tbuckley/cabot-search huggingface dataset:
Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice
Authors: Kate Smith-Jackson, Yi Yang, Harriet Denton, Isabel Y. Pappworth, Katie Cooke, Paul N. Barlow, John P. Atkinson, M. Kathryn Liszewski, Matthew C. Pickering, David Kavanagh, H. Terence Cook, Kevin J. Marchbank
Journal: Journal of Clinical Investigation (2019)

Atypical hemolytic uremic syndrome (aHUS) is frequently associated in humans with loss-of-function mutations in complement-regulating proteins or gain-of-function mutations in complement-activating proteins. Thus, aHUS provides an archetypal complement-mediated disease with which to model new therapeutic strategies and treatments. Herein, we show that, when transferred to mice, an aHUS-associated gain-of-function change (D1115N) to the complement-activation protein C3 results in aHUS. Homozygous C3 p.D1115N (C3KI) mice developed spontaneous chronic thrombotic microangiopathy together with hematuria, thrombocytopenia, elevated creatinine, and evidence of hemolysis. Mice with active disease had reduced plasma C3 with C3 fragment and C9 deposition within the kidney. Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI mice from thrombotic microangiopathy and aHUS. Thus, our data provide in vivo modeling evidence that gain-of-function changes in complement C3 drive aHUS. They also show that long-term C5 deficiency is not accompanied by development of other renal complications (such as C3 glomerulopathy) despite sustained dysregulation of C3. Our results suggest that this preclinical model will allow testing of novel complement inhibitors with the aim of developing precisely targeted therapeutics that could have application in many complement-mediated diseases.
Abstract 18656: The Effect of Targeted Temperature Management is Dependent Upon the Duration of Out-of-hospital Cardiac Arrest
Authors: Ian R Drennan, Steve Lin, Kevin E Thorpe, Jason E Buick, Sheldon Cheskes, Laurie J Morrison
Journal: Circulation (2015)

Introduction: Targeted temperature management (TTM) reduces neurologic injury from out-of-hospital cardiac arrest (OHCA). As the risk of neurologic injury increases with prolonged cardiac arrests, the benefit of TTM may depend upon cardiac arrest duration. We hypothesized that there is a time-dependent effect of TTM on neurologic outcomes from OHCA. Methods: Retrospective, observational study of the Toronto RescuNET Epistry-Cardiac Arrest database from 2007 to 2014. We included adult (&gt;18) OHCA of presumed cardiac etiology that remained comatose (GCS&lt;10) after a return of spontaneous circulation. We used multivariable logistic regression to determine the effect of TTM and the duration of cardiac arrest on good neurologic outcome (Modified Rankin Scale (mRS) 0-3) and survival to hospital discharge while controlling for other known predictors. Results: There were 1496 patients who met our inclusion criteria, of whom 981 (66%) received TTM. Of the patients who received TTM, 59% had a good neurologic outcome compared to 39% of patients who did not receive TTM (p&lt; 0.001). After adjusting for the Utstein variables, use of TTM was associated with improved neurologic outcome (OR 1.60, 95% CI 1.10-2.32; p = 0.01) but not with survival to discharge (OR 1.23, 95% CI 0.90-1.67; p = 0.19). The impact of TTM on neurologic outcome was dependent on the duration of cardiac arrest (p&lt;0.05) (Fig 1). Other significant predictors of good neurologic outcome were younger age, public location, initial shockable rhythm, and shorter duration of cardiac arrest (all p values &lt; 0.05). A subgroup analysis found the use of TTM to be associated with neurologic outcome in both shockable (p = 0.01) and non-shockable rhythms (p = 0.04) but was not associated with survival to discharge in either group (p = 0.12 and p = 0.14 respectively). Conclusion: The use of TTM was associated with improved neurologic outcome at hospital discharge. Patients with prolonged durations of cardiac arrest benefited more from TTM.
Abstract 14121: A New Physical Rehabilitation Program Based on Adaptation to Myocardial Ischemia is Cardioprotective for Patients With Ischemic Heart Disease: A Manifestation of Ischemic Preconditioning?
Authors: Nadezhda P Lyamina, Elena V Kotelnikova, Ella S Karpova, Valery N Senchikhin, Tatyana P Lipchanskaya, Svetlana V Lyamina, H. F Downey, Eugenia B Manukhina
Journal: Circulation (2013)

Ischemic preconditioning (IP) triggers mechanisms that are cardioprotective during subsequent, non-fatal myocardial ischemia. Thus, exercise strenuous enough to produce transient myocardial ischemia may evoke IP and confer protection to myocardium of patients with ischemic heart disease (IHD). Patients with stable IHD (age 38-65 y; ejection fraction >40%), incomplete revascularization after transcutaneous coronary angioplasty, and positive results of a diagnostic exercise stress test were studied. The IP group (53.9± 6.2 y; n=11) performed 10 treadmill exercise sessions at 70-80% of diagnostic intensity with a 48 h interval between sessions. Each training session continued until ST depression and/or angina occurred (15-25 min initially, 30-50 min after 10 sessions). The control (C) group (56.1± 4.8 y, n=10) performed 10 standard 30-min rehabilitation exercise training sessions at 50-60% of diagnostic intensity for 30 min each, with a 48 h interval between sessions. Monitored safety indices, ECG, blood pre...
Abstract 11417: Drug Abuse and Abdominal Pain: A case of Cocaine Induced Renal and Cardiac Infarction
Authors: Rohit Malhotra, Anupam Kotwal, Joel Gore
Journal: Circulation (2015)

Introduction: A 35 year old man presented with sudden onset left-sided chest pain and left flank pain. He had known non-ischemic cardiomyopathy (EF of 40-45%), non compliant with treatment. He was in severe pain with left costovertebral angle tenderness. Initial investigations showed a WBC count of 12,000, troponin of 3.72 and a urinalysis significant for 2+ proteins but no RBCs. Initial ECG showed &lt;1 mm ST segment elevations with T wave inversions in inferior leads. Cardiac catheterization, did not demonstrate any flow limiting disease. Serial ECGs demonstrated a resolution of the aforementioned changes and his troponins trended down. Further review revealed an extensive history of cocaine use confirmed with a positive urine drug screen. Due to worsening abdominal pain, a CT abdomen with contrast was done which showed an acute segmental infarct on the upper pole of left kidney, but a CT angiogram did not show any evidence of obstructing vascular lesion or dissection. He was discharged on oral oxycodone, diltiazem and lisinopril.The patient returned in one week with exertional chest pain that was relieved with sublingual nitroglycerin. ECG on admission showed diffuse T wave inversions which improved in 6 hours. A repeat urine drug screen was positive for cocaine. Troponins peaked at 5.03. He then complained of persistent right flank pain and a repeat CT angiogram showed a new moderate-sized segmental infarct in the mid-pole of the right kidney. His pain was managed with oxycodone and he was eventually discharged home with isosorbide mononitrate, amlodipine and lisinopril. Conclusions: Renal infarcts may be sometimes missed in the absence of imaging, but must be suspected in drug users with flank pain and inferior EKG changes. In this case, it was hypothesized that renal arterial vasospasm led to the infarct; an extension of the known effect of cocaine on coronary vessels. This case highlights the importance of ruling out renal infarction as a cause for persistent abdominal pain. Identification of the cause of infarction is important, so as not to subject patients to long term anticoagulation. Guidelines for the treatment of drug induced renal infarction are lacking and the approach to such patients, as with all substance abusers, is abstinence.
"Switch" Transmembrane Immunomodulatory Proteins (TIPs) Consisting of High-Affinity PD-1 Extracellular Domains (PD-1 vIgDs) and Costimulatory Intracellular Domains Potently Enhance the Activity of TCR-Engineered T Cells
Authors: Steven D Levin, Hieu Nguyen, Joseph Kuijper, Rebecca P Wu, Ryan Swanson, Stanford L. Peng
Journal: Blood (2018)
A Second Opinion From Observational Data on Second-line Diabetes Drugs
Authors: Alison Callahan, Nigam H. Shah
Journal: JAMA Network Open (2018)

Matthew J. O’Brien, MD, MSc; Susan L. Karam, MD; Amisha Wallia, MD, MS; Raymond H. Kang, MA; Andrew J. Cooper, MSc; Nicola Lancki, MPH; Margaret R. Moran, MPH; David T. Liss, PhD; Theodore A. Prospect, FSA, MAAA; Ronald T. Ackermann, MD, MPH
Pattern of Immune-Mediated Toxicities in Patients with Myelodysplastic Syndrome (MDS) Treated with Nivolumab and Ipilimumab
Authors: Caitlin R. Rausch, Shilpa Paul, Guillermo Montalban Bravo, Elias J. Jabbour, Naval G. Daver, Yesid Alvarado, Courtney D. DiNardo, Farhad Ravandi, Gautam Borthakur, Prithviraj Bose, Naveen Pemmaraju, Kiran Naqvi, Steven M. Kornblau, Jorge E. Cortes, Tapan M. Kadia, Marina Y. Konopleva, Maro N. Ohanian, Sherry A. Pierce, Yvonne Gasior, Christopher B. Benton, Nitin Jain, Koichi Takahashi, Lucia Masarova, Michael Andreeff, Zeev E. Estrov, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2018)
Postural and Daily Variations in the Single-Breath Diffusion Capacity of the Lungs for Carbon Monoxide
Authors: Mikael Grönkvist, M. LaPelusa, Mikael Gennser, Christiano Antonio Machado-Moreira
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Postural and Daily Variations in the Single-Breath Diffusion Capacity of the Lungs for Carbon Monoxide
Abstract MP52: Population Health Impact of Sodium Glucose Co-Transporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in US Adults With Type 2 Diabetes
Authors: Girish Nadkarni, Priti Poojary, Rocco Ferrandino, Aparna Saha, Kinsuk Chauhan, Madhu Mazumdar, Steven Coca, Bart S Ferket
Journal: Circulation (2018)

Introduction: Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists have been introduced as novel antidiabetic agents, but their potential health impact in the US is unknown. We assessed the number of potentially eligible type 2 diabetes (T2D) patients, as well as projected changes in death and complication rates for nationwide use. Methods: Based on inclusion criteria of SGLT2i and GLP-1 receptor agonist RCTs, we determined eligibility in a weighted sample of 69.2M T2D patients from 2007-2014 National Health and Nutrition Examination Survey (NHANES) data. We employed a validated microsimulation model based on the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to simulate virtual life courses of eligible US patients. Pooled hazard ratios from meta-analyses of published RCTs were applied to model death and non-fatal adverse event rates with SGLT2i and GLP-1 receptor agonist use. Results: The proportion eligible in NHANES was 9.2% (95% CI 7.3-11.1), which translates into ~6.4M US adults. Simulated 10-year mortality (32.5%) decreased by 4.6% (95% CI 2.7-7.3) with SGLT2i and by 2.9% (95% CI 1.6-4.8) with GLP-1 receptor agonists. Mean life expectancy was 16.5 y, and increased by 1.3 y (95% CI 0.6-2.2) with SGLT2i and by 0.8 y (95% CI 0.4-1.5) with GLP-1 receptor agonists. With SGLT2i, lifetime heart failure risk decreased by 7.4% (95% CI 4.1-12.3) and end-stage renal disease (ESRD) risk decreased by 0.4% (95% CI -0.1-0.9). Improvements in these event risks were uncertain with GLP-1 receptor agonist use (Figure). With lifetime SGLT2i use, fracture risk increased from 16.9 to 22.4% (95% CI of Δ 2.5-9.6) and amputation risk rose from 5.7 to 11.2% (95% CI of Δ 2.3-9.5). Conclusions: Nationwide use of SGLT2i or GLP-1 receptor agonists may save over 8 or 5M life years, respectively. Moreover, SGLT2i may avoid over 470K new cases of heart failure and over 28K ESRD cases. Further research should illuminate whether these benefits outweigh additional costs and harms.
BRCAPRO 6.0 model validation in male patients presenting for <i>BRCA</i> testing.
Authors: Zahi Ibrahim Mitri, Michelle Jackson, Carolyn Garby, Sharon Hermes Giordano, Gabriel N. Hortobagyi, Claire Singletary, S. Shahrukh Hashmi, Banu Arun, Jennifer Keating Litton
Journal: Journal of Clinical Oncology (2014)

1559 Background: Male breast cancer accounts for < 1% of male cancers. Patients carrying a BRCA mutation are at higher risk of developing breast, pancreatic and prostate cancers among others. BRCAPRO is a risk model used during counseling to estimate risk of being BRCA+. The purpose of this analysis is to evaluate the accuracy of BRCAPro 6.0 in estimating the risk of a man carrying a BRCA mutation. Methods: This IRB-approved retrospective chart review was of 147 male patients who presented to MD Anderson Cancer Center between 02/1997 and 09/ 2011 for genetic counseling and had BRCA testing performed. All patients had their BRCAPRO risk assessment calculated by using the BRCAPro 6.0 clinical cancer gene assessment software (http://www4.utsouthwestern.edu/breasthealth/cagene/). The statistical software SPSS 20.0 was used to obtain results including descriptive statistics, independent sample t-test and receiver operating curve (ROC). Results: The median age of the cohort was 59 years (18-87). Of the 147 patients, 53 (36%) tested positive and 94 (64%) tested negative for a BRCA mutation. Among those who tested positive, 22 patients had a positive BRCA1 mutation, 30 had a positive BRCA2 mutation, and one patient was positive for both BRCA1 and BRCA2 mutation. Of the 147 patients, 50 (36%) underwent predictive testing for a known family mutation. Median BRCAPro score for all patients was 12.16 (range: 0.02-100), 48.93 (range: 0.02-100) for patients who tested positive, and 5.96 (range: 0.05-51.16) in those who tested negative. Forty-five patients (31%) had breast cancer, 16 of which tested positive for a BRCA mutation. 37 patients (25%) had no cancer diagnosis, and 65 patients (44%) carried a different cancer diagnosis: pancreatic (26%) and prostate (12%) cancer were the most common. There were 23 patients (16%) with multiple cancer diagnosis. Independent samples Mann-Whitney test revealed a significant difference between positive and negative test results for BRCAPro 6.0 (p<0.001). The ROC curve had an AUC of 0.819 and a standard error of 0.038. Conclusions: Given the results of the analysis, BRCAPro 6.0 appears to be a good predictive test to determine BRCA carrier risk in male patients. These results should be further evaluated in a larger cohort.
<i>IGH</i> translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes
Authors: Hong Fang, Kaaren K. Reichard, Kari G. Rabe, Curtis A. Hanson, Timothy G. Call, Wei Ding, Saad S. Kenderian, Eli Muchtar, Susan M. Schwager, Jose F. Leis, Asher A. Chanan‐Khan, Susan L. Slager, Esteban Braggio, Stephanie A. Smoley, Neil E. Kay, Tait D. Shanafelt, Daniel L. Van Dyke, Sameer A. Parikh
Journal: American Journal of Hematology (2018)

The prevalence, clinicopathologic correlates, and outcomes of previously untreated chronic lymphocytic leukemia (CLL) patients with IGH‐BCL2 and IGH‐BCL3 translocations are not well known. Using the Mayo Clinic CLL database, we identified patients seen between March 1, 2002 and September 30, 2016 who had FISH testing performed within 3 years of CLL diagnosis. The prognostic profile, time to first therapy (TTT), and overall survival (OS) of patients with IGH‐BCL2 and IGH‐BCL3 translocation were compared to patients without these abnormalities (non‐ IGH group). Of 1684 patients who met the inclusion criteria, 38 (2.2%) had IGH‐BCL2 , and 16 (0.9%) had IGH‐BCL3 translocation at diagnosis. Patients with IGH‐BCL3 translocation were more likely to have high and very‐high CLL‐International Prognostic Index, compared to patients with IGH‐BCL2 translocation and the non‐ IGH group. The 5‐year probability of requiring therapy was significantly higher for IGH‐BCL3 compared to IGH‐BCL2 and non‐ IGH groups (84% vs 33% vs 29%, respectively, P &lt; 0.0001). The 5‐year OS was significantly shorter for IGH‐BCL3 compared to IGH‐BCL2 and non‐ IGH groups (45% vs 89% vs 86%, respectively, P &lt; 0.0001). On multivariable analyses, IGH‐BCL3 translocation was associated with a shorter TTT (hazard ratio [HR] = 2.7; P = 0.005) and shorter OS (HR = 5.5; P &lt; 0.0001); IGH‐BCL2 translocation did not impact TTT and OS. In conclusion, approximately 3% of all newly diagnosed CLL patients have either an IGH‐BCL2 or IGH‐BCL3 translocation. Patients with IGH‐BCL3 translocations have a distinct prognostic profile and outcome. These results support the inclusion of an IGH probe during the routine evaluation of FISH abnormalities in newly diagnosed CLL.
Abstract 19030: Echocardiographic and Computational Assessment of Cardiovascular Remodeling Following Thoracic Endovascular Aortic Repair
Authors: Theodorus M van Bakel, Christopher J Arthurs, Foeke J Nauta, Allen Jin, Kim A Eagle, Joost A van Herwaarden, Frans L Moll, Santi Trimarchi, Himanshu J Patel, Carlos A Figueroa
Journal: Circulation (2017)

Introduction: The compliance of the aorta serves an important function to reduce the impedance and workload for cardiac ejection. Stent grafts currently used for thoracic endovascular aortic repair...
Preliminary Clinical Results of a Phase 1 Study Evaluating the Safety and Anti-Tumor Activity of ACTR707 in Combination with Rituximab in Subjects with Relapsed or Refractory CD20+ B-Cell Lymphoma
Authors: Ian W. Flinn, Jonathon B. Cohen, Luke P. Akard, Samantha Jaglowski, Michael Vasconcelles, Ann Ranger, Patricia Harris, Francis Payumo, Greg Motz, Veronika Bachanova
Journal: Blood (2018)
Post-Transplant Cyclophosphamide Ameliorates Lethal Thymic GVHD By Restoring Regulatory and Effector T Cell Homeostasis in Recipients with Prior PD-1 Blockade Therapy
Authors: Shuntaro Ikegawa, Yusuke Meguri, Takumi Kondo, Hiroyuki Sugiura, Yasuhisa Sando, Makoto Nakamura, Miki Iwamoto, Yoshinobu Maeda, Ken-Ichi Matsuoka
Journal: Blood (2018)
Abstract 15751: A New Role of Sox6 in Renin Regulation
Authors: Jose Gomez, Eric Sum, Anna Keyte, Conrad Hodgkinson, Mary Hutson, Victor Dzau, Maria Mirotsou
Journal: Circulation (2014)

Introduction: The renin-angiotensin system (RAS) is an important component of blood pressure regulation in mammals. Renin catalyzes the rate limiting step of RAS, is produced and stored by Juxtaglomerular (JG) cells in the kidney. However, the transcriptional mechanisms that govern the specification of renin expressing cells under normal or pathophysiological conditions remain poorly understood. During blood pressure changes the number of adult renal cells expressing renin increase through a process termed JG recruitment. We found that this process involves differentiation mesenchymal stromal-like cells (MSC) to renin expressing cells. Our aim in this study was to determine new regulators of renin cell fate during kidney development and JG recruitment. Methods: Gene expression profiles of MSC and JG cells were performed with Affymetrix Mouse 430 2.0 array. In vitro assays were performed in adult renal MSCs isolated from C57BL6 Ren1c YFP mice. Renin expression in vitro was induced by treatment with IBMX and Forskolin. MSC were transduced with lentivirus carrying vectors for Sox6, Sox6 shRNA or controls. Ex vivo analysis was performed in embryonic kidneys (14.5 dpc) isolated and transduced with Sox6 or scrambled shRNA, kidneys were then cultured for 4 days and the expression of Sox6 and Renin analyzed by IHC. Results: Data showed that the transcription factor Sox6 is expressed in renin producing cells in the developing kidney (n=4) and in the adult kidney after stimulation that promotes JG recruitment (n=3). Overexpression of Sox6 (n=3, P&lt;0.05) enhanced differentiation of renal MSCs to renin producing cells in vitro , and Sox6 knockdown reduced differentiation of renal MSC to renin producing cells in vitro (6-fold, n=4, P&lt;0.01). Furthermore, knockdown of Sox6 in an ex vivo model of kidney development resulted in a 5-fold reduction in renin expressing cells (n=4, P&lt;0.05). Conclusion: These results support a novel role for Sox6 in the development of renin expressing cells. This may have implications for renal development and physiology, opening new possibilities of addressing questions regarding both developmental and physiological regulation of renin.
Effectiveness of rivastigmine in Alzheimer's disease (multiple letters) [3]
Authors: P Bentham, R Gray, E Sellwood, J Raftery, M Rosler, C E Selai, M R Trimble, M N Rossor, R J Harvey, J G Storosum, B J Van Zwieten-Boot, Elferink Aja.
Journal: BMJ (1999)
Abstract 10658: Relationship Between Poor Health Literacy and Heart Failure Readmissions
Authors: Susan Robinson, Michele M Pelter, Thomas Nesbitt, Debra Moser, Steve M Paul, Lawton S Cooper, Kathleen Dracup
Journal: Circulation (2012)

Background: Patients admitted with heart failure (HF) are often readmitted again. This poses a large public health burden and has become a compelling topic in the readmission healthcare reform deba...
A lethal pneumonia model of Acinetobacter baumannii: an investigation in immunocompetent mice
Authors: X. Zeng, H. Gu, Y. Cheng, K.-R. Jia, D. Liu, Y. Yuan, Z.-F. Chen, L.-S. Peng, Q.-M. Zou, Y. Shi
Journal: Clinical Microbiology and Infection (2018)
A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity
Authors: Daniel F. Zegarra-Ruiz, Asmaa El Beidaq, Alonso J. Iñiguez, Martina Lubrano Di Ricco, Silvio Manfredo Vieira, William E. Ruff, Derek Mubiru, Rebecca L. Fine, John Sterpka, Teri M. Greiling, Carina Dehner, Martin A. Kriegel
Journal: Cell Host & Microbe (2018)
Abstract 15350: The Relationship Between the Volume of Epicardial Adipose Tissue and the Infarct Size in Patients With a First STEMI: Cardiac MRI Study
Authors: Masaomi Gohbara, Noriaki Iwahashi, Masaaki Konishi, Nobuhiko Maejima, Kengo Tsukahara, Yoshio Tahara, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2013)

Purpose: Epicardial adipose tissue (EAT), which is the visceral fat deposited around the heart, has been considered as an endocrine organ, and it secretes pro-inflammatory and anti-inflammatory cyt...
Outbreaks of Cyclosporiasis — United States, June–August 2013
Authors: M. desVignes-Kendrick, Kaye Reynolds, Teresa Lee, Linda Gaul, Kate Klein, Kari Irvin, Allison Wellman, Angela Hardin, Ian Williams, Ryan Wiegand, Julie Harris, Monica Parise, Francisca Abanyie, R. Reid Harvey
Journal: MMWR Morbidity and Mortality Weekly Report (2013)
Abstract 18342: Management and Outcomes of Myocardial Infarction in the Age of Direct Oral Anticoagulants for Atrial Fibrillation: A Report From The NCDR Action Registry - GWTG
Authors: Dmitriy N Feldman, Tracy Wang, Anita Y Chen, Rajesh V Swaminathan, Luke K Kim, S. Chiu Wong, Robert M Minutello, Geoffrey W Bergman, Harsimran S Singh, Christopher Madias
Journal: Circulation (2017)

Introduction: Limited data are available regarding contemporary management of myocardial infarction (MI) in atrial fibrillation (AF) patients taking warfarin (WF) or direct oral anticoagulants (DOA...