tbuckley/cabot-search huggingface dataset:
Abstract 18315: The Association of Age and Pulse Pressure to Serious Adverse Events in the SPRINT Trial
Authors: Ashok Krishnaswami, Dae H Kim, Daniel E Forman, Matthew S Maurer, Karen P Alexander, Michael W Rich
Journal: Circulation (2017)

Introduction: Appropriate hypertension management requires further understanding of the relationship between pulse pressure (PP, mmHg), chronological age (years) and intensity of blood pressure tre...
First-in-Human Phase I, Dose-Escalation and -Expansion Study of Telisotuzumab Vedotin, an Antibody–Drug Conjugate Targeting c-Met, in Patients With Advanced Solid Tumors
Authors: John H. Strickler, Colin D. Weekes, John Nemunaitis, Ramesh K. Ramanathan, Rebecca S. Heist, Daniel Morgensztern, Eric Angevin, Todd M. Bauer, Huibin Yue, Monica Motwani, Apurvasena Parikh, Edward B. Reilly, Daniel Afar, Louie Naumovski, Karen Kelly
Journal: Journal of Clinical Oncology (2018)

This first-in-human study evaluated telisotuzumab vedotin (Teliso-V), formerly called ABBV-399, an antibody-drug conjugate of the anti-c-Met monoclonal antibody ABT-700 and monomethyl auristatin E.For dose escalation, three to six patients with advanced solid tumors were enrolled in eight cohorts (0.15 to 3.3 mg/kg). The dose-expansion phase enrolled patients with non-small-cell lung cancer (NSCLC) with c-Met-overexpressing tumors (c-Met positive; immunohistochemistry membrane H-score ≥ 150). Patients received Teliso-V monotherapy intravenously on day 1 once every 3 weeks. Safety, tolerability, pharmacokinetics, and maximum tolerated dose were determined.Forty-eight patients were enrolled (median age, 65 years; 35.4% NSCLC; median four prior therapies). One patient each in the 3.0-mg/kg (n = 9) and 3.3-mg/kg (n = 3) cohorts experienced dose-limiting toxicities. Although the maximum tolerated dose was not formally identified, the recommended phase II dose was defined as 2.7 mg/kg on the basis of overall safety and tolerability. The most frequent treatment-emergent adverse events (any grade) were fatigue (42%), nausea (27%), constipation (27%), decreased appetite (23%), vomiting (21%), dyspnea (21%), diarrhea (19%), peripheral edema (19%), and neuropathy (17%). The most frequent Teliso-V-related grade ≥ 3 adverse events were fatigue, anemia, neutropenia, and hypoalbuminemia (4% each). Teliso-V and total antibody pharmacokinetics were approximately dose proportional, with a mean harmonic half-life of 2 to 4 days each. Prospective screening identified 35 (60%) of 58 patients with c-Met-positive NSCLC. Of 16 patients with c-Met-positive NSCLC who were treated with Teliso-V 2.4 to 3.0 mg/kg, three (18.8%; 95% CI, 4.1% to 45.7%) achieved a partial response (median response duration, 4.8 months; median progression-free survival, 5.7 months; 95% CI, 1.2 months to 15.4 months). No other patients experienced a response.Teliso-V monotherapy demonstrated favorable safety and tolerability profiles, with encouraging evidence of antitumor activity in patients with c-Met-positive NSCLC.
Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial
Authors: Yuko Kaneko, Hideto Kameda, Kei Ikeda, Tomonoti Ishii, Kosaku Murakami, Hyota Takamatsu, Yoshiya Tanaka, Takayuki Abe, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2018)

Objective To evaluate the efficacy and safety of tocilizumab, an interleukin-6 receptor antibody, in patients with adult-onset Still’s disease. Methods In this double-blind, randomised, placebo-controlled phase III trial, 27 patients with adult-onset Still’s disease refractory to glucocorticoids were randomised to tocilizumab at a dose of 8 mg/kg or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients received open-label tocilizumab for 40 weeks subsequently. The primary outcome was American College of Rheumatology (ACR) 50 response at week 4. The secondary outcomes included ACR 20/50/70, systemic feature score, glucocorticoid dose and adverse events at each point. Results In the full analysis set, ACR50 response at week 4 was achieved in 61.5% (95% CI 31.6 to 86.1) in the tocilizumab group and 30.8% (95% CI 9.1 to 61.4) in the placebo group (p=0.24). The least squares means for change in systemic feature score at week 12 were –4.1 in the tocilizumab group and –2.3 in the placebo group (p=0.003). The dose of glucocorticoids at week 12 decreased by 46.2% in the tocilizumab group and 21.0% in the placebo group (p=0.017). At week 52, the rates of ACR20, ACR50 and ACR70 were 84.6%, 84.6% and 61.5%, respectively, in both groups. Serious adverse events in all participants who received one dose of tocilizumab were infections, aseptic necrosis in the hips, exacerbation of adult-onset Still’s disease, drug eruption and anaphylactic shock. Conclusion The study suggests that tocilizumab is effective in adult-onset Still’s disease, although the primary endpoint was not met and solid conclusion was not drawn.
Psychotherapeutics for Chronic Pain Extends Beyond Cognitive Behavioral Therapy—Reply
Authors: M. Carrington Reid, Charles R. Henderson, Bahar Niknejad
Journal: JAMA Internal Medicine (2018)

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Woltman’s Sign of Hypothyroidism
Authors: Yorihiro Iwasaki, Kenji Fukaya
Journal: New England Journal of Medicine (2018)

A 53-year-old man presented to the endocrinology clinic with fatigue and sensitivity to cold. A physical examination showed delayed relaxation of the ankle jerk reflex — Woltman’s sign, shown in a video — and laboratory evaluation confirmed a diagnosis of primary hypothyroidism.
The HEART Score for Suspected Acute Coronary Syndrome in U.S. Emergency Departments
Authors: Adam L. Sharp, Yi-Lin Wu, Ernest Shen, Rita Redberg, Ming-Sum Lee, Maros Ferencik, Shaw Natsui, Chengyi Zheng, Aniket Kawatkar, Michael K. Gould, Benjamin C. Sun
Journal: Journal of the American College of Cardiology (2018)
Aged human skin accumulates mast cells with altered functionality that localize to macrophages and vasoactive intestinal peptide‐positive nerve fibres
Authors: S.M. Pilkington, M.J. Barron, R.E.B. Watson, C.E.M. Griffiths, S. Bulfone‐Paus
Journal: British Journal of Dermatology (2018)

Skin health declines with age and this is partially attributed to immunosenescence. Mast cells (MCs) are innate immune cells that coordinate tissue immune responses integral to skin homeostasis and disease.
Abstract 19945: Acute Alcohol Intoxication and Hemorrhagic Shock Lead to Microvascular Hyperpermeability and Cardiovascular Arrhythmias
Authors: Srinivas M Tipparaju, Travis M Doggett, Jared Tur, Sachin L Badole, Kalyan C Chapalamadugu, Jerome W Breslin
Journal: Circulation (2015)

Background: Binge drinking combined with trauma is a major cause of mortality in US. It is known that acute alcohol intoxication (AAI) causes deleterious electrical changes in the heart, including involving QTc dispersion. We also recently demonstrated that acute alcohol intoxication (AAI) increases microvascular permeability. In the current study we investigated the consequences of combined hemorrhagic shock and resuscitation (HSR) and AAI on both microvascular permeability and cardiac electrical activity. Hypothesis and Methods: We hypothesized that AAI combined with HSR causes microvascular leakage and electrical dysfunction in the heart. We used an established rat model of AAI/HSR to test the microvascular and cardiac effects. Results: We identified that combined AAI/HSR significantly (p&lt;0.0007) prolongs the QTc interval (ms) compared to control water fed, sham rats (190.8±7.1 vs. 138.4±4.4, p&lt;0.05). Ex vivo acquired left ventricular monophasic action potential (AP) data revealed increased AP duration in the AAI/HSR group at 20 (9.7±0.6 vs. 5.5±0.2; p&lt;0.0004 ), 50 (16±1.1 vs. 8.8±0.6; p&lt;0.001), and 70% (24.7±2.4 vs. 19.5±0.5; p&lt;0.03) repolarization level relative to water/sham controls. Microvascular hyperpermeability was apparent in the mesenteric microcirculation in the AAI/HSR group compared to AAI/sham, water/HSR, and water/sham controls (IOI of 1061.7±208 HSR-alcohol vs. 698.4±311 HSR-water, p&lt;0.05; vs. 209.5±42 sham-alcohol, p&lt;0.001; and vs. 62.3±9 sham-water, p&lt;0.001). Conclusions: We report for the first time the cardiovascular hallmarks of AAI/HSR associated injury, which include prolonged QTc and AP durations and elevated microvascular permeability.
AB1343 Prevalence of autoimmune diseases in catalonia: a population based study using a public big data analytics (PADRIS)
Authors: A. Sisó-Almirall, B. Kostov, E. Martínez Carbonell, S. Retamozo, A. Flores-Chavez, S. González-Martínez, P. Brito-Zerón, A. Dedéu Baraldés, J. Benavent Àreu, M. Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To analyse the prevalence of autoimmune diseases (ADs) in Catalonia by using a public big data program (Public Data Analysis for Health Research and Innovation Program, PADRIS) <h3>Methods</h3> We used the health insurance database of the Catalan National Health Insurance (CNHI) which includes all catalan population registered as insured population in 2016. The sample included 7,483,761 inhabitants. ADs were identified according to the corresponding International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. A total of 33 autoimmune diseases were analysed classified in 4 main categories: rheumatic, systemic, organ-specific and immunodeficiency/autoinflammatory. The prevalence of ADs was calculated as the number of ADs patients divided by the total CNHI beneficiaries in the same year (rate per 1 00 000 persons, 95% confidence intervals -CI-) <h3>Results</h3> The overall prevalence of ADs was 1202 per 1 00 000 persons (95% CI 1,194–1,209); the prevalence was 1455 (95%CI 1,443–1,467) in women and 939 (95%CI 929–949) in men. ADs were classified as organ-specific (43%), systemic (33%), rheumatic (23%) and immunodeficiency/autoinflammatory (1%) autoimmune diseases. The ADs with the highest prevalence rates included psoriasis (282 cases per 100,000, 95% CI 278–286), rheumatoid arthritis (RA) (178 cases per 100,000, 95% CI 175–181), polymyalgia rheumatic (98 cases per 100,000, 95% CI 96–101), spondyloarthropathies (92 cases per 100,000, 95% CI 90–94), systemic lupus erythematosus (SLE) (68 cases per 100,000, 95% CI 66–70) and Sjögren's syndrome (59 cases per 100,000, 95% CI 57–61). In 26 (79%) of the 33 ADs, the female:male ratio was higher than 1; the highest ratios were reported for Sjögren's syndrome (10.5:1), primary biliary cholangitis (5.8:1), SLE (5.4:1), systemic sclerosis (3.4:1) and rheumatoid arthritis (2.6:1). An enhanced prevalence of ADs was reported in Southern regions (1225 cases per 1 00 000 persons in Barcelona/Tarragona regions -CI95% 1,216–1,233- vs 1075 cases per 1 00 000 persons in Girona/Lleida regions -CI95% 1,056–1,093-, p&lt;0.001). <h3>Conclusions</h3> Nearly 90 000 catalans are classified as having an autoimmune disease, representing a prevalence of 1.2% of the total catalan population, a rate which reaches 1.5% in women. The highest frequencies are reported for psoriasis (0.28%), rheumatoid arthritis (0.18%), polymyalgia rheumatica (0.10%), spondyloarthropathies (0.09%), lupus (0.07%) and Sjögren syndrome (0.06%). <h3>Disclosure of Interest</h3> None declared
Recommendations for acquisition, interpretation and reporting of whole body low dose CT in patients with multiple myeloma and other plasma cell disorders: a report of the IMWG Bone Working Group
Authors: Lia A. Moulopoulos, Vassilis Koutoulidis, Jens Hillengass, Elena Zamagni, Jesus D. Aquerreta, Charles L. Roche, Suzanne Lentzsch, Philippe Moreau, Michele Cavo, Jesus San Miguel, Meletios A. Dimopoulos, S. Vincent Rajkumar, Brian G. M. Durie, Evangelos Terpos, Stefan Delorme
Journal: Blood Cancer Journal (2018)

Abstract Whole Body Low Dose CT (WBLDCT) has important advantages as a first-line imaging modality for bone disease assessment in patients with plasma cell disorders and has been included in the 2014 International Myeloma Working Group (IMWG) criteria for multiple myeloma (MM) definition. Nevertheless, standardization guidelines for the optimal use of WBLDCT in MM patients are still lacking, preventing its more widespread use, both in daily practice and clinical trials. The aim of this report by the Bone Group of the IMWG is to provide practical recommendations for the acquisition, interpretation and reporting of WBLDCT in patients with multiple myeloma and other plasma cell disorders.
Brexit: no deal would be “disaster” for patients in Northern Ireland, GP leader warns
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Doctors and patients in Northern Ireland are being failed by politicians in the Brexit negotiations, the Royal College of General Practitioners’ conference has heard.

In a lively Question Time -style debate at the college’s annual conference, John O’Kelly, a GP in Derry, Northern Ireland, and former chair of RCGP Northern Ireland, told the panel that his practice had staff and patients who lived either side of the Irish border …
ACTINOMYCIN-D DOWNREGULATES SOX-2 AND REDUCES TUMOUR GROWTH IN A PRE-CLINICAL MODEL OF GLIOBLASTOMA
Authors: Jessica Taylor, Alina Pandele, Gabriella Forte, Helen Parker, Mark Elvin, Alan Dickson, Catherine Mcbain, Brian Bigger
Journal: Neuro-Oncology (2018)

Actinomycin-D (ACTD) is antineoplastic antibiotic and is used to treat a variety of childhood cancers, including neuroblastoma. Few studies have investigated the efficacy of ACTD in high grade glioma; however our 3D-high throughput assay system has identified ACTD to be highly cytotoxic over a panel of twelve patient-derived glioma stem-like cell lines (GSCs). Here, we validate ACTD as a potential repurposed therapeutic for glioblastoma through the use of three-dimensional GSC culture and a patient-derived xenograft (PDX) model of glioblastoma. Patient-derived GSCs were stably transduced with luciferase-expressing lentivirus to allow for reproducible in vivo assessment of orthotopic brain tumours by bioluminescence imaging (BLI). GSCs were treated in vitro with ACTD at established IC50 concentrations. Downregulation of SOX-2, a stem cell transcription factor, was investigated via western blot in cell lysates and through immunohistological assessment of murine brain tissue. Tumour growth in a recurrent PDX orthotopic model was tracked via BLI over a period of eight weeks. Treatment with ACTD was shown to significantly reduce tumour growth in a recurrent GBM PDX model, when compared to the current standard of care, temozolomide. We also demonstrate that ACTD specifically down-regulates the expression of SOX-2 both in vitro and in vivo. These findings indicate that ACTD could deplete the cancer stem-cell population within the tumour mass, ultimately leading to a delay in tumour progression.
Abstract 13440: The Asp358 A/C Polymorphism in Interleukin-6 Receptor Gene as a Novel Predictor of Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery in Chinese Han Population
Authors: Fangqin Wu, Shu Ding, Xinwei Feng, Meng Yu, Sai Lu, Haibo Zhao, Ying Wu
Journal: Circulation (2015)

Objective: Growing evidences suggest that genetic variation in inflammatory cytokines may play a key role in the development of postoperative atrial fibrillation (POAF). This study aimed to examine the association between three single-nucleotide polymorphisms in interleukin-6 receptor (IL-6R) gene Asp 358 A/C, IL-6 gene -174 G/C and -597 G/A and POAF following coronary artery bypass grafting (CABG). Methods: This prospective study enrolled 371 Chinese Han patients undergoing first time isolated CABG. The primary endpoint was the occurrence of POAF lasting ≥ 5mins. The patients were grouped as either POAF or non-POAF according to their ECGs, which were continuously monitored for the first 7 postoperative days. Genotypes for IL-6R gene Asp358 A/C, IL-6 gene -174 G/C and -597 G/A were determined. Multivariate logistic regression analysis was performed to identify independent risk factors for POAF. Results: Overall, 112 (30.2%) patients developed POAF. There was no significant difference in demographic and clinic data between the two groups, except that patients in the POAF group were significantly older than those in the non-POAF group (p &lt; 0.001), patients who had POAF appeared to have cerebrovascular disease more frequently than those who did not have POAF(p &lt; 0.05). Although frequencies of alleles and genotypes of IL-6 gene -174 G/C and -597 G/A polymorphism were similar in both groups, the CC genotype distribution and C allele frequencies of IL-6R gene Asp358 A/C were significantly higher in patients with POAF than those without POAF (p = 0.003). Univariate logistic analysis showed that the CC genotype for IL-6R gene Asp358 A/C, age, and history of cerebrovascular disease emerged as predictors of POAF. Multivariate analysis shows that the CC genotype for IL-6R gene Asp358 A/C and age were independent predictors of POAF. The adjusted (OR 2.06; 95% CI, 1.16 - 3.63; p = 0.01) of the CC genotype for IL-6R gene Asp358 A/C for predicting POAF was even greater than the unadjusted (OR 1.22; 95% CI, 1.01- 1.64; p = 0.04). Conclusions: This study suggests IL-6R gene Asp358 A/C polymorphism may contribute to the genetic susceptibility of POAF after CABG in Chinese Han population.
Abstract 15187: High Triglycerides Increase Cardiovascular Events, Medical Costs, and Resource Utilization in a Real-World Analysis of Statin-Treated Patients With High Cardiovascular Risk and Well-Controlled Low-Density Lipoprotein Cholesterol
Authors: Peter P Toth, Craig Granowitz, Michael Hull, Djibril Liassou, Amy Anderson, Sephy Philip
Journal: Circulation (2017)

Introduction: The AHA recognizes high TG as an important CV risk factor. The landmark REDUCE-IT study is prospectively evaluating the effects of adding a high-dose omega-3 fatty acid to statin ther...
Front &amp; Back Matter
Authors: Gen Kanayama, James I. Hudson, Harrison G. Pope Jr., Misari Oe, Ulrich Schnyder, Sonja Schumacher, Christoph Mueller-Pfeiffer, Frank H. Wilhelm, Nilüfer Kalebasi, Daniel Roos, Martin Hersberger, Chantal Martin-Soelch, Maurizio Fava, David Mischoulon, Dan Iosifescu, Janet Witte, Michael Pencina, Martina Flynn, Linda Harper, Michael Levy, Karl Rickels, Mark Pollack, Martin Franklin, Edna B. Foa, Helen Blair Simpson, Michael J. Maher, John S. Ogrodniczuk, Carlos Sierra Hernandez, Ingrid Sochting, Anthony S. Joyce, William E. Piper, M.E. Beutel, J. Wiltink, Y. Till, P.S. Wild, T. Münzel, F.M. Ojeda, T. Zeller, R.B. Schnabel, K. Lackner, M. Blettner, I. Zwiener, M. Michal, Anna Ogliari, Marco Battaglia, Elizabeth Maloney, Jin-Mann S. Lin, Christine Heim, William C. Reeves, Urs M. Nater, Zoltan Kozinszky, Robert B. Dudas, Iván Devosa, Sarolta Csatordai, Éva Tóth, Dávid Szabó, János Sikovanyecz, Katalin Barabás, Attila Pál, Elena Tomba, A.M.M. De Vries, V. Forni, R. Voellinger, Yuanjia Wang, Allan Zuckoff, Melanie M. Wall, F. Stiefel, Satz Mengensatzproduktion, Druck Reinhardt Druck Basel, Druck Reinhardt Druck Basel
Journal: Psychotherapy and Psychosomatics (2012)
New Tools in the Ebola Arsenal
Authors: Inger K. Damon, Pierre E. Rollin, Mary J. Choi, Ray R. Arthur, Robert R. Redfield
Journal: New England Journal of Medicine (2018)

New Tools in the Ebola Arsenal In an ongoing outbreak of Ebola virus disease in the Democratic Republic of Congo, some patients have received investigational agents that are approved for compassionate use. Efforts are under way to develop a clinical trial that can provide generalizable results.
The MEK inhibitor selumetinib ([SEL], AZD6244, ARRY-142886) plus irinotecan (IRI) as second-line therapy for KRAS-mutated (KRASm) metastatic colorectal cancer (CRC).
Authors: Howard S. Hochster, Wells A. Messersmith, Bert H. O'Neil, Susan G. Groshen, Heinz-Josef Lenz, Deirdre Jill Cohen, Crystal Shereen Denlinger, Philip Jordan Gold, S. Gail Eckhardt, Gershon Y. Locker, Patricia Ames, Marti McKinley, Lawrence P. Leichman
Journal: Journal of Clinical Oncology (2013)

3587 Background: There are few therapies for second-line KRASm CRC. Inhibiting downstream signal transduction may offer therapeutic options. Use of selumetinib (MEK 1/2 inhibitor; AstraZeneca) is supported by preclinical and clinical evidence. We designed a dose-finding/phase II study of IRI + SEL in KRASm CRC. Methods: Eligibility included: KRASm or BRAFm CRC with measurable disease progressing after 1st-line therapy with an oxalipatin + bevacizumab regimen; PS 0-1; acceptable organ function. Patients (Pts) were treated with IRI 180 mg/m2 iv q2w and SEL 50 or 75 mg po bid. Dose escalation was traditional 3+3 (50 mg bid SEL, then 75 mg bid). In Part B/phase II, primary endpoint was PI-determined response rate (RR) by RECIST. A Simon 2-stage design allowed expansion to 45 pts if ≥1 responses in 20 pts was seen; ≥4/45 responses would be encouraging, when compared to historical RR of 4% (and median PFS 2.5 mo) [EPIC, Sobrero 2008], with approximately 90% power to detect an ORR of 15% at the 10% alpha level (one-sided). Results: N =32 pts entered; 31 treated. Median age was 54 (27-75) yrs; 18 male and 24 Caucasian. The first 3 pts tolerated SEL 50 mg bid without DLT and the remaining 28 were treated at 75 bid. Median number of cycles on study was 3.5 and median PFS was 3.4 mo. Grade 3 AEs included (N): diarrhea 3, fatigue 2, neutropenia 2, and 1 each thrombocytopenia, enteritis, GI bleed, rash. There was one Grade 4 neutropenia. The best PI-reported response included 3 (10%) confirmed PR and 16 (52%) SD [including 1 unconfirmed PR]. 6 patients were on study for more than 6 (up to 22) months. The study was terminated early due to non-protocol considerations. Conclusions: In this small study, the RR of 10% and med PFS of 3.4 mo in pts with KRASm CRC treated with IRI + SEL in 2 nd line are promising compared with prior studies in non-selected patients. MEK inhibition in KRASm CRC should be explored further. Supported in part by AstraZeneca.
Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma
Authors: Christian U. Blank, Elisa A. Rozeman, Lorenzo F. Fanchi, Karolina Sikorska, Bart van de Wiel, Pia Kvistborg, Oscar Krijgsman, Marlous van den Braber, Daisy Philips, Annegien Broeks, Johannes V. van Thienen, Henk A. Mallo, Sandra Adriaansz, Sylvia ter Meulen, Loes M. Pronk, Lindsay G. Grijpink-Ongering, Annemarie Bruining, Rachel M. Gittelman, Sarah Warren, Harm van Tinteren, Daniel S. Peeper, John B. A. G. Haanen, Alexander C. J. van Akkooi, Ton N. Schumacher
Journal: Nature Medicine (2018)