tbuckley/cabot-search huggingface dataset:
Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy
Authors: Kevin A. Hay, Jordan Gauthier, Alexandre V. Hirayama, Jenna M. Voutsinas, Qian Wu, Daniel Li, Ted A. Gooley, Sindhu Cherian, Xueyan Chen, Barbara S. Pender, Reed M. Hawkins, Aesha Vakil, Rachel N. Steinmetz, Gary Schoch, Aude G. Chapuis, Brian G. Till, Hans-Peter Kiem, Jorge D. Ramos, Mazyar Shadman, Ryan D. Cassaday, Utkarsh H. Acharya, Stanley R. Riddell, David G. Maloney, Cameron J. Turtle
Journal: Blood (2019)
Abstract 13100: Thyroid Dysfunction, Cardiovascular Risk Factors, and Incident Cardiovascular Events: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Seth S Martin, Natalie Daya, Pamela L Lutsey, Kunihiro Matsushita, Anna Fretz, John W McEvoy, Roger S Blumenthal, Josef Coresh, Michael W Steffes, Philip Greenland, Anna Kottgen, Elizabeth Selvin
Journal: Circulation (2015)

Introduction: Data remain inconclusive on the relation of thyroid dysfunction to atherosclerotic cardiovascular disease risk, particularly with respect to stroke. In addition, prior studies have lacked measurement of T3, the final active form of thyroid hormone. Methods: We examined the cross-sectional and prospective associations of thyroid dysfunction with cardiovascular risk factors and events in the community-based ARIC Study. Participants had thyroid measures obtained in an ancillary study at visit 2 (1990-92) and were free of pre-existing cardiovascular disease. We evaluated thyroid function using clinical categories and also log-transformed T3. Cross-sectional outcomes were hypertension, diabetes, and dyslipidemia. Prospective outcomes were adjudicated fatal and non-fatal myocardial infarction and stroke, which are the outcomes of the 2013 ACC/AHA guidelines. Results: Among 11,359 participants (mean age 57±6 years, 58% women), 2.2% had overt hypothyroidism, 4.8% subclinical hypothyroidism, 3.3% subclinical hyperthyroidism, and 1.8% overt hyperthyroidism. Compared with euthyroidism, all thyroid dysfunction groups had similar age, sex, and race-center adjusted prevalences of hypertension and diabetes. Regarding dyslipidemia, mean adjusted differences in LDL cholesterol were 15.1 (95% CI 10.5, 19.7) and 3.2 (0.0, 6.4) mg/dL in those with overt and subclinical hypothyroidism relative to euthyroidism; an opposite pattern was seen in overt and subclinical hyperthyroidism [-10.8 (-15.9, -5.7) and -3.9 (-7.7, -0.1) mg/dL, respectively]. During a median follow-up of 20 years, 966 myocardial infarctions and 721 strokes occurred, with no unadjusted or adjusted associations observed with baseline thyroid function groups or by concentration of T3 (Table). Conclusion: Thyroid dysfunction is associated with a modest alteration in the lipid profile and no long-term differences in incidence of myocardial infarction or stroke.
Transnasal Endoscopy in Unsedated Children With Eosinophilic Esophagitis Using Virtual Reality Video Goggles
Authors: Nathalie Nguyen, William J. Lavery, Kelley E. Capocelli, Clinton Smith, Emily M. DeBoer, Robin Deterding, Jeremy D. Prager, Kristina Leinwand, Greg E. Kobak, Robert E. Kramer, Calies Menard-Katcher, Glenn T. Furuta, Dan Atkins, David Fleischer, Matthew Greenhawt, Joel A. Friedlander
Journal: Clinical Gastroenterology and Hepatology (2019)
Consistent Benefit of L-Glutamine Observed across Patients with Low, Medium, and High Number of Crises Reported in the Year Prior to Screening -- Analysis from the Phase 3 Study of L-Glutamine in Sickle Cell Anemia
Authors: Yutaka Niihara, Charles William Stark, Rafael Razon, Lan T Tran, Joseph M Becerra, Eduard H. Panosyan, Joseph Louis Lasky
Journal: Blood (2018)
Cell Type-Specific Deregulation of Polypyrimidine Tract- Binding Proteins (PTBPs) Drive Aberrant Splicing in Multiple Myeloma (MM) and Acute Myeloid Leukemia (AML)
Authors: Sophia Adamia, Sigitas J Verselis, Teru Hideshima, Michael P. Chu, Shruti Bhatt, David P. Steensma, Daniel J Deangelo, Richard M. Stone, Daniel G. Tenen, Linda M. Pilarski, James D. Griffin, Kenneth Anderson
Journal: Blood (2018)
Long-term Outcomes of Endovascular and Open Repair for Traumatic Thoracic Aortic Injury
Authors: Yu-Ting Cheng, Chi-Tung Cheng, Shang-Yu Wang, Victor Chien-Chia Wu, Pao-Hsien Chu, An-Hsun Chou, Ching-Chang Chen, Po-Jen Ko, Kuo-Sheng Liu, Shao-Wei Chen
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Thoracic endovascular aortic repair (TEVAR) has been adopted rapidly for treating traumatic thoracic aortic injury (TAI). The long-term durability and efficacy remain unknown. <h3>Objective</h3> To determine the long-term outcomes of thoracic endovascular aortic repair and those of open repair (OR) for traumatic TAI. <h3>Design, Setting, Participants</h3> This nationwide cohort study used Taiwan's National Health Insurance Database to evaluate patients with traumatic TAI between January 1, 2004, and December 31, 2013. This single-payer National Health Insurance program covered more than 99.9% of the Taiwanese population. Those who received OR or TEVAR for TAI by propensity score matching were included. Data analysis was conducted in October 2017. <h3>Exposures</h3> Thoracic endovascular aortic repair vs open repair. <h3>Main Outcomes and Measures</h3> In-hospital outcomes, all-cause mortality, aorta reintervention, and stroke during follow-up. <h3>Results</h3> Of the 287 patients (mean [SD] age, 41.66 [17.98] years; 80.5% male) who received OR or TEVAR for TAI, propensity score matching yielded 100 patients each in the OR and TEVAR groups. After propensity score matching, in-hospital mortality risk was significantly lower in the TEVAR group (9 [9.0%]) than in the OR group (27 [27.0%]; TEVAR vs open repair: odds ratio, 0.27; 95% CI, 0.12-0.60). With a mean (SD) follow-up of 2.80 (2.63) years, the proportion of survivors was 71.9% at 1 year, 70.8% at 2 years, 68.2% at 3 years, and 65.1% at 5 years in the OR group vs 88.9% at 1 year, 88.9% at 2 years, 88.9% at 3 years, and 88.9% at 5 years in the TEVAR group (log-rank test,<i>P</i> &lt; .001). The TEVAR group had only 2 events (2%) of late reintervention and 1 event (1%) of late cerebrovascular accident. The proportion of freedom from reintervention was 100% at 1 year, 100% at 2 years, 100% at 3 years, and 100% at 5 years in the OR group vs 97.4% at 1 year, 97.4% at 2 years, 97.4% at 3 years, and 97.4% at 5 years in the TEVAR group (log-rank test,<i>P</i> = .18). <h3>Conclusion and Relevance</h3> Compared with OR, TEVAR was associated with better long-term outcomes, mainly owing to lower mortality during the perioperative period. In addition, TEVAR was associated with a similar rate of survival and reintervention after hospital discharge.
Ronald George Clark: pioneer in the development of surgical nutrition
Authors: Helen Saul
Journal: BMJ (2019)

Ronald Clark (“Ron”) had a deep interest in nutrition and the metabolic response to acute disease and injury. He led research in this area for more than two decades as professor of surgery at the University of Sheffield (1971-93).

Unusually for the 1970s, Clark’s research unit brought together trainee surgeons and postgraduate and postdoctoral biochemists, who worked collaboratively on glucose and salt metabolism. Much of his work related to life support in intensive care at a time when artificial nutrition was in its infancy. Brian Rowlands, now professor emeritus at the University of Nottingham, was Clark’s lecturer in surgery in the mid-1970s. He said that Clark took a holistic approach, which aimed to ensure that patients appeared in surgery well prepared and were looked after afterwards: “A lot of the concepts Ron espoused became essential building blocks on which successful modern intensive care units were built.”

Clark’s career was similarly holistic. Aside from his research, he was a surgeon, teacher, and mentor; an effective manager who became dean of Sheffield University Medical School; and a longstanding member of the General Medical Council. He was pro vice chancellor of Sheffield University at a time of rapid expansion, and the first in its history to be asked to serve an extra year. Throughout it all, he was renowned for his patience and calm, along with the ability to come up with a well timed quip to liven up the dullest of meetings.

His medical career is all the more remarkable as it almost didn’t happen at all.

Clark was born in Aberdeen, the second child of George and Gladys Clark. He was educated at Aberdeen Academy and had a happy and mainly healthy childhood. He left school at 16 with no idea what he wanted to do; it was 1944 and, with …
Endometrial Tumor Immune Response: Predictive Biomarker of Response to Immunotherapy
Authors: Mary M. Mullen, David G. Mutch
Journal: Clinical Cancer Research (2019)

Abstract The tumor-specific immune response in endometrial cancer is variable within molecular subtypes. Thus, the tumor immune response offers a novel biomarker, separate from molecular subtypes, to predict which patients might respond to immunotherapy. See related article by Talhouk et al., p. 2537
The Importance of Blood Pressure Gradients in the Brain
Authors: J. David Spence
Journal: JAMA Neurology (2019)

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Dose-Adjusted Teddi-R Induces Durable Complete Remissions in Relapsed and Refractory Primary CNS Lymphoma
Authors: Mark Roschewski, Michail S. Lionakis, Christopher Melani, John A. Butman, Stefania Pittaluga, A. Nicole Lucas, Seth M. Steinberg, Elaine S. Jaffe, Richard F. Little, Louis M. Staudt, Wyndham H. Wilson
Journal: Blood (2018)
Pharmacogenomic Variants and Drug Interactions Identified Through the Genetic Analysis of Clozapine Metabolism
Authors: Antonio F. Pardiñas, Mariana Nalmpanti, Andrew J. Pocklington, Sophie E. Legge, Christopher Medway, Adrian King, John Jansen, Marinka Helthuis, Stanley Zammit, James MacCabe, Michael J. Owen, Michael C. O’Donovan, James T.R. Walters
Journal: American Journal of Psychiatry (2019)

Objective: Clozapine is the only effective medication for treatment-resistant schizophrenia, but its worldwide use is still limited because of its complex titration protocols. While the discovery of pharmacogenomic variants of clozapine metabolism may improve clinical management, no robust findings have yet been reported. This study is the first to adopt the framework of genome-wide association studies (GWASs) to discover genetic markers of clozapine plasma concentrations in a large sample of patients with treatment-resistant schizophrenia. Methods: The authors used mixed-model regression to combine data from multiple assays of clozapine metabolite plasma concentrations from a clozapine monitoring service and carried out a genome-wide analysis of clozapine, norclozapine, and their ratio on 10,353 assays from 2,989 individuals. These analyses were adjusted for demographic factors known to influence clozapine metabolism, although it was not possible to adjust for all potential mediators given the available data. GWAS results were used to pinpoint specific enzymes and metabolic pathways and compounds that might interact with clozapine pharmacokinetics. Results: The authors identified four distinct genome-wide significant loci that harbor common variants affecting the metabolism of clozapine or its metabolites. Detailed examination pointed to coding and regulatory variants at several CYP* and UGT* genes as well as corroborative evidence for interactions between the metabolism of clozapine, coffee, and tobacco. Individual effects of single single-nucleotide polymorphisms (SNPs) fine-mapped from these loci were large, such as the minor allele of rs2472297, which was associated with a reduction in clozapine concentrations roughly equivalent to a decrease of 50 mg/day in clozapine dosage. On their own, these single SNPs explained from 1.15% to 9.48% of the variance in the plasma concentration data. Conclusions: Common genetic variants with large effects on clozapine metabolism exist and can be found via genome-wide approaches. Their identification opens the way for clinical studies assessing the use of pharmacogenomics in the clinical management of patients with treatment-resistant schizophrenia.
Omalizumab: Efficacy and Safety in Mast Cell Disorders
Authors: Richard Lemal, Guillemette Fouquet, Louis Terriou, Mélanie Vaes, Cristina Livideanu, Laurent Frenzel, Stéphane Barete, Danielle Canioni, Ludovic Lhermitte, Jacques-Olivier Bay, Julien Rossignol, Michel Arock, Olivier Lortholary, Olivier Hermine
Journal: Blood (2018)
Abstract 15192: Implementation of the Hospital Readmissions Reduction Program, Readmissions, and Mortality in Heart Failure
Authors: Ankur Gupta, Larry A Allen, Deepak L Bhatt, Margueritte Cox, Adam D DeVore, Paul A Heidenreich, Adrian F Hernandez, Eric D Peterson, Roland A Matsouaka, Clyde W Yancy, Gregg C Fonarow
Journal: Circulation (2017)

Introduction: Public reporting of hospitals’ 30-day risk-standardized readmission rates following heart failure hospitalization, and penalizing for higher rates, has been associated with a reduction in 30-day readmissions, but has raised concerns for unintended consequences. Hypothesis: To examine the association of the Hospital Readmissions Reduction Program (HRRP) with readmissions and mortality among patients hospitalized with heart failure within prospective registry that allows for detailed risk adjustment. Methods: Interrupted time series and survival analysis of index heart failure hospitalizations from January 2006 to December 2014 in 115,245 fee-for-service Medicare beneficiaries across 416 U.S. hospital sites participating in Get With The Guidelines-Heart Failure. Main exposure was time intervals in relation to the HRRP: before (January 2006 to March 2010), during (April 2010 to September 2012), and after (October 2012 to December 2014, penalties phase) the HRRP implementation. Primary outcomes ...
Characteristics and survival among early onset and standard onset colorectal cancer by race.
Authors: Ana Acuna Villaorduna, Sanjay Goel
Journal: Journal of Clinical Oncology (2019)

522 Background: The incidence of early-onset colorectal cancer (EO) is increasing. Guidelines recommend to start screening colonoscopy at 45 yo in Non-Hispanic Black (NHB). We compare the clinical features and outcomes between EO and standard-onset (SO) colorectal cancer (CRC) among racial groups. Methods: Patients with CRC adenocarcinoma; available race/ethnicity and stage were identified using the SEER registry. Clinical features and 5 year-overall survival (OS) is described by racial and age groups. Results: 190 670 patients were identified. EO rates were higher for minorities than NHW. Median age at diagnosis in EO was 44 and was similar among racial groups; while it was 71 in SO, being lower among minorities compared to NHW (67 vs. 72 years, p &lt; 0.01). Left-sided tumors accounted for 77.4% of tumors in EO while it was 60.8% in SO for minorities versus NHW. The most common CRC location for EO was the rectum and sigmoid colon for SO. EO was most commonly diagnosed as stage III. Surgery and radiation rates were higher for EO for all stages. OS was higher in all stages of EO compared to SO. Conclusions: EO frequency is higher in all minority groups and most commonly located in the rectum. Despite higher stage and grade, OS is higher for EO which might be due to higher treatment rates. Early screening should be extended to all minority groups. [Table: see text]
Abstract 12668: Geriatric Patients Admitted for Heart Failure are Less Likely to Have Follow-up Appointments Scheduled Prior to Discharge
Authors: Parag Goyal, Ashley N Beecy, Madeline Sterling, John T Ruffino, Sonal Mehta, Mark S Lachs, Erica C Jones, Evelyn M Horn
Journal: Circulation (2015)

Introduction: Post-discharge medical follow-up among geriatric patients admitted with heart failure (HF) is especially important given high rates of multimorbidity and polypharmacy. Hypothesis: Patients admitted with HF aged ≥65 years will have a high rate of follow-up appointments (FUA) scheduled upon discharge from the hospital. Methods: We studied patients discharged home from a medicine service with principal diagnosis of HF at an academic hospital in NYC during 2013-2014. Patients discharged to hospice were excluded. We collected demographics, hospitalization characteristics, clinical indices, and FUA data by chart review. Results: . 796 unique patients were hospitalized with HF, among whom 443 (56%) had an FUA scheduled prior to discharge. Patients who did not have an FUA were older, more commonly white, and less likely to have Medicaid (Table). They had higher LVEF and higher rates of HFpEF (LVEF≥50%) compared to those with an FUA. Patients with and without an FUA were similar with respect to rates of coronary artery disease (CAD), RV dysfunction, valvular disease, atrial fibrillation/flutter (AF), and ventricular tachycardia. Patients also had similar rates of non-cardiac comorbidities irrespective of having an FUA, with the exception of COPD, which was more common among those with an FUA. Despite increased rates of CAD, AF, COPD, gastrointestinal bleeding, cancer, and cerebrovascular accidents, patients aged ≥65 years were less likely to have an FUA (52% vs. 65%, p=0.001). In multivariate analysis controlling for race, insurance, COPD, and HFpEF, age ≥65 remained independently associated with not having a scheduled FUA upon hospital discharge (OR 1.45, [1.02 to 2.05], p=0.03). Conclusions: Despite higher burden of both cardiac and non-cardiac disease, patients aged ≥65 years admitted with HF were less likely to have a follow-up appointment upon discharge. This highlights an important disparity in care of the geriatric population that must be addressed.
Would hemodialysis patients benefit from a Staphylococcus aureus vaccine?
Authors: Roisin Connolly, Mark D. Denton, Hilary Humphreys, Rachel M. McLoughlin
Journal: Kidney International (2019)

Staphylococcus aureus bloodstream infection can have potentially catastrophic consequences for patients on hemodialysis. Consequently, an effective vaccine to prevent S aureus infection would have a significant influence on morbidity and mortality in this group. To date, however, efforts to develop a vaccine have been unsuccessful. Previous antibody-inducing vaccine candidates did not prevent or attenuate S aureus infection in clinical trials. Recent advances have helped to elucidate the role of specific T-cell subsets, notably T-helper cell 1 and T-helper cell 17, in the immune response to S aureus. These cells are essential for coordinating an effective phagocytic response via cytokine production, indirectly leading to destruction of the organism. It is now widely accepted that next-generation S aureus vaccines must also induce effective T-cell-mediated immunity. However, there remains a gap in our knowledge: how will an S aureus vaccine drive these responses in those patients most at risk? Given that patients on hemodialysis are an immunocompromised population, in particular with specific T-cell defects, including defects in T-helper cell subsets, this is likely to affect their ability to respond to an S aureus vaccine. We urgently need a better understanding of T-cell-mediated immunity in this cohort if an efficacious vaccine is ever to be realized for these patients.
The relationship between aortoiliac calcification and long-term outcome in rectal cancer resection.
Authors: Katrina Knight, Kate Boland, Donald C McMillan, Paul G. Horgan, Campbell SD Roxburgh, James Hugh Park
Journal: Journal of Clinical Oncology (2019)

705 Background: The interaction between host and tumour factors is an important determinant of long-term outcome following rectal cancer resection. At cellular level, hypoxia within the tumour microenvironment stimulates neovascularisation, alters tumour metabolism and is implicated in dissemination and metastases. At host level, restricted blood flow to the tumour may play a role in tumour hypoxia. Significant calcification of the distal aortic and iliac arteries could result in impaired rectal perfusion. We aimed to investigate the relationship between aortoiliac calcification (AC) and long-term outcome following rectal cancer resection. Methods: Patients were identified from a prospectively maintained database. Recurrence and survival data were abstracted. On staging CT images, the sum of calcified quadrants of the distal aorta and iliac arteries at the level of the bifurcation was calculated. ROC analysis was used to identify the optimum threshold for determining significant calcification. Results: Between 2008-2016, 181 patients with available CT scans underwent surgery for rectal cancer. Most were male (60%), aged over 65 (53%) and TNM stage II/III (72%). Median follow-up was 63 months. Significant AC was identified in 44 patients (24%). Recurrence occurred in 42 patients: local in 16 (9%) and systemic in 26 (14%) patients. Recurrence was associated with significant AC (p = 0.017), TNM stage (p = 0.002) and venous invasion (p = 0.006). When considering those with and without significant AC, there were differences in the rates of local (11% vs. 8%) and systemic (25% vs. 11%) recurrence respectively (p = 0.043). On univariate Cox regression analysis, overall survival was related to age (p = 0.012), ASA grade (p = 0.042) and significant AC (p = 0.001). On multivariate analysis, significant AC (p = 0.011) was the only independent predictor of overall survival. Conclusions: The burden of aortoiliac calcification appears to play an important role in influencing long-term outcome following rectal cancer resection, independent of traditional determinants such as TNM stage and ASA grade. While validation is required, further investigation of the mechanism underlying this relationship is warranted.
Peroral cholangiopancreatoscopy as a rescue method for a trapped pancreatic guidewire
Authors: Rodrigo Mansilla-Vivar, Noelia Alonso-Lázaro, Lidia Argüello-Viudez, Marta Ponce Romero, Marco Bustamante-Balen, Vicente Pons Beltrán
Journal: Endoscopy (2019)

Peroral cholangiopancreatoscopy is an endoscopic technique that enables direct visual examination and video-guided tissue sampling. The technique has improved the ability to identify pancreaticobiliary diseases and has been useful for treating complex bile and pancreatic duct stones [1] [2] [3]. It is increasingly being used as a therapeutic procedure [4].