tbuckley/cabot-search huggingface dataset:
Risk Factors Associated With Atrioventricular Block
Authors: Tuomas Kerola, Antti Eranti, Aapo L. Aro, M. Anette Haukilahti, Arttu Holkeri, M. Juhani Junttila, Tuomas V. Kenttä, Harri Rissanen, Eric Vittinghoff, Paul Knekt, Markku Heliövaara, Heikki V. Huikuri, Gregory M. Marcus
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Pacemaker implantations as a treatment for atrioventricular (AV) block are increasing worldwide. Prevention strategies for AV block are lacking because modifiable risk factors have not yet been identified. <h3>Objective</h3> To identify risk factors for AV block in community-dwelling individuals. <h3>Design, Setting, and Participants</h3> In this population-based cohort study, data from the Mini-Finland Health Survey, conducted from January 1, 1978, to December 31, 1980, were used to examine demographics, comorbidities, habits, and laboratory and electrocardiographic (ECG) measurements as potential risk factors for incident AV block. Data were ascertained during follow-up from January 1, 1987, through December 31, 2011, using a nationwide registry. A total of 6146 community-dwelling individuals were included in the analysis performed from January 15 through April 3, 2018. <h3>Main Outcomes and Measures</h3> Incidence of AV block (hospitalization for second- or third-degree AV block). <h3>Results</h3> Among the 6146 participants (3449 [56.1%] women; mean [SD] age, 49.2 [12.9] years), 529 (8.6%) had ECG evidence of conduction disease and 58 (0.9%) experienced a hospitalization with AV block. Older age (hazard ratio [HR] per 5-year increment, 1.34; 95% CI, 1.16-1.54;<i>P</i> &lt; .001), male sex (HR, 2.04; 95% CI, 1.19-3.45;<i>P</i> = .01), a history of myocardial infarction (HR, 3.54; 95% CI, 1.33-9.42;<i>P</i> = .01), and a history of congestive heart failure (HR, 3.33; 95% CI, 1.10-10.09;<i>P</i> = .03) were each independently associated with AV block. Two modifiable risk factors were also independently associated with AV block. Every 10–mm Hg increase in systolic blood pressure was associated with a 22% higher risk (HR, 1.22; 95% CI, 1.10-1.34;<i>P</i> = .005), and every 20-mg/dL increase in fasting glucose level was associated with a 22% higher risk (HR, 1.22; 95% CI, 1.08-1.35;<i>P</i> = .001). Both risk factors remained statistically significant (HR for systolic blood pressure, 1.26 [95% CI, 1.06-1.49;<i>P</i> = .007]; HR for glucose level, 1.22 [95% CI, 1.04-1.43;<i>P</i> = .01]) after adjustment for major adverse coronary events during the follow-up period. In population-attributable risk assessment, an estimated 47% (95% CI, 8%-67%) of AV blocks may have been avoided if all participants exhibited ideal blood pressure and 11% (95% CI, 2%-21%) may have been avoided if all had a normal fasting glucose level. <h3>Conclusions and Relevance</h3> In this analysis of data from a population-based cohort study, suboptimal blood pressure and fasting glucose level were associated with AV block. These results suggest that a large proportion of AV blocks are assocated with these risk factors, even after adjusting for other major adverse coronary events.
Reported Levels of Upset in Youth After Routine Trauma Screening at Mental Health Clinics
Authors: Ane-Marthe Solheim Skar, Silje Mørup Ormhaug, Tine K. Jensen
Journal: JAMA Network Open (2019)

Clinical guidelines recommend routine screening for trauma at youth mental health clinics. However, many clinicians are concerned that screening may be upsetting both for youths who have been exposed to trauma and for those who have not.To investigate levels of upset following routine trauma screening and whether type of trauma and symptoms of posttraumatic stress were associated with level of upset.Survey study in which data from routine screening for trauma exposure and trauma-related symptoms were collected from January 1, 2015, to December 31, 2017. Nearly half (n = 40) of all youth mental health clinics in Norway submitted survey data. Participants included youths aged 6 to 18 years referred to treatment.The trauma screening inventory, Child & Adolescent Trauma Screening Questionnaire, was administered. Self-reported levels of upset after initial screening were scored on a scale ranging from 1 (not upsetting) to 7 (very upsetting).Among 10 157 youths aged 6 to 18 years (mean [SD] age, 13.0 [3.1] years; 5320 [55.0%] female), surveyed, 8021 (79.1%) reported exposure to at least 1 potentially traumatizing event and a mean (SD) of 2.44 (2.27) different types of events (range, 0-15). Only 453 participants (4.5%) reported high levels of upset, while 2757 participants (27.2%) reported moderate levels of upset and 6942 participants (68.4%) reported no or low levels of upset. Youths who had been exposed to any type of traumatic event reported significantly higher levels of upset compared with those reporting no trauma exposure, and a higher number of reported traumatic events was associated with a higher level of upset (point estimate, 0.23; 95% CI, 0.22-0.24; P < .001). Among participants who reported trauma, exposure to sexual abuse (point estimate, 0.87; 95% CI, 0.77-0.95; P < .001) and higher levels of posttraumatic stress symptoms (point estimate, 0.05; 95% CI, 0.04-0.05; P < .001) were associated with higher levels of upset.A high level of trauma exposure was found among youths referred to youth mental health clinics, but trauma screening was well tolerated, with most participants reporting no or low levels of upset. These findings can be used to support therapists and health care leaders in implementing routine trauma screening to better identify youths who are in need of trauma-focused treatment.
Getting Coverage Right for 500 Million Indians
Authors: Sarthak Das, Ashish K. Jha
Journal: New England Journal of Medicine (2019)

India's health reform, Ayushman Bharat ("long life for India"), has two pillars: health insurance covering up to $7,000 of care per year for the poorest 500 million people (regardless of preexisting conditions) and reinvestment in primary care.
DIAGNOSTIC YIELD AND ACCURACY OF SMALL BOWEL ULTRASONOGRAPHY COMPARED TO CAPSULE ENTEROSCOPY FOR THE DIAGNOSIS OF SMALL BOWEL DISEASES
Authors: L Elli, E Centorrino, S Orlando, A Costantino, M Fraquelli, M Vecchi
Journal: Endoscopy (2019)

Capsule enteroscopy (VCE) is considered the reference standard for the assessment of small bowel disorders since it has the highest diagnostic yield for the detection of luminal and mucosal alterations. There are no studies comparing VCE with small bowel ultrasonography (B-US): the aim of this study was to compare the diagnostic yield of VCE and B-US in the diagnosis of small bowel disorders.
EARLY EXPERIENCE OF ENDOSCOPIC SUBSEROSAL DISSECTION (ESSD) FOR GASTRIC TUMORS
Authors: J Cho, S Yun, M Yang, Y Lee, B Kim, J Kim
Journal: Endoscopy (2019)

Most of gastric subepithelial tumors confined to submucosa can be resected by endoscopy. The endoscopic subtumorial resection for lesions originating from muscularis propria has been performed for the mass with submucosal or intramuscular growing only. Until now, the data for endoscopic subserosal dissection of gastric tumor was very rare.
Patient-Specific Tumor Growth Trajectories Determine Persistent and Resistant Cancer Cell Populations during Treatment with Targeted Therapies
Authors: Clemens Grassberger, David McClatchy, Changran Geng, Sophia C. Kamran, Florian Fintelmann, Yosef E. Maruvka, Zofia Piotrowska, Henning Willers, Lecia V. Sequist, Aaron N. Hata, Harald Paganetti
Journal: Cancer Research (2019)

Abstract The importance of preexisting versus acquired drug resistance in patients with cancer treated with small-molecule tyrosine kinase inhibitors (TKI) remains controversial. The goal of this study is to provide a general estimate of the size and dynamics of a preexisting, drug-resistant tumor cell population versus a slow-growing persister population that is the precursor of acquired TKI resistance. We describe a general model of resistance development, including persister evolution and preexisting resistance, solely based on the macroscopic trajectory of tumor burden during treatment. We applied the model to 20 tumor volume trajectories of EGFR-mutant lung cancer patients treated with the TKI erlotinib. Under the assumption of only preexisting resistant cells or only persister evolution, it is not possible to explain the observed tumor trajectories with realistic parameter values. Assuming only persister evolution would require very high mutation induction rates, while only preexisting resistance would lead to very large preexisting populations of resistant cells at the initiation of treatment. However, combining preexisting resistance with persister populations can explain the observed tumor volume trajectories and yields an estimated preexisting resistant fraction varying from 10−4 to 10−1 at the time of treatment initiation for this study cohort. Our results also demonstrate that the growth rate of the resistant population is highly correlated to the time to tumor progression. These estimates of the size of the resistant and persistent tumor cell population during TKI treatment can inform combination treatment strategies such as multi-agent schedules or a combination of targeted agents and radiotherapy. Significance: These findings quantify pre-existing resistance and persister cell populations, which are essential for the integration of targeted agents into the management of locally advanced disease and the timing of radiotherapy in metastatic patients.
Risks of High Coronary Artery Calcium
Authors: Kashif Shaikh, Matthew J. Budoff
Journal: JAMA Cardiology (2019)

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ROLE OF DOUBLE CHANNEL ENDOSCOPE (DCE) IN ENDOSCOPIC MUCOSAL RESECTION (EMR) COMPARED WITH CONVENTIONAL SINGLE CHANNEL ENDOSCOPE (SCE): EFFECTIVENESS AND SAFETY
Authors: S Sevilla-Ribota, T Gonzalez-Lopez, C Juarez-Perez, P Gullon, E Vazquez-Sequeiros, D Juzgado-Lucas
Journal: Endoscopy (2019)

EMR may present up to 25% complications and 15% recurrences. Polypectomy assisted with DCE has not been studied. Main objetives were determine clinical success and safety of EMR-DCE compared to SCE.
Mitochondrial Function, Skeletal Muscle Metabolism, and Iron Deficiency in Heart Failure
Authors: Peter van der Meer, Haye H. van der Wal, Vojtech Melenovsky
Journal: Circulation (2019)

Iron deficiency is one of the most prevalent comorbidities in chronic heart failure (HF), affecting more than half of all HF patients.The detrimental clinical and prognostic consequences of iron deficiency have been stressed by numerous studies. 1 However, the pathophysiology of iron deficiency in HF is largely unclear.Although anemia, as a consequence of iron deficiency, may seem a reasonable explanation for the adverse effects, iron deficiency without anemia was also strongly and independently associated with impaired quality of life, exercise intolerance, and mortality. 1Furthermore, the beneficial effects of intravenous iron in iron-deficient HF patients (ie, improvement in exercise tolerance, New York Heart Association Functional Classification, and quality of life) were irrespective of attained hemoglobin levels. 2,3These findings shifted the focus from hemoglobin toward more direct effects of iron itself on nonhematopoietic tissues that are important for exercise capacity, such as skeletal and cardiac muscle.It has also been acknowledged that the exercise intolerance of chronic HF patients is not solely explained by peripheral muscle underperfusion associated with cardiac dysfunction.5][6] Impaired mitochondrial respiration and contractility of iron-deficient human cardiomyocytes could be rescued by adding transferrin-bound iron to these cells. 4A more direct way to study the effects of iron status on exercise tolerance is to analyze mitochondrial respiratory function in skeletal muscle biopsies. 7However, this method provides static results and is associated with excessive burden to the patients, especially when multiple biopsies are taken.To study the consequences of iron deficiency on exercise capacity, a more dynamic approach is needed.Phosphorus-31 magnetic resonance spectroscopy ( 31 P MRS) is such a method, allowing noninvasive, real-time, in vivo measurement of oxidative skeletal muscle metabolism, both at rest and during exercise.With a phosphorus-31 coil, phosphorus-containing metabolites such as phosphocreatine (PCr), inorganic phosphate, and adenosine triphosphate (ATP) can be detected and quantified in human tissue.The high-energy bond between creatine and a phosphate group makes PCr a rapidly available anaerobic store of chemical energy in skeletal muscle cells.During exercise, PCr is depleted by donating high-energy phosphate groups to ADP, which converts into ATP, and the tight balance between ATP use and production is therefore kept intact.This process, facilitated by the enzyme creatine kinase, is later reverted in postexercise rest to regenerate the PCr pool from creatine and ATP.The largest portion of all ATP is derived by mitochondrial processes, of which many are iron-dependent.Iron is directly involved in several complexes of the respiratory chain, containing iron-sulfur clusters, but is also
Mammographic density change and risk of breast cancer
Authors: S. Azam, M. Eriksson, A. Sjölander, R. Hellgren, M. Gabrielson, K. Czene, P. Hall
Journal: Annals of Oncology (2019)

Background: Mammographic density (MD) is a strong risk factor for breast cancer. We examined the association between annual MD change and risk of breast cancer, and how adding annual MD change to baseline measure of MD influenced risk prediction of breast cancer. Methods: We used the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort (N = 43,347 Swedish women), with full access to risk factors for breast cancer and pre-diagnostic mammograms. MD was measured as dense area (cm2) using the STRATUS method. We calculated the relative MD area change between repeated examinations. Relative MD area change was categorized as stable (less than 10% decrease per year) and decrease (more than 10% decrease per year). Cox proportional hazard regression (HR) estimated the association of breast cancer with MD change. Interaction analyses investigated how relative MD change modifies the association between baseline MD and breast cancer risk. All statistical tests were two-sided. Results: Women who did not experience a MD decrease over time had a 27% significantly increased risk of breast cancer (HR = 1.27; 95% CI = 1.02 to 1.59) compared to those who decreased by at least 10% per year. The increased risk was confined to postmenopausal women. Stratifying women based on baseline MD did not seem to add to risk prediction with the exception of women in the lowest baseline MD group where women did not experience a MD decrease had a 74% higher risk (HR = 1.74; 95% CI = 1.10 to 2.75), again only seen in postmenopausal women. Conclusions: Our results suggest that annual MD change influences breast cancer risk in postmenopausal women but that adding MD change to baseline MD do not seem to substantially improve breast cancer risk prediction. Legal entity responsible for the study: Per Hall (Principle investigator). Funding: Märit and Hans Rausing's Inititive Against Breast Cancer. Disclosure: All authors have declared no conflicts of interest.
BRCA mutations among triple negative breast cancer without family history of breast and ovarian cancer: The Modena family cancer clinic experience
Authors: E. Molinaro, M. Venturelli, A. Toss, C. Piombino, E. Barbieri, L. Marcheselli, I. Marchi, E. Tagliafico, S. Cascinu, L. Cortesi
Journal: Annals of Oncology (2019)

Background: Because of the high costs associated with genetic analyses, BRCA1/2-testing has traditionally been restricted to breast cancer patients having an 'a priori high risk' of being a carrier. Particularly, according to The National Institute for Health and Care Excellence (NICE) in the UK, BRCA testing should be offered to breast cancer patients with a probability of having a mutation ≥ 10%. Regardless of family history, International Guidelines include among the BRCA testing Criteria, a personal history of triple negative breast cancer diagnosed ≤ 60 years. According to previous research, 15-30% of unselected TNBC had confirmed BRCA mutations. Whereas, among patients without breast/ovarian cancer family history mutation prevalence decrease to 6-15 %. Methods: In the archives of the Modena Family Cancer Clinic, we identified 126 patients diagnosed with TNBC without family history of breast/ovarian cancer, which underwent BRCA-genetic testing. Mutation prevalence and clinical-pathological characteristics were evaluated. Results: Among 126 triple-negative breast cancer patients without a family history of breast and/or ovarian cancer, a total of 20 patients (15.8%) were BRCA mutation carriers: 18 BRCA1 (14.2%), 2 BRCA2 (1.5%), 2 BRCA2 VUS (1.5%). The mutation prevalence was 7/20 (35%) in the age group 30-39 years, 9/55 (16.3%) in 40-49, 4/48 (8.3%) in 50-59, 0/1 (0%) in 60-69 and 0/2 (0%) in 70-79. BRCA1 patients were younger at diagnosis (44 yrs) than non-carriers (48 yrs). Histotype, tumor grade, ki-67 and the presence of second primary BC were equally distributed between carriers and non-carriers. Conclusions: Our results are aligned with the recent results of the German Consortium for Hereditary Breast and Ovarian Cancer, and justify BRCA mutation screening among women with TNBC diagnosed before the age of 60 years and no family history. Legal entity responsible for the study: Laura Cortesi. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
IL‐6 Trans‐signaling Controls Liver Regeneration After Partial Hepatectomy
Authors: Nastaran Fazel Modares, Robin Polz, Fereshteh Haghighi, Larissa Lamertz, Kristina Behnke, Yuan Zhuang, Claus Kordes, Dieter Häussinger, Ursula R. Sorg, Klaus Pfeffer, Doreen M. Floss, Jens M. Moll, Roland P. Piekorz, M. Reza Ahmadian, Philipp A. Lang, Jürgen Scheller
Journal: Hepatology (2019)

Interleukin‐6 (IL‐6) is critically involved in liver regeneration after partial hepatectomy (PHX). Previous reports suggest that IL‐6 trans‐signaling through the soluble IL‐6/IL‐6R complex is involved in this process. However, the long‐term contribution of IL‐6 trans‐signaling for liver regeneration after PHX is unknown. PHX‐induced generation of the soluble IL‐6R by ADAM (a disintegrin and metallo) proteases enables IL‐6 trans‐signaling, in which IL‐6 forms an agonistic complex with the soluble IL‐6 receptor (sIL‐6R) to activate all cells expressing the signal‐transducing receptor chain glycoprotein 130 (gp130). In contrast, without activation of ADAM proteases, IL‐6 in complex with membrane‐bound IL‐6R and gp130 activates classic signaling. Here, we describe the generation of IL‐6 trans‐signaling mice, which exhibit boosted IL‐6 trans‐signaling and abrogated classic signaling by genetic conversion of all membrane‐bound IL‐6R into sIL‐6R proteins phenocopying hyperactivation of ADAM‐mediated shedding of IL‐6R as single substrate. Importantly, although IL‐6R deficient mice were strongly affected by PHX, survival and regeneration of IL‐6 trans‐signaling mice was indistinguishable from control mice, demonstrating that IL‐6 trans‐signaling fully compensates for disabled classic signaling in liver regeneration after PHX. Moreover, we monitored the long‐term consequences of global IL‐6 signaling inhibition versus IL‐6 trans‐signaling selective blockade after PHX by IL‐6 monoclonal antibodies and soluble glycoprotein 130 as fragment crystallizable fusion, respectively. Both global IL‐6 blockade and selective inhibition of IL‐6 trans‐signaling results in a strong decrease of overall survival after PHX, accompanied by decreased signal transducer and activator of transcription 3 phosphorylation and proliferation of hepatocytes. Mechanistically, IL‐6 trans‐signaling induces hepatocyte growth factor production by hepatic stellate cells. Conclusion: IL‐6 trans‐signaling, but not classic signaling, controls liver regeneration following PHX.
Polypes coliques: Quelle prévalence? Quels facteurs associés?
Authors: A Ben Mohamed, M Mahmoudi, L Hamzaoui, M Medhioub, A Khsiba, MM Azouz
Journal: Endoscopy (2019)

Le taux de détection des adénomes et des polypes est corrélé au risque de cancer colorectal et il est par conséquent considéré comme un marqueur de qualité de la coloscopie. Le but de notre travail était de rechercher la prévalence des polypes ainsi que les facteurs associés à leur détection en pratique quotidienne.
Oral mucosal changes associated with primary diseases in other body systems
Authors: Sharon Elad, Yehuda Zadik, Jack G. Caton, Joel B. Epstein
Journal: Periodontology 2000 (2019)

Abstract Systemic diseases may manifest in the oral cavity. This chapter reviews the oral mucosal pathology in blood diseases, gastrohepatic diseases, kidney diseases, immunologic and connective tissue diseases, endocrine diseases, pulmonary diseases, nutritional deficiencies, dermatologic diseases, as well as cancer‐associated oral mucosal conditions. The oral mucosa is one of the most commonly affected tissues and may present with unique clinical appearances. Oral mucosal involvement may be the first presentation of the systemic disease or reflect activity or progression of the primary condition. Therefore, it is of importance to be familiar with oral mucosal manifestations of these systemic diseases.
COLONOSCOPY WITH THE 3D NAVIGATION SYSTEM SCOPEPILOT VERSUS STANDARD COLONOSCOPY
Authors: N Tscherwinski, F Straulino, A Genthner, S Kangalli, A Eickhoff
Journal: Endoscopy (2019)

The successful coecal intubation is a challenge but also a quality indicator in colonoscopy. Loop formation can complicate the advancement of the endoscope or even prevent reaching the coecum. The 3D navigation system SCOPEPILOT by Pentax allows a real time position monitoring of the endoscope during colonoscopy and should facilitate the intubation of the coecum. The aim of this study was to compare the coecal intubation time with and without SCOPEPILOT.