tbuckley/cabot-search huggingface dataset:
Black-White Differences in Incident Fatal, Nonfatal, and Total Coronary Heart Disease
Authors: Lisandro D. Colantonio, Christopher M. Gamboa, Joshua S. Richman, Emily B. Levitan, Elsayed Z. Soliman, George Howard, Monika M. Safford
Journal: Circulation (2017)

Blacks have higher coronary heart disease (CHD) mortality compared with whites. However, a previous study suggests that nonfatal CHD risk may be lower for black versus white men.We compared fatal and nonfatal CHD incidence and CHD case-fatality among blacks and whites in the Atherosclerosis Risk in Communities study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS) by sex. Participants 45 to 64 years of age in ARIC (men=6479, women=8488) and REGARDS (men=5296, women=7822), and ≥65 years of age in CHS (men=1836, women=2790) and REGARDS (men=3381, women=4112), all without a history of CHD, were analyzed. Fatal and nonfatal CHD incidence was assessed from baseline (ARIC=1987-1989, CHS=1989-1990, REGARDS=2003-2007) through up to 11 years of follow-up.Age-adjusted hazard ratios comparing black versus white men 45 to 64 years of age in ARIC and REGARDS were 2.09 (95% confidence interval, 1.42-3.06) and 2.11 (1.32-3.38), respectively, for fatal CHD, and 0.82 (0.64-1.05) and 0.94 (0.69-1.28), respectively, for nonfatal CHD. After adjustment for social determinants of health and cardiovascular risk factors, hazard ratios in ARIC and REGARDS were 1.19 (95% confidence interval, 0.74-1.92) and 1.09 (0.62-1.93), respectively, for fatal CHD, and 0.64 (0.47-0.86) and 0.67 (0.48-0.95), respectively, for nonfatal CHD. Similar patterns were present among men ≥65 years of age in CHS and REGARDS. Among women 45 to 64 years of age in ARIC and REGARDS, age-adjusted hazard ratios comparing blacks versus whites were 2.61 (95% confidence interval, 1.57-4.34) and 1.79 (1.06-3.03), respectively, for fatal CHD, and 1.47 (1.13-1.91) and 1.29 (0.91-1.83), respectively, for nonfatal CHD. After multivariable adjustment, hazard ratios in ARIC and REGARDS were 0.67 (95% confidence interval, 0.36-1.24) and 1.00 (0.54-1.85), respectively, for fatal CHD, and 0.70 (0.51-0.97) and 0.70 (0.46-1.06), respectively, for nonfatal CHD. Racial differences in CHD incidence were attenuated among older women. CHD case fatality was higher among black versus white men and women, and the difference remained similar after multivariable adjustment.After accounting for social determinants of health and risk factors, black men and women have similar risk for fatal CHD compared with white men and women, respectively. However, the risk for nonfatal CHD is consistently lower for black versus white men and women.
An Outbreak of Synthetic Cannabinoid–Associated Coagulopathy in Illinois
Authors: Amar H. Kelkar, Nichole A. Smith, Annia Martial, Harsha Moole, Michael D. Tarantino, Jonathan C. Roberts
Journal: New England Journal of Medicine (2018)

In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant.We reviewed physician-reported data from patients admitted to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April 21, 2018, and included in a case series adult patients who met the criteria used to diagnose synthetic cannabinoid-associated coagulopathy. A confirmatory anticoagulant poisoning panel was ordered at the discretion of the treating physician.A total of 34 patients were identified as having synthetic cannabinoid-associated coagulopathy during 45 hospitalizations. Confirmatory anticoagulant testing was performed in 15 of the 34 patients, and superwarfarin poisoning was confirmed in the 15 patients tested. Anticoagulant tests were positive for brodifacoum in 15 patients (100%), difenacoum in 5 (33%), bromadiolone in 2 (13%), and warfarin in 1 (7%). Common symptoms at presentation included gross hematuria in 19 patients (56%) and abdominal pain in 16 (47%). Computed tomography was performed to evaluate abdominal pain and revealed renal abnormalities in 12 patients. Vitamin K1 (phytonadione) was administered orally in all 34 patients and was also administered intravenously in 23 (68%). Red-cell transfusion was performed in 5 patients (15%), and fresh-frozen plasma infusion in 19 (56%). Four-factor prothrombin complex concentrate was used in 1 patient. One patient died from complications of spontaneous intracranial hemorrhage.Our data indicate that superwarfarin adulterants of synthetic cannabinoids can lead to clinically significant coagulopathy. In our series, in most of the cases in which the patient presented with bleeding diathesis, symptoms were controlled with the use of vitamin K1 replacement therapy. The specific synthetic cannabinoid compounds are not known.
Abstract 11032: Impact of Obesity on Grading of Aortic Stenosis (a SEAS Substudy)
Authors: Barbara P Rogge, Mai Tone Lønnebakken, Dana Cramariuc, Edda Bahlmann, Nikolaus Jander, Christa Gohlke-Bärwolf, Terje R Pedersen, Eva Gerdts
Journal: Circulation (2013)

Background: We hypothesized that the disproportionate increase of body surface area (BSA) in obesity may lead to overestimation of aortic valve stenosis (AS) severity when the indexed valve area is used. Methods: Baseline data from 1524 patients enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study were used to calculate aortic valve area (AVA) and pressure recovery adjusted AVA (energy loss [EL]) and their indexed values (AVAI and ELI). Obesity was defined as body mass index (BMI) ≥30 kg/m2. Results: Peak aortic jet velocity, mean aortic gradient, AVA and EL did not differ between obese (n=321) and non-obese (n=1203) patient groups. A total of 225 patients had non-severe AS by AVA (>1.0 cm2), but severe AS by AVAI ( 1.0 cm2), but severe by ELI (<0.6 cm2/m2) (ELI/EL inconsistency). Compared to non-obese patients, more obese patients (23% vs. 13%) had AVAI/AVA inconsistency (p<0.01) (Fig.1). Adjustment for ...
Modulating NRF2 in Disease: Timing Is Everything
Authors: Matthew Dodson, Montserrat Rojo de la Vega, Aram B. Cholanians, Cody J. Schmidlin, Eli Chapman, Donna D. Zhang
Journal: The Annual Review of Pharmacology and Toxicology (2018)

The transcription factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) is a central regulator of redox, metabolic, and protein homeostasis that intersects with many other signaling cascades. Although the understanding of the complex nature of NRF2 signaling continues to grow, there is only one therapeutic targeting NRF2 for clinical use, dimethyl fumarate, used for the treatment of multiple sclerosis. The discovery of new therapies is confounded by the fact that NRF2 levels vary significantly depending on physiological and pathological context. Thus, properly timed and targeted manipulation of the NRF2 pathway is critical in creating effective therapeutic regimens. In this review, we summarize the regulation and downstream targets of NRF2. Furthermore, we discuss the role of NRF2 in cancer, neurodegeneration, and diabetes as well as cardiovascular, kidney, and liver disease, with a special emphasis on NRF2-based therapeutics, including those that have made it into clinical trials.
Improving efficiency of exam room use at a comprehensive cancer center.
Authors: Jing Jing Wang Yakowec, Emily Regan, Andrew J. Wagner, Christina Isabella Herold
Journal: Journal of Clinical Oncology (2018)

307 Background: Efficient use of exam rooms is crucial to be able to accommodate increasing patient volumes. One workflow approach that takes patients into an exam room only when the provider is ready can free up space for other patient-provider pairs (co-rooming), in contrast to rooming the patient before knowing the provider’s readiness status (sequential-rooming). We conducted a pilot to implement co-rooming on the breast cancer patient floor at Dana-Farber Cancer Institute (DFCI) and to assess whether patient time alone in exam rooms is reduced. Methods: As part of the planning for the co-rooming pilot, root cause analysis, current state sequential-rooming workflow mapping, and proposed future state co-rooming workflow mapping were performed. In the pilot group, clinic assistants roomed a patient only if the provider verbally expressed readiness within 10 minutes. The real-time locating system (RTLS) database was leveraged to generate baseline and pilot data. For 5 providers, patient time alone in an exam room on 5 and 3 consecutive baseline (2/17/17 – 3/17/17) and pilot (3/24/17 – 4/7/17) Friday mornings, respectively, were analyzed using the XbarS statistical process control chart method. Results: At baseline, the mean patient time alone in an exam room was 14 minutes (range 0-86). During pilot mornings, the mean patient time alone was reduced to 4 minutes (range 0-20), which was statistically significantly lower than the baseline mornings. The table below provides the XbarS chart data for the mean time alone +/- 3-sigma. Conclusions: In our pilot, patient time alone in an exam room was significantly decreased by changing from a sequential-rooming process to a co-rooming process, with minimal disruption to workflow. Co-rooming can reduce inefficient exam room use. [Table: see text]
Argentinean Jewish population frequencies for common mutations in BRCA1, BRCA2, and CHEK2.
Authors: Paola Jablonski, Lucas Alterman, Eduardo Pastene, Lina Núñez, Rita Valdez, Graciela Mercado, Gabriel Ercoli, Mariel Ormazabal, Daniel E. Levy, Hugo Gass, Roxana Cerretini
Journal: Journal of Clinical Oncology (2014)

1539 Background: Specific founder mutations 187_188delAG; 5385_5386insC and A1708E in BRCA1 and 6174delT and IVS2+1G>A in BRCA2 have been reported in Jews of Israel and United States. Moderate penetrance alleles 1100 delC, p.I157T and c.IVS2 +1G>A in CHEK2 gene explain part of non-BRCA aggregation of breast cancer (BC) in this ethnic group. The Jewish population of Argentina is the largest in Latin America and the third in the American continent and their genetic epidemiology is unknown. The aim of this study was to screening for these alleles in an Argentinean series of Jewish high risk families for BC/ovarian cancer (OC). Methods: A total of 183 DNA samples were genotype by sequencing for BRCA1/2 mutations and by PCR-RFLP for CHEK2 variants. Results: Among 135 unrelated proband cases, 67% were only BC, 4% BC and OC, 6% BC and other cancer; 8% OC, 2% Melanoma, 2% other cancer and 11% asymptomatic individuals. Overall, 20% were mutation carriers, 65,4% in BRCA1, 11/187_188delAG, 6/5385_5386insC and 34,6% in BRCA2, 9/6174delT. One patient was double heterozygous for 187_188delAG-6174delT. Five of the seven OC were in 187_188delAG probands. All the 5385_5386insC carriers with BC were bilateral or associated with other cancer. The 5385_5386insC mutation was found in carriers in whom the diagnoses of BC/OC were made at an earlier age. Seven intronic BRCA1/BRCA2 variants including two previously unreported IVS1-106 A>G in BRCA1 and IVS1-36 C>T in BRCA2 and the missense variant c.6100 C>T in BRCA2 were observed. Bioinformatics predictions suggested that the non coding variants could be polymorphisms and the missense mutation could modify the structure of the BRCA2 protein and their function. The BRCA1/BRCA2 A1708E and c.67+1G>A mutations and the CHEK2 variants were not found in this series. Conclusions: This study demonstrates that 187_188delAG; 5385_5386insC and 6174delT mutations were seen in a significant proportion of Argentinean Ashkenazim high risk families of undergoing genetic testing for BC/OC. The two founder mutations A1708E and c.67+1G>A in Jews of Sephardic origin and the three of most predisposing variants of CHEK2 did not have major contribution in our population.
The effect of prior treatment on clinical outcomes in patients with achalasia undergoing peroral endoscopic myotomy
Authors: Zu-Qiang Liu, Quan-Lin Li, Wei-Feng Chen, Xiao-Cen Zhang, Qiu-Ning Wu, Ming-Yan Cai, Wen-Zheng Qin, Jian-Wei Hu, Yi-Qun Zhang, Mei-Dong Xu, Li-Qing Yao, Ping-Hong Zhou
Journal: Endoscopy (2018)

Abstract Background Peroral endoscopic myotomy (POEM) is a treatment option for patients with previous surgical or endoscopic treatment. We aimed to evaluate the influence of prior treatment on perioperative and follow-up outcomes in patients undergoing POEM. Methods From August 2010 to December 2014, a total of 1384 patients with achalasia underwent POEM at our center. We retrospectively reviewed 849 patients who completed follow-up. Patients with an Eckardt score ≥ 4 after POEM were considered to have a clinical failure. We compared variables between patients with and without prior treatment. We analyzed risk factors for perioperative major adverse events, and clinical reﬂux and failure during follow-up. Results 245 patients (28.9 %) had undergone prior treatment, and 34 patients (4.0 %) experienced a major adverse event associated with the POEM procedure. During a median follow-up of 23 months (range 1 – 71), clinical reflux occurred in 203 patients (23.9 %) and clinical failure was recorded for 94 patients (11.1 %). Patients with prior treatment had a longer procedure duration (P = 0.001) and longer hospital stay after POEM (P = 0.001). Prior treatment was not an independent risk factor for major adverse events or clinical reflux (odds ratio [OR] 1.19, P = 0.65; OR 1.26, P = 0.19; logistic regression), but it did increase the rate of clinical failure during follow-up (hazard ratio 1.90, P = 0.002; Cox regression). Conclusions POEM was performed safely with a low rate of major adverse events in patients with achalasia who had undergone prior surgical or endoscopic treatment. However, prior treatment increased the risk of clinical failure after POEM.
Downregulation of miR‐145‐5p contributes to hyperproliferation of keratinocytes and skin inflammation in psoriasis
Authors: J.J. Yan, M. Qiao, R.H. Li, X.T. Zhao, X.Y. Wang, Q. Sun
Journal: British Journal of Dermatology (2018)

The extensive involvement of microRNAs (miRNAs) in the pathogenesis of psoriasis is well documented. However, little is known about the contribution of specific miRNAs to the prevalence of this disease. To explore the role of miR‐145‐5p in psoriasis. miRNA microarray analysis was performed in four patients with psoriasis and four controls. Quantitative reverse‐transcriptase polymerase chain reaction and fluorescence in situ hybridization were used to identify the dysregulated miRNAs. Luciferase assays were performed to determine whether miR‐145‐5p targets mixed‐lineage kinase (MLK)3. CCK‐8 assay and Magnetic Luminex Assay were performed to measure cell proliferation and chemokine secretion. Western blot analysis was used to investigate the protein levels of MLK3 and its downstream effectors. Mouse models of psoriasis were established for in vivo experiments. miR‐145‐5p was downregulated in psoriatic lesional skin. Luciferase assays showed that MLK3 is a direct target of miR‐145‐5p. Overexpression of miR‐145‐5p in normal human epidermal keratinocytes (NHEKs) suppressed cell proliferation and secretion of chemokines. In contrast, silencing miR‐145‐5p promoted NHEK proliferation and increased chemokine secretion. Silencing MLK3 abrogated miR‐145‐5p inhibitor‐induced promotion of cell proliferation and chemokine expression. miR‐145‐5p regulates nuclear factor‐κB and signal transducer and activator of transcription 3 by targeting MLK3. Delivery of agomiR‐145‐5p into the skin decreased epidermal hyperplasia and ameliorated psoriasis‐like dermatitis. Delivery of antagomiR‐145‐5p led to the opposite effects. Our findings indicate that miR‐145‐5p negatively regulates proliferation and chemokine secretion of NHEKs by targeting MLK3, and downregulation of miR‐145‐5p contributes to skin inflammation in psoriasis lesions.
Strategies supporting reduced hospitalization rates in a successful OCM practice.
Authors: Molly Mendenhall, Amy Sheldrick, Karyn M. Dyehouse, Andrew S Guinigundo, David Michael Waterhouse
Journal: Journal of Clinical Oncology (2018)

139 Background: Team-based implementation of care is a foundational tenant to reducing avoidable ER visits and hospitalizations. This care strategy supports the OCM mission of improving quality and reducing cost through practice transformation. Methods: Comprehensive care team: Physician, Advanced Practice Provider, Nurse Navigator, Financial Navigator, Phone Triage Nurse; Consistent Message: “Call Us Early – Call Us First” campaign. Verbal and written instructions at all staff member touch points, emphasizing patient responsibility to call before going to the hospital; Supporting infrastructure: 2-hour teaching visit with the entire care team prior to all new treatments; Triage Phone Unit, COME HOME (Barbara McAneny, M.D.) triage pathways – 38 symptom and 27 symptom f/u pathways modified; Blocked time-slots at all offices for same-day APP triage appts; Proactive ER and hosp f/u calls. Results: 2017 phone triage data: 9,841 total symptoms calls. 2,476 same day visits. 338 ER saves. 67 ER f/u calls (Nov/Dec 17’ only). OCM pt survey scores improved and internal Netpromoter scores remained stable. Conclusions: A comprehensive team-based patient navigation strategy, supported by consistent “Call Us First” messaging, symptom pathways and same-day patient access, resulted in decreased hospitalization without commensurate increases in ER visits or 24hr observation stays. Pt satisfaction was not impacted negatively. [Table: see text]
Abstract 14551: Müller Maneuver as a Tool for Stress Echocardiography in Evaluation of Exercise Capacity in Patients With Dilated Cardiomyopathy
Authors: Takeshi Onoue, Shota Fukuda, Atsushi Hayashi, Soushi Hei, Yuichiro Kado, Mai Iwataki, Kyoko Otani, Ritsuko Kohno, Yasushi Oginosawa, Masaru Araki, Shinjo Sonoda, Masaaki Takeuchi, Haruhiko Abe, Yutaka Otsuji
Journal: Circulation (2016)

Introduction: Muller maneuver (MM), which is a forced inspiration against a closed airway, has been incorporated as one of the physiologic, non-invasive stress tests. Increasing negative intrathora...
Abstract 17635: Angiopoietin-like 3 and Cardiovascular Events in Patients With Peripheral Arterial Disease
Authors: Carsten T Herz, Clemens Hoebaus, Renate Koppensteiner, Gerit H Schernthaner
Journal: Circulation (2016)

Introduction: Angiopoietin-like protein 3 (ANGPTL3), which is primarily expressed in the liver, is associated with an altered serum lipoprotein profile due to its inhibitory effects on lipoprotein lipase as well as endothelial cell lipase activity. Hypothesis: We investigated whether increased serum ANGPTL3 contributes to the progression of atherosclerosis by examining its association with adverse events in patients with peripheral arterial disease (PAD), a population at very high risk for cardiovascular events. Methods: We measured serum ANGPTL3 levels in 326 PAD patients in an observational study, at baseline and at a follow-up visit five years later. Adverse outcome was defined as the composite of death, myocardial infarction or stroke (MACE) during the same period. The changes between the ANGPTL3 values of the two visits (Δ) were calculated and correlated with the changes in other risk factors. Results: At baseline, ANGPTL3 (46.7 [34.1 - 59.3] ng/ml) correlated with total cholesterol (R=0.304, p<0.001...
Deletion 6q Drives T-cell Leukemia Progression by Ribosome Modulation
Authors: Stéphanie Gachet, Tiama El-Chaar, David Avran, Eulalia Genesca, Frédéric Catez, Samuel Quentin, Marc Delord, Gabriel Thérizols, Delphine Briot, Godelieve Meunier, Lucie Hernandez, Marika Pla, Willem K. Smits, Jessica G. Buijs-Gladdines, Wouter Van Loocke, Gerben Menschaert, Isabelle André-Schmutz, Tom Taghon, Pieter Van Vlierberghe, Jules P. Meijerink, André Baruchel, Hervé Dombret, Emmanuelle Clappier, Jean-Jacques Diaz, Claude Gazin, Hugues de Thé, François Sigaux, Jean Soulier
Journal: Cancer Discovery (2018)

Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14, SYNCRIP (encoding hnRNP-Q) and SNHG5 (that hosts snoRNAs), both involved in regulating RNA maturation and translation. Combined silencing of both genes, but not of either gene alone, accelerated leukemogeneis in a Tal1/Lmo1/Notch1-driven mouse model, demonstrating the tumor-suppressive nature of the two-gene region. Proteomic and translational profiling of cells in which we engineered a short 6q deletion by CRISPR/Cas9 genome editing indicated decreased ribosome and mitochondrial activities, suggesting that the resulting metabolic changes may regulate tumor progression. Indeed, xenograft experiments showed an increased leukemia-initiating cell activity of primary human leukemic cells upon coextinction of SYNCRIP and SNHG5. Our findings not only elucidate the nature of 6q deletion but also highlight the role of ribosomes and mitochondria in T-ALL tumor progression. SIGNIFICANCE: The oncogenic role of 6q deletion in T-ALL has remained elusive since this chromosomal abnormality was first identified more than 40 years ago. We combined genomic analysis and functional models to show that the codeletion of two contiguous genes at 6q14 enhances malignancy through deregulation of a ribosome-mitochondria axis, suggesting the potential for therapeutic intervention.This article is highlighted in the In This Issue feature, p. 1494.
Arthritis Prevalence: Which Case Definition Should Be Used for Surveillance? Comment on the Article by Jafarzadeh and Felson
Authors: Louise B. Murphy, Jeffrey J. Sacks, Charles G. Helmick, Teresa J. Brady, Kamil E. Barbour, Jennifer M. Hootman, Michael A. Boring, Susan Moss, Dana Guglielmo, Kristina A. Theis
Journal: Arthritis & Rheumatology (2018)