong, David S

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Hematology, Lymphoma, Orphan Drug, Clinical Trials and Supportive Activities, Biotechnology, Rare Diseases, Genetics, Clinical Research, Cancer, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Oligonucleotides, Oligonucleotides, Antisense, STAT3 Transcription Factor, Young Adult, STAT3, Anti-sense oligonucleotide, Diffuse large B-cell lymphoma, DLBCL, Clinical trial, Immunotherapy, JAK-STAT, Immunology, Oncology and carcinogenesis
Abstract

BackgroundThe Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival. While multiple therapies inhibit upstream signaling, there has been limited success in selectively targeting STAT3 in patients. Antisense oligonucleotides (ASOs) represent a compelling therapeutic approach to target difficult to drug proteins such as STAT3 through of mRNA targeting. We report the evaluation of a next generation STAT3 ASO (AZD9150) in a non-Hodgkin's lymphoma population, primarily consisting of patients with DLBCL.MethodsPatients with relapsed or treatment refractory lymphoma were enrolled in this expansion cohort. AZD9150 was administered at 2 mg/kg and the 3 mg/kg (MTD determined by escalation cohort) dose levels with initial loading doses in the first week on days 1, 3, and 5 followed by weekly dosing. Patients were eligible to remain on therapy until unacceptable toxicity or progression. Blood was collected pre- and post-treatment for analysis of peripheral immune cells.ResultsThirty patients were enrolled, 10 at 2 mg/kg and 20 at 3 mg/kg dose levels. Twenty-seven patients had DLBCL. AZD9150 was safe and well tolerated at both doses. Common drug-related adverse events included transaminitis, fatigue, and thrombocytopenia. The 3 mg/kg dose level is the recommended phase 2 dose. All responses were seen among DLBCL patients, including 2 complete responses with median duration of response 10.7 months and 2 partial responses. Peripheral blood cell analysis of three patients without a clinical response to therapy revealed a relative increase in proportion of macrophages, CD4+, and CD8+ T cells; this trend did not reach statistical significance.ConclusionsAZD9150 was well tolerated and demonstrated efficacy in a subset of heavily pretreated patients with DLBCL. Studies in combination with checkpoint immunotherapies are ongoing.Trial registrationRegistered at ClinicalTrials.gov: NCT01563302 . First submitted 2/13/2012.

Published
2018

17. The impact of the time of day on metabolic responses to exercise in adults: A systematic and meta-analysis review.

Author

Dighriri, Anas, Timraz, Maha, Rosaini, Nur Dania, Alkhayl, Faris, Boyle, James G, Logan, Greig, and Gray, Stuart R

Subjects
*CONTINUOUS glucose monitoring, *CIRCADIAN rhythms, *EXERCISE therapy, *DATABASE searching, *ADULTS
Abstract

The aim of the current study is to investigate whether the time of day at which exercise is performed affects metabolic, glucose and insulin responses to exercise in adults. Databases were searched for randomised controlled (parallel and crossover) trials with participants aged from 18 to 65 year, an intervention of any exercise carried out at a specific time of the day and compared to any exercise carried out at a different time of the day. From 2458 screened articles, 12 studies were included in the systematic review of which 5 studies were included in the meta-analyses which compared 24 h continuous glucose monitoring (CGM) data, between morning and afternoon/evening exercise, on the day exercise was performed (SMD = 0.12 [−0.22–0.46] p = 0.76) and the day after exercise (SMD = −0.02 [−0.36–0.33] p = 0.94. Similar findings were observed in the wider systematic review with a general unclear risk of bias and a low certainty in these data. The results indicate that there is no clear effect of the time of the day on metabolic responses to exercise and exercise at any time of day should be the goal of public health strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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18. The health and quality of life of dental workers in jordan during COVID-19: A cross-sectional study.

Author

Al-Hourani, Zeid A., Almhdawi, Khader A., AlBakri, Isra A., Alibrahim, Anas N., and Obeidat, Donia

Subjects
CROSS-sectional method, HEALTH status indicators, RESEARCH funding, STATISTICAL sampling, QUESTIONNAIRES, DESCRIPTIVE statistics, WORK experience (Employment), ANXIETY, DENTISTS, QUALITY of life, PSYCHOLOGICAL stress, DATA analysis software, PSYCHOLOGICAL tests, COVID-19 pandemic, INDUSTRIAL hygiene, MENTAL depression
Abstract

BACKGROUND: Dental team members are susceptible to high mental and physical stress levels, which could have increased during the Coronavirus disease 2019 (COVID-19). OBJECTIVE: This study aimed to evaluate Jordanian dental workers' health-related quality of life (HRQoL) and determine its predictors during the COVID-19 Pandemic. METHODS: This was a cross-sectional survey study conducted on dental team members, namely; Dentists, dental Assistants, and Dental Technicians. The survey questionnaire was composed of questions related to stress during COVID-19, a short-form survey of 12 items (SF-12), a Depression, Anxiety, and Stress scale (DASS-21), and a Nordic musculoskeletal disorder questionnaire (NMQ). Descriptive analyses were used to describe the main outcome measures, and multiple variable regression analysis was conducted to identify the quality of life predictors. RESULTS: Participants' HRQoL measured by SF-12 showed a mean±SD score of 67.1±17.19 for the physical component and 54.51±20.27 for the mental component. The Nordic scale showed symptoms of lower back pain as 63.9% over 12 months, 32% over 12 months' functional limitation symptoms, and 45% in 7 days The regression model was found strong for our study with 53.8% variations (r2 = 0.538, F = 43.739, P < 0.001) in health-related quality of life. CONCLUSIONS: Our study concluded that the level of HRQoL among Jordanian dental specialists during COVID-19 was observed to impact levels of physical and mental well-being which negatively influence the quality of life. Predictive factors like depression, stress, anxiety, musculoskeletal health, and individual everyday quality of life significantly affect the HRQoL of dental specialists. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci.

Author

Khanshour, Anas M, Kou, Ikuyo, Fan, Yanhui, Einarsdottir, Elisabet, Makki, Nadja, Kidane, Yared H, Kere, Juha, Grauers, Anna, Johnson, Todd A, Paria, Nandina, Patel, Chandreshkumar, Singhania, Richa, Kamiya, Nobuhiro, Takeda, Kazuki, Otomo, Nao, Watanabe, Kota, Luk, Keith DK, Cheung, Kenneth MC, Herring, John A, Rios, Jonathan J, Ahituv, Nadav, Gerdhem, Paul, Gurnett, Christina A, Song, You-Qiang, Ikegawa, Shiro, and Wise, Carol A

Subjects
Biological Sciences, Genetics, Pediatric, Human Genome, Prevention, 2.1 Biological and endogenous factors, Aetiology, Musculoskeletal, ABO Blood-Group System, Adolescent, Cadherins, Child, Ethnicity, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Musculoskeletal Diseases, Polymorphism, Single Nucleotide, SOXD Transcription Factors, Scoliosis, Young Adult, Medical and Health Sciences, Genetics & Heredity
Abstract

Adolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups. Three novel loci that surpassed genome-wide significance were uncovered in intragenic regions of the CDH13 (P-value_rs4513093 = 1.7E-15), ABO (P-value_ rs687621 = 7.3E-10) and SOX6 (P-value_rs1455114 = 2.98E-08) genes. Restricting the analysis to females improved the associations at multiple loci, most notably with variants within CDH13 despite the reduction in sample size. Genome-wide gene-functional enrichment analysis identified significant perturbation of pathways involving cartilage and connective tissue development. Expression of both SOX6 and CDH13 was detected in cartilage chondrocytes and chromatin immunoprecipitation sequencing experiments in that tissue revealed multiple HeK27ac-positive peaks overlapping associated loci. Our results further define the genetic architecture of AIS and highlight the importance of vertebral cartilage development in its pathogenesis.

Published
2018

20. Genital burns in the United States: Disproportionate prevalence in the pediatric population.

Author

Tresh, Anas, Baradaran, Nima, Gaither, Thomas W, Fergus, Kirkpatrick B, Liaw, Aron, Balakrishnan, Ashwin, Hampson, Lindsay A, and Breyer, Benjamin N

Subjects
Genitalia, Humans, Burns, Hospitalization, Prevalence, Multivariate Analysis, Logistic Models, Age Distribution, Sex Distribution, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Infant, Infant, Newborn, United States, Female, Male, Young Adult, Burn, Epidemiology, Genital, Pediatric, Urology, and over, Preschool, Newborn, Injury (total) Accidents/Adverse Effects, Clinical Research, Injuries and Accidents, Emergency & Critical Care Medicine, Clinical Sciences
Abstract

Introduction and objectivesTo describe the epidemiology of genital burns in the U.S. and investigate the underlying etiology.MethodsThe National Electronic Injury Surveillance System database was queried for individuals who sustained genital burns from 2000 to 2016. We collected data on age, gender, injury diagnosis, disposition, and causative agents. Multivariate analysis was performed to determine predictors of hospitalization.ResultsWe estimate 17,026 (95% CI 16,649-17,404) cases of genital burns presented to emergency departments nationally. Genital burns occurred more in males than females (12,295 vs 4,731). Scalding (57.9%) was the most common mechanism of injury and hot water (35.7%) the most common causative agent. Significant predictors of hospitalization on multivariate analysis were multi-surface (OR 4.4), scalding (OR 11.5) and thermal burns (OR 27.9). Children ages 0-2 had the highest prevalence of genital burns, and children ages 0-12 comprised 37.1% of the study. For children

Published
2018

21. Association of Patient Volume With Online Ratings of California Urologists

Author

Murphy, Gregory P, Awad, Mohannad A, Tresh, Anas, Gaither, Thomas W, Osterberg, E Charles, Baradaran, Nima, and Breyer, Benjamin N

Subjects
California, Clinical Competence, Female, Humans, Internet, Male, Patients, Public Opinion, Retrospective Studies, Urology
Abstract

This study evaluates Medicare billing data to examine whether urologists with higher patient volume have lower online ratings from patients.

Published
2018

22. Changes in Coronary Plaque Volume: Comparison of Serial Measurements on Intravascular Ultrasound and Coronary Computed Tomographic Angiography.

Author

Nakanishi, Rine, Alani, Anas, Matsumoto, Suguru, Li, Dong, Fahmy, Michael, Abraham, Jeby, Dailing, Christopher, Broersen, Alexander, Kitslaar, Pieter H, Nasir, Khurram, Min, James K, and Budoff, Matthew J

Subjects
Coronary Vessels, Humans, Disease Progression, Coronary Angiography, Ultrasonography, Interventional, Follow-Up Studies, Prospective Studies, Middle Aged, Female, Male, Coronary Artery Disease, Plaque, Atherosclerotic, Computed Tomography Angiography, Coronary angiography/methods, coronary vessels/diagnostic imaging, disease progression, image interpretation, computer-assisted, plaque, atherosclerotic/diagnostic imaging, predictive value of tests, prospective studies, time factors, tomography, x-ray computed/methods, ultrasonography, interventional/methods, image interpretation, computer-assisted, plaque, atherosclerotic/diagnostic imaging, ultra-sonography, interventional/methods, Ultrasonography, Interventional, Plaque, Atherosclerotic, tomography, x-ray computed/methods, ultrasonography, Cardiovascular System & Hematology
Abstract

Serial measurements of coronary plaque volume have been used to evaluate drug efficacy in atherosclerotic progression. However, the usefulness of computed tomography for this purpose is unknown. We investigated whether the change in total plaque volume on coronary computed tomographic angiography is associated with the change in segment plaque volume on intravascular ultrasound. We prospectively enrolled 11 consecutive patients (mean age, 56.3 ± 5 yr; 6 men) who were to undergo serial invasive coronary angiographic examinations with use of grayscale intravascular ultrasound and coronary computed tomography, performed

Published
2018

23. The relationship between cardio‐ankle vascular index and subclinical atherosclerosis evaluated by cardiac computed tomographic angiography

Author

Matsumoto, Suguru, Nakanishi, Rine, Luo, Yanting, Kim, Michael, Alani, Anas, Nezarat, Negin, Dailing, Christopher, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Aging, Heart Disease, Heart Disease - Coronary Heart Disease, Prevention, Atherosclerosis, Cardiovascular, Adult, Aged, Ankle Brachial Index, Asymptomatic Diseases, Chi-Square Distribution, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Coronary Stenosis, Female, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Pilot Projects, Plaque, Atherosclerotic, Predictive Value of Tests, Prognosis, Prospective Studies, Risk Factors, Severity of Illness Index, cardio-ankle vascular index, subclinical atherosclerosis, cardiac computed tomography angiopgaphy, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundThe cardio-ankle vascular index (CAVI) is a new noninvasive index to evaluate arterial stiffness. We investigated whether CAVI can predict severity, extent, and burden of coronary artery disease by comparing results with cardiac computed tomographic angiography (CCTA).HypothesisCAVI may predict the presence of subclinical atherosclerosis.MethodsWe prospectively enrolled 95 patients (66% male; mean age, 50 ± 16 years) who underwent both CCTA and CAVI consecutively. We evaluated if CAVI correlated with (1) severe stenosis (≥50%); (2) plaque extent, determined by a segment-involvement score (SIS), defined by the total number of coronary artery segments containing any plaque; and (3) plaque burden, determined by a segment-stenosis score (SSS), defined by the extent of obstruction of coronary luminal diameter in individual coronary artery segments.ResultsBivariate analysis showed a statistically significant relationship not only between CAVI and SIS, but also between CAVI and SSS (r2 = 0.4, P < 0.0001 for SIS; r2 = 0.36, P < 0.0001 for SSS). Multivariable logistic analysis demonstrated that CAVI is significantly associated with SSS >5 (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.1-7.8, P = 0.03) and SIS >5 (OR: 2.3, 95% CI: 1.1-5.8, P = 0.02), but not severe stenosis (OR: 1.7, 95% CI: 0.9-4.3, P = 0.13), after adjusting for age, sex, chest pain, hypertension, dyslipidemia, family history, diabetes, and current smoking.ConclusionsWe demonstrated that CAVI had a significant relationship with subclinical coronary atherosclerosis evaluated by CCTA, especially in relation to plaque burden and plaque extent, but not severe stenosis. Thus, CAVI may reflect coronary atherosclerosis burden more than severity.

Published
2017

24. A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma

Author

Batlevi, Connie L, Crump, Michael, Andreadis, Charalambos, Rizzieri, David, Assouline, Sarit E, Fox, Susan, Jagt, Richard HC, Copeland, Amanda, Potvin, Diane, Chao, Richard, and Younes, Anas

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Lymphoma, Clinical Research, Orphan Drug, Rare Diseases, Hematology, Cancer, 6.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Benzamides, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Histone Deacetylase Inhibitors, Humans, Kaplan-Meier Estimate, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Pyrimidines, Recurrence, Treatment Outcome, diffuse large B-cell lymphoma, follicular lymphoma, histone deacetylase, mocetinostat, phase 2 study, Cardiorespiratory Medicine and Haematology, Immunology, Cardiovascular medicine and haematology
Abstract

Deregulation of histone deacetylase (HDAC) is important in the pathogenesis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Mocetinostat, an isotype-selective HDAC inhibitor, induces accumulation of acetylated histones, cell cycle arrest and apoptosis in several cancers. This phase 2 study evaluated mocetinostat in patients with relapsed/refractory (R/R) DLBCL and FL. Seventy-two patients received mocetinostat (starting doses: 70-110 mg TIW, 4-week cycles). The best overall response rate (95% CI) was 18·9% (7·2, 32·2) for the DLBCL cohort (n = 41), and 11·5% (1·7, 20·7) for the FL cohort (n = 31). Responses were durable (≥90 days in 7 of 10 responses). Overall, 54·1% and 73·1% of patients derived clinical benefit (response or stable disease) from mocetinostat in the DLBCL and FL cohorts, respectively. Progression-free survival ranged from 1·8 to 22·8 months and 11·8 to 26·3 months in responders with DLBCL and FL, respectively. The most frequent treatment-related adverse events were fatigue (75·0%), nausea (69·4%) and diarrhoea (61·1%). Although mocetinostat had limited single-agent activity in R/R DLBCL and FL, patients with clinical benefit had long-term disease control. The safety profile was acceptable. This drug class warrants further investigation, including identifying patients more likely to respond to this agent, or in combination with other agents.

Published
2017

25. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD.

Author

Naz, Shama, Kolmert, Johan, Yang, Mingxing, Reinke, Stacey N, Kamleh, Muhammad Anas, Snowden, Stuart, Heyder, Tina, Levänen, Bettina, Erle, David J, Sköld, C Magnus, Wheelock, Åsa M, and Wheelock, Craig E

Subjects
Humans, Pulmonary Disease, Chronic Obstructive, Phosphoric Diester Hydrolases, MicroRNAs, Respiratory Function Tests, Chromatography, Liquid, Cross-Sectional Studies, Smoking, Sex Factors, Oxidative Stress, Middle Aged, Sweden, Female, Male, Statistics as Topic, Metabolomics, Pulmonary Disease, Chronic Obstructive, Chromatography, Liquid, Respiratory System, Medical and Health Sciences
Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10-7). Sex stratification indicated that the separation was driven by females (p=2.4×10-7) relative to males (p=4.0×10-4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10-3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p

Published
2017

26. Presence, Characteristics, and Volumes of Coronary Plaque Determined by Computed Tomography Angiography in Young Type 2 Diabetes Mellitus.

Author

Nezarat, Negin, Budoff, Matthew J, Luo, Yanting, Darabian, Sirous, Nakanishi, Rine, Li, Dong, Sheidaee, Nasim, Kim, Michael, Alani, Anas, Matsumoto, Suguru, Rahmani, Sina, Kanisawa, Mitsuru, Ceponiene, Indre, Osawa, Kazuhiro, Qi, Hong, Hamal, Sajad, Kitslaar, Pieter, Broersen, Alexander, Flores, Ferdinand, Ipp, Eli, and Khazai, Bahram

Subjects
Coronary Vessels, Humans, Diabetes Mellitus, Type 2, Coronary Angiography, Prognosis, Severity of Illness Index, Prevalence, Survival Rate, Case-Control Studies, Follow-Up Studies, Prospective Studies, Reproducibility of Results, Adult, California, Female, Male, Atherosclerosis, Coronary Artery Disease, Plaque, Atherosclerotic, Computed Tomography Angiography, Heart Disease, Biomedical Imaging, Clinical Research, Heart Disease - Coronary Heart Disease, Aging, Cardiovascular, Prevention, Diabetes, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology
Abstract

Prevention and management of coronary artery disease (CAD) is of great concern in patients with diabetes mellitus. Although the impact of coronary atherosclerosis is described well for subjects older than 40 years, the prevalence and types of coronary atherosclerosis in young patients are not well known. The aim of this study was to evaluate the prevalence, extent, severity, and volumes of coronary plaque in type 2 diabetes mellitus (T2DM) population younger than of 40 years. This prospective study enrolled 181 subjects (25-40 year old) undergoing coronary computed tomography angiography, with 86 T2DM and 95 nondiabetic age/gender-matched subjects. Coronary artery calcium (CAC), plaque assessment including total segment stenosis (sum of individual segmental stenosis), total plaque scores (sum of semiquantitative segmental plaque burden), segment involvement scores (number of segments with plaque) were evaluated. In addition, we quantitatively measured plaque volumes in total, fibrous, fibrous fatty, dense calcified, and low-attenuation plaque using novel plaque software. Compared with nondiabetic patients, the prevalence of CAD, calcified, and noncalcified plaques was higher in patients with T2DM (19% vs 58%; p

Published
2017

27. Aortic plaque dehiscence caused by rotational atherectomy with Kokeshi phenomenon in a patient with aortic stenosis successfully treated with transcatheter aortic valve replacement

Author

Syedah Aleena Haider, Anas Jawaid, Thomas Stuver, and Syed Yaseen Naqvi

Subjects
Atherectomy, Coronary, Transcatheter Aortic Valve Replacement, Percutaneous Coronary Intervention, Humans, Female, General Medicine, Aortic Valve Stenosis, Coronary Vessels
Abstract

Rotational atherectomy (RA) is an important interventional technique to facilitate effective percutaneous coronary intervention of severely calcified lesions. Despite the improved probability of better procedural outcomes during angioplasty, the use of RA is associated with an inherent risk of complications. Here, we present a case of a woman in her mid-90s with severe aortic stenosis (AS) who underwent RA facilitated angioplasty of the right coronary artery (RCA), with the procedure complicated by the Kokeshi phenomenon. Manual traction to retrieve the burr resulted in dehiscence of an aortic plaque near the ostium of the RCA. Unfortunately, the patient’s risk profile precluded surgery. After a multidisciplinary discussion, a self-expanding Core Valve Evolut R prosthesis (Medtronic, Minneapolis, Minnesota, USA) was successfully implanted, with improvement in the AS and stabilisation of the aortic plaque. This is the first reported case of successful non-operative management of a mobile-aortic plaque caused by RA with a transcatheter prosthesis.

Published
2024

28. Extra-coronary calcification (aortic valve calcification, mitral annular calcification, aortic valve ring calcification and thoracic aortic calcification) in HIV seropositive and seronegative men: Multicenter AIDS Cohort Study

Author

Rezaeian, Panteha, Miller, P Elliott, Haberlen, Sabina A, Razipour, Aryabod, Bahrami, Hossein, Castillo, Romeo, Witt, Mallory D, Kingsley, Lawrence, Palella, Frank J, Nakanishi, Rine, Matsumoto, Suguru, Alani, Anas, Jacobson, Lisa P, Post, Wendy S, and Budoff, Matthew J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, HIV/AIDS, Clinical Research, Infectious Diseases, Cardiovascular, Heart Disease - Coronary Heart Disease, Heart Disease, Infection, Good Health and Well Being, Adult, Aged, Aorta, Thoracic, Aortic Diseases, Aortic Valve, Aortography, Biomarkers, Calcinosis, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Coronary Vessels, HIV Infections, HIV Seronegativity, HIV Seropositivity, Heart Valve Diseases, Humans, Inflammation Mediators, Logistic Models, Male, Middle Aged, Mitral Valve, Multidetector Computed Tomography, Multivariate Analysis, Odds Ratio, Plaque, Atherosclerotic, Prevalence, Prognosis, Prospective Studies, Risk Factors, United States, Vascular Calcification, Extra-coronary calcification, HIV, Coronary plaque morphology, Inflammatory biomarkers, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Applied computing
Abstract

IntroductionPrevious studies have demonstrated an association between HIV infection and coronary artery disease (CAD); little is known about potential associations between HIV infection and extra-coronary calcification (ECC).MethodsWe analyzed 621 HIV infected (HIV+) and 384 HIV uninfected (HIV-) men from the Multicenter AIDS Cohort Study who underwent non-contrast computed tomography (CT) from 2010-2013. Agatston scores were calculated for mitral annular calcification (MAC), aortic valve calcification (AVC), aortic valve ring calcification (AVRC), and thoracic aortic calcification (TAC). The associations between HIV infection and the presence of each type of ECC (score > 0) were evaluated by multivariable logistic regression. We also evaluated the association of ECC with inflammatory biomarker levels and coronary plaque morphology.ResultsAmong HIV+ and HIV- men, the age-standardized prevalences were 15% for TAC (HIV+ 14%/HIV- 16%), 10% for AVC (HIV+ 11%/HIV- 8%), 24% for AVRC (HIV+ 23% HIV- 24%), and 5% for MAC (HIV+ 7%/HIV- 3%). After adjustment, HIV+ men had 3-fold greater odds of MAC compared to HIV- men (OR = 3.2, 95% CI: 1.5-6.7), and almost twice the odds of AVC (1.8, 1.1-2.9). HIV serostatus was not associated with TAC or AVRC. AVRC was associated with higher Il-6 and sCD163 levels. TAC was associated with higher ICAM-1, TNF-α RII, and Il-6 levels. AVC and AVRC calcification were associated with presence of non-calcified plaque in HIV+ but not HIV- men.ConclusionHIV infection is an independent predictor of MAC and AVC. Whether these calcifications predict mortality in HIV+ patients deserves further investigation.

Published
2016

29. The Cardiovascular Trial of the Testosterone Trials

Author

alamir, Moshrik Abd, Ellenberg, Susan S, Swerdloff, Ronald S, Wenger, Nanette K, Mohler, Emile R, Lewis, Cora E, Barrett-Conner, Elizabeth, Nakanishi, Rine, Darabian, Sirous, Alani, Anas, Matsumoto, Suguru, Nezarat, Negin, Snyder, Peter J, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Heart Disease, Aging, Cardiovascular, Clinical Research, Atherosclerosis, Heart Disease - Coronary Heart Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Aged, Androgens, Coronary Angiography, Coronary Artery Disease, Disease Progression, Double-Blind Method, Hormone Replacement Therapy, Humans, Hypogonadism, Male, Testosterone, Tomography, X-Ray Computed, cardiovascular disease, coronary artery plaque progression, coronary computed tomographic angiography, randomized controlled trial, testosterone, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundData from prior studies have yielded inconsistent results on the association of serum testosterone levels with the risk for cardiovascular disease. There are no clinical trial data on the effects of testosterone replacement therapy on plaque progression.ObjectiveWe designed a study to investigate the effect of testosterone therapy on coronary artery plaque progression using serial coronary computed tomographic angiography (CCTA). In this paper, we describe the study design, methods, and characteristics of the study population.MethodsThe Cardiovascular Trial of the Testosterone Trials (TTrials; NCT00799617) is a double-blind, placebo-controlled trial of 1 year of testosterone therapy in men 65 years or older with clinical manifestations of androgen deficiency and unequivocally low serum testosterone concentrations (

Published
2016

30. The Cardiovascular Trial of the Testosterone Trials: rationale, design, and baseline data of a clinical trial using computed tomographic imaging to assess the progression of coronary atherosclerosis.

Author

Abd Alamir, Moshrik, Ellenberg, Susan S, Swerdloff, Ronald S, Wenger, Nanette K, Mohler, Emile R, Lewis, Cora E, Barrett-Conner, Elizabeth, Nakanishi, Rine, Darabian, Sirous, Alani, Anas, Matsumoto, Suguru, Nezarat, Negin, Snyder, Peter J, and Budoff, Matthew J

Subjects
Humans, Hypogonadism, Disease Progression, Testosterone, Androgens, Tomography, X-Ray Computed, Coronary Angiography, Hormone Replacement Therapy, Double-Blind Method, Aged, Male, Coronary Artery Disease, cardiovascular disease, coronary artery plaque progression, coronary computed tomographic angiography, randomized controlled trial, testosterone, Tomography, X-Ray Computed, Cardiovascular System & Hematology, Clinical Sciences
Abstract

BackgroundData from prior studies have yielded inconsistent results on the association of serum testosterone levels with the risk for cardiovascular disease. There are no clinical trial data on the effects of testosterone replacement therapy on plaque progression.ObjectiveWe designed a study to investigate the effect of testosterone therapy on coronary artery plaque progression using serial coronary computed tomographic angiography (CCTA). In this paper, we describe the study design, methods, and characteristics of the study population.MethodsThe Cardiovascular Trial of the Testosterone Trials (TTrials; NCT00799617) is a double-blind, placebo-controlled trial of 1 year of testosterone therapy in men 65 years or older with clinical manifestations of androgen deficiency and unequivocally low serum testosterone concentrations (

Published
2016

31. Aged Garlic Extract Reduces Low Attenuation Plaque in Coronary Arteries of Patients with Metabolic Syndrome in a Prospective Randomized Double-Blind Study 1–3

Author

Matsumoto, Suguru, Nakanishi, Rine, Li, Dong, Alani, Anas, Rezaeian, Panteha, Prabhu, Sach, Abraham, Jeby, Fahmy, Michael A, Dailing, Christopher, Flores, Ferdinand, Hamal, Sajad, Broersen, Alexander, Kitslaar, Pieter H, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Heart Disease - Coronary Heart Disease, Aging, Cardiovascular, Clinical Trials and Supportive Activities, Nutrition, Atherosclerosis, Heart Disease, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Calcium, Coronary Artery Disease, Coronary Vessels, Disease Progression, Double-Blind Method, Female, Garlic, Humans, Male, Metabolic Syndrome, Middle Aged, Phytotherapy, Plant Extracts, Plaque, Atherosclerotic, Prospective Studies, Risk Factors, atherosclerosis, cardiac ct, garlic, progression, randomized trial, Animal Production, Food Sciences, Nutrition and Dietetics, Nutrition & Dietetics, Animal production, Food sciences, Nutrition and dietetics
Abstract

BackgroundAlthough several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification, its effect on noncalcified plaque (NCP) has been unclear.ObjectiveThis study investigated whether AGE reduces coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with metabolic syndrome (MetS).MethodsFifty-five patients with MetS (mean ± SD age: 58.7 ± 6.7 y; 71% men) were prospectively assigned to consume 2400 mg AGE/d (27 patients) or placebo (28 patients) orally. Both groups underwent CCTA at baseline and follow-up 354 ± 41 d apart. Coronary plaque volume, including total plaque volume (TPV), dense calcium (DC), NCP, and low-attenuation plaque (LAP), were measured based upon predefined intensity cutoff values. Multivariable linear regression analysis, adjusted for age, gender, number of risk factors, hyperlipidemia medications, history of coronary artery disease, scan interval time, and baseline %TPV, was performed to examine whether AGE affected each plaque change.ResultsThe %LAP change was significantly reduced in the AGE group compared with the placebo group (-1.5% ± 2.3% compared with 0.2% ± 2.0%, P = 0.0049). In contrast, no difference was observed in %TPV change (0.3% ± 3.3% compared with 1.6% ± 3.0%, P = 0.13), %NCP change (0.2% ± 3.3% compared with 1.4% ± 2.9%, P = 0.14), and %DC change (0.2% ± 1.4%, compared with 0.2% ± 1.7%, P = 0.99). Multivariable linear regression analysis found a beneficial effect of AGE on %LAP regression (β: -1.61; 95% CI: -2.79, -0.43; P = 0.008).ConclusionsThis study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910.

Published
2016

32. Diagnostic performance of transluminal attenuation gradient and fractional flow reserve by coronary computed tomographic angiography (FFRCT) compared to invasive FFR: a sub-group analysis from the DISCOVER-FLOW and DeFACTO studies

Author

Nakanishi, Rine, Matsumoto, Suguru, Alani, Anas, Li, Dong, Kitslaar, Pieter H, Broersen, Alexander, Koo, Bon-Kwon, Min, James K, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Cardiovascular, Heart Disease - Coronary Heart Disease, Clinical Research, Atherosclerosis, Heart Disease, Biomedical Imaging, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Aged, Area Under Curve, Cardiac Catheterization, Coronary Angiography, Coronary Artery Disease, Coronary Stenosis, Female, Fractional Flow Reserve, Myocardial, Hemodynamics, Humans, Male, Middle Aged, Multidetector Computed Tomography, Observer Variation, Predictive Value of Tests, Prognosis, ROC Curve, Reproducibility of Results, Severity of Illness Index, Coronary computed tomographic angiography, Fractional flow reserve, Transluminal attenuation gradient, Diagnostic accuracy, Cardiorespiratory Medicine and Haematology, Nuclear Medicine & Medical Imaging, Cardiovascular medicine and haematology
Abstract

Although coronary computed tomographic angiography (CCTA) has been a robust diagnostic tool to identify anatomical significance of coronary artery disease (CAD), the utility of CCTA to assess hemodynamic significance of CAD remains unclear. We investigated the diagnostic performance of transluminal attenuation gradient (TAG) and fractional flow reserve derived from CCTA (FFRCT) to predict lesion-specific ischemia by invasive FFR. We identified 103 patients with suspected or known CAD enrolled from the DISCOVER-FLOW and DeFACTO studies who underwent invasive coronary angiography with FFR and high quality ≥64-slice CCTA. Diagnostic performance for predicting abnormal invasive FFR (≤0.80) was assessed for TAG [≤-1.1 HU/mm by the area under the curve (AUC) by receiver-operating characteristic curve analysis (ROC)], FFR(CT) (≤0.80), and CCTA stenosis (≥50%). On a per-vessel analysis (n = 146), 52 vessels (35.6%) had ischemia by invasive FFR. The sensitivity, specificity, positive predictive value and negative predictive value were 53.8, 45.7, 35.4, 64.2% for TAG, 82.7, 74.5, 64.2, 88.6% for FFR(CT), 84.6, 39.4, 43.6, 82.2% for CCTA stenosis, respectively. The AUC by ROC curve analysis for FFR(CT) (0.79) demonstrated greater discrimination of hemodynamic ischemia compared to TAG (0.50, p < 0.0001 vs. FFR(CT)), CCTA stenosis (0.62, p = 0.0004 vs. FFR(CT)) and the combination of the two (0.63, p = 0.004 vs. FFR(CT)). These results remained consistent regardless of the number of CCTA slices. FFR(CT) allows identification of lesion-specific ischemia using invasive FFR as a reference standard with greater diagnostic accuracy than TAG, CCTA stenosis, or the combination of the two.

Published
2015

33. Massive left ventricular calcification

Author

Alani, Anas, Nakanishi, Rine, Matsumoto, Suguru, Abraham, Jeby, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Aged, 80 and over, Calcinosis, Cardiomyopathies, Heart Ventricles, Humans, Male, Radiography, Thoracic, Tomography, X-Ray Computed, Ventricular calcification, Cardiac computed tomography, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Published
2015

34. The relationship between coronary artery calcium score and the long-term mortality among patients with minimal or absent coronary artery risk factors

Author

Nakanishi, Rine, Li, Dong, Blaha, Michael J, Whelton, Seamus P, Matsumoto, Suguru, Alani, Anas, Rezaeian, Panteha, Blumenthal, Roger S, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease, Prevention, Cardiovascular, Clinical Research, Aging, Heart Disease - Coronary Heart Disease, Detection, screening and diagnosis, 2.4 Surveillance and distribution, 4.1 Discovery and preclinical testing of markers and technologies, Aetiology, Good Health and Well Being, Aged, Calcium, Coronary Angiography, Coronary Artery Disease, Coronary Vessels, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Assessment, Risk Factors, Tomography, X-Ray Computed, United States, Vascular Calcification, Coronary artery calcification, Long-term, Mortality risk, Low risk, Risk factor, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundCoronary artery calcium (CAC) is strongly predictive of all-cause mortality in intermediate-risk groups, but this relationship is not well defined in very low-risk individuals. We investigated the relationship between CAC scoring and the long-term all-cause mortality among patients with ≤ 1 cardiovascular disease (CVD) risk factor.MethodsWe analyzed a retrospective cohort of 5584 asymptomatic patients with no known CVD (mean 56.6 ± 11.6 years, 69%men) and ≤ 1 risk factor who were physician referred for a CAC scan. Mortality was ascertained through linkage with the Social Security Death Index. We calculated the prevalence of CAC stratified by age and risk factors. We also examined the association between CAC and mortality using multivariable Cox Proportional hazards models.ResultsDuring a mean follow-up of 10.4 ± 3.1 years, 168 individuals (3.0%) died. Overall, 54.5% of patients had a CAC >0 and 9.8% had CAC ≥ 400. There was a greater risk of mortality with increasing CAC 1-99 (HR 1.9, 95% CI 1.2-3.1), 100-399 (HR 2.1, 95% CI 1.2-3.6) and ≥ 400 (HR 2.8, 95% CI 1.6-4.8) compared to CAC=0 (p

Published
2015

35. Katanin p80 Regulates Human Cortical Development by Limiting Centriole and Cilia Number

Author

Hu, Wen F, Pomp, Oz, Ben-Omran, Tawfeg, Kodani, Andrew, Henke, Katrin, Mochida, Ganeshwaran H, Yu, Timothy W, Woodworth, Mollie B, Bonnard, Carine, Raj, Grace Selva, Tan, Thong Teck, Hamamy, Hanan, Masri, Amira, Shboul, Mohammad, Saffar, Muna Al, Partlow, Jennifer N, Al-Dosari, Mohammed, Alazami, Anas, Alowain, Mohammed, Alkuraya, Fowzan S, Reiter, Jeremy F, Harris, Matthew P, Reversade, Bruno, and Walsh, Christopher A

Subjects
Congenital Structural Anomalies, Pediatric, Rare Diseases, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Adenosine Triphosphatases, Animals, Case-Control Studies, Cell Proliferation, Centrioles, Cerebral Cortex, Cilia, Embryo, Mammalian, Embryonic Development, Fibroblasts, Hedgehog Proteins, Humans, Katanin, Mice, Microcephaly, Mutation, Pedigree, RNA Splicing, White People, Zebrafish, Neurosciences, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose in vivo functions are incompletely understood. Human mutations in KATNB1, which encodes the noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development.

Published
2014

36. Effects of hospital facilities on patient outcomes after cancer surgery

Author

Knight, Sr, Chu, K, Lapitan, Mc, Dare, Aj, Pius, R, Shaw, Ca, Drake, Tm, Norman, L, Ademuyiwa, Ao, Adisa, Ao, Aguilera, Ml, Al-Saqqa, Sw, Al-Slaibi, I, Bhangu, A, Biccard, Bm, Brocklehurst, P, Costas-Chavarri, A, Elhadi, M, Fairfield, Cj, Fitzgerald, Je, Ghosh, D, Glasbey, J, Henegouwen, Miv, Ingabire, Jca, Kingham, Tp, Lawani, I, Lieske, B, Lilford, R, Martin, J, Mclean, Ka, Moore, R, Morton, D, Nepogodiev, D, Ntirenganya, F, Pata, F, Pinkney, T, Stephen, R Knight, Catherine, A Shaw, Riinu, Pius, Thomas, M Drake, Lisa, Norman, Adesoji, O Ademuyiwa, Adewale, O Adisa, Maria Lorena Aguilera, Sara, W Al-Saqqa, Ibrahim, Al-Slaibi, Aneel, Bhangu, Bruce, M Biccard, Peter, Brocklehurst, Ainhoa, Costas-Chavarri, Kathryn, Chu, Anna, Dare, Muhammed, Elhadi, Cameron, J Fairfield, J Edward Fitzgerald, Dhruv, Ghosh, James, Glasbey, Mark, I van Berge Henegouwen, C Allen Ingabire, J, T Peter Kingham, Marie Carmela Lapitan, Ismaïl, Lawani, Bettina, Lieske, Richard, Lilford, Janet, Martin, Kenneth, A McLean, Rachel, Moore, Dion, Morton, Dmitri, Nepogodiev, Faustin, Ntirenganya, Francesco, Pata, Thomas, Pinkney, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Aya, Riad, Hosni Khairy Salem, Joana, Simões, Richard, Spence, Neil, Smart, Stephen, Tabiri, Hannah, Thomas, Thomas, G Weiser, Malcolm, West, John, Whitaker, Ewen, M Harrison, Arben, Gjata, Maria Marta Modolo, Sebastian, King, Erick, Chan, Sayeda Nazmun Nahar, Ade, Waterman, Dominique, Vervoort, Alemayehu Ginbo Bedada, Bernardo De Azevedo, Ana Gabriela Figueiredo, Manol, Sokolov, Venerand, Barendegere, Gerald, Ekwen, Arnav, Agarwal, Qinyang, Liu, Juan Camilo Correa, Kalisya Luc Malemo, Jacques, Bake, Jakov, Mihanovic, Kamila, Kunčarová, Julius, Orhalmi, Hosni, Salem, Jyri, Teras, Aristotelis, Kechagias, Alexis, P Arnaud, Judith, Lindert, Vasileios, Kalles, Maria-Lorena, Aguilera-Arevalo, Gustavo, Recinos, Zsolt, Baranyai, Basant, Kumar, Harish Neelamraju Lakshmi, Sanoop Koshy Zachariah, Philip, Alexander, Sunil Kumar Venkatappa, Pramesh, C, Radhian, Amandito, Christina, Fleming, Luca, Ansaloni, Gianluca, Pellino, Ahmed, M Altibi, Ibrahim, Nour, Intisar, Hamdun, Ali, M Ghellai, Donatas, Venskutonis, Tomas, Poskus, Justas, Zilinskas, Precious, Malemia, Yong Yong Tew, Elaine, Borg, Sarah, Ellul, Fatima Zahraa Wafqui, David, W Borowski, Anne Sophie van Dalen, Cameron, Wells, Harissou, Adamou, Adesoji, Ademuyiwa, Adewale, Adisa, Kjetil, Søreide, Sara Al Saqqa, Osaid, Alser, Haya, Tahboub, Helmut Alfredo Segovia Lohse, Sebastian Shu Yip, Piotr, Major, António Sampaio Soares, Matei Razvan Bratu, Andrey, Litvin, Armen, Vardanyan, Ahmad, Gudal, Naif, Albati, Jovan, Juloski, Miran, Rems, Sarah, Rayne, Stephanie Van Straten, Yoshan, Moodley, Irene Ortega Vázquez, Jaime, Ruiz-Tovar, Kithsiri Janakantha Senanayake, Sujeewa Priyantha Bandara Thalgaspitiya, Omer Abdelbagi Omer, Anmar, Homeida, Yucel, Cengiz, Daniel, Clerc, Muhammad, Alshaar, Hanen, Bouaziz, Yuksel, Altinel, Matthew, Doe, Maryna, Freigofer, Ella, Teasdale, Rakan, Kabariti, Joshua Michael Clements, Stephen Richard Knight, Ahsan, Ashfaq, Ijeoma, Azodo, Gabriela, Wagner, Ivan, Trostchansky, Mayaba, Maimbo, David, Linyama, Helidon, Nina, Amanda, Zeko, Claudio Gabriel Fermani, Santiago, Villalobos, Federico, Carballo, Pablo, Farina, Sebastian, Guckenheimer, Marilla, Dickfos, Ankit, Ajmera, Chester, Chong, Ralph, Gourlay, Sikandar, Hussaini, Yi Jia Lee, Adeeb, Majid, Peter, Martin, Rebecca, Miles, Owen James Morris, Jamie, Phua, William, Ridley, Tarunpreet, Saluja, Ryan Renxin Tan, Jen, Teh, Anna, Wells, Bharti, Arora, Qaasim, Dollie, Debbie, Ho, Yanru, Ma, Omattage Mahasha Perera, Anthony, Truong, Amanda Caroline Dawson, Bryan, Lim, Upuli, Pahalawatta, Jacqueline, Phan, Xiao-Ming Sarah Woon-Shoo-Tong, Andrea, Yeoh, Lillian, Charman, Andrew, Drane, Sharon, Laura, Charmaine Chu Wen Lo, Amy, Mozes, Rita, Poon, Hao Han Tan, Ellen, Wall, Prakshi, Chopra, Jasmine De Giovanni, Bal, Dhital, Brian, Draganic, Alexander, Duller, Jonathan, Gani, Yao Kuan Goh, Jun Young Jeong, Brendan, Mcmanus, Prakash, Nagappan, Peter, Pockney, Anya, Rugendyke, Mahsa, Sarrami, Stephen, Smith, Vanessa, Wills, Hsu Ven Wong, Geoffrey, Ye, Geoffrey, Zhang, Ethan, Brooker, Daniel, Feng, Bonnie, Lau, Carlin, Ngai, Sarah, Birks, David, Gyorki, Jaime Otero de Pablos, Ali, Abbosh, Chris, Gillespie, Ahmed, Mahmoud, Bianca, Kwan, Joshua, Lawson, Andrea, Warwick, Janne, Bingham, Andrew, J Cockbain, Nagendra Naidu Dudi-Venkata, Jordan, Ellaby-Hall, Ben, Finlay, Emily, Humphries, Jade, Pisaniello, Monique, Pisaniello, Salma, Salih, Tarik, Sammour, Haidar Hadri Abd Wahab, April De Silva, Nicola, Hayward, Kartik, Iyer, Guy, Maddern, Gian Andrea Prevost, Naga, Annapureddy, Krishna Pranathi Settipalli, Jeremy, Yeo, Lucy, Hempenstall, Lily, Pham, Shaun, Purcell, Cherry, Talavera, Ashish, I Vaska, Gurpreet, Chaggar, Phillip, Chrapko, Annelise, Cocco, Sarah Michelle Crystal Jade Coulter-Nile, Grahame, Ctercteko, James, French, Houchen, Gong, Martijn, Gosselink, Thuvarahan, Jegathees, Ivan, Jin, Michelle, Kalachov, Kathryn, Kiefhaber, Katherine, Lee, Jason, Luong, Steven, Phan, Henry, Pleass, Kelly, Veale, Zhi, Zeng, Angela, Au, Ashe, Debiasio, Idy, Deng, Jananee, Myooran, Amrita, Nair, Peter, Stewart, Anton, Stift, Lukas Walter Unger, Kerstin, Wimmer, Nabila, Ahmed, Syed, Hasan, Saber, Rahman, Margaret, O'Shea, Greg, Padmore, Adrian, Peters, Pietro, Perduca, Guenda, Pulcina, Nicolas, Tinton, Frederic, Buxant, Elsa, Dabin, Giulia, Garofalo, Francis, Dossou, Freddy Houehanou Rodrigue Gnangnon, Yacoubou Imorou Souaibou, Pako, Motlaleselelo, Omphile, Tlhomelang, Igor Lima Buarque, Gustavo Mendonça Ataíde Gomes, Aldo Vieira Barros, Ilia, Batashki, Nikolai, Damianov, Vladislav, Stoyanov, Dragomir, Dardanov, Svilen, Maslyankov, Plamen, Petkov, George, Todorov, Evgeni, Zhivkov, Aygulya, Akisheva, Miguel Angel Castilla Moreno, Geno, Genov, Ivelina, Ilieva, Tsvetomir, Ivanov, Martin, Karamanliev, Azhar, Khan, Emil, Mitkov, Tsanko, Yotsov, Boyko, Atanasov, Nikolay, Belev, Mihail, Slavchev, Carlos, Nsengiyumva, Elgan, Jones, Simon, Stock, Steve, Kyota, James, Brown, Tresor Mabanza, K, Lemery Nigo Samuel, Chidi, Otuneme, Ngwang, Prosper, Franklin, Umenze, Marylise, Boutros, Natasha, Caminsky, Sinziana, Dumitra, Richard, Garfinkle, Dominique, Morency, Ebram, Salama, Alexander, Banks, Lorenzo, Ferri, Haitian, He, Amit, Katz, Alexander Sender Liberman, Sarkis, Meterissian, Allison, Pang, Elena, Parvez, Usmaan, Hameed, Fahima, Osman, Sangita, Sequeira, Natalie, Coburn, Alisha, Jaffer, Paul, Karanicolas, Matthew, Mosseler, Reilly, Musselman, Xinyuan, Liu, Ching Wan Yip, Juan Sebastian Garces-Otero, Carolina, Guzman, Sebastian, Sierra, Andres Uribe Valencia, Paulo Andrés Cabrera Rivera, Saul, Camelo, Andrea, Gonzalez, Alejandro, González-Orozco, Manuel Santiago Mosquera Paz, Carlos J- Perez Rivera, Felipe, Gonzalez, Andres, Isaza-Restrepo, Laura, Nino-Torres, Natalia Arias Madrid, Maria Clara Mendoza Arango, Justin, Tsandiraki, Damir, Jemendžić, Branislav, Kocman, Oliver, Šuman, Renata, Canic, Darko, Jurišić, Ivana, Karakas, Ana Krizanovic Rupcic, Vlatka, Pitlovic, Josip, Samardžić, Mario, Kopljar, Ivan, Bacic, Edgar, Domini, Robert, Karlo, Danijela, Miljanić, Andrea, Simic, Mariam, Ahmed, Majdi Al Nassrallah, Rabiya, Altaf, Talal, Amjad, Ruba, Eltoum, Heba, Haidar, Alhassan, Hassan, Omar, Khalil, Marwan, Qasem, Rommel, Ramesh, Gautham, Sajith, Maham, Wisal, Jan, Žatecký, Michele, Bujda, Katerina, Jirankova, Ales, Paclik, Aya, Abdallah, Mariam Abdulgawad Almogy, Esraa Ayman El-Sawy, Ahmed Moustafa ElFayoumy, Nourhan, Elghareeb, Nourhan Ahmed Esmat, Ahmed, Fadel, Abdullah, Habater, Heba, Hamdy, Amr, Hefni, Marwa, Kamal, Norhan Mohamed Abobakr, Ahmed, Sayed, Nancy, Shaker, Ehab, Taha, Hoda, Tharwat, Omar, Zakaria, Ibrahem, Abdelmotaleb, Ali, Al-Dhufri, Hamza, S Al-Himyari, Enas El Sheikh, Asmaa, Eldmaty, Aya, Elkhalawy, Ahmed, M Elkhashen, Kithara, Magdy, Safa, Mostafa, Habib Doutoum Sadia, Mohamed Mahmoud Saleh, Dina, Samir, Mohamed Yahia Mohamed Ali, Mahmoud, A Nassar, Samar, Abdelhady, Aly, Abdelrazek, Israa, Abdelsalam, Aya, El-Sawy, Eman, Essam, Mohamed, Gadelkarim, Khaled, Ghaly, Mohamed, Hassabalnaby, Rana, Masarani, Nourhan Mohamed Shaaban, Ahmed, Sabry, Menatalla, Salem, Nourhan Akram Soliman, Diaaaldin, Zahran, Moustafa Ramadan Abou El Soud, Esraa Tarek Badr, Hala, Borham, Nehal, Elmeslemany, Mohammad, Elsayed, Fawzia, Elsherif, Sara, Eslam, Gehad, Gaber, Sondos, Ibrahim, Yara, Kamh, Abdelrahman, Mahmoud, Shimaa Gamal Mohamed, Eman, Morshedy, Cinderella, Omar, Fatima Salem Soliman, Shaza, Abdelkawy, Naglaa, Abdelmohsen, Mahmoud, Abdelshakour, Ahmed, Dahy, Norhan, Gamal, Mohammed, Gamal, Ahmad, Hasan, Helal, Hetta, Nehad, Mousa, Mohamed, Omar, Somia, Rabie, Mahmoud, Saad, Bakeer, Saleh, Marwa Sayed Mohamed, Muhammad, Shawqi, Heba Abdelhady Mousa, Mostafa, Alnoury, Mohamed, Elbealawy, Ahmed, Elshafey, Muhammad Essam Ibrahim El Desouki Muhammad Ahmed, Mennatullah, Ghonaim, Fawzy, Hgag, Mohamed, Ibrahim, Mahmoud, Morsy, Mohamed Reda Loaloa, Ahmed, Refaat, Hadeer, Samir, Fatma, Shahien, Mohamed, Sobhy, Fathy, Sroor, Esraa, Abdellatif, Marina, Adel, Amr Abdelghani Afifi, Eman, Afifi, Marco, Antaky, Amr, Dawoud, Naira El Zoghby, Amira, El-Remaily, Ali Abdelazez Elzanfaly, Ahmed, Gadallah, Fatma Alzahraa Gamal, Omar, Hashem, Shrouk Medhat Youssef, Aliaa Muhammad Attyah, Malak, Munir, Omar, Shazly, Esraa, Taha, Karim, Wilson, Sawsan, Adel, Asmaa, Ali, Esraa, Eid, Esraa, Elhelow, Marwa, Elmahdy, Bassant, Elshatby, Amany Hossam El-Din Zakaria, Ahmad, Hossny, Eman, Ibrahim, Ahmed, M Yonis, Maram, Metwalli, Basant, Yousry, Esraa, Zid, Mina, A Yacoub, Ahmed, Abdelhakim, Nervana, Abouelsoad, Mo'Min, Alkhatib, Ahmed, Ashraf, Alaa, Ashraf, Yasmin, Elazab, Mahmoud, Elfanty, Osama, Elkabir, Mai, Elsayed, Ahmed, Elshimy, Hager, Elsobky, John, Eskander, Ahmed, Gad, Ward, Hamsho, Noura Khaled Abdelwahed, Menna, Magdy, Dalia, Moharam, Abeer, Osama, Shereen, Ramadan, Radwa, Roum, Taqwa, Sayed, Tarneem, Shehada, Ahmed Mohy Zidan, Khalid, Abbas, Amr, Ali, Mohamed, Attia, Mohamed, Balata, Ayman El Nakeeb, Mohamed Ibrahim Elsayed Elewaily, Ahmed, Elfallal, Hossam, Elfeki, Ahmed, Elkhadragy, Sameh, Emile, Helmy, Ezzat, Hasnaa, Hosni, Islam, Mansour, Waleed, Omar, Gehad, Othman, Kareem, Sadek, Mostafa, Shalaby, Noura, Shehab-Eldeen, Rawda Anas Khalifa, Helmy, Badr, Mostafa, Eldeep, Ahmed, Eldeep, Amany Eldoseuky Mohammed, Salwa, Khallaf, Eman Magdy Hegazy, Rokia, Mahmoud, Pola, Mikhail, Mahmoud, Morsi, Sara, Mowafy, Dina, Raafat, Amina, Safy, Marwa, Sera, Ahmed Shible Sera, Mostafa Salim Mohamed AbdAllah, Muhammad, Abdelkader, Abdulrahman Osama Abdou, Ahmedgaber, Ahmed, Shireen, Gaafar, Fatma Ibrahim Negm, Mina, Lapic, Ahmed, Maher, Hagar, Mahmoud, Ahmed, Mostafa, Mohamed, Samir, Fatma, Samy, Nourhan, Semeda, Hind, I Shalaby, Alaa, El-Taweel, Ahmed Galal Elnagar, Ahmed Gamal Hemidan, Mohamed, Hussein, Ahmed, A Kandil, Moawad, Mf, Ayat Allah Nasser Hamamah, Mostafa, 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Hompes, Marianne Kalff, Merel Elisabeth Stellingwerf, Pieter Tanis, Mark van Berge Henegouwen, Elise Maria van Praag, Daan Wisselink, Michael Gerhards, Josephine Lopes Cardozo, Emma Westerduin, Joske de Jonge, Aaw van Geloven, Kaz van Schilt, Frank den Boer, Simone Stoots, Stijn Vlek, Jamie Adams, Ibrahim S Al-Busaidi, Gabrielle Budd, Seung Il Choi, Michael Jen Jie Chu, Anurag Ganugapati, Lucy McKinstry, Rebecca Pascoe, Simon Richards, Kenrick Rosser, Annie Stevenson, Rebecca White, Shebani Farik, Jin Kwun, Ahmed Murad, Sarah Cowan, Timothy Hall, Michael Hayton, Laminou Malam Sani, Souleymane Oumarou Garba, Harissou Adamou, Ibrahim Amadou Magagi, Oumarou Habou, Halima Aliyu, Muhammad Daniyan, Tunde T Sholadoye, Lawal Abdullahi, Lofty-John Anyanwu, Aminu Mohammad Mohammad, Abubakar Bala Muhammad, Abdurrahman Abba Sheshe, Ibrahim Suleiman, Alaba Adesina, Ajibola Awolowo, Clement Onuoha, Omotayo Salami, Ogechukwu Taiwo, Agboola Taiwo, Stephen Kache, Jerry Godfrey Makama, Danjuma Sale, Olajide Abiola, Akinlabi Ajao, Anthony Ajiboye, Amarachukwu Etonyeaku, Julius Olaogun, Ademola Adebanjo, Opeoluwa Adesanya, Michael Olatunji Afolayan, Olanrewaju Balogun, Ayomide Makanjuola, Samuel Nwokocha, Rufus Wale Ojewola, Thomas Olagboyega Olajide, Adewale Aderounmu, Abdul-Rashid Adesunkanmi, Adewale Adisa, Augustine Agbakwuru, Adeleke Akeem Aderogba, Olusegun Isaac Alatise, Olukayode Arowolo, Oladejo Lawal, Tajudeen Mohammed, Chinedu Ndegbu, Olalekan Olasehinde, Funmilola Wuraola, Akinbolaji Akinkuolie, Amarachukwu Etonyeaku, Arinzechukwu Mosanya, Omobolaji Ayandipo, Peter Elemile, Taiwo Akeem Lawal, Samuel Ali Sani, Stephen Garba, Rebecca Hauwa Sani, Samson Olori, Henry Onyebuashi, Ifeanyi Umoke, Adedire Adenuga, Ademola Adeyeye, Olufemi Habeeb, Bashir Lawal, Abdulrasheed Nasir, Eirik Kjus Aahlin, Didrik Kjønås, Elisabeth Myrseth, Jibran Abbasy, Abdul Alvi, Omair Saleem, Asma Afzal, Anam Nazir, Muhammad Farooq, Ayesha Liaqat, Syed Asghar Naqi, Ali Raza, Muzna Sarfraz, Muhammad Sarwar, Muntaha Banglani, Ambreen Munir, Rahmat Sehrish, Bushra Ayub, Raza Sayyed, Amna Altaf, Saima Ayub, Ahmad Uzair Qureshi, Komal Saeed, Bilal Syed, Sana Amir Akbar, Abdul Wahid Anwer, Ruqayya Naheed Khan, Amina Iqbal Khan, Shahid Khattak, Sameen Mohtasham, Muhammad Asad Parvaiz, Aamir Ali Syed, Abdul Basit Ansari, Noman Shahzad, Tanwir Khaliq, Isbah Rashid, Shahzad Hussain Waqar, Hasan Abu Al-Saleem, Amjad Abu Alqumboz, Mohammad Alqadi, Adham Amro, Rawan Assa, Eman Awesat, Rawan Ayyad, Mohammed Hammad, Ayat Haymony, Bassel Hijazi, Bara Hmeidat, Rowaa Lahaseh, Aseel Qawasmi, Alaa Rajabi, Mohammed Shehada, Sundus Shkokani, Yasmine Yaghi, Nadine Yaghi, Mohammad AlZohour, Mohammad Farid, Yousef Mahmoud Habes, Wesam Juba, Yanal Nubani, Abdelrahman Rabee, Mohammad Sa'deh, Saeed Abed, Iyad Al Basos, Mohammad Alswerki, Dina Ashour, Israa Awad, Samar Diab, Alaa El Jamassi, Sahar El-Kahlout, Somaya Elhout, Ahmed N K Hajjaj, Doaa Hasanain, Baraa Nabil Hajjaj, Mohammed Obaid, Eman Saikaly, Ahmed Salhi, Hiba Al-Tammam, Murad Almasri, Muath Baniowda, Doha Beshtawi, Ali Horoub, Rami Misk, Bayan Mohammad, Rami Qasrawi, Tasnim Sholi, Samar Abu-Nimeh, Abrar Abu-Srour, Sadi A Abukhalaf, Samer Adawi, Barah Alsalameh, Kholoud Ayesh, Muawiyah Elqadi, Ahmad Hammouri, Fatima Karim Mustafa, Natalie Marzouqa, Shatha Melhem, Dima Miqdad, Balqees Mohamad, Mhammed Rawhi, Ayman B Abu Ahammala, Ahmed Abu Ataya, Israa Abu Jayyab, Samar Al-Shwaikh, Othman Alagha, Mohammed Alasttal, Haneen Awadallah, Mahmood Elblbessy, Jehad Fares, Akram Jarbou, Ibtisam Mahfouz, Moath A Albahnasawi, Asmaa' Abo Mahadi, Hasan Abuelhatal, Ayham Abuelqomboz, Abdelrahman Almoqayyad, Abdallah Alwali, Reem Balaawi, Mahmoud Hamouda, Mohammed Humeid, Abdullah Jedyan, Tasneem Mahmoud Abu Hamam, Ghadeer Matar, Ali Salem, Tahani Samra, Nureddin Shaheen, Karam Shihada, Ayoob A Nemer, Mahmoud Abu Al Amrain, Abdulwhhab Abu Alamrain, Najlaa Abu Jamie, Mohammed R Abu-Rous, Nada Alfarra, Mohammed AlTaweel, Noor Alwhaidi, Ramadan Hamed, Bader Saqqa, Ahmad Shaheen, Dana Aljaber, Loay Aljaberi, Malak Alwaheidi, Assef Jawaada, Hani Khaldi, Rami Qahoush, Jalil Qari, Rana Saadeh, Ahlam Salim, Aseel Yacoub, Abbas Abbas, Rana Abu Shua'ib, Baraa Abu Zainah, Mahmoud AbuSirrees, Basheer Babaa, Ola Barhoush, Asef Belal Qadomi, Laith Daraghmeh, Reema Haji, Alaa Khatatbeh, Lana Khatib, Salsabeel Qarariah, Yara Quzmar, Khalil Safadi, Roqaya Salameh, Mohammad Hassan, Shifaa Herzallah, Loai Massad, Ahmed Nazzal, Ranin Nazzal, Dennis Escobar, Gustavo Miguel Machain V, Agustin Rodriguez Gonzalez, Jorge Emerson Chachaima Mar, Nathaly Olga Chinchihualpa Paredes, Vicente Cuba, Walter Lopez, Maria Milagros Niquen Jimenez, Nestor Alberto Sanchez Bartra, Olenka Sapallanay Ojeda, Diego Sequeiros, Andrea Toscano Pacheco, María Vergara, Sol Abarca, Rodrigo Alcorta, Giuliano Borda-Luque, Ivan Edward Eusebio Zegarra, Claudia Luján López, Mirella Marrufo, Cinthya Mogrovejo, Andrea Nomura, Yamile Rodríguez Angeles, Maitza Rosario 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B., Shahzad, N., Khaliq, T., Rashid, I., Waqar, S. H., Abu Al-saleem, H., Abu Alqumboz, A., Alqadi, M., Amro, A., Assa, R., Awesat, E., Ayyad, R., Hammad, M., Haymony, A., Hijazi, B., Hmeidat, B., Lahaseh, R., Qawasmi, A., Rajabi, A., Shehada, M., Shkokani, S., Yaghi, Y., Yaghi, N., Alzohour, M., Farid, M., Habes, Y. M., Juba, W., Nubani, Y., Rabee, A., Sa'Deh, M., Abed, S., Al basos, I., Alswerki, M., Ashour, D., Awad, I., Diab, S., El Jamassi, A., El-Kahlout, S., Elhout, S., Hajjaj, A. N. K., Hasanain, D., Nabil hajjaj, B., Obaid, M., Saikaly, E., Salhi, A., Al-Tammam, H., Almasri, M., Baniowda, M., Beshtawi, D., Horoub, A., Misk, R., Mohammad, B., Qasrawi, R., Sholi, T., Abu-Nimeh, S., Abu-srour, A., Abukhalaf, S. A., Adawi, S., Alsalameh, B., Ayesh, K., Elqadi, M., Hammouri, A., Karim Mustafa, F., Marzouqa, N., Melhem, S., Miqdad, D., Mohamad, B., Rawhi, M., Abu Ahammala, A. 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K., Rencuzogullari, A., Isik, A., Leventoglu, S., Yalcinkaya, A., Yuksel, O., Kalayci, M. U., Kara, Y., Sarici, I. S., Akin, A., Alemdag, G. N., Arslan, E., Baki, B. E., Bodur, M. S., Calik, A., Candas Altinbas, B., Cihanyurdu, I., Erkul, O., Gul, B., Guner, A., Kose, B., Semiz, A., Sevim, Tayar, S., Tomas, K., Tufek, O. Y., Turkyilmaz, S., Ulusahin, M., Usta, A., Yildirim, R., Guler, S. A., Tatar, O. C., Varol, E., Kirimtay, B., Uysal, M., Yildiz, A., Kose, E., Ciftci, A. B., Colak, E., Eraslan, H., Kucuk, G. O., Yemez, K., Lule, H., Bienfait, M., Bua, E., Okalany, N., Basarab, M., Bielosludtsev, O., Kolhanova, K., Perepelytsia, K., Romanukha, K., Savenkov, D., Siryi, S., Tereshchenko, M., Viacheslav, N., Volovetskyi, A., Kebkalo, A., Tryliskyy, Y., Tyselskiy, V., Bruce, E., Chow, B. L., Iddles, E., Mcguckin, S., Newall, N., Ramsay, G., Sharma, P., Stewart, C., Wong, J., Badran, A., Bath, M., Belais, F., Butt, E., Joshi, K., Kapur, M., Shaw, M., Townson, A., Williams, C. Y. K., Gray, T., Greig, R., Husain, M., Murray, E., Mustafa, A., Asif, A., Gokul, A., Shah, M., Akitikori, M. T., Charalabopoulos, A., Davidson, S., Mcnally, S., Rupani, S., Juma, F., Mills, S. C., Muirhead, L., Sellars, K., Walsh, U., Warren, O., Chambers, A., Hunt, R., Boyce, S., Cornwall, H., Tol, I., Argyriou, E. O., Eardley, N., Povey, M., Aithie, J. M. S., Irfan, A., Mcguigan, M. -C., Starr, R., Warren, C. R., Archibald, J., Kirby, G., Kisyov, I., Khoo, C. K., Lee, R., Photiou, D., Davis, R., Prasad, U., Yang, P. Z., Bird, J., Leung, E., Summerour, V., Currow, C., Kiam, J., Tan, G. J. S., Muthusami, A., Pegba-Otemolu, I., Urbonas, T., Nunoo-Mensah, J., Smolskas, E., Boddy, A., Gravante, G., Hunter, D., Andrew, D., Koh, A., Thompson, A., Adams, L., Clements, H. 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S., Mitchell, R., Monaghan, E., Crawford, J., Moug, S., Blackwell, J., Boyd-Carson, H., Herrod, P., Al-Allaf, O., Beattie, M., Bullock, C., Burman, S., Clark, G., Flamey, N., Flannery, O., Harding, A., Kodiatt, B., Lawday, S., Mahapatra, S., Mukundu Nagesh, N., Ng, M., Rye, D., Yoong, A., Clark, L., Deans, C., Edirisooriya, M., Carrington, E. V., Wong, T. L. E., Yusuf, B., Chamberlain, C., Duke, K., Kmiotek, E., Botes, A., Condie, N., Schrire, T., Shah, R., Thomas-Jones, I., Yates, C., Anthony, N., Matthews, E., Sahnan, K., Tankel, J., Tucker, S., Winter Beatty, J., Ziprin, P., Duggan, W., Kantartzi, A., Sridhar, S., Khaw, R. A., Srivastava, P., Underwood, C., Alves do Canto Brum, H., Chopra, S., Davis, L., Hughes, R., Tulley, J., Alberts, J., Athisayaraj, T., Olugbemi, M., Ahmad, K., Chan, C., Chapman, G., Fleming, H., Fox, B., Grewar, J., Hulse, K., Rutherford, D., Sinead, M., Speake, D., Vaughan-Shaw, P. G., Christodoulides, N., Kudhail, S., Welch, M., Husaini, S. M., Lambracos, S., Anyanwu, C., Suresh, R., Thomas, J. S., Gleeson, E., Platoff, R., Saif, A., Enumah, Z., Etchill, E., Gabre-Kidan, A., Bernstein, M., Carrano, F. M., Connors, J., Lynn, P., Melis, M., Newman, E., Foster, D. S., Perrone, K., Titan, A., Ahmad, S., Bafford, A. C. M. D., Dal Molin, M., Hanna, N., Zafar, S. N., Hemmila, M., Napolitano, L., Wong, J. J., Chandler, J., Wood, L., Wren, S., Ottesen, T., You, L., Yu, K., Arcienega Yanez, M. D. P., Ferreira Fernandes, M., Gonzalez, D., Cubas, S., Gonzalez, M. C., Zubiaurre, V., Demolin, R., Giroff, N., Sciuto, P., Campos, M., Rodriguez Cantera, G., Deepika, G., Simuchimba, E., Bulaya, A., Chibuye, C., Chirengendure, B., Kabale, M. -R., Kabongo, K., Munthali, J., Mweso, O., Pikiti, F., Otieno, J., Lai, L. T., Blackman, B., Subramaniam, S., Karim, R., Kok, N., Lee, Y. D., Ali, S., Sinha, A., Corrigan, R., Barnes, N., Wong, F., Dennis, G., Jedamzik, J., Phillips, E., Piette, W., Van hentenryck, M., Koco, H., Lawani, S., Kassa, M. W., Santos Bezerra, T., Gribnev, P., Dimitrov, D., Krastev, P., Oum, S., Bonghaseh, D. T., Al Farsi, M., Alsharqawi, N., Acevedo, V., Castillo Barbosa, A. C., Giron, F., Leon Rodriguez, J. P., Kucan, D., Rosko, D., Barsic, N., Zupan, D., Hegazi, A., Truncikova, V., Fryba, V., Mohamed, M., Nagi, A., Rashad Temerik, A., Elshawy, M. E., Mahmoud, M. I., Anwar, M., Rageh, T., Elmokadem, A., Gaballa, K., Teppo, S., Pengerma, P., Ballouhey, Q., Bergeat, D., Weyl, A., Hain, E., Gyedu, A., Yenli, E., Osei-Poku, D., Rompou, V. -A., Zoikas, A., Gaitanidis, A., Koukis, G., Perivoliotis, K., Tavlas, P., Galanos-Demiris, K., Zografos, G., Karavokyros, I., Xanthopoulou, G., Iordanidou, E., Ayau, F., Garcia, A., Damjan, P., Wason, D., B L, A., Rangganata, E., Kamath, P., O'Connor, D. B., Pinto, M., Perrone, F., Tropeano, F. P., Troilo, F., Bossi, D., Scala, D., Pulitano, L., Carella, M., Pietrabissa, A., Gori, A., Giraudo, G., De Simone, V., Russo, A. A., Braccio, B., Al-Taher, R., Athamneh, S., Parker, A., Sawiee, A., Kattia, A., Tababa, O., Shaeeb, Z., Syminas, V., Jurgaitis, J., Damuleviciene, G., Svagzdys, S., Razafimanjato, N. N. M., Chieng Loo, L., Tiong, I. C., Wan Muhmad, W. F., Vijeyan, H., Li Ying, T., Grech, G., Arrangoiz, R., Jimenez Ley, V. B., Arizpe, D., Lagunes Lara, E., Castro Lopez, E. V., Eaazim, J., Gordinou de Gouberville, M., Bastiaenen, V., Rottier, S., Nahab, F., Ji, M. Y., Seyoji, M., Nwachukwu, C., Emeghara, O., Muhammed, S. E., Idowu, A., Sowemimo, O., Ogundoyin, O., Akande, O., Lott, A., Nadeem, M., Laghari, A. A., Loya, A., Mushtaq, H., Abdullah, M. T., Abuhilal, B., Atawneh, M., Hamdan, H., Alhabil, B., Srour, A., Mousa, I., Da Silva Medina, L., Bartosiak, K., Ferreira, P., Francisco, V., Lemos, R., Frutuoso, L., Fernandes, S., Fonseca, T., Pereira, J., Rachadell, J., Torre, A., Madeira Martins, F., Carvalho, A. C., Rodrigues Ferreira, J., Ribeiro da Silva, B., Devesa, H., Vieira, A., Monica, I., Amaro, M., Sousa, D., Reia, M., Louro, J., Martins, A., Dominguez, J., Santos, I., Freitas Oliveira, N. M., Pereira, J. C., Silva-Vaz, P., Freire, L., Escrevente, R., Negoita, V. M., Shakhmatov, D., Nezerwa, Y., Radulovic, R., Obery, G., Viljoen, F., Mendes, T., Suarez, A., Moncada, E., Fernandez-Hevia, M., Curtis Martinez, C., Gil Garcia, J. M., Gonzalez Zunzarren, M., Idris, T., Eklov, K., Grahn, O., Amin, L., Blomqvist, M., Ajani, C., Kraus, R., Seeger, N., Willemin, M., Rayya, F., Ayash, M., Msouti, R., Kannas, I., Abazid, E., Esper, A., Slim, S., Kavcar, A. S., Aytac, E., Dural, A. C., Ilker, A., Eray, I. C., Kurnaz, E., Altiner, S., Tepe, M. D., Sahin, C., Savli, E., Innocent, A., Babirye, L., Diachenko, A., Hordoskiy, V., Curry, H., Chau, C. Y. C., Robertson, H., Lennon, H., Loi, L., Kirkham, E., Mccann, C., Watts, D., Gurung, B., Wilson, M., Tribedi, T., Garofalo, E., Zahra, B., Macdonald, S., Daniels, I., Ng, N., Khosla, S., Olivier, J., Yue, S. Y. P., Suresh, G., Wellington, J., Lorejo, E., Mossaad, M., Crutcher, M., Alimi, M., Baiu, I., Abdou, H., Conway, A., Peck, C., Perdomo Perez, M. A., Zulu, S., Nakazwe, M., Burger, S., Davies, J., Donaldson, R., Ede, C., Garden, O. J., Lesetedi, C., Mabedi, C., Magill, L., Makinde Alakaloko, F., Makupe, A., Monahan, M., Mulira, S., Muller, E., Musowoyo, J., Olory-Togbe, J. L., Roberts, T., Smith, M., Tayler, V., Windsor, J., Yepez, R., Sundar, S., Runigamugabo, E., Verjee, A., Chen, J., Daya, L., El Aroussi, N., Farina, V., Gnintedeme Olivier, T., Gonzales Nacarino, M., Hammani, A., Honjo, S., Jacobs, R., Kimura, H., Nkoronko, M., Oscullo Yepez, J. J., Pin Hung, W., Raj, A., Romani Pozo, A., Rommaneh, M., Sassamela Fabiano, S. C., Shiroma Gago, C. M., Srinivas, A., Sung, C. -Y., Tai, A., Valle Aranda, Y. C., Venturini, S., Wilguens Lartigue, J., Public and occupational health, AMS - Sports, APH - Health Behaviors & Chronic Diseases, CCA - Cancer Treatment and quality of life, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, and Albarella, Sara

Subjects
global surgery, hospitals, humans, income, neoplasms, postoperative period, poverty, prospective studies, no keywords listed, General Medicine, Prospective Studie, Hospital, Settore MED/18 - Chirurgia Generale, outcome, Hospitals, Humans, Income, Neoplasms, surgery, Postoperative Period, Poverty, Prospective Studies, cancer surgery, Human, hospital facilities
Abstract

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p

Published
2022

37. Recent Improvement in Coronary Computed Tomography Angiography Diagnostic Accuracy

Author

Alani, Anas, Nakanishi, Rine, and Budoff, Matthew J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease - Coronary Heart Disease, Atherosclerosis, Biomedical Imaging, Clinical Research, Heart Disease, Cardiovascular, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Artifacts, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Coronary Circulation, Coronary Vessels, Humans, Myocardial Perfusion Imaging, Percutaneous Coronary Intervention, Predictive Value of Tests, Reproducibility of Results, Severity of Illness Index, Stents, Tomography, X-Ray Computed, Treatment Outcome, Vascular Calcification, Vascular Patency, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Although invasive coronary angiography has been the gold standard for evaluating coronary artery disease (CAD), it should not be routinely performed as an initial test to assess CAD in subjects with suspected CAD by the recent guidelines, due to cost, invasiveness, and measurable risk. Coronary computed tomography angiography (CCTA) is a rapidly growing, noninvasive imaging modality that developed quickly over the last decade, and its role for evaluation of CAD becomes of great promise with high diagnostic accuracy. Although artifact issues have created some challenges for CCTA, recent advances-including the introduction of more detectors, leading to broader coverage, and faster and higher-definition scanners-allow improved precision and fewer uninterpretable studies. This review article summarizes the current key literature regarding the diagnostic accuracy of CCTA in native coronary arteries, stents, coronary artery bypass grafts, lesions with high calcification, and the functional assessment of CAD.

Published
2014

38. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers

Author

Vivek Subbiah, Robert J. Kreitman, Zev A. Wainberg, Anas Gazzah, Ulrik Lassen, Alexander Stein, Patrick Y. Wen, Sascha Dietrich, Maja J. A. de Jonge, Jean-Yves Blay, Antoine Italiano, Kan Yonemori, Daniel C. Cho, Filip Y. F. L. de Vos, Philippe Moreau, Elena Elez Fernandez, Jan H. M. Schellens, Christoph C. Zielinski, Suman Redhu, Aislyn Boran, Vanessa Q. Passos, Palanichamy Ilankumaran, Yung-Jue Bang, Institut Català de la Salut, [Subbiah V] Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. [Kreitman RJ] Laboratory of Molecular Biology, National Institutes of Health, Bethesda, MD, USA. [Wainberg ZA] Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. [Gazzah A] Drug Development Department (DITEP), Gustave Roussy Cancer Institute, Villejuif, France. [Lassen U] Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. [Stein A] Department of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [Elez Fernandez E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, and Medical Oncology

Subjects
Proto-Oncogene Proteins B-raf, Pyridones, Clinical Trials and Supportive Activities, Immunology, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Pyrimidinones, Adenocarcinoma, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Medical and Health Sciences, Quimioteràpia combinada, General Biochemistry, Genetics and Molecular Biology, neoplasias [ENFERMEDADES], Rare Diseases, SDG 3 - Good Health and Well-being, Clinical Research, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Antineoplastic Combined Chemotherapy Protocols, Humans, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], Cancer, Càncer - Tractament, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Imidazoles, Evaluation of treatments and therapeutic interventions, General Medicine, Glioma, Hematology, Brain Disorders, Neoplasms [DISEASES], Brain Cancer, Anomalies cromosòmiques, 6.1 Pharmaceuticals, Mutation, Digestive Diseases
Abstract

BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110.

Published
2023

39. Effect of caloric intake and macronutrient composition on intestinal cholesterol absorption and bile acids in patients with obesity

Author

Anas Mohamad Hashem, Lizeth Cifuentes, Gerardo Calderon, Maria Laura Ricardo-Silgado, Daniel Gonzalez-Izundegui, Alejandro Campos, Alison McRae, Shawna Franks, Maria Daniela Hurtado, Duane Burton, Xuan-Mai Petterson, Ian R. Lanza, Michael Camilleri, and Andres Acosta

Subjects
Bile Acids and Salts, Cholesterol, Hepatology, Intestinal Absorption, Physiology, Physiology (medical), Gastroenterology, Humans, Nutrients, Obesity, Energy Intake, Diet, Fat-Restricted
Abstract

Obesity is associated with alterations in cholesterol and bile acid (BA) metabolism. However, the interaction among dietary intake, cholesterol absorption, and BA metabolism in patients with obesity remains unclear. We conducted a 4-wk nutritional intervention nonrandomized clinical trial with three different sequential diets for a week in the following order: regular diet (RD); high calorie, high-fat diet (HCHF), washout period on RD; and low-calorie, low-fat diet (LCLF). We provided participants with meal replacements during HCHF and LCLF diets. A total of 16 participants completed the study [

Published
2023

40. Cardiovascular Complications During Delivery Admissions Associated With Assisted Reproductive Technology (from a National Inpatient Sample Analysis 2008 to 2019)

Author

Salman Zahid, Anas Hashem, Anum S. Minhas, Colleen M. Harrington, Odayme Quesada, Niti R. Aggarwal, Chrisandra L. Shufelt, Valerie L. Baker, and Erin D. Michos

Subjects
Hospitalization, Heart Failure, Inpatients, Pre-Eclampsia, Reproductive Techniques, Assisted, Pregnancy, Humans, Female, Cardiology and Cardiovascular Medicine
Abstract

Women who conceive through assisted reproductive technology (ART) have a known increased risk of obstetric complications. However, whether ART is also associated with higher risk of developing cardiovascular complications during delivery admissions has not been well established. We used data from the National Inpatient Sample (2008 to 2019) and used the International Classification of Diseases codes to identify delivery hospitalizations and ART procedures. A total of 45,867,086 weighted delivery cases were identified, of which 0.24% were among women who conceived through ART (n = 108,542). Women with an ART history were older at the time of delivery (median 35 vs 28 years, p0.01) and had a higher prevalence of hypertension, gestational diabetes, and dyslipidemia (all, p0.01). After adjustment for age, race/ethnicity, co-morbidities, multiple gestation, insurance, and income, ART remained an independent predictor of peripartum cardiovascular complications, including pre-eclampsia/eclampsia (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.45 to 1.51), heart failure (aOR 1.94, 95% CI 1.10 to 3.40), and cardiac arrhythmias (aOR 1.39, 95% CI 1.30 to 1.48), compared with natural conception. Likewise, the risk of acute kidney injury (aOR 2.57, 95% CI 2.25 to 2.92), ischemic stroke (aOR 1.73, 95% CI 1.24 to 2.43), hemorrhagic stroke (aOR 1.63, 95% CI 1.27 to 2.11), pulmonary edema (aOR 2.29, 95% CI 2.02 to 2.61), and venous thromboembolism (aOR 1.92, 95% CI 1.63 to 2.25) were higher with ART. However, odds of developing peripartum cardiomyopathy or acute coronary syndrome were not associated with ART. Length of stay (3 vs 2 days, p0.01) and cost of hospitalization ($5,903 vs $3,922, p0.01) were higher for deliveries among women with a history of ART. In conclusion, women who conceived with ART had higher risk of pre-eclampsia, heart failure, arrhythmias, stroke, and other complications during their delivery hospitalizations. This may, in part, contribute to their increased resource utilization seen.

Published
2023

41. Palliative Inotropes in Advanced Heart Failure: Comparing Outcomes Between Milrinone and Dobutamine

Author

FARHAD SAMI, PRAKASH ACHARYA, GRACE NOONAN, STEVEN MAURIDES, ANAS ABUDAN AL-MASRY, SUHAIB BAJWA, NIKHIL PARIMI, ILHAM BODA, CHRISTINA TRAN, AMANDEEP GOYAL, IOANNIS MASTORIS, TARUN DALIA, ANDREW SAUER, ADRIAN VAN BAKEL, and ZUBAIR SHAH

Subjects
Adult, Heart Failure, Cardiotonic Agents, Dobutamine, Adrenergic beta-Antagonists, Humans, Cardiology and Cardiovascular Medicine, Milrinone, Retrospective Studies
Abstract

We sought to describe and compare outcomes among advanced patients with heart failure (not candidates for orthotopic heart transplant/left ventricular assist device) on long-term milrinone or dobutamine, which are not well-studied in the contemporary era.We included adults with refractory stage D heart failure who were not candidates for orthotopic heart transplant or left ventricular assist device and discharged on palliative dobutamine or milrinone. The primary outcome was 1-year survival. A 6-month predictor of survival analysis was conducted. A total of 248 patients (133 on milrinone, 115 on dobutamine) were included. There were no differences in baseline comorbidities between milrinone and dobutamine cohorts, except for the prevalence of chronic kidney disease, which was higher in the dobutamine group. On discharge, the proportion of patients on beta-blockers and mineralocorticoid antagonists was higher in milrinone group. Overall, the 1-year mortality rate was 70%. The dobutamine cohort had a significantly higher 1-year mortality rate (84% vs 58%, P0.001). The type of inotrope did not predict survival at 6 months when adjusted for discharge medications and comorbidities. Beta-blockers and angiotensin-converting enzyme/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor continued at discharge predicted survival at 6 months.The 1-year mortality from palliative inotropes remains high. Compared with dobutamine, use of milrinone was associated with improved survival owing to better optimization of guideline-directed medical therapy, primarily beta-blocker therapy.

Published
2022

42. Functionalized-DNA nanostructures as potential targeted drug delivery systems for cancer therapy

Author

Ajay Kumar, Anas Ahmad, Md Meraj Ansari, Vemana Gowd, Summya Rashid, Anis Ahmad Chaudhary, Hassan Ahmed Rudayni, Sulaiman A. Alsalamah, and Rehan khan

Subjects
Cancer Research, Drug Delivery Systems, Neoplasms, Humans, Nanotechnology, DNA, Nanostructures
Abstract

Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy.

Published
2022

43. Effect of Novel Programming on Inappropriate Implantable Cardioverter-Defibrillator Therapy in Patients With Very Low Ejection Fraction (from A MADIT-RIT)

Author

Anas, Jawaid, Moulin, Chokshi, Wojciech, Zareba, Claudio, Schuger, James, Daubert, Scott, McNitt, Jagmeet, Singh, Ilan, Goldenberg, and Valentina, Kutyifa

Subjects
Risk Factors, Electric Countershock, Tachycardia, Ventricular, Humans, Equipment Failure, Stroke Volume, Cardiology and Cardiovascular Medicine, Ventricular Function, Left, Defibrillators, Implantable
Abstract

The Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy showed a significant reduction in the risk of inappropriate therapy in patients with a programmed high-rate cutoff ≥200 beats per minute or delayed therapy for events ≥170 beats per minute compared with conventional programming. We aimed to characterize outcomes by left ventricular ejection fraction (LVEF) ranges for patients with high-rate, delayed, or conventional implantable cardioverter-defibrillator programming. We assessed the effect of LVEF (LVEFlt;15%, LVEF 15% to 25%, LVEFgt;25%) on the risk of inappropriate conventional implantable cardioverter-defibrillator therapy and death in Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy. Inappropriate therapies and death were independently evaluated by the adjudication committee. Statistical methods involved Kaplan-Meier time-to-event graphs and Cox proportional hazards regression analyses. The study involved 140 patients (9%) with LVEF 15%, 585 with LVEF 15% to 25% (39%), and 774 with LVEFgt;25% (52%). High-rate or delayed programming significantly reduced the risk of inappropriate therapy compared with conventional programming in patients with all LVEFs (plt;0.001 for all LVEF). Patients with LVEFlt;15% had an exceptional 97% lower risk of inappropriate therapy, with high-rate programming than conventional programming (hazard ratio 0.028, p = 0.001), without an increase in mortality. High-rate and delayed programming is superior to conventional programming in all LVEF ranges, without adverse effects.

Published
2022

44. Effects of COVID‐19 pandemic on anatomy education of medical and dental students of Pakistan; a reality check

Author

Amber, Salman, Anas Sarwar, Qureshi, Zaima, Umar, Momna, Riaz, Muhamad, Usman, Saba, Zulfiqar, Uzma, Ali, and Humaima, Saeed

Subjects
Students, Medical, Communicable Disease Control, Students, Dental, Humans, COVID-19, Pakistan, Radiology, Nuclear Medicine and imaging, Surgery, Anatomy, Pandemics, Education, Medical, Undergraduate, Pathology and Forensic Medicine
Abstract

Virtual anatomy education was the only way that supported the learning process of the students during the forced lockdown time of COVID-19 pandemic. The intention of the current study was to apprehend the expected challenges experienced by the medical and dental students during their cyber anatomy classes.This study was carried on 300 1st and 2nd year medical and dental students who joined their respective college in January 2020, and consented to participate in the study. A multiple choice questionnaire regarding their stance about these online classes was formed and student's feedback was taken.Most (80%) of the students longed for their traditional anatomy learning i.e., dissection courses, didactic lectures, interaction and motivation from their mentors and peer. The students blamed the learning without live dissections, models and microscopic slides for their lack of confidence. More than 80% students blamed inappropriate gadgets, absence of high-band internet connections, as possible barriers in their digital learning. Lack of self-motivation was considered by 66% students.This situation of anatomy education while lockdown was not intentional and should not be taken as the silver bullet solution for a subject like anatomy. Although students had to face a lot of challenges but this shift to online mode went swiftly at the time of health crisis. This digital learning may extend for an indefinite period, the students' feedback will be helpful in bringing appropriate and timely modifications in digital anatomy education.

Published
2022

45. Is fundus first laparoscopic cholecystectomy a better option than conventional laparoscopic cholecystectomy for difficult cholecystectomy? A systematic review and meta-analysis

Author

Ibrahım Umar Garzali, Anas Aburumman, Yousef Alsardia, Belal Alabdallat, Saad Wraikat, and Ali Aloun

Subjects
Adult, Male, Cholecystectomy, Laparoscopic, Humans, Cholecystectomy, Surgery, Prospective Studies, Gallstones, Retrospective Studies
Abstract

The gallstone disease prevalence is up to 27% in the general adult population. Though most of the patients are asymptomatic, about 1-4% of these patients became symptomatic every year and will require treatment. Fundus first laparoscopic cholecystectomy (FFLC) was first reported by Cooperman in 1990 when he utilized the approach to safely perform LC for patients with acute cholecystitis and dense adhesion around the calot's triangle which precluded safe dissection. Some surgeons reported that the FFLC may be quicker than the traditional dissection starting at the Calot's triangle, although no randomized trial has been undertaken to confirm that. We aim to perform this systematic review and meta-analysis to compare outcome of fundal first laparoscopic cholecystectomy with conventional laparoscopic cholecystectomy. Three reviewers independently searched the Pubmed, medline, google schoolar, Cochrane library and Embase databases for prospective or retrospective articles comparing outcomes of fundus first LC and conventional LC. The search terms were "retrograde cholecystectomy", "antegrade cholecystectomy", "fundus first cholecystectomy", "fundus down cholecystectomy", and "dome down cholecystectomy". Studies were selected based on predetermined criteria and data were extracted from the study for meta-analysis. Twelve studies were included for meta-analysis. Our analysis revealed that FFLC is associated with less conversion to open surgery, less time of surgery, less risk of bile duct injuries and shorter duration of hospital stay compared conventional cholecystectomy in patients with difficult cholecystectomy. In conclusion, fundus first laparoscopic cholecystectomy is a safer alternative to conventional laparoscopic cholecystectomy in patients with difficult cholecystectomy.

Published
2022

46. Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients <60 Years of Age

Author

Mohamed M, Gad, Islam Y, Elgendy, Anas M, Saad, Ahmed N, Mahmoud, Toshiaki, Isogai, Johnny, Chahine, Amer N, Kadri, Ravi, Ghanta, Ernesto, Jimenez, Samir R, Kapadia, and Hani, Jneid

Subjects
Heart Valve Prosthesis Implantation, Male, Transcatheter Aortic Valve Replacement, Postoperative Complications, Treatment Outcome, Risk Factors, Aortic Valve, Humans, Female, Aortic Valve Stenosis, Hospital Mortality, General Medicine, Cardiology and Cardiovascular Medicine
Abstract

Transcatheter aortic valve replacement (TAVR) is an alternative therapeutic modality to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS). In the current analysis, we compare the characteristics and outcomes of AVR procedures in patients60 years of age.We queried the Nationwide Readmissions Database for all AVR hospitalizations in patients 18-59 years of age between January 2012 and December 2017. We performed a propensity score matching analysis (1:1) and compared baseline characteristics, procedural complications, and outcomes between TAVR and SAVR patients.A total of 72,356 hospitalizations for AVR were identified in patients60 years of age. Compared to their SAVR counterparts, TAVR patients were older (52.5 ± 7.6) vs. 48.8 ± 9.6, p0.001), more likely to be women (37.9% vs. 28.0%, p0.001), and have history of prior radiation (8.3% vs. 0.7%, p0.001). After propensity score matching, TAVR patients had lower procedural complications, but a similar mortality rate compared to SAVR patients (2.9% vs. 3.0%, p = 0.77). TAVR was associated with a shorter length of hospital stay [4 [2-9] vs. 6 [5-11], p0.001), but no significant difference in the 30-day readmission rate was noted (16.2% vs. 16.8%, p-value = 0.49).Our study demonstrates favorable short-term outcomes in younger patients undergoing TAVR, which improved over time. Further investigation of long-term outcomes in TAVR performed younger patients is warranted to draw a comprehensive picture of TAVR safety and efficacy in low-risk patients.

Published
2022

47. Structure-guided design and development of cyclin-dependent kinase 4/6 inhibitors: A review on therapeutic implications

Author

Mohd. Yousuf, Manzar Alam, Anas Shamsi, Parvez Khan, Gulam Mustafa Hasan, Qazi M. Rizwanul Haque, and Md. Imtaiyaz Hassan

Subjects
Structural Biology, Neoplasms, Cell Cycle, Cyclin-Dependent Kinase 4, Humans, Antineoplastic Agents, Cyclin-Dependent Kinase 6, General Medicine, Protein Kinase Inhibitors, Molecular Biology, Biochemistry
Abstract

Cyclin-dependent kinase 6 (EC 2.7.11.22) play significant roles in numerous biological processes and triggers cell cycle events. CDK6 controlled the transcriptional regulation. A dysregulated function of CDK6 is linked with the development of progression of multiple tumor types. Thus, it is considered as an effective drug target for cancer therapy. Based on the direct roles of CDK4/6 in tumor development, numerous inhibitors developed as promising anti-cancer agents. CDK4/6 inhibitors regulate the G1 to S transition by preventing Rb phosphorylation and E2F liberation, showing potent anti-cancer activity in several tumors, including HR+/HER2- breast cancer. CDK4/6 inhibitors such as abemaciclib, palbociclib, and ribociclib, control cell cycle, provoke cell senescence, and induces tumor cell disturbance in pre-clinical studies. Here, we discuss the roles of CDK6 in cancer along with the present status of CDK4/6 inhibitors in cancer therapy. We further discussed, how structural features of CDK4/6 could be implicated in the design and development of potential anti-cancer agents. In addition, the therapeutic potential and limitations of available CDK4/6 inhibitors are described in detail. Recent pre-clinical and clinical information for CDK4/6 inhibitors are highlighted. In addition, combination of CDK4/6 inhibitors with other drugs for the therapeutic management of cancer are discussed.

Published
2022

48. Two‐year outcomes after transcatheter aortic valve‐in‐valve implantation in degenerated surgical valves

Author

Abdelrahman I. Abushouk, Omar Abdelfattah, Mohamed M. Gad, Anas Saad, Essa Hariri, Toshiaki Isogai, Shashank Shekhar, Grant W. Reed, Rishi Puri, James Yun, Patrick R. Vargo, Aaron J. Weiss, Daniel Burns, Shinya Unai, Zoran Popovic, Serge C. Harb, Amar Krishnaswamy, Lars G. Svensson, Douglas R. Johnston, and Samir R. Kapadia

Subjects
Male, Bioprosthesis, Reoperation, Heart Valve Prosthesis Implantation, Aortic Valve Stenosis, General Medicine, Prosthesis Failure, Transcatheter Aortic Valve Replacement, Treatment Outcome, Aortic Valve, Heart Valve Prosthesis, Humans, Female, Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine, Aged
Abstract

Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has emerged in recent years as a safe alternative to redo surgery in high-risk patients. Although early results are encouraging, data beyond short-term outcomes are lacking. Herein, we aimed to assess the 2-year outcomes after ViV-TAVI.Patients undergoing ViV-TAVI for degenerated surgical valves between 2013 and 2019 at the Cleveland Clinic were reviewed. The coprimary endpoints were all-cause mortality and congestive heart failure (CHF) hospitalizations. We used time-to-event analyses to assess the primary outcomes. Further, we measured the changes in transvalvular gradients and the incidence of structural valve deterioration (SVD).One hundred and eighty-eight patients were studied (mean age = 76 years; 65% males). At 2 years of follow-up, all-cause mortality and CHF hospitalizations occurred in 15 (8%) and 28 (14.9%) patients, respectively. On multivariable analysis, the postprocedural length of stay was a significant predictor for both all-cause mortality (hazard ratio [HR] = 1.1; 95% confidence interval [CI]: 1.01, 1.19) and CHF hospitalization (HR = 1.16; 95% CI: 1.07, 1.27). However, the internal diameter of the surgical valve was not associated with significant differences in both primary endpoints. For hemodynamic outcomes, nine patients (4.8%) developed SVD. The mean and peak transvalvular pressure gradients remained stable over the follow-up period.ViV-TAVI for degenerated surgical valves was associated with favorable 2-year clinical and hemodynamic outcomes. Further studies are needed to better understand the role of ViV-TAVI as a treatment option in the life management of aortic valve disease.

Published
2022

49. Epigenetic gene alterations in metastatic solid tumours: results from the prospective precision medicine MOSCATO and MATCH-R trials

Author

Patricia, Martin-Romano, Leo, Colmet-Daage, Daphne, Morel, Capucine, Baldini, Loic, Verlingue, Rastilav, Bahleda, Anas, Gazzah, Stephan, Champiat, Andree, Varga, Jean Marie, Michot, Maud, Ngo-Camus, Claudio, Nicotra, Aurelien, Marabelle, Jean Charles, Soria, Etienne, Rouleau, Ludovic, Lacroix, Antoine, Hollebecque, Christophe, Massard, and Sophie, Postel-Vinay

Subjects
Cancer Research, Oncology, Neoplasms, Mutation, Exome Sequencing, Biomarkers, Tumor, Humans, Precision Medicine, Epigenesis, Genetic
Abstract

Although the role of epigenetic alterations in oncogenesis has been well studied, their prevalence in metastatic solid tumours is still poorly described. We therefore aimed at: (i) describing the presence of epigenetic gene alterations (EGA) - defined by an alteration in a gene encoding an epigenetic regulator; and (ii) evaluating their relationship with clinical characteristics and outcome in patients (pts) included in prospective molecular profiling trials.On-purpose tumour biopsies from pts with metastatic solid tumours enrolled in the Gustave Roussy-sponsored MOSCATO (NCT01566019) and MATCHR (NCT02517892) trials were molecularly profiled using whole exome sequencing (WES). Alterations in 176 epigenetic genes were assessed and classified as pathogenic variants (PV) or non-pathogenic variants by a molecular tumour board. Clinical characteristics and outcome were collected.Between Dec 2011 and Oct 2016, WES was successfully performed in 292 pts presenting various solid tumours. We found 496 epigenetic gene alterations in 134 patients (49%), including 237 pathogenic variants in 86 patients; 63 tumour samples (47%) presented ≥3 EGAs. The median number of previous treatment lines was 3 (1-10). The most frequently altered genes were KMT2D and KMT2C (16% each), ARID1A and SETD2 (10% each) and KMT2A (8%).; 31% of EGA co-occurred with a driver gene alteration (p amp;lt; 0.001). Outcome was not correlated with the presence of EGA.Epigenetic alterations occur frequently in metastatic solid tumours. With the current development of epigenetic modifiers, they increasingly represent actionable targets. Such genes should now be systematically analysed in molecular profiling studies.

Published
2022

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