tbuckley/cabot-search huggingface dataset:
Abstract 16888: Comparing Adverse Clinical Outcomes Between Drug Eluting Stents and Bare Metal Stents in Patients Undergoing Non-Cardiac Surgery: a Meta-Analysis
Authors: Sagar Ranka, Udit Joshi, Abhushan Poudyal, Harsh Rawal, Ahmed A Kolkailah, Sisir Siddamsetti, Ezequiel Munoz, Jaykumar Sreenivasan, Jai Parekh, Setri Fugar, Jose Sleiman
Journal: Circulation (2018)

Introduction: History of coronary stents is risk factor for short term adverse clinical events (ACE) after a non-cardiac surgery (NCS). Safety of Drug-Eluting Stent (DES) or Bare-Metal Stent (BMS) has been studied in such patients, but no clear optimal choice of stent type exists. Thus, we performed a meta-analysis to compare the two stents in patients undergoing NCS. Methods: PubMed, Medline, EMBASE databases were queried from inception to January 2018 for all studies comparing DES vs BMS in patients undergoing NCS. ACE was defined as 30-day event rate of myocardial infarction (MI) or death after NCS. Two subgroups created by difference in time from stent placement to NCS: Within 30-45 days and &gt;45 days after stent placement. Random effect model was used to estimate the odds ratio (OR). Two tailed p value &lt; 0.05 were considered significant. Results: Four retrospective cohort studies with 6708 patients were identified. Out of 2597 BMS patients, 8.9% had an ACE compared to rate of 6.5% ACE in DES patients (n=4111). In the overall cohort, there was no difference was observed with either stent type irrespective of duration of NCS after stent placement (OR: 0.85, 95% CI 0.70-1.03, P=0.46). In patients undergoing NCS shortly(30-45days) after stent placement, no significant difference in ACE was observed {Odds Ratio (OR): 0.90, CI 0.63-1.28, P=0.82}. Similarly, no difference was noted in ACE in patients undergoing NCS after 45 days of stent placement (OR: 0.88, CI 0.56-1.40, P=0.10). Conclusion: In patients undergoing NCS after coronary stenting, there is no difference in rate of ACE with BMS vs DES placement. Thus, choice of stent may not play a role in prediction of adverse clinical outcomes after an non-cardiac surgery.
Pituitary-Tumor Endocrinopathies
Authors: Shlomo Melmed
Journal: New England Journal of Medicine (2020)

Pituitary adenomas account for about 15% of intracranial tumors. Clinical manifestations of disease reflect the oversecretion of the involved hormone, most commonly growth hormone, prolactin, corticotropin, or thyrotropin. Diagnosis and management of these disorders are reviewed.
Duchenne muscular dystrophy: assistive technology and preparing for employment
Authors: Andrew O Frank
Journal: BMJ (2020)

Fox and colleagues discuss Duchenne muscular dystrophy (DMD) and its management.1 They correctly report that most people with DMD live well into adulthood and that some will be able to gain employment. This needs to be prepared for by talking to the parents about helping their child develop self-confidence and social skills, …
Anti-cancer gene expression profile of curcumin identifies new therapeutic targets in squamous cell lung carcinoma in vitro
Authors: S. Sen, A. Singh, A. Pal, C. Sharma, R. Kar, N. Singh
Journal: Journal of Clinical Oncology (2007)

18203 Background: Lung cancer is notorious for early metastasis and very high mortality, worldwide. Curcumin, a chemopreventive has also shown chemotherapeutic potential but its mechanisms are still not well understood. In this study, the genes targeted by Curcumin were investigated to identify new targets for the therapy of squamous cell lung carcinoma (SCC) in vitro. Methods: Lung squamous cell carcinoma cells (H520) were cultured in DMEM with 10% FCS. They were treated with Curcumin (25μM) for 24 hours. Apoptosis was detected by morphological examination, MTT assay, flowcytometry and TUNEL assay. Microarray analysis of gene expression profiles on curcumin treatment was done. Real time quantitative RT-PCR confirmed the results. Results: Curcumin (25μM for 24 hours) caused 29.8 ± 2.1% cytotoxicity (MTT assay). Apoptosis was corroborated by flowcytometry (23.7 ± 1.4%) and TUNEL (21.6 ± 1.8%). Using microarray analysis, 34 genes were seen to be upregulated and 31 genes downregulated after curcumin treatment. Several apoptosis related genes were upregulated including GADD45a (3.36 fold), transcription factor Egr-1 (2.2 fold) and Peroxiredoxin-I (2 fold). In addition, Angiopoietin-2 (Ang-2), an angiogenic factor that promotes angiogenesis and tumor invasion was downregulated (1.7 fold). Real time quantitative RT-PCR confirmed the results. Conclusions: This study helps to identify novel putative intervention sites as targets for curcumin in the therapy of squamous cell lung carcinoma (SCC) in vitro and can contribute to better understanding of lung tumorigenesis and anticancer therapy. No significant financial relationships to disclose.
Prenatal, Early-Life, and Childhood Exposure to Air Pollution and Lung Function: The ALSPAC Cohort
Authors: Yutong Cai, Anna L. Hansell, Raquel Granell, Marta Blangiardo, Mariagrazia Zottoli, Daniela Fecht, John Gulliver, A. John Henderson, Paul Elliott
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Exposure to air pollution during intrauterine development and through childhood may have lasting effects on respiratory health.Objectives: To investigate lung function at ages 8 and 15 years in relation to air pollution exposures during pregnancy, infancy, and childhood in a UK population-based birth cohort.Methods: Individual exposures to source-specific particulate matter ≤10 μm in aerodynamic diameter (PM10) during each trimester, 0-6 months, 7-12 months (1990-1993), and up to age 15 years (1991-2008) were examined in relation to FEV1% predicted and FVC% predicted at ages 8 (n = 5,276) and 15 (n = 3,446) years using linear regression models adjusted for potential confounders. A profile regression model was used to identify sensitive time periods.Measurements and Main Results: We did not find clear evidence of a sensitive exposure period for PM10 from road traffic. At age 8 years, 1 μg/m3 higher exposure during the first trimester was associated with lower FEV1% predicted (-0.826; 95% confidence interval [CI], -1.357 to -0.296) and FVC% predicted (-0.817; 95% CI, -1.357 to -0.276), but similar associations were seen for exposures for other trimesters, 0-6 months, 7-12 months, and 0-7 years. Associations were stronger among boys, as well as children whose mother had a lower education level or smoked during pregnancy. For PM10 from all sources, the third trimester was associated with lower FVC% predicted (-1.312; 95% CI, -2.100 to -0.525). At age 15 years, no adverse associations with lung function were seen.Conclusions: Exposure to road-traffic PM10 during pregnancy may result in small but significant reductions in lung function at age 8 years.
Abstract P343: Associations of Adipose Tissue Distribution With Hypertension and Diabetes in African Ancestry Men: A Novel Approach Using Compositional Data Analysis
Authors: Curtis Tilves, Allison Kuipers, Joseph Zmuda, J. J Carr, James G Terry, Sangeeta Nair, Shyamal Peddada, Clareann H Bunker, Victor Wheeler, Iva Miljkovic
Journal: Circulation (2020)

Background: Adipose tissue (AT) distribution, which differs by race/ethnicity, can differentially impact risk for cardiometabolic disease. Traditional analyses using AT volumes tend to place all ATs in a regression model, estimating an increase in one AT volume while “holding other volumes constant”; however, the compositional nature of the data suggests the other ATs cannot remain constant. Compositional data analysis (CODA) methods eliminate this concern by comparing logratios of components. CODA was designed for analyses of data like those of body composition , but has yet to be used in this field. We demonstrate the use of CODA for the comparison of visceral AT (VAT) and subcutaneous AT of the abdomen (ASAT) and thigh (TSAT) with prevalence of cardiometabolic diseases. Methods: This cross-sectional analysis used 615 African Caribbean men from Tobago aged 50-91 years (mean age 63.6 years, mean BMI 27.7 kg/m 2 ). AT volumes were obtained from CT scans of the abdomen (VAT and ASAT) and of the mid-thigh (TSAT). An additive log2 ratio transformation was applied to the ATs to generate the VAT, ASAT, and TSAT component effects relative to the other tissues captured in the respective CT scan. Ordinal logistic regression analyses were performed for increasing hypertension or glucose impairment categories (defined in Table) after adjustment for age, disease status, and lifestyle factors. Results: After full adjustment (Table), a 2-fold higher ASAT volume (relative to other abdominal tissues) was associated with higher odds, and a 2-fold higher TSAT volume (relative to other thigh tissues) was associated with lower odds, of being in a higher hypertension category. After BMI adjustment, no AT was associated with glucose impairment category. VAT was not a significant predictor for either outcome in African Ancestry men. Conclusion: CODA methods, which avoid problematic assumptions made in traditional analyses, found significant and opposing associations of TSAT and ASAT with hypertension categories in African Ancestry men.
Abstract MP64: Associations of Pre-pregnancy BMI and Maternal Glycemia in Pregnancy With Maternal and Child Microbiome Five Years After Birth: Results From the Genetics of Glucose Regulation in Gestation and Growth (Gen3G) Prospective Cohort
Authors: Fan Jia, Moira K Differding, Myriam Doyon, Patrice Perron, Luigi Bouchard, Renée Guérin, Eric Massé, Marie-France Hivert, Noel T Mueller
Journal: Circulation (2020)

Introduction: Maternal pre-pregnancy obesity and gestational diabetes increase future risk of obesity in the mother and child. Obesity and diabetes have been associated with lower gut microbiome diversity. To our knowledge, no studies have examined if maternal pre-pregnancy body mass index (ppBMI) and maternal glycemia during pregnancy are prospectively associated with gut microbiome diversity in mothers and their children in mid-childhood. Hypothesis: We hypothesized that higher maternal ppBMI and maternal glycemia are associated with lower gut microbiome diversity in mothers and their children 5 years after birth. Methods: Gen3G is pre-birth cohort of mother-child dyads, &gt;18 yrs who visited a pregnancy clinic in Sherbrooke, Canada. Oral glucose tolerance tests (OGTT) were administered in second trimester of pregnancy. A total of 178 mother-child pairs (not on antibiotics in the month prior to visit) provided stool, anthropometric measurements and lifestyle information 5 years after birth. Maternal overweight and obesity were defined as 25-30 kg/m 2 and &gt;=30 kg/m 2 respectively. From the stool, we extracted microbial DNA and sequenced the V4 region of the 16S ribosomal subunit. We used linear regression to model the association of ppBMI and glucose values during OGTT with maternal and child gut microbiome Shannon diversity, adjusted for confounders ( see footnote of Figure ). Results: Maternal ppBMI showed U-shaped associations with gut microbiome diversity of both mothers and children 5 years after birth ( Figure, left panels ). Higher 1h-glucose post-OGTT was associated in a dose-response fashion with lower gut microbiome diversity in mothers (p for trend &lt;0.001) and children (p for trend &lt;0.001) 5 years after birth ( Figure, right panels ). Conclusion: Higher glycemia in pregnancy, and to a lesser extent ppBMI, was prospectively associated with lower gut microbiome diversity in mother-child pairs 5 years after birth, even after adjustment for confounders and mother and child BMI measured 5 years after birth.
Over-the-scope clip for anastomotic leak after total gastrectomy
Authors: Pedro Currais, Susana Mão de Ferro, Joana Castela, António Dias Pereira
Journal: Endoscopy (2020)

A 57-year-old man who underwent total gastrectomy for gastric adenocarcinoma presented with fever and elevated inflammatory markers on postoperative day 2. Computed tomography (CT) scan and esophagogastroduodenoscopy (EGD) were unremarkable. The patient developed an evisceration and intra-abdominal infected collection, which was managed with a new surgical intervention and antibiotic treatment. He was discharged on postoperative day 33.
Pathological Complete Response in Conversion Hepatectomy Induced by Lenvatinib for Advanced Hepatocellular Carcinoma
Authors: Ryota Matsuki, Kirio Kawai, Yutaka Suzuki, Masaharu Kogure, Tetsuya Nakazato, Daisuke Naruge, Naohiro Okano, Satowa Seki, Yoshihiko Ohmori, Naohiro Kawamura, Hiroshi Kamma, Tadakazu Hisamatsu, Junji Shibahara, Toshiyuki Mori, Junji Furuse, Yoshihiro Sakamoto
Journal: Liver Cancer (2020)
<b>Ethnic Disparities in </b>Imaging<b>Utilization at Diagnosis of Non-Small Cell Lung Cancer</b>
Authors: Rustain L Morgan, Sana D Karam, Cathy J Bradley
Journal: JNCI Journal of the National Cancer Institute (2020)

Prior research demonstrated statistically significant racial disparities related to lung cancer treatment and outcomes. We examined differences in initial imaging and survival between blacks, Hispanics, and non-Hispanic whites.
New method for rapid and dynamic quantification of elastase activity on sputum neutrophils from patients with cystic fibrosis using flow cytometry
Authors: Matthias Hagner, Dario L. Frey, Matteo Guerra, A. Susanne Dittrich, Victoria S. Halls, Sabine Wege, Felix J.F. Herth, Carsten Schultz, Marcus A. Mall
Journal: European Respiratory Journal (2020)

<b>Small molecule FRET flow cytometry is a new method that enables rapid and sensitive quantification of surface-bound elastase activity on sputum neutrophils from patients with cystic fibrosis and potentially other neutrophilic airway diseases</b>http://bit.ly/2IegeSB
Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis
Authors: Meletios A. Dimopoulos, Ruben Niesvizky, Katja Weisel, David S. Siegel, Roman Hajek, María-Victoria Mateos, Michele Cavo, Mei Huang, Anita Zahlten-Kumeli, Philippe Moreau
Journal: Blood Cancer Journal (2020)

The phase 3 A.R.R.O.W. study demonstrated that treatment with once-weekly carfilzomib (70 mg/m
Abstract 30: Steps-per-day And Cardiovascular Disease Mortality In Older Women: The OPACH Study
Authors: Andrea Z LaCroix, John Bellettiere, Chongzhi Di, Michael J Lamonte
Journal: Circulation (2020)

Background: For decades, common knowledge was that 10,000 steps/day is good for health. That estimate was not empirically-based or developed with older adults in mind. The 2018 Physical Activity Guideline Advisory Committee called the lack of dose-response analyses between steps/day and clinical outcomes a major gap in the literature in need of further study. Methods: During 2012-2014, 6,379 women average age 79±7 measured steps using accelerometers worn on their waist for 7 days then were followed to March 31, 2017. Hazard ratios (HR) and 95% confidence intervals (CIs) for cardiovascular disease (CVD) mortality were estimated across quartiles of steps/day using Cox proportional hazard models adjusting for demographic, behavioral, and health-related covariates. Analyses were run with and without additional adjustment for BMI, CVD-risk biomarkers including systolic blood pressure, lipid and glucose levels, and accelerometer-measured stepping cadence (a measure step intensity). Dose-response analyses were conducted with nonlinear Cox models using restricted cubic splines with 3, 4, and 5 knots. Results: Covariate-adjusted HRs (95% CIs) across increasing quartiles of steps/day were 1.00 (ref.); 0.48 (0.32, 0.73); 0.56 (0.35, 0.90); 0.25 (0.11, 0.54); p-trend &lt;0.001. HRs (95% CIs) comparing quartile 2 to quartile 1 after additional adjustment were: for BMI [ 0.21 (0.09, 0.49); overall p-trend &lt;0.001]; CVD-risk biomarkers [ 0.22 (0.09, 0.53); overall p-trend &lt;0.001]; and step cadence [ 0.34 (0.14, 0.80); overall p-trend =0.004]. The dose-response association is in Figure 1. Conclusions: Steps are easily understood by the general population and can be reliably measured using wearable devices and smart phones. The observed independent inverse associations between steps/day and CVD mortality showed protective associations at steps/day far below the commonly used 10,000. This shows promise that older-adult-specific steps/day recommendations might help promote cardiovascular health in an aging population.
Preferences for adjuvant chemotherapy (ACT) in early breast cancer: The benefits needed to make extended treatment with docetaxel, doxorubicin, and CMF worthwhile
Authors: V. Duric, P. Francis, J. Simard-Lebrun, A. Chan, J. Chirgwin, V. Harvey, A. Sullivan, R. Simes, A. S. Coates, M. Stockler
Journal: Journal of Clinical Oncology (2007)

6528 Background: Small benefits are judged sufficient to make ACT worthwhile by women who have had either 6 cycles of CMF or 4 cycles of AC. We sought to determine the benefits needed to make longer and more intensive regimens worthwhile. Methods: 293 women who completed ACT 3 to 39 months earlier were presented 4 hypothetical scenarios based on known survival times (5 and 15 years) and rates (65% and 85% at 5 years) without ACT using validated, standardised interviews. 179 were in a randomized trial (BIG 02–98) testing addition of docetaxel (T) to a standard regimen including doxorubicin (A) and classical CMF; 114 were treated outside of the trial at the same centres. Women also rated their recollections of health-related quality of life during ACT. Results: The median age was 55 (range 25 to 78), 36% had a college or university degree, and 62% had dependants. The regimens (and their duration) in the trial were: 4 cycles of A or AC then 3 cycles of CMF (24w) in 31% of the women; 4 cycles of AT followed by 4 cycles of CMF (24w) in 29%; and 3 cycles of A then 3 cycles of T then 3 cycles of CMF (30w) in 40%. The regimens outside of the trial were: 4 cycles of AC (12w) in 52%; 6 cycles of CMF (24w) in 20%; and 4 cycles of AC then 3 cycles of CMF (24w) in 23%. A 2% gain in 5-year survival rates or a 6-month gain in survival duration was judged sufficient to make ACT worthwhile by 62–67% of women. Gains of more than 5% in 5-year survival rates or more than 2 years in survival duration were judged necessary to make ACT worthwhile by 10–20% of women. Women's preferences were strongly associated with the aversiveness of their treatment. Women who had more problems with physical well-being, coping with treatment, and nausea or vomiting judged larger benefits necessary to make their ACT worthwhile (p&lt;.0001). Preferences were unaffected by chemotherapy regimen, duration, context in a trial, age, time between treatment and interview, and social circumstances (p&gt;.2). Conclusions: As in previous studies, small benefits were judged sufficient to make ACT worthwhile, even if it lasted 6–7 months, and included docetaxel, doxorubicin and CMF. No significant financial relationships to disclose.
Response to: ‘Do 2019 European League against rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus also indicate the disease activity?’ by Teng <i>et al</i>
Authors: Martin Aringer, Karen Costenbader, Thomas Dörner, Sindhu R Johnson
Journal: Annals of the Rheumatic Diseases (2020)

The letter by Dr Teng and colleagues1 describes an interesting intellectual exercise. In showing that the scores of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus (SLE)2 3 correlate very well (r=0.81) with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in their SLE patient cohort, they have added disease activity to the concepts inter-related to the new SLE criteria. These relationships, which were discussed for SLE disease severity or ‘ominousity’ early in the criteria development process,2 3 may have more overlap than we usually think based on theoretical concepts. In this way, the data by Dr Teng …
The multifaceted role of ischemia/reperfusion in sickle cell anemia
Authors: Robert P. Hebbel, John D. Belcher, Gregory M. Vercellotti
Journal: Journal of Clinical Investigation (2020)

Sickle cell anemia is a unique disease dominated by hemolytic anemia and vaso-occlusive events. The latter trigger a version of ischemia/reperfusion (I/R) pathobiology that is singular in its origin, cyclicity, complexity, instability, perpetuity, and breadth of clinical consequences. Specific clinical features are probably attributable to local I/R injury (e.g., stroke syndromes) or remote organ injury (e.g., acute chest syndrome) or the systematization of inflammation (e.g., multifocal arteriopathy). Indeed, by fashioning an underlying template of endothelial dysfunction and vulnerability, the robust inflammatory systematization no doubt contributes to all sickle pathology. In this Review, we highlight I/R–targeting therapeutics shown to improve microvascular blood flow in sickle transgenic mice undergoing I/R, and we suggest how such insights might be translated into human therapeutic strategies.
Dissecting the Tumor–Immune Landscape in Chimeric Antigen Receptor T-cell Therapy: Key Challenges and Opportunities for a Systems Immunology Approach
Authors: Gregory M. Chen, Andrew Azzam, Yang-Yang Ding, David M. Barrett, Stephan A. Grupp, Kai Tan
Journal: Clinical Cancer Research (2020)

The adoptive transfer of genetically engineered chimeric antigen receptor (CAR) T cells has opened a new frontier in cancer therapy. Unlike the paradigm of targeted therapies, the efficacy of CAR T-cell therapy depends not only on the choice of target but also on a complex interplay of tumor, immune, and stromal cell communication. This presents both challenges and opportunities from a discovery standpoint. Whereas cancer consortia have traditionally focused on the genomic, transcriptomic, epigenomic, and proteomic landscape of cancer cells, there is an increasing need to expand studies to analyze the interactions between tumor, immune, and stromal cell populations in their relevant anatomical and functional compartments. Here, we focus on the promising application of systems biology to address key challenges in CAR T-cell therapy, from understanding the mechanisms of therapeutic resistance in hematologic and solid tumors to addressing important clinical challenges in biomarker discovery and therapeutic toxicity. We propose a systems biology view of key clinical objectives in CAR T-cell therapy and suggest a path forward for a biomedical discovery process that leverages modern technological approaches in systems biology.