tbuckley/cabot-search huggingface dataset:
Abstract 17087: VNS Induced Early Suppression of the Excessive Inflammatory Response May Contribute to its Beneficial Effects on Chronic Heart Failure
Authors: Akiko Nishizaki, Keita Saku, Takuya Kishi, Tomomi Ide, Kenji Sunagawa
Journal: Circulation (2015)

Background: The inflammatory response plays a pivotal role in the pathogenesis of chronic heart failure (CHF). Although vagal nerve stimulation (VNS) improves CHF, the central mechanism remains unclear. Since VNS exerts powerful anti-inflammatory effects, we investigated how VNS impacts on the inflammatory regulation and the development of CHF. Methods: In 8 weeks old Sprague-Dawley rats, we created large myocardial infarction (MI) and started VNS 2 weeks after MI. We adjusted the intensity of VNS below the threshold of bradycardia (20 Hz, 1.5±0.9 volts, 10 sec on, 50 sec off). In the first group (EARLY) (CHF: n=8, VNS: n=13), we continued VNS for 3 days and evaluated the early impact of VNS on inflammation on the 3rd day. In the second group (LATE) (CHF: n=13, VNS: n=13), we continued VNS for 4 weeks and evaluated cardiac remodeling and function on the last day. Results: In EARLY, hemodynamic parameters or plasma BNP as an index of CHF did not change significantly. In contrast, VNS halved the invasion of CD 68 positive cells in the left ventricle (LV) (CHF: 295.1±142.1, VNS: 110.7±59.6 counts/mm2, p&lt;0.01), and markedly reduced interleukin-1β (IL-1β) not only in plasma (CHF: 75.7±27.6, VNS: 32.9±6.8 pg/mL, p&lt;0.01) but also in the heart (CHF: 13.2±4.6, VNS: 9.3±2.4 pg/mg, p&lt;0.05) and spleen (CHF: 170.2±65, VNS: 115.4±58.8 pg/mg, p&lt;0.05). TNF-α, IL-6, HMGB-1 and CRP remained unchanged. In addition, VNS significantly reduced the expression of TGF-β in LV which is a key mediator of fibroblast activation (CHF: 31±4.0, VNS: 16.6±2.0 %, p&lt;0.01). In LATE, VNS significantly decreased cardiac fibrosis (Masson’s trichrome stain) (CHF: 4.4±0.7, VNS: 2.9±1.1 %, p&lt;0.01), heart weight (CHF: 3.7±0.5, VNS: 3.2±0.5 g/kg, p&lt;0.01) and LVEDP (CHF: 24.2±5.0, VNS: 17.5±7.1 mmHg, p&lt;0.01), suggesting that VNS prevented cardiac remodeling and preserved LV function. Conclusion: VNS significantly decreased the invasion of macrophage, IL-1β and TGF-β production from the beginning of VNS initiation, and resulted in the decrease of cardiac fibrosis and the improvement of cardiac remodeling as well as cardiac function. VNS induced early suppression of the excessive inflammatory response may lead to its late beneficial effects on CHF.
Performance on cancer quality measures: Ethnicity, insurance, and census division disparities.
Authors: Amanda Browner, Bryan E. Palis, E. Greer Gay, Katherine Mallin, Ryan M. McCabe, Matt Facktor, Ted James, Lawrence N. Shulman
Journal: Journal of Clinical Oncology (2018)

34 Background: Since enactment of Healthy People 2000 (ODPHP.gov, nd), a focus has been to reduce disparity by achieving health equity across all people. We examined disparity for five cancer quality measures with high performance rates (PRs) ( &gt; 85%). Methods: Five measures developed by the Commission on Cancer and endorsed by the National Quality Forum were evaluated for potential ethnicity, insurance, and Census Division disparities. Data from the National Cancer Database were used to examine hospital-level PRs on adjuvant chemotherapy for ER neg breast ca (MAC), hormone therapy for ER+ breast ca (HT), resection of at least 12 nodes in a colon resection (12RLN), and adjuvant chemotherapy for stage III colon ca (ACT) measures for patients diagnosed in 2015. Patients receiving radiation after breast conservation surgery (BCSRT) were diagnosed in 2014 to ensure complete treatment follow-up. Results: Significant disparities exist for all measures on ethnicity between non-Hispanic whites and Hispanics. The least variation of ethnicity occurred within 12RLN (non-significant). Variability within insurance was found most frequently with HT and BCSRT measures, not insured/Medicaid versus Medicare, and not insured/Medicaid versus Private respectively. Location disparity exists for all measures, with South Central states’ significantly lower PRs. Further investigation should focus on access, insurability, and delivery of care to better understand and eliminate disparities. Conclusions: Cancer quality measures, which show high performance nationally, show significant performance variability reflective of on-going disparities of care. [Table: see text]
The estrogen–macrophage interplay in the homeostasis of the female reproductive tract
Authors: Giovanna Pepe, Massimo Locati, Sara Della Torre, Federica Mornata, Andrea Cignarella, Adriana Maggi, Elisabetta Vegeto
Journal: Human Reproduction Update (2018)

Estrogens are known to orchestrate reproductive events and to regulate the immune system during infections and following tissue damage. Recent findings suggest that, in the absence of any danger signal, estrogens trigger the physiological expansion and functional specialization of macrophages, which are immune cells that populate the female reproductive tract (FRT) and are increasingly being recognized to participate in tissue homeostasis beyond their immune activity against infections. Although estrogens are the only female gonadal hormones that directly target macrophages, a comprehensive view of this endocrine-immune communication and its involvement in the FRT is still missing.Recent accomplishments encourage a revision of the literature on the ability of macrophages to respond to estrogens and induce tissue-specific functions required for reproductive events, with the aim to envision macrophages as key players in FRT homeostasis and mediators of the regenerative and trophic actions of estrogens.We conducted a systematic search using PubMed and Ovid for human, animal (rodents) and cellular studies published until 2018 on estrogen action in macrophages and the activity of these cells in the FRT.Our search identified the remarkable ability of macrophages to activate biochemical processes in response to estrogens in cell culture experiments. The distribution at specific locations, interaction with selected cells and acquisition of distinct phenotypes of macrophages in the FRT, as well as the cyclic renewal of these properties at each ovarian cycle, demonstrate the involvement of these cells in the homeostasis of reproductive events. Moreover, current evidence suggests an association between estrogen-macrophage signaling and the generation of a tolerant and regenerative environment in the FRT, although a causative link is still missing.Dysregulation of the functions and estrogen responsiveness of FRT macrophages may be involved in infertility and estrogen- and macrophage-dependent gynecological diseases, such as ovarian cancer and endometriosis. Thus, more research is needed on the physiology and pharmacological control of this endocrine-immune interplay.
Abstract 13968: Automated Pulse Detection is Achieved by Analysis of the Activity Level and Periodicity of Accelerometer Signals Acquired at the Carotid Site
Authors: Kiran H Dellimore, Ralph Wijshoff, Jakob van de Laar, Jens Muehlsteff, James K Russell, Pia Hubner, Fritz Sterz
Journal: Circulation (2016)

Introduction: Manual palpation during cardiopulmonary resuscitation (CPR) is the gold standard for pulse assessment by professional rescuers. However, this method is unreliable and time-consuming. A fast, reliable, and objective assessment of pulse presence remains an unmet need. Hypothesis: Automatic pulse presence detection is feasible by assessing the activity level and periodicity of accelerometer (ACC) signals acquired at the carotid site during CPR. Methods: A 2-step classification algorithm was developed using the activity level and periodicity of ACC signals to identify 4 categories: ‘Pulse’ (low activity and periodic), ‘No-pulse’ (low-activity and aperiodic), ‘CPR’ (high activity and periodic) or ‘Artifact’ (high activity and aperiodic). This approach uses 3 features extracted from non-overlapping 3 s windows of data: signal energy, peak prominence and rate. The algorithm analyzes the norm of the 3-axis ACC signals, computed after normalization by the gravitational constant and filtering between 0.5 and 12 Hz. The classifier was trained on data from 5 male patients (age range = 45-70 years) undergoing CPR in a hospital, with ACC signals sampled at 125 Hz. The performance was assessed by benchmarking against manual classification of artefacts, chest compressions, pulses, and pulse absence by visual inspection of all signals done by experts in the field. Results: Activity classification in all cases yielded sensitivity and specificity &gt;90.3% and &gt;88.8%, respectively (Fig. 1). For CPR classification the sensitivity and specificity was &gt;71.9% and &gt;71.6%, respectively, while for pulse classification the sensitivity and specificity was &gt;51.9% and &gt;39.5%, respectively. Conclusions: Automated pulse presence detection based on the activity level and periodicity of ACC signals at the carotid site is feasible with reasonable sensitivity and specificity. Automatic ACC-based pulse palpation could provide objective pulse detection support during CPR.
OP0264 Glucosepane : a new biomarker of the severity of osteoarthritis
Authors: N. Rabbani, U. Ahmed, C. Lambert, C. Legrand, A. Anwar, K. Rajpoot, S. Pasha, R.K. Davidson, I.M. Clark, P.J. Thornalley, Y. Henrotin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Glycation, oxidation and nitration of proteins are reactions involved in accelerated ageing of tissues. The products of these reactions are used as biomarkers of chronic pathologies such as diabetes or chronic inflammatory states. <h3>Objectives</h3> In this work, we studied by mass spectrometry the levels of amino acids and glycated, oxidised or nitrated proteins in culture media of chondrocytes cultivated in multi-layers and in the blood of guinea pigs or osteoarthritis patients. <h3>Methods</h3> Sixty male, 3-week-old Dunkin-Hartley guinea pigs were used in this work. At 4-weeks-old and 8 week intervals until week 36, twelve animals were sacrificed and histological severity of knee osteoarthritis evaluated and cartilage rheological properties. Human patients with early and advanced osteoarthritis and healthy subjects were recruited. Human chondrocytes cultured in multilayers were treated for 10 days with interleukin (IL) −1β. Amino acids and glycated, oxidised and nitrated proteins were analysed in the serum of guinea pigs, osteoarthritis patients and in the culture medium conditioned by chondrocytes by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry using the Acquity UPLC system. <h3>Results</h3> Severity of osteoarthritis increased progressively in guinea pigs with age. Glycated, oxidised and nitrated amino acids were increased markedly at week 36. Glucosepane and dityrosine increased progressively from weeks 20 and 28, respectively. Glucosepane was positively correlated with the OA histological severity (r=0.58, p&lt;0.0001) and the Young's modulus (r=0.52–0.56, p&lt;0.0001). Oxidation free adducts were positively correlated with OA severity (p&lt;0.0009–0.0029) and hydroxyproline with cartilage thickness (p&lt;0.0003–0.003). In the clinical study, plasma glucosepane was increased 38% in patients with early osteoarthritis (p&lt;0.05) and 6-fold in patients with advanced osteoarthritis (p&lt;0.001) compared to healthy subjects. IL-1β increased the release of glycated, oxidised and nitrated products from chondrocytes <i>in vitro</i>. <h3>Conclusions</h3> The glycation, oxidation and nitration of proteins are reactions related to the severity of osteoarthritis. The products of these reactions are measurable in blood by mass spectrometry and could be biomarkers of osteoarthritis. More specifically, glucosepane is an advanced glycation product very strongly increased in the severe form of the disease. In conclusion, serum glucosepane is a potential biomarker for diagnosis and progression of osteoarthritis. <h3>Disclosure of Interest</h3> None declared
Abstract 10275: Aortic Dilatation is Common in Hypertrophic Cardiomyopathy
Authors: Jeffrey B Geske, Nicholas M Orme, A J Tajik, Steve R Ommen
Journal: Circulation (2015)

Introduction: Aortic dilatation has been associated with various cardiac conditions, although its prevalence and clinical correlates in hypertrophic cardiomyopathy (HCM) remains unclear. Hypothesis: We hypothesized that tubular ascending aorta dilatation would be common in a large referral population of patients with HCM. Furthermore, we hypothesized that aortic size would correlate with age and presence of left ventricular outflow tract obstruction. Methods: 1704 patients with HCM underwent echocardiographic measurement of the tubular ascending aorta during index evaluation at a tertiary HCM referral center. End-diastolic ascending aorta dimension was indexed to body surface area, with dilatation defined as two standard deviations above normal (&gt;19 mm/m2). Aortic size and presence of aortic enlargement were correlated with clinical and echocardiographic parameters. Results: Aortic dilatation was present in 304 patients with HCM (18%). Indexed ascending thoracic aorta dimension was 16.5 (IQR 17.8-18.2) mm/m2 (Figure 1). Indexed dimension increased linearly with age (R=0.53, p&lt;0.0001). Women and patients with a history of systemic hypertension were more likely to have aortic enlargement (29.8% vs 9.9% and 24.1% vs 10.6%, p&lt;0.0001 for both). There was a correlation between resting left ventricular outflow tract gradient and indexed aortic dimension (R=0.12, p&lt;0.0001) and patients with either resting (≥30 mmHg) or provocable obstruction (≥50 mmHg) were more likely to have aortic enlargement (19.6% vs 14.3%, p=0.006). Conclusions: In this large cohort of patients with HCM, aortic dilatation was common. Key correlates of aortic enlargement included age, female sex, history of hypertension and left ventricular outflow tract obstruction. Given an increased prevalence of aortic dilatation in HCM, further study is needed on the clinical impact of aortic dilatation.
Implementation of oral chemotherapy management program in the large integrated health care system and its impact on patient safety.
Authors: Jessica Yoo, Salin Nhean, Prabha Vogel, Igor I. Rybkin, Diana Kostoff
Journal: Journal of Clinical Oncology (2018)

279 Background: Oral chemotherapy is a progressively growing portion of antineoplastic agents. Although convenient for the patient, it creates a unique challenges for the drug complacency and safety. To address these issues variety of programs and solutions were proposed, ranging from the smart pill bottles and mobile phone applications to telemedicine monitoring programs. This presentation describes development and implementation of the integrated monitoring program within a large health care system and assess impact of this program on patients safety and compliance. Methods: This is a retrospective, quasi-experimental study that compared outcomes of the patients treated with capecitabine, before and after implementation of OCMP (Oral Chemotherapy Management Program) in the Henry Ford Health System. The primary outcome was incidence of all grade and specifically grade 3-4 toxicities commonly associated with capecitabine. Secondary outcomes included emergency department (ED) visits and hospitalizations due to toxicity, adherence rates, and number of clinical interventions. Results: The incidence of adverse effects of Any Grade was significantly lower in the post-OCMP group compared to pre-OCMP group (70.3% vs 58.9%; 95% CI, 0.39-0.94; P = 0.03). All grade and grade 3-4 nausea, vomiting and diarrhea along with grade 3-4 hand-foot syndrome were significantly lower in the post-OCMP group, as well as decreased ED visits (18.9% vs. 8.6%; P = 0.005) and hospitalizations due to toxicities (17.1% vs. 6.3%; P = 0.002). The study also found higher adherence rates in the post-OCMP group. In the post-OCMP period, more than 50% of the patients required clinical interventions by OCMP nurse, mostly for side effect management. Conclusions: Administration of capecitabine on OCMP reduced rate of higher grade adverse events, most likely due to early intervention. OCMP implementation was associated with decreased rate of ED visits and hospitalizations due to the side effects. Patients who were managed by OCMP had higher adherence rates to the prescribed oral chemotherapy.
Clinical decision support to reduce laterality ordering errors for breast imaging procedures.
Authors: Karen Hernandez, Mahmoud El-Tamer, Jonathan Gurman, Robin Moulder, Reshma Nevrekar, Donna Robinson, Kimberly Sarwan-Vega, Svetlana Granovsky
Journal: Journal of Clinical Oncology (2018)

241 Background: Data showed 46 modifications to breast imaging orders upon patient arrival to the Radiology Department, in a 4 month period (Sept-Dec 2014.) Upon further investigation, we found that patients were arriving in radiology, scheduled for exams for which the laterality needed to be modified prior to the exam. (The most frequent occurrence was a patient with a history of a unilateral mastectomy, arriving in radiology for a bilateral mammogram.) These laterality order errors were traced back to either the referring LIP requesting the exam, or to the referring office’s clerical staff transcribing the order. The ordering errors came from many different referring services. Methods: Our objective was to develop Clinical Decision Support in our Clinical Information System (CIS,) to offer an upfront alert of a potentially incorrect laterality when a user was entering or transcribing an order, prompting the user to confirm that the correct exam had been ordered before scheduling took place. The Health Informatics team developed a Medical Logic Module (MLM) in CIS which cross-checks the surgical history in the Clinical Documentation Operative Notes with the current CIS order; if a mismatch is found, the alert fires. Results: In the first 2 months (Dec 2016-Jan 2017), 110 alerts were generated. Fifty-seven alerts flagged users of incorrect orders which were corrected before being scheduled; 21 MLM alerts were acknowledged and comments entered explaining the need for the test; 32 alerts did not generate an order (and in most of these instances, the user backed out and entered the incorrect order again; upon the second time seeing the alert, they changed the order, resulting in many of the 57 changed orders referenced above). Conclusions: The MLM alert allows for immediate feedback to the user entering an order with a potentially incorrect laterality. Not only does this reduce the time and burden associated with investigating and modifying these orders upon patient arrival; more importantly, it ensures orders are entered correctly from the start, reducing the possibility of an incorrect exam taking place.
The Association of Severe Diabetic Retinopathy With Cardiovascular Outcomes in Long-standing Type 1 Diabetes: A Longitudinal Follow-up
Authors: Drazenka Pongrac Barlovic, Valma Harjutsalo, Daniel Gordin, Milla Kallio, Carol Forsblom, George King, Per-Henrik Groop
Journal: Diabetes Care (2018)

OBJECTIVE It is well established that diabetic nephropathy increases the risk of cardiovascular disease (CVD), but how severe diabetic retinopathy (SDR) impacts this risk has yet to be determined. RESEARCH DESIGN AND METHODS The cumulative incidence of various CVD events, including coronary heart disease (CHD), peripheral artery disease (PAD), and stroke, retrieved from registries, was evaluated in 1,683 individuals with at least a 30-year duration of type 1 diabetes drawn from the Finnish Diabetic Nephropathy Study (FinnDiane). The individuals were divided into four groups according to the presence of diabetic kidney disease (DKD) and/or SDR (+DKD/+SDR, +DKD/−SDR, −DKD/+SDR, and −DKD/−SDR) at baseline visit. Furthermore, age-specific incidences were compared with 4,016 control subjects without diabetes. SDR was defined as laser photocoagulation and DKD as estimated glomerular filtration rate &amp;lt;60 mL/min/1.73 m2. RESULTS During 12,872 person-years of follow-up, 416 incident CVD events occurred. Even in the absence of DKD, SDR increased the risk of any CVD (hazard ratio 1.46 [95% CI 1.11–1.92]; P &amp;lt; 0.01), after adjustment for diabetes duration, age at diabetes onset, sex, smoking, blood pressure, waist-to-hip ratio, history of hypoglycemia, and serum lipids. In particular, SDR alone was associated with the risk of PAD (1.90 [1.13–3.17]; P &amp;lt; 0.05) and CHD (1.50 [1.09–2.07; P &amp;lt; 0.05) but not with any stroke. Moreover, DKD increased the CVD risk further (2.85 [2.13–3.81]; P &amp;lt; 0.001). However, the risk was above that of the control subjects without diabetes also in patients without microvascular complications, until the patients reached their seventies. CONCLUSIONS SDR alone, even without DKD, increases cardiovascular risk, particularly for PAD, independently of common cardiovascular risk factors in long-standing type 1 diabetes. More remains to be done to fully understand the link between SDR and CVD. This knowledge could help combat the enhanced cardiovascular risk beyond currently available regimens.
Myofibroblast-Specific TGFβ Receptor II Signaling in the Fibrotic Response to Cardiac Myosin Binding Protein C-Induced Cardiomyopathy
Authors: Qinghang Meng, Bidur Bhandary, Md Shenuarin Bhuiyan, Jeanne James, Hanna Osinska, Iñigo Valiente-Alandi, Kritton Shay-Winkler, James Gulick, Jeffery D. Molkentin, Burns C. Blaxall, Jeffrey Robbins
Journal: Circulation Research (2018)

Rationale: Hypertrophic cardiomyopathy occurs with a frequency of about 1 in 500 people. Approximately 30% of those affected carry mutations within the gene encoding cMyBP-C (cardiac myosin binding protein C). Cardiac stress, as well as cMyBP-C mutations, can trigger production of a 40kDa truncated fragment derived from the amino terminus of cMyBP-C (Mybpc3 40kDa ). Expression of the 40kDa fragment in mouse cardiomyocytes leads to hypertrophy, fibrosis, and heart failure. Here we use genetic approaches to establish a causal role for excessive myofibroblast activation in a slow, progressive genetic cardiomyopathy—one that is driven by a cardiomyocyte-intrinsic genetic perturbation that models an important human disease. Objective: TGFβ (transforming growth factor-β) signaling is implicated in a variety of fibrotic processes, and the goal of this study was to define the role of myofibroblast TGFβ signaling during chronic Mybpc3 40kDa expression. Methods and Results: To specifically block TGFβ signaling only in the activated myofibroblasts in Mybpc3 40kDa transgenic mice and quadruple compound mutant mice were generated, in which the TGFβ receptor II (TβRII) alleles ( Tgfbr2 ) were ablated using the periostin ( Postn ) allele, myofibroblast-specific, tamoxifen-inducible Cre ( Postnmcm ) gene-targeted line. Tgfbr2 was ablated either early or late during pathological fibrosis. Early myofibroblast-specific Tgfbr2 ablation during the fibrotic response reduced cardiac fibrosis, alleviated cardiac hypertrophy, preserved cardiac function, and increased lifespan of the Mybpc3 40kDa transgenic mice. Tgfbr2 ablation late in the pathological process reduced cardiac fibrosis, preserved cardiac function, and prolonged Mybpc3 40kDa mouse survival but failed to reverse cardiac hypertrophy. Conclusions: Fibrosis and cardiac dysfunction induced by cardiomyocyte-specific expression of Mybpc3 40kDa were significantly decreased by Tgfbr2 ablation in the myofibroblast. Surprisingly, preexisting fibrosis was partially reversed if the gene was ablated subsequent to fibrotic deposition, suggesting that continued TGFβ signaling through the myofibroblasts was needed to maintain the heart fibrotic response to a chronic, disease-causing cardiomyocyte-only stimulus.