tbuckley/cabot-search huggingface dataset:
Abstract P222: Vitamin D and Airway Inflammation in Adolescent Asthmatics
Authors: Douglas Mansell, Robert Freishtat
Journal: Circulation (2019)

Background: Over 25 million people are afflicted with asthma in the U.S. alone, with a higher incidence among adolescents, especially among the African American and Latino population. There has been a focus on the role of low levels of vitamin D (25(OH)D) and asthma severity. The high prevalence of vitamin D insufficiency has been shown to correlate with the high prevalence of asthma in urban youth. Although underlying mechanisms are not clear, vitamin D may regulate inflammation by increased production of anti - inflammatory compounds (Il-10, cAMP, MKP1). Therefore, the objective of this study is to determine which anti-inflammatory mediators are differentially expressed in asthmatic epithelium when exposed to 25(OH)D in conjunction with dexamethasone. The hypothesis is that low levels of vitamin D will be associated with a more pronounced inflammatory milieu and reduced anti-inflammatory response. Methods: Nasal epithelial cells and demographic data were collected as part of the NIMHD R01 grant funded AsthMaP2 project (pediatric asthma cohort study lead by Robert Freishtat M.D) from urban youth between ages six and 20 years of age with physician-diagnosed asthma for &gt;1 year. Cells were cultured for 90 minutes ex vivo with varying levels of Dexamethasone with or without 25(OH)D (6 conditions). mRNA was profiled using Illumina and validated using NanoString. Network and functional analyses were performed using Ingenuity Pathway Analysis. Confirmatory experiments were performed on human asthmatic and non-asthmatic bronchial epithelial cells exposed to 25(OH)D with or without Dex. Intracellular cAMP was measured with ELISA. Results: Of 214 AsthMaP2 participants, 53% were male and (97%) had persistent asthma. The mean (SE) age=10.9(0.4) years, BMI percentile for age=72.1(3)%, and serum 25(OH)D=19.5(0.9) ng/mL. Whole transcriptome analyses of nasal epithelial cells (n=7) showed 34 transcripts differentially expressed in all exposure conditions (p≤0.01). Pathways analysis identified cAMP signaling as a top activated pathway impacted by 25(OH)D. Intracellular cAMP levels were 10-fold higher in asthmatic (n=3) vs. non-asthmatic (n=3) tracheal bronchial epithelial cells at baseline (p=0.009). While this difference persisted through 15 minutes of exposure to 25(OH)D with or without DEX, there were no significant changes in intracellular cAMP from baseline in response to exposure conditions. Conclusions: The average level of 25(OH)D among both asthmatics and non-asthmatics were deficient. While data show that cAMP is constitutively expressed higher in asthmatics in comparison to non-asthmatics, manipulations of vitamin D level did not alter cAMP levels. Additional experiments using a larger sample size are required to further test the proposed effects of vitamin D, with special focus on cAMP as a transient mediator of inflammation regulation in asthmatic airways.
Utility of CD3+ T- lymphocyte chimerism following myeloablative allogeneic hematopoietic stem cell transplant (HSCT): A single center experience.
Authors: Andrea O. Akpoguma, Lindsay Dozeman, Sarah C Mott, Margarida De Magalhaes-Silverman
Journal: Journal of Clinical Oncology (2015)

e18003 Background: The utility of routine chimerism analysis following allogeneic HSCT with myeloablative conditioning remains controversial and its impact on relapse and survival is unclear. In this single-center study we evaluated the utility of CD3+ T-lymphocyte chimerism in patients (pts) undergoing busulfan containing myeloablative HSCT for myeloid neoplasms. Methods: A retrospective review of 184 pts undergoing allogeneic HSCT for myeloid neoplasms at our institution from 2003-2013 was performed. Of this group, 99 pts had chimerism studies performed. Median age of pts was 55 (range 19-74) with 63 pts having AML, 7 CML and 29 MDS/MPN. Myeloablative doses of busulfan with fludarabine or cyclophosphamide were used. Eighty two donors were HLA matched and 17 were HLA mismatched. CD3+ T-lymphocyte chimerism was performed around 30 and 90 days post-transplant. Full donor chimerism was defined as donor hematopoiesis of >95%. Cox proportional hazards regression models were used to test the prognostic effect of variables under consideration on overall survival (OS) and relapse free survival (RFS). Follow-up was defined as time from transplant to death from any cause for OS, and to relapse for RFS. CD3+ T- lymphocyte chimerism was utilized as a time-dependent variable. Results: CD3+ T-lymphocyte chimerism levels at 30 and 90 days were not predictive of OS or RFS (see table). There was also no statistical difference in OS or RFS for age at transplant, HLA match vs mismatch, CR at transplant, disease category, and related vs unrelated donor, gender, ASBMT risk or regimen. GVHD was significant associated with OS but not RFS. More specifically, Grade III-IV acute GVHD had significantly worse outcomes (p=0.01, HR 2.91, CI 1.27-6.66) compared to no acute GVHD. Conclusions: In our experience, CD3 + T-chimerism levels following busulfan containing myeloablative allogeneic HSCT for myeloid neoplasms are not a predictor of overall survival or disease relapse. HR 95% CI P-value Overall Survival CD3+ 30 days ≤95% vs >95% 1.17 0.55 2.52 0.68 CD3+ 90 days ≤95% vs >95% 1.15 0.51 2.62 0.73 Relapse Free Survival CD3+ 30 days ≤95% vs >95% 1.08 0.43 2.69 0.88 CD3+ 90 days ≤95% vs >95% 2.02 0.77 5.29 0.15
Ambulance Density and Outcomes After Out-of-Hospital Cardiac Arrest
Authors: Richard Chocron, Thomas Loeb, Lionel Lamhaut, Daniel Jost, Frédéric Adnet, Eric Lecarpentier, Wulfran Bougouin, Franckie Beganton, Philippe Juvin, Eloi Marijon, Xavier Jouven, Alain Cariou, Florence Dumas
Journal: Circulation (2019)

In out-of-hospital cardiac arrest (OHCA), geographic disparities in outcomes may reflect baseline variations in patients' characteristics but may also result from differences in the number of ambulances providing basic life support (BLS) and advanced life support (ALS). We aimed at assessing the association between allocated ambulance resources and outcomes in OHCA patients in a large urban community.From May 2011 to January 2016, we analyzed a prospectively collected Utstein database for all OHCA adults. Cases were geocoded according to 19 neighborhoods and the number of BLS (firefighters performing cardiopulmonary resuscitation and applying automated external defibrillator) and ALS ambulances (medicalized team providing advanced care such as drugs and endotracheal intubation) was collected. We assessed the respective associations of Utstein parameters, socioeconomic characteristics, and ambulance resources of these neighborhoods using a mixed-effect model with successful return of spontaneous circulation as the primary end point and survival at hospital discharge as a secondary end point.During the study period, 8754 nontraumatic OHCA occurred in the Greater Paris area. Overall return of spontaneous circulation rate was 3675 of 8754 (41.9%) and survival rate at hospital discharge was 788 of 8754 (9%), ranging from 33% to 51.1% and from 4.4% to 14.5% respectively, according to neighborhoods ( P<0.001). Patient and socio-demographic characteristics significantly differed between neighborhoods ( P for trend <0.001). After adjustment, a higher density of ambulances was associated with successful return of spontaneous circulation (respectively adjusted odds-ratio [aOR], 1.31 [1.14-1.51]; P<0.001 for ALS ambulances >1.5 per neighborhood and aOR, 1.21 [1.04-1.41]; P=0.01 for BLS ambulances >4 per neighborhood). Regarding survival at discharge, only the number of ALS ambulances >1.5 per neighborhood was significant (aOR, 1.30 [1.06-1.59] P=0.01).In this large urban population-based study of out-of-hospital cardiac arrests patients, we observed that allocated resources of emergency medical service are associated with outcome, suggesting that improving healthcare organization may attenuate disparities in prognosis.
MRI-TRUS fusion-guided biopsy in obese patients: Does it reduce risk of prostate cancer upgrade on final pathology compared to systematic 12-core biopsy?
Authors: Samuel A Gold, Jonathan Bloom, Amir H Lebastchi, Graham Hale, Sherif Mehralivand, Thomas Sanford, Peter L. Choyke, Baris Turkbey, Peter A. Pinto
Journal: Journal of Clinical Oncology (2019)

110 Background: Epidemiologic data suggests a link between obesity and increased risk of aggressive prostate cancer (PCa). Therefore, the accurate detection of prostate cancer is paramount in obese men. We sought to characterize the PCa lesions seen on multiparametric magnetic resonance imaging (mpMRI) in both obese (OB) and non-obese (nOB) patients. In addition, we examined whether obesity affects the accuracy of fusion biopsy (FBx) versus systematic biopsy (SBx). Methods: Data from patients who underwent FBx, SBx, or both, and subsequent prostatectomy at a single institution between 2007-2017 were reviewed. Men were stratified into three groups based on body mass index (BMI): normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0). mpMRIs were analyzed to determine prostate size, lesion size, lesion location, and evidence of ≥T3 disease. FBx and SBx were compared to prostatectomy specimens. These variables were then analyzed between the OB and nOB groups. Results: 487 patients were included: 109 (19%) normal weight, 266 (48%) overweight, and 185 (33%) obese. No statistical differences were noted in age, PSA, or clinical stage. mpMRI showed similar prostate size, index and total lesion diameter, lesion location, and Prostate Imaging Reporting and Data System (PIRADS) score between BMI categories. In OB patients, FBx was better able to predict final Gleason score (GS) than SBx, 60% vs 47%, p = 0.0474, OR 1.67 (1.00-2.80). The rate of upgrading after SBx was higher for OB men versus nOB men, 44% vs 34%, p = 0.034, OR 1.52 (1.01-2.29). However, risk of upgrading returned to that of nOB men with FBx, 20% vs 17%, p = 0.538, OR 1.21 (0.658-2.23). Conclusions: FBx is a more accurate measure of the true GS in OB patients than SBx, and there is a significantly greater risk of underrepresenting PCa on SBx in OB patients. These findings were not associated with differences in prostate sizes and lesion characteristics on mpMRI. This suggests that obesity may cause technical challenges with prostate biopsies that may be overcome by improved visualization and targeting of FBx.
Monotherapy with tenofovir disoproxil fumarate for adefovir-resistant vs. entecavir-resistant chronic hepatitis B: A 5-year clinical trial
Authors: Young-Suk Lim, Geum-Youn Gwak, Jonggi Choi, Yung Sang Lee, Kwan Soo Byun, Yoon Jun Kim, Byung Chul Yoo, So Young Kwon, Han Chu Lee
Journal: Journal of Hepatology (2019)
Breast Arterial Calcium
Authors: Renato Quispe, Mahmoud Al-Rifai, Philip A. Di Carlo, Erin D. Michos, Nivee P. Amin, Sina Kianoush, Catherine E. Handy, John W. McEvoy, Michael J. Blaha, Khurram Nasir, Roger S. Blumenthal, Rajesh Tota-Maharaj, Joao A.C. Lima, Josep Comin-Colet, Miguel Cainzos-Achirica
Journal: JACC. Cardiovascular imaging (2019)
Abstract 006: Mapping Geographic Variation of Atherosclerotic Cardiovascular Disease Risk: 2013 Pooled Models Overpredict the Risk in United States Veterans
Authors: Yuk-Lam Ho, Jason L Vassy, Xuan-Mai Nguyen, Laura Tarko, Sridharan Raghavan, Ashley Galloway, Luc Djousse, Peter W Wilson, David R Gagnon, Kelly Cho
Journal: Circulation (2019)

Introduction: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity in the U.S. We mapped ACC/AHA ASCVD risk in U.S. Veterans outpatients across U.S. geographic regions. Methods: We computed 10-year ASCVD risk using the 2013 ACC/AHA risk calculator with risk factor values derived from electronic health records and compared the estimates to observed ASCVD rates within Veterans Health Administration (VHA) population. We mapped the standardized differences in the observed and predicted risk at the county level using ArcGIS software. Results: There were 1.48 million VHA users between 2002-2007 aged 40 to 79 with median 10 years of follow-up. Mean age was 60 years, 96% were male, and 80% were white. The average 10-year predicted ASCVD risk after adjustment for true follow-up time at baseline was 13.8%, and the average observed risk was 6.6%, an overestimation of 7.2%. At baseline, 43.1% of patients were taking anti-hypertensive medications and 20.3% were taking statins. After updating risk factor statuses two years following baseline, 75.9% were taking anti-hypertensive medication, 42.6% were takings statins, and average predicted risk was dropped to 12.1%. In sex- and race-specific analyses the 2013 ACC/AHA risk calculator over-estimated 10-year ASCVD risk in white female, non-white female, white male, and non-white male by 2.0%, 2.0%, 8.1% and 4.8%, respectively. The greatest over-predictions in 10-year ASCVD risks were observed in western Arizona, southern California, southern Florida and Pennsylvania. These regions had higher percentages of white male VHA users compared to national averages. Conclusion: The 2013 ACC/AHA risk equation generally over-predicts ASCVD risk in the VHA population, particularly among white male Veterans. Increased anti-hypertensive and statin therapy with continual care at VHA was also associated with lower ASCVD risk. The mapping of these results allowed an overall visualization of the geographic variation across the U.S.
Diagnostic Accuracy of Positron Emission Tomography/Computed Tomography of the Head, Neck, and Chest for Giant Cell Arteritis: A Prospective, Double‐Blind, Cross‐Sectional Study
Authors: Anthony M. Sammel, Edward Hsiao, Geoffrey Schembri, Katherine Nguyen, Janice Brewer, Leslie Schrieber, Beatrice Janssen, Peter Youssef, Clare L. Fraser, Elizabeth Bailey, Dale L. Bailey, Paul Roach, Rodger Laurent
Journal: Arthritis & Rheumatology (2019)

Objective Positron emission tomography/computed tomography ( PET / CT ) has not been well studied as a first‐line test for giant cell arteritis ( GCA ), due, in part, to historical limitations in visualizing the cranial arteries. The Giant Cell Arteritis and PET Scan ( GAPS ) study was therefore carried out to assess the accuracy of a newer generation PET / CT of the head, neck, and chest for determining a diagnosis of GCA . Methods In the GAPS study cohort, 64 patients with newly suspected GCA underwent time‐of‐flight PET / CT (1‐mm slice thickness from the vertex to diaphragm) within 72 hours of starting glucocorticoids and before undergoing temporal artery biopsy ( TAB ). Two physicians with experience in PET reviewed the patients’ scans in a blinded manner and reported the scans as globally positive or negative for GCA . Tracer uptake was graded across 18 artery segments. The clinical diagnosis was confirmed at 6 months’ follow‐up. Results In total, 58 of 64 patients underwent TAB , and 12 (21%) of the biopsies were considered positive for GCA . Twenty‐one patients had a clinical diagnosis of GCA . Compared to TAB , the sensitivity of PET / CT for a diagnosis of GCA was 92% (95% confidence interval [95% CI ] 62–100%) and specificity was 85% (95% CI 71–94%). The negative predictive value ( NPV ) was 98% (95% CI 87–100%). Compared to clinical diagnosis, PET / CT had a sensitivity of 71% (95% CI 48–89%) and specificity of 91% (95% CI 78–97%). Interobserver reliability was moderate (κ = 0.65). Among the enrolled patients, 20% had a clinically relevant incidental finding, including 7 with an infection and 5 with a malignancy. Furthermore, 5 (42%) of 12 TAB ‐positive GCA patients had moderate or marked aortitis. Conclusion The high diagnostic accuracy of this PET / CT protocol would support its use as a first‐line test for GCA . The NPV of 98% indicates the particular utility of this test in ruling out the condition in patients considered to be at lower risk of GCA . PET / CT had benefit over TAB in detecting vasculitis mimics and aortitis.
Comparison of Peripheral Blood Stem Cell Mobilization for Multiple Myeloma Patients over 70 Years of Age with Younger Patients
Authors: Ning Dong, David S Siegel, Phyllis McKiernan, Noa Biran, Alan P Skarbnik, David H. Vesole, Andrew L. Pecora, Scott D. Rowley, Michele L. Donato
Journal: Blood (2018)
Cumulative Toxicity in Targeted Therapies: What to Expect at the Recommended Phase II Dose
Authors: Maria-Athina Altzerinakou, Laurence Collette, Xavier Paoletti
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background In the era of molecularly targeted agents (MTAs), it is recommended to account for toxicity over several cycles to identify the recommended phase II dose (RP2D). We investigated the relationship between the risk of toxicity at cycle 1 and the cumulative incidence of toxicity over subsequent cycles in trials of single MTAs. Methods On individual patient data from 26 phase I clinical trials of single MTAs provided by the National Cancer Institute, we estimated the probability of first-severe toxicity per treatment cycle as well as the cumulative incidence at, below, and above the maximum tolerated dose (MTD). Toxicity was further subclassified into nonhematologic and hematologic. A prediction table was developed to estimate the cumulative incidence up to six cycles based on the toxicity rate observed in the first cycle. Results Overall, 942 patients were included. For patients treated at the MTD, the probability of first-severe toxicity decreased from 24.8% (95% prediction interval [PI] = 20.3% to 32.9%) to 2.2% (95% PI = 0.1% to 7.7%) from cycle 1 to 6, whereas the cumulative incidence of toxicity reached 51.7% (95% PI = 40.5% to 66.3%) after six cycles. Toxicity rates ranging from 20.0% to 30.0% in the first cycle were associated with 46.8% (95% PI = 39.5% to 54.2%) and 65.8% (95% PI = 57.7% to 73.1%) cumulative incidence after six cycles. Conclusion This study examined the risk of severe toxicity over time of single MTAs. The cumulative incidence of toxicity at the MTD was higher than the usually accepted toxicity targets, challenging the definition of the RP2D of MTAs. The prediction table may help calibrate the target rate at the RP2D.
Can integrated clinical simulation trainings improve person-centred maternity care? Results from a pilot project in Ghana
Authors: P Afulani, R Aborigo, S Cohen, C Moyer, D Walker, J Williams
Journal: The Lancet Global Health (2019)

BackgroundPerson-centred maternity care (PCMC) is maternity care that is responsive to and respectful of women's needs and values. It is a key dimension of quality, capturing the experience of interpersonal dimensions of care. Poor PCMC contributes to high maternal mortality not only directly but also indirectly through decreased demand for services. Although there is growing recognition of the importance of PCMC to maternal and child health outcomes, there is a paucity of data on interventions that aim to integrate a person-centred approach to maternity care. In this study, we aimed to evaluate the effect of an integrated simulation training on provision of PCMC.MethodsThe pilot PCMC training project was launched in a rural district in Northern Ghana in April, 2017. To improve quality of care, including PCMC, we integrated specific components of such care, emphasising dignity and respect, communication and autonomy, and supportive care, into a simulation training to improve identification and management of obstetric and neonatal emergencies. 43 providers in the district participated in two 2-day trainings led by PRONTO international trainers. Six providers were then trained as simulation facilitators, and they led refresher sessions every month for 4 months at the five highest-volume delivery facilities in the district. We conducted surveys at baseline and endline with women who had recently given birth to assess their experiences of care using a 24-item version of the 30-item PCMC scale.FindingsWe included data from 215 baseline surveys, conducted in March and April, 2017, and 318 surveys at endline in November, 2017. Women at endline reported higher PCMC scores than did women at baseline. The average PCMC score increased from 35·9 (SD 6·3) at baseline to 51·5 (12·9) at endline, a change of 43% (p<0·001). Scores on the subscales also increased between baseline and endline: from 13·6 (2·4) to 15·7 (3·3) for dignity and respect (p<0·001), 8·3 (3·2) to 15·6 (6·5) for communication and autonomy (p<0·001), and 14·0 (3·5) to 20·3 (5·1) for supportive care (p<0·001). The greatest increase was in communication and autonomy which increased by 87%. These differences remain significant (p<0·001) in multilevel multivariate analysis controlling for several potential confounders and accounting for clustering at the facility level.InterpretationOur findings suggest that integrated training that gives health-care providers the opportunity to learn, practise, and reflect on their provision of PCMC has the potential to improve care in low-resource settings. Incorporating such trainings into pre-service and in-service training of providers will help advance global efforts to promote PCMC.FundingUSAID Systems for Health.
School Mobility and Its Impact on Student Health—Reply
Authors: Rebecca N. Dudovitz, Paul J. Chung, Mitchell D. Wong
Journal: JAMA Pediatrics (2019)

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