tbuckley/cabot-search huggingface dataset:
Coronary Heart Disease
Authors: RICHARD H. HELFANT, JAMES S. FORRESTER, JOHN R. HAMPTON, JACOB I. HAFT, HARVEY G. KEMP, RICHARD GORLIN
Journal: Circulation (1970)

Right atrial pacing was performed in 41 subjects with coronary heart disease. Twenty developed angina pectoris during pacing, while 21 did not. The extent of coronary artery disease, as judged by selective cinearteriography, was similar in the two groups. Both had significant increases in heart rate and pressure-time per minute, but there was no significant difference in either of these parameters between groups. Among the hemodynamic parameters measured, the only statistically significant change was in the cardiac index which fell slightly but significantly in the angina group. There were no differences in myocardial oxygen extraction either within each group or between groups. In the angina group, however, 14 of 20 subjects exhibited abnormal myocardial lactate metabolism during pacing. The mean change was highly significant (P < 0.01). In the nonangina group, eight of 21 subjects had abnormal lactate metabolism during pacing and the mean change was significant (P < 0.05). There was no correlation between abnormal lactate metabolism and electrocardiographic evidence of myocardial ischemia in either group. Sublingual nitroglycerin, given to five subjects with angina while pacing was continued, resulted in prompt relief of symptoms, but abnormal lactate metabolism and ST-segment depression were unaffected after 10 min. By contrast, when anginal symptoms were relieved in five subjects by cessation of pacing, symptomatic improvement was accompanied by marked improvement in lactate metabolism after 10 min. Although angina pectoris appears to be related statistically to subnormal left ventricular function and abnormal lactate metabolism, there is significant individual variation.
Bowel Perforation by Intrauterine Device
Authors: Takeshi Okamoto, Katsuyuki Fukuda
Journal: Clinical Gastroenterology and Hepatology (2020)

A 41-year-old woman presented for a colonoscopy after a positive fecal occult blood test. She had no significant medical or surgical history and was asymptomatic. Colonoscopy incidentally revealed perforation of the sigmoid colon by a thin plastic object (Figure A). On detailed questioning, the patient recalled having an intrauterine device inserted 10 years ago in the United Kingdom before moving overseas. Computed tomography (Figure B and C) revealed a thin, Y-shaped foreign object in the peritoneal cavity. The patient was diagnosed with colonic perforation by an intrauterine device. The device was removed laparoscopically, and a partial sigmoidectomy was performed. The postsurgical course was uneventful. Uterine perforation is a rare complication of intrauterine device insertions that can subsequently lead to bowel perforation.
Uterine Fibroid Embolization
Authors: Scott C. Goodwin, James B. Spies
Journal: New England Journal of Medicine (2009)

A 45-year-old woman presents with severe menorrhagia and dysmenorrhea and is found to have several large uterine fibroids. She does not want to undergo hysterectomy, so she is advised to consider uterine fibroid embolization. Embolization is a nonsurgical intervention that causes infarction of the fibroid. Fertility may be impaired by the procedure, and repeat interventions are necessary in some patients.
Association of Residency Training With Metabolic Measures
Authors: Takahiro Matsuo, Gautam A. Deshpande, Hiroko Arioka, Daiki Kobayashi
Journal: JAMA Network Open (2020)

This cohort study investigates body mass index, body fat percentage, and laboratory measures of lifestyle-related clinical parameters in a population of medical residents compared with matched non–health care practitioner controls.
2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure
Authors: Clyde W. Yancy, Mariell Jessup, Biykem Bozkurt, Javed Butler, Donald E. Casey, Monica M. Colvin, Mark H. Drazner, Gerasimos Filippatos, Gregg C. Fonarow, Michael M. Givertz, Steven M. Hollenberg, JoAnn Lindenfeld, Frederick A. Masoudi, Patrick E. McBride, Pamela N. Peterson, Lynne Warner Stevenson, Cheryl Westlake
Journal: Journal of the American College of Cardiology (2016)
Abstract 13919: Association of Lung Diffusion Capacity With Cardiac Remodeling and Risk of Heart Failure in the Community
Authors: Patrick Field, Vanessa Xanthakis, Gary F Mitchell, George O’Connor, Susan Cheng, Ramachandran S Vasan
Journal: Circulation (2018)

Lung function abnormalities are ubiquitous in patients with heart failure (HF). It is unclear, however, if abnormal lung diffusion capacity antedates HF, or is associated with cardiac remodeling pa...
Causes of Death Among Stillbirths
Journal: JAMA (2011)

Context-Stillbirth affects 1 in 160 pregnancies in the United States, equal to the number of infant deaths each year.Rates are higher than those of other developed countries and have stagnated over the past decade.There is significant racial disparity in the rate of stillbirth that is unexplained.Objective-To ascertain the causes of stillbirth in a population that is diverse by race/ethnicity and geography. Design, Setting, andParticipants-A population-based study from March 2006 to September 2008 with surveillance for all stillbirths at 20 weeks or later in 59 tertiary care and community hospitals in 5 catchment areas defined by state and county boundaries to ensure access
Associations Of VEGF and VEGFR2 Polymorphisms With Increased Risk and Aggressiveness Of Multiple Myeloma
Authors: Angelo Borsarelli Carvalho Brito, Leisa Lopes Aguiar, Gislaine Borba Oliveira, Gustavo Jacob Lourenco, Carmino Antonio De Souza, José Vassallo, Carmen Silvia Passos Lima
Journal: Blood (2013)
Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab
Authors: Inbal Haya Shafran, Farideh Alasti, Josef S Smolen, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2020)

Background Rheumatoid arthritis (RA) is characterised by clinical joint swelling and elevation of acute phase reactant levels, typically measured by the C-reactive protein (CRP). Clinical and inflammatory responses are usually concordant, except for inhibition of IL-6, which often disproportionally reduces the CRP due to direct inhibition of its hepatic production. We investigated whether pre-treatment CRP is a useful marker that can guide a preferential treatment choice towards IL-6 inhibition. Methods Data of 1126 treatment courses with tocilizumab (TCZ; early RA), 250 courses of rituximab (RTX; established RA) and 249 courses of methotrexate (MTX; established RA) were analysed. We compared clinical disease activity index (CDAI) values and change along 24 weeks’ follow-up to CRP values at baseline or its early change. We validated the results using data from a separate TCZ trial in early RA. Results CRP levels in the TCZ group on average dropped by 74% within 4 weeks. Patients who attained CDAI remission at 24 weeks on TCZ had the highest baseline CRP levels while patients in high disease activity had the lowest; this association was reverse in the RTX and MTX groups. TCZ patients who achieved remission at 24 weeks showed the largest reductions of CRP levels by week 4 compared with those reaching higher disease activity states. Early CRP non-response was indicative of a risk of not achieving clinical treatment goals (p=0.038). Conclusion Baseline CRP appears to have a positive association with reaching the therapeutic target on TCZ treatment, but is a negative predictor for RTX and MTX. Patients on TCZ without an early CRP response have a lower chance of achieving remission. CRP and its early course may inform, to some extent, the estimation of potential therapeutic success in patients with RA.
Accounting for Confounding in Observational Studies
Authors: Brian M. D'Onofrio, Arvid Sjölander, Benjamin B. Lahey, Paul Lichtenstein, A. Sara Öberg
Journal: Annual Review of Clinical Psychology (2020)

The goal of this review is to enable clinical psychology researchers to more rigorously test competing hypotheses when studying risk factors in observational studies. We argue that there is a critical need for researchers to leverage recent advances in epidemiology/biostatistics related to causal inference and to use innovative approaches to address a key limitation of observational research: the need to account for confounding. We first review theoretical issues related to the study of causation, how causal diagrams can facilitate the identification and testing of competing hypotheses, and the current limitations of observational research in the field. We then describe two broad approaches that help account for confounding: analytic approaches that account for measured traits and designs that account for unmeasured factors. We provide descriptions of several such approaches and highlight their strengths and limitations, particularly as they relate to the etiology and treatment of behavioral health problems.
TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition
Authors: Semi Kim, Heekyung Jung, Kwang Pyo Lee, So Jeong Park, Ji Hyun Park, Hyo Jeong Hong, Young Woo Park, Young-Kyu Park
Journal: Cancer Research (2008)

5371  TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon, and gastric cancer tissues. However, the biological functions of TMPRSS4 in cancer are unknown. Here we show, using RT-PCR, that TMPRSS4 is highly elevated in lung cancer tissues compared with normal tissues and is also broadly expressed in a variety of human cancer cell lines. Knockdown of TMPRSS4 by siRNA treatment in lung and colon cancer cell lines was associated with reduction of cell invasion and cell-matrix adhesion as well as modulation of cell proliferation. Conversely, the invasiveness, motility, and adhesiveness of SW480 colon carcinoma cells were significantly enhanced by TMPRSS4 overexpression. Enhanced invasion might be associated with serine proteolytic activity of TMPRSS4. Furthermore, overexpression of TMPRSS4 induced loss of E-cadherin-mediated cell-cell adhesion, concomitant with the induction of SIP1/ZEB2, an E-cadherin transcriptional repressor, and led to epithelial-mesenchymal transition events, including morphological changes, actin reorganization and upregulation of mesenchymal markers. TMPRSS4-overexpressing cells also displayed markedly increased metastasis to the liver in nude mice upon intrasplenic injection. Taken together, these studies suggest that TMPRSS4 controls the invasive and metastatic potential of human cancer cells by facilitating an epithelial-mesenchymal transition; TMPRSS4 may be a potential therapeutic target for cancer treatment.
‘ONE-STOP-SHOPPING’: SAFETY OF COMBINING TRANSCATHETER AORTIC VALVE REPLACEMENT AND LEFT ATRIAL APPENDAGE OCCLUSION
Authors: Adrian Attinger-Toller, Oliver Senn, Francesco Maisano, Samera Shakir, Steffen Glöckler, Ronald Binder, Stefan Stortecky, Bernhard Meier, Fabian Nietlispach
Journal: Journal of the American College of Cardiology (2015)
Synchronous dynamics for cognitive coordination: But how?
Authors: M.-A. Tagamets, Barry Horwitz
Journal: Behavioral and Brain Sciences (2003)

Abstract Although interesting, the hypotheses proposed by Phillips &amp; Silverstein lack unifying structure both in specific mechanisms and in cited evidence. They provide little to support the notion that low-level sensory processing and high-level cognitive coordination share dynamic grouping by synchrony as a common processing mechanism. We suggest that more realistic large-scale modeling at multiple levels is needed to address these issues.
Phase I study of everolimus combined with metformin for patients with advanced cancer.
Authors: Remco Jurriaan Molenaar, Tim van de Venne, Mariette Weterman, Heinz-Josef Klumpen, Ron Mathot, Dirk Richel, Johanna Wilmink
Journal: Journal of Clinical Oncology (2016)

e14088 Background: Only few types of malignancies demonstrate clinical responses to single-agent therapy with the mTOR inhibitor everolimus. Fundamental research suggests that a combination regimen with the mitochondrial respiration inhibitor metformin may have synergistic anti-tumour effects and reduce the possibility of therapy resistance, compared with everolimus as a single-agent therapy. Methods: 9 patients with advanced metastatic cancer were enrolled and treated with 5-10 mg everolimus qd and 500 mg metformin bid in a 3+3 dose-escalation scheme. Our objectives were to determine the dose limiting toxicity (DLT), maximum tolerated dose (MTD), toxic effects, pharmacokinetics and evidence of anti-tumour activity of the aforementioned combination. For pharmacokinetic analyses, 12 h drug concentration-curves were obtained of both everolimus and metformin in the presence and absence of the other drug, analyzed using PK Solver and compared using paired t-tests. Results: We enrolled 9 patients with a median age of 58 years (range: 51-69), who stayed on the study for a median duration of 48 days (range: 4-78). 6 patients discontinued their participation due to toxicity and 3 patients because of progressive disease. Of the 5 patients who entered the study at the starting dose level of 10 mg everolimus qd and 500 mg metformin bid, 3 experienced a DLT. We de-escalated the dose level to 5 mg everolimus qd and continued 500 mg metformin bid, at which 1 out of 4 patients experienced a DLT. After 9 weeks of treatment, 3 patients were still on the study and all had stable disease. In 5 evaluable patients, metformin was eliminated slower when co-administered with everolimus. The metformin T1/2 increased from 4.2 to 9.0 h when co-administered with everolimus (P = 0.03), whereas there was no difference in clearance (61.1 vs 64 L/h, P = 0.55). Conclusions: Despite pre-clinical evidence of a synergistic anti-tumour effect of everolimus and metformin, this combination is poorly tolerated in patients with advanced cancer. This may be due to the slower elimination of metformin and has implications for daily practice, especially for cancer patients with diabetes that are treated with everolimus and at the same time use the widely prescribed biguanide metformin.
Testing an Old Therapy Against a New Disease: Convalescent Plasma for COVID-19
Authors: Rita Rubin
Journal: JAMA (2020)

Chenguang Shen, PhD; Zhaoqin Wang, PhD; Fang Zhao, PhD; Yang Yang, MD; Jinxiu Li, MD; Jing Yuan, MD; Fuxiang Wang, MD; Delin Li, PhD; Minghui Yang, PhD; Li Xing, MM; Jinli Wei, MM; Haixia Xiao, PhD; Yan Yang, MM; Jiuxin Qu, MD; Ling Qing, MM; Li Chen, MD; Zhixiang Xu, MM; Ling Peng, MM; Yanjie Li, MM; Haixia Zheng, MM; Feng Chen, MM; Kun Huang, MM; Yujing Jiang, MM; Dongjing Liu, MD; Zheng Zhang, MD; Yingxia Liu, MD; Lei Liu, MD
Nervous and Mental Diseases.
Journal: JAMA (1901)

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Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities
Authors: Suzy Varderidou-Minasian, Magdalena J. Lorenowicz
Journal: Theranostics (2020)

Mesenchymal stem/stromal cells (MSCs) are important players in tissue homeostasis and regeneration owing to their immunomodulatory potential and release of trophic factors that promote healing.They have been increasingly used in clinical trials to treat multiple conditions associated with inflammation and tissue damage such as graft versus host disease, orthopedic injuries and cardiac and liver diseases.Recent evidence demonstrates that their beneficial effects are derived, at least in part, from their secretome.In particular, data from animal models and first-in-man studies indicate that MSC-derived extracellular vesicles (MSC-EVs) can exert similar therapeutic potential as their cells of origin.MSC-EVs are membranous structures loaded with proteins, lipids, carbohydrates and nucleic acids, which play an important role in cell-cell communication and may represent an attractive alternative for cell-based therapy.In this article we summarize recent advances in the use of MSC-EVs for tissue repair.We highlight several isolation and characterization approaches used to enrich MSC-derived EVs.We discuss our current understanding of the relative contribution of the MSC-EVs to the immunomodulatory and regenerative effects mediated by MSCs and MSC secretome.Finally we highlight the challenges and opportunities, which come with the potential use of MSC-EVs as cell free therapy for conditions that require tissue repair.
Abstract 15536: Targeting a Gpcr, Prokineticin Receptor-1, Protects Heart Against Doxorubicin-Mediated Cardiotoxicity
Authors: Canan G Nebigil, Adeline Gasser, Marine Charavin, Brigitte Escoubet, Anais Audebrand, Michael W Chan, Daniela Cardinale, Larent Desaubry
Journal: Circulation (2018)

Introduction: Doxorubicin (DOX) as the commonly used anthracycline is one of the most effective antitumor agents against a variety of cancers including triple-negative breast cancer (TNBC). Its use...
Ex vivo lung sonography: Morphological-ultrasound relationships
Authors: Andrea Smargiassi, Riccardo Inchingolo, Gino Soldati, Cosimo Damiano Inchingolo, Salvatore Valente
Journal: European Respiratory Journal (2011)

The nature of lung ultrasound “artifacts” (B-lines, White Lung) has not yet been determined. We need to know what pathological structure and what physical mechanism create artifacts. We believe that lung ultrasonographic imaging is the acoustic behavior of ultrasounds crossing substrates of variable porosity or density.

Each of 5 New Zeeland white rabbit right lungs was sequentially inserted in cylindrical, rigid, hermetically sealed containers, with different volumes of 50 mL, 30 mL, 20 mL and 15 mL. Both lung and internal space of each container communicated with external air through a cork cap: the former through a cannula connected to trachea lumen and the latter through a tube connected to an aspiration system. Each system underwent negative pressure to get different known degrees of lung inflation. Densities were obtained for each lung at each level of inflation. Every lung was studied through ultrasonography and then sectioned and analyzed to correlate images with histological appearance.

In normal lung the variation of the pleural plane from specular reflector to generator of acoustic interference recognizes a mechanism which is related to values of tissue density. Artifacts described in lung ultrasonography as B-lines and White Lung appear in the normal lung through air dependent or weight dependent increases in density.

Conclusion: Ultrasound lung artifacts are density or porosity related. B-Lines and white lung (as in pathological conditions) can be reproduced in normal lungs that are deflated (ie denser or less porous) to levels of density which are not realizable under in vivo physiological conditions (< 0,45 g/mL). This mechanism is at the base of the genesis of artifacts also in the pathologic lung.
Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study
Authors: Cristina Bezzio, Simone Saibeni, Angela Variola, Mariangela Allocca, Alessandro Massari, Viviana Gerardi, Valentina Casini, Chiara Ricci, Fabiana Zingone, Arnaldo Amato, Flavio Caprioli, Marco Vincenzo Lenti, Chiara Viganò, Marta Ascolani, Fabrizio Bossa, Fabiana Castiglione, Claudio Cortelezzi, Laurino Grossi, Monica Milla, Daniela Morganti, Luca Pastorelli, Davide Giuseppe Ribaldone, Alessandro Sartini, Alessandra Soriano, Gianpiero Manes, Silvio Danese, Massimo Fantini, Alessandro Armuzzi, Marco Daperno, Gionata Fiorino
Journal: Gut (2020)

COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear.This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death).Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death.Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.
Accreditation's role in reducing medical errors
Authors: D. S O'Leary
Journal: BMJ (2000)

The admonition “First, do no harm,” paraphrased from the Hippocratic oath,1 has long been a guiding principle for the practice of medicine and the delivery of healthcare services around the world. But harm is done every day in health care. This has been well documented in the medical literature.2 Now public awareness of medical errors and unexpected adverse patient outcomes is growing.3 We have a serious problem, and it cries for timely, effective solutions. No one feels this more keenly than practising physicians, healthcare executives, and the overseers of healthcare quality. Effective solutions, however, are proving to be a daunting challenge.

The oversight of healthcare quality in the United States is accomplished both through professionally based, private sector accrediting bodies and through federal and state regulatory agencies. Many variations of this framework are now increasingly in evidence throughout the world. The initial model for external quality oversight in the United States was created by physicians in 1917. The resulting hospital standardisation programme …