tbuckley/cabot-search huggingface dataset:
Abstract 17989: Association of Serial Changes of Left Ventricular Diastolic Function with Cardiovascular and Non-cardiovascular Mortality Over Time
Authors: Garvan C Kane, Barry L Karon, Steven J Jacobsen, Margaret M Redfield, Richard J Rodeheffer
Journal: Circulation (2012)

Background:  While the presence & severity of changes in diastolic function over time are related to heart failure, little is known about age-dependent longitudinal changes & their relationship to mortality. We assessed the hypothesis that serial changes in diastolic function correlate with mortality.   Methods:  Analysis was based on a prospective community-based cohort of participants enrolled in the Olmsted County Heart Function Study. Randomly selected participants ≥45 yrs (n = 2042) underwent clinical evaluation, medical record abstraction, & comprehensive Doppler echocardiography (1997-2000). After 4 years, participants were invited to return (2001-2004) with n = 1402 of 1960 surviving, 72%) returning. All cause & disease specific mortality was assessed over a further 8±2 yrs. LV diastolic function was graded as normal, mild, moderate/severe by validated Doppler techniques.   Results:  During the 4±0.3 years between exams, the prevalence of diastolic dysfunction increased from 23.8% (95% CI 21.2%-26.4%) to 39.2% (95% CI, 36.3%-42.2%; P    Conclusion:  Abnormalities on serial assessment by Doppler echocardiography of diastolic function are associated with mortality. While diastolic dysfunction is related to non-CV death, this association appears to be a reflection of age & comorbidities rather than a direct association. However diastolic dysfunction is associated with CV mortality independent of age and comorbidities.
Monitoring Neuromuscular Function
Authors: Rafael Ortega, Sorin J. Brull, Richard Prielipp, Alexander Gutierrez, Rossemary De La Cruz, Christopher M. Conley
Journal: New England Journal of Medicine (2018)

This video demonstrates the assessment of neuromuscular function after administration of neuromuscular blocking agents. Because these agents can be lethal, clinicians should be familiar with the use of nerve stimulators and monitors in the assessment of neuromuscular function.
Abstract 15866: Relative Wall Thickness in Shockable vs. Non-shockable Sudden Cardiac Arrest in the Community
Authors: Aapo L Aro, Carmen Teodorescu, Audrey Uy-Evanado, Kyndaron Reinier, Derek Phan, Karen Gunson, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2016)

Introduction:  Shockable initial rhythms (VT/VF) during sudden cardiac arrest (SCA) are associated with considerably better resuscitation outcomes than non-shockable rhythms (pulseless electrical activity [PEA] or asystole), but factors associated with these arrhythmias are poorly understood. By analyzing archived echocardiogram reports, we examined the potential role of relative wall thickness (RWT) as a determinant for shockable vs. non-shockable SCA.   Methods:  All SCA victims in a Northwest US metro region (population 1 million) were prospectively identified 2002 - 2015, and their medical records reviewed. 385 subjects with an echocardiogram performed prior to SCA, and with documented initial SCA rhythm available were included in the analysis. Association of RWT (2xPWd/LVEDD) and LV ejection fraction (EF) with initial rhythm was studied.   Results:  Initial rhythm was VT/VF in 178 (46%) and non-shockable (PEA/asystole) in 207 (54%) subjects. Subjects with VT/VF were younger (65.6±13.5 vs 68.6±13.4yrs, p=0.032) and more likely male (77.5% vs 59.9%, p 0.56).   Conclusions:  In the community, decreased RWT was strongly associated with VT/VF as the initial rhythm in SCA. These findings have mechanistic and clinical implications for improving resuscitation outcomes from SCA.
To Care Is Human — Collectively Confronting the Clinician-Burnout Crisis
Authors: Victor J. Dzau, Darrell G. Kirch, Thomas J. Nasca
Journal: New England Journal of Medicine (2018)

Interview with Dr. Tait Shanafelt on causes of burnout and efforts to improve support for clinicians. (13:21)Download The National Academy of Medicine, the Association of American Medical Colleges, and the Accreditation Council for Graduate Medical Education have launched a national Action Collaborative on Clinician Well-Being and Resilience to combat the clinician-burnout crisis.
Experts urge addition of folic acid to flour to halt “avoidable tragedy” of birth defects
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The UK government has been urged to fortify flour with folic acid to prevent birth defects, after a reappraisal of existing evidence concluded that there was “no scientific basis” for setting an upper level of folate intake.

Researchers at Queen Mary University of London and the School of Advanced Study at the University of London concluded that there were “elementary” flaws in a previous analysis from the US Institute of Medicine that suggested that the daily dose of folic acid should not exceed 1 mg.1

Health experts said it would be “an avoidable tragedy” and a “dereliction of public health duty” if the UK government failed to fortify flour on …
Markers of early progressive renal decline in type 2 diabetes suggest different implications for etiological studies and prognostic tests development
Authors: Natalia Nowak, Jan Skupien, Adam M. Smiles, Masayuki Yamanouchi, Monika A. Niewczas, Andrzej T. Galecki, Kevin L. Duffin, Matthew D. Breyer, Nick Pullen, Joseph V. Bonventre, Andrzej S. Krolewski
Journal: Kidney International (2018)
Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma
Authors: Frederick F. Lang, Charles Conrad, Candelaria Gomez-Manzano, W.K. Alfred Yung, Raymond Sawaya, Jeffrey S. Weinberg, Sujit S. Prabhu, Ganesh Rao, Gregory N. Fuller, Kenneth D. Aldape, Joy Gumin, Luis M. Vence, Ignacio Wistuba, Jaime Rodriguez-Canales, Pamela A. Villalobos, Clemens M.F. Dirven, Sonia Tejada, Ricardo D. Valle, Marta M. Alonso, Brett Ewald, Joanna J. Peterkin, Frank Tufaro, Juan Fueyo
Journal: Journal of Clinical Oncology (2018)

Purpose DNX-2401 (Delta-24-RGD; tasadenoturev) is a tumor-selective, replication-competent oncolytic adenovirus. Preclinical studies demonstrated antiglioma efficacy, but the effects and mechanisms of action have not been evaluated in patients. Methods A phase I, dose-escalation, biologic-end-point clinical trial of DNX-2401 was conducted in 37 patients with recurrent malignant glioma. Patients received a single intratumoral injection of DNX-2401 into biopsy-confirmed recurrent tumor to evaluate safety and response across eight dose levels (group A). To investigate the mechanism of action, a second group of patients (group B) underwent intratumoral injection through a permanently implanted catheter, followed 14 days later by en bloc resection to acquire post-treatment specimens. Results In group A (n = 25), 20% of patients survived &gt; 3 years from treatment, and three patients had a ≥ 95% reduction in the enhancing tumor (12%), with all three of these dramatic responses resulting in &gt; 3 years of progression-free survival from the time of treatment. Analyses of post-treatment surgical specimens (group B, n = 12) showed that DNX-2401 replicates and spreads within the tumor, documenting direct virus-induced oncolysis in patients. In addition to radiographic signs of inflammation, histopathologic examination of immune markers in post-treatment specimens showed tumor infiltration by CD8 + and T-bet + cells, and transmembrane immunoglobulin mucin-3 downregulation after treatment. Analyses of patient-derived cell lines for damage-associated molecular patterns revealed induction of immunogenic cell death in tumor cells after DNX-2401 administration. Conclusion Treatment with DNX-2401 resulted in dramatic responses with long-term survival in recurrent high-grade gliomas that are probably due to direct oncolytic effects of the virus followed by elicitation of an immune-mediated antiglioma response.
Abstract 13924: Unresolved Medical Conditions have become the Leading Cause of Death in Children with Heart Disease
Authors: Tobias R Schlingmann, Ravi R Thiagarajan, Kimberlee Gauvreau, Kimberly C Lofgren, Michael Zaplin, Jean A Connor, Pedro J del Nido, James E Lock, Kathy J Jenkins
Journal: Circulation (2011)

Background: Despite significant surgical and medical advances over the past decades, there has been a low but persistent mortality rate for children with heart disease as well as adults with congen...
Long-term clinical effects of early thymectomy: Associations with autoimmune diseases, cancer, infections, and atopic diseases
Authors: Judith Gudmundsdottir, Jonas Söderling, Håkan Berggren, Sólveig Óskarsdóttir, Martin Neovius, Olof Stephansson, Olov Ekwall
Journal: Journal of Allergy and Clinical Immunology (2018)
Sixty seconds on . . . loneliness
Authors: Anne Gulland
Journal: BMJ (2018)

Sorry about that but here’s some good news—the government has appointed Tracey Crouch as the UK’s very first minister for loneliness. The government made the appointment after accepting all the recommendations of a commission on loneliness, set up after the murder of MP Jo Cox. Loneliness was an issue that was close to Cox’s heart.

There is a wealth of statistics on the …
Skeletal Muscle Quality Beyond Average Muscle Attenuation: A Proposal of Skeletal Muscle Phenotypes to Predict Short-Term Survival in Patients With Endometrial Cancer
Authors: Camila Santos Rodrigues, Gabriela Villaça Chaves
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Increasing evidence links sarcopenia and cancer prognosis, but limited data have focused on whether and to what extent muscle radiodensity can impact cancer outcomes. This study was conducted to investigate whether skeletal muscle mass, when divided into subranges of low or high radiodensity, improves prediction of short-term survival in patients with endometrial cancer (EC). Four skeletal muscle phenotypes were proposed to assess which is the best predictor of 1-year mortality. Methods: Patients with EC who had CT images available within 30 days before treatment (n=208) were enrolled in a retrospective cohort. CT images at the third lumbar vertebra (L3) were used to assess overall skeletal muscle index (SMI), which was then divided into subranges of radiation attenuation: low- and high-radiodensity SMI. The average muscle radiation attenuation (AMA) was also assessed. SMI and AMA were categorized as below or above the median and as below or above 30 Hounsfield units (HU), respectively, to construct 4 skeletal muscle phenotypes: "high SMI + high AMA"; "low SMI + high AMA"; "high SMI + low AMA"; and "low SMI + low AMA". One-year survival was evaluated using the Kaplan-Meier method and Cox multiple regression analysis. Results: All of the skeletal muscle parameters, except the SMI, were significantly associated with shorter 1-year survival. The skeletal muscle phenotype of "low SMI + low AMA" showed the strongest association with 1-year mortality (hazard ratio, 5.36; 95% CI, 1.70–16.51). Conclusions: The additional value of classifying the skeletal muscle into subranges of radiodensity should be explored in the future. Evaluating the impact of skeletal muscle phenotypes on cancer prognosis is promising and must be assessed in further studies.
Turkish medical leaders are arrested after protesting against Syria incursion
Authors: Owen Dyer
Journal: BMJ (2018)

The senior leadership of the Turkish Medical Association (TTB) is either in detention or being hunted by police after authorities issued arrest warrants for 11 of its administrators including its chair, Rasit Tukel.1 Several hours after the first dawn raids eight of the 11 doctors were in custody, the ministry said, while police operations continued in eight provinces to find the others.

The Ankara public prosecutor’s office said that those apprehended would be questioned on suspicion of “making propaganda for a terrorist organisation,” “praising crimes and criminals,” and “inciting the public to hatred or hostility”—referring to a statement by the TTB on 24 January in which doctors called for a halt to Turkey’s …
Population-based cancer screening programmes in low-income and middle-income countries: regional consultation of the International Cancer Screening Network in India
Authors: Sudha Sivaram, Gautam Majumdar, Douglas Perin, Ashrafun Nessa, Mireille Broeders, Elsebeth Lynge, Mona Saraiya, Nereo Segnan, Rengaswamy Sankaranarayanan, Preetha Rajaraman, Edward Trimble, Stephen Taplin, GK Rath, Ravi Mehrotra
Journal: The Lancet Oncology (2018)
Pre-existing Immunity to Oncolytic Virus Potentiates Its Immunotherapeutic Efficacy
Authors: Jacob M. Ricca, Anton Oseledchyk, Tyler Walther, Cailian Liu, Levi Mangarin, Taha Merghoub, Jedd D. Wolchok, Dmitriy Zamarin
Journal: Molecular Therapy (2018)

Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle Disease Virus (NDV) as a model, we explore the effects of pre-existing anti-viral immunity on therapeutic efficacy in syngeneic mouse tumor models. Unexpectedly, we find that while pre-existing immunity to NDV limits its replication in tumors, tumor clearance, abscopal anti-tumor immune effects, and survival are not compromised and, on the contrary, are superior in NDV-immunized mice. These findings demonstrate that pre-existing immunity to NDV may increase its therapeutic efficacy through potentiation of systemic anti-tumor immunity, which provides clinical rationale for repeated therapeutic dosing and prompts investigation of such effects with other OVs. Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle Disease Virus (NDV) as a model, we explore the effects of pre-existing anti-viral immunity on therapeutic efficacy in syngeneic mouse tumor models. Unexpectedly, we find that while pre-existing immunity to NDV limits its replication in tumors, tumor clearance, abscopal anti-tumor immune effects, and survival are not compromised and, on the contrary, are superior in NDV-immunized mice. These findings demonstrate that pre-existing immunity to NDV may increase its therapeutic efficacy through potentiation of systemic anti-tumor immunity, which provides clinical rationale for repeated therapeutic dosing and prompts investigation of such effects with other OVs.
Abstract 65: Latrophilin-2 is a Specific Cell-surface Marker for Cardiac Progenitor Cells and Specifies Cardiac Lineage Commitment and Development
Authors: Hyun-Jai Cho, Choon-Soo Lee, Jin-Woo Lee, Jung-Kyu Han, Han-Mo Yang, Yoo-Wook Kwon, Hyo-Soo Kim
Journal: Circulation Research (2016)

Backgrounds: The identification of a lineage-specific marker plays a pivotal role in understanding developmental process and is utilized to isolate a certain cell type with high purity for the therapeutic purpose. We here report a new cardiac-specific marker, and demonstrate its functional significance in the cardiac development. Methods and Results: When mouse pluripotent stem cells (ES and iPS cells) were stimulated with BMP4, Activin A, bFGF and VEGF, they differentiated into cardiac cells. To screen cell-surface expressing molecules on cardiac progenitor cells compared to undifferentiated mouse iPS and ES cells, we isolated Flk1+/PDGFRa+ cells at differentiation day 4 and performed microarray analysis. Among candidates, we identified a new G protein-coupled receptor, Latrophilin-2 (LPHN2) whose signaling pathway and its effect on cardiac differentiation is unknown. In sorting experiments under cardiac differentiation condition, LPHN2+ cells derived from pluripotent stem cells strongly expressed cardiac-related genes (Mesp1, Nkx2.5, aMHC and cTnT) and exclusively gave rise to beating cardiomyocytes, as compared with LPHN2- cells. LPHN2-/- mice revealed embryonically lethal and huge defects in cardiac development. Interestingly, LPHN2+/- heterozygotes were alive and fertile. For the purpose of cardiac regeneration, we transplanted iPS-derived LPHN2+ cells into the infarcted heart of adult mice. LPHN2+ cells differentiated into cardiomyocytes, and systolic function of left ventricle was improved and infarct size was reduced. We confirmed LPHN2 expression on human iPS and ES cell-derived cardiac progenitor cells and human heart. Conclusions: We demonstrate that LPHN2 is a functionally significant and cell-surface expressing marker for both mouse and human cardiac progenitor and cardiomyocytes. Our findings provide a valuable tool for isolating cardiac lineage cells from pluripotent stem cells and an insight into cardiac development and regeneration.
Prevalence of Pulmonary Embolism in Patients With Syncope
Authors: Giorgio Costantino, Martin H. Ruwald, James Quinn, Carlos A. Camargo, Frederik Dalgaard, Gunnar Gislason, Tadahiro Goto, Kohei Hasegawa, Padma Kaul, Nicola Montano, Anna-Karin Numé, Antonio Russo, Robert Sheldon, Monica Solbiati, Benjamin Sun, Giovanni Casazza
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> Sparse data and conflicting evidence exist on the prevalence of pulmonary embolism (PE) in patients with syncope. <h3>Objective</h3> To estimate the prevalence of PE among patients presenting to the emergency department (ED) for evaluation of syncope. <h3>Design, Setting, and Participants</h3> This retrospective, observational study analyzed longitudinal administrative data from 5 databases in 4 different countries (Canada, Denmark, Italy, and the United States). Data from all adult patients (aged ≥18 years) who presented to the ED were screened to identify those with syncope codes at discharge. Data were collected from January 1, 2000, through September 30, 2016. <h3>Main Outcomes and Measures</h3> The prevalence of PE at ED and hospital discharge, identified using codes from the<i>International Classification of Diseases</i>, was considered the primary outcome. Two sensitivity analyses considering prevalence of PE at 90 days of follow-up and prevalence of venous thromboembolism were performed. <h3>Results</h3> A total of 1 671 944 unselected adults who presented to the ED for syncope were included. The prevalence of PE, according to administrative data, ranged from 0.06% (95% CI, 0.05%-0.06%) to 0.55% (95% CI, 0.50%-0.61%) for all patients and from 0.15% (95% CI, 0.14%-0.16%) to 2.10% (95% CI, 1.84%-2.39%) for hospitalized patients. The prevalence of PE at 90 days of follow-up ranged from 0.14% (95% CI, 0.13%-0.14%) to 0.83% (95% CI, 0.80%-0.86%) for all patients and from 0.35% (95% CI, 0.34%-0.37%) to 2.63% (95% CI, 2.34%-2.95%) for hospitalized patients. Finally, the prevalence of venous thromboembolism at 90 days ranged from 0.30% (95% CI, 0.29%-0.31%) to 1.37% (95% CI, 1.33%-1.41%) for all patients and from 0.75% (95% CI, 0.73%-0.78%) to 3.86% (95% CI, 3.51%-4.24%) for hospitalized patients. <h3>Conclusions and Relevance</h3> Pulmonary embolism was rarely identified in patients with syncope. Although PE should be considered in every patient, not all patients should undergo evaluation for PE.
Mutation detection in circulating tumor DNA in stage I vs. later stage cancer samples.
Authors: Aaron Chen, Sean Li, Jair Jaboni, Megan Anselmo, Julie A Neidich, Glenn D Braunstein, Anja Kammesheidt
Journal: Journal of Clinical Oncology (2016)

e23046 Background: Tumor cells release small DNA fragments into the bloodstream as circulating tumor DNA (ctDNA), a subset of cell-free DNA (cfDNA). CancerIntercept is a CLIA validated, laboratory-developed blood test that can be used by physicians as a screening tool for the detection of biomarkers associated with specific cancer types in patients without a cancer diagnosis but at high risk for developing a cancer or as a test to monitor patients who have been diagnosed with cancer. The assay detects the presence of 96 mutations in nine genes (BRAF, CTNNB1, EGFR, FOXL2, GNAS, KRAS, NRAS, PIK3CA, TP53). Since less has been published about ctDNA mutation detection in patients with early stage cancers, we sought to determine the frequency detected in these patients in comparison to those with stage III or IV tumors. Methods: 45 commercial plasma samples from individuals with stage I-II cancer and 36 samples from patients with stage III-IV cancer were analyzed. Cancer types included breast, colorectal, \endometrial, gastric, lung, melanoma, ovarian, pancreatic, thyroid, head and neck, and prostate cancer. Clinical information such as grade, TNM, tumor size, lymph node status was available for most samples. For each sample, 1-2 ml of frozen plasma were processed, cfDNA isolated, and run on the 96 mutation panel for ctDNA enrichment followed by next-generation sequencing. Results: Six of the 42 stage I specimens (14%) had at least one positive mutation above limit of detection (2/6 gastric, 3/7 pancreatic, 1/8 thyroid cancer). One pancreatic cancer sample had two mutations. Notably these mutations were detected in individuals with stage IA, T1N0M0 tumors. 18 (50%) of the stage III-IV samples had mutations detected (3/9 breast, 6/9 colorectal, 3/7 lung, 1/1 endometrial, 3/7 pancreatic, 1/1 gastric, 1/1 ovarian). The mutations found in the stage I cancers include recurrent mutations in TP53, GNAS and KRAS. The later stage samples harbored mutations in all of the genes except BRAF and FOXL2, and several samples had multiple mutations and higher on average copy numbers. Conclusions: Overall the ctDNA mutation rate in the stage I cancers we examined was 14%, while stage III-IV samples had a higher mutation rate (50%) and higher numbers of mutations per sample.