tbuckley/cabot-search huggingface dataset:
Trunk involvement and peau d'orange aspect are poor prognostic factors in eosinophilic fasciitis (Shulman disease): A multicenter retrospective study of 119 patients
Authors: Elina Zuelgaray, Sylvie Chevret, Marie Jachiet, Patrice Cacoub, Jean-Emmanuel Kahn, Matthieu Groh, Brigitte Granel, Manon Scafi, Loïk Geffray, François Chasset, Marc Gatfosse, Arsène Mekinian, Bertrand Lioger, Alfred Mahr, Francis Gaches, Martin Michaud, Isabelle Ludot, Florence Cordoliani, Adèle de Masson, Charles Cassius, Frédérique Retornaz, Alexandra Audemard-Verger, Céline Lartigau-Roussin, Mélanie Roriz, Benjamin Chaigne, Valérie Pallure, Isabelle Marie, Brice Castel, Valentine Loustau, Laurent Chiche, Pierre-Edouard Gavand, Pascal Cathebras, Stéphane Barete, Camille Frances, Emilie Brenaut, Yves Allenbach, Olivier Benveniste, Nicolas Noel, Geoffrey Urbanski, Olivier Hinschberger, Didier Bessis, Martine Bagot, Jean-David Bouaziz, Damien Sène
Journal: Journal of the American Academy of Dermatology (2020)
University of California pays out $73m to 6600 patients of gynaecologist charged with sexual assaults
Authors: Owen Dyer
Journal: BMJ (2020)

The University of California has agreed to pay $73m (£55.2m; €61.7m) to settle allegations that it failed to prevent a gynaecologist’s sexual abuse of hundreds or possibly thousands of female patients.

James Heaps, 67, is also charged with 20 felonies, including two counts of sexual exploitation of a patient, eight counts of sexual battery by fraud, and seven counts of sexual penetration of a person unconscious of the nature of the act by fraudulent representation.

Several women have said that he simulated intercourse, often roughly, with an ultrasound probe. He also made inappropriate sexual comments to patients and touched women sexually during exams without wearing gloves.

The class action lawsuit that led to the settlement was brought by …
AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer
Authors: Michael J. Giffin, Keegan Cooke, Edward K. Lobenhofer, Juan Estrada, Jinghui Zhan, Petra Deegen, Melissa Thomas, Christopher M. Murawsky, Jonathan Werner, Siyuan Liu, Fei Lee, Oliver Homann, Matthias Friedrich, Joshua T. Pearson, Tobias Raum, Yajing Yang, Sean Caenepeel, Jennitte Stevens, Pedro J. Beltran, Jude Canon, Angela Coxon, Julie M. Bailis, Paul E. Hughes
Journal: Clinical Cancer Research (2020)

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with a high relapse rate, limited therapeutic options, and poor prognosis. We investigated the antitumor activity of AMG 757, a half-life extended bispecific T-cell engager molecule targeting delta-like ligand 3 (DLL3)-a target that is selectively expressed in SCLC tumors, but with minimal normal tissue expression.
Abstract 13932: Lung-targeted Sin3a Gene Therapy as a Promising Strategy to Restore Bmpr2 Expression in Pulmonary Arterial Hypertension
Authors: Malik Bisserier, Prabhu Mathiyalagan, Yassine Abdeldjebbar, Shihong Zhang, Firas Elmastour, Peter Dorfmüller, Marc Humbert, Yassine Sassi, Thomas Weber, Frederic Perros, Susmita Sahoo, Lahouaria Hadri
Journal: Circulation (2020)

Background: Pulmonary arterial hypertension (PAH) is a fatal lung disease of multifactorial etiology, with no curative treatment. Several studies have previously suggested that hypermethylation of the BMPR2 promoter may be associated with gene repression and disease progression. However, the underlying mechanisms have yet to be discovered. Sin3A/B (Switch-Independent 3) plays a critical role in the transcriptional regulation of genes through various epigenetic mechanisms. Here, we investigated for the first time the role of SIN3a in the regulation of BMPR2 methylation and expression in PAH. Methods: Expression of SIN3a was analyzed by qRT-PCR and western blot in lung tissues from PAH patients and rodent models of PAH. Using a gain- and loss-of-function approach, we investigated the role of SIN3a on cell proliferation (BrdU assay) and migration (Boyden chamber assay), and BMPR2 levels in primary human pulmonary arterial smooth muscle cells (hPASMC) and endothelial cells (hPAEC). The methylation level was analyzed by MS-PCR. The therapeutic potential of SIN3a was tested in vivo in the Sugen/Hypoxia (SuHx) mouse and monocrotaline (MCT) rat models of PAH using an adeno-associated virus 1 encoding human SIN3a. Results: We found a significant downregulation of SIN3a expression in the lung samples from PAH patients, SuHx mice, and MCT rats. In hPASMC and hPAEC, our results showed that SIN3a inhibits cell proliferation, migration, and upregulates BMPR2 through two distinct pathways. In hPASMC, our data showed that SIN3a upregulates BMPR2 expression by inhibiting the methylation level of the BMPR2 promoter. In hPAEC, SIN3a restored BMPR2 expression independently of the methylation status by upregulating the FOXK2 transcription factor. In vivo , our results showed that restoring SIN3a expression by gene therapy significantly decreased MCT- and SuHx-induced PAH as illustrated by decreased vascular and RV remodeling, hypertrophy, PAP and RVSP. Conclusions: Altogether, our study revealed that SIN3a plays a critical role in the regulation of BMPR2 expression by modulating the lung epigenetic landscape. Additionally, our study identifies lung-targeted SIN3a gene therapy as a new promising therapeutic strategy for treating PAH patients.
Abstract 13648: Effect of Omega-3 Fatty Acids on Progression of Coronary Artery Calcium Score in Subjects With Stable Coronary Artery Disease on Statin Therapy
Authors: Maral Amangurbanova, Bhavya Vemuri, Abdul Aziz Asbeutah, Essa H Hariri, Francine K Welty
Journal: Circulation (2019)

Introduction: Computed tomographic-based coronary artery calcium (CAC) scores are a reliable measure of subclinical coronary artery disease (CAD). Statins have been shown to accelerate CAC formatio...
Moderation of Prazosin’s Efficacy by Alcohol Withdrawal Symptoms
Authors: Rajita Sinha, Stephanie Wemm, Nia Fogelman, Verica Milivojevic, Peter M. Morgan, Gustavo A. Angarita, Gretchen Hermes, Helen C. Fox
Journal: American Journal of Psychiatry (2020)

Objective: Alcohol use disorder (AUD) is a leading cause of global disease burden. Chronic, heavy use increases the likelihood of alcohol withdrawal symptoms and associated secondary outcomes of alcohol craving and mood, anxiety, and sleep disturbances, which are predictive of poor treatment outcomes. The authors examined whether alcohol withdrawal symptoms moderate the efficacy of prazosin in reducing alcohol intake and associated secondary outcomes. Methods: A 12-week, double-blind, randomized, controlled proof-of-concept trial of prazosin (16 mg/day, with a 2-week titration) was conducted in community-recruited adults with current alcohol dependence (N=100) with varying levels of alcohol withdrawal symptoms assessed at treatment entry. Primary outcomes were daily self-reported drinking days and heavy drinking days, and secondary outcomes were average drinks/day and mood, anxiety, craving, and sleep quality ratings. Results: Modified intent-to-treat analyses indicated a significant interaction of alcohol withdrawal symptom score by treatment by full-dose treatment period (weeks 3–12) for drinking days, heavy drinking days, and average drinks/day. By week 12, participants with high alcohol withdrawal symptoms on prazosin reported 7.07% heavy drinking days and 27.46% drinking days, while those on placebo had 35.58% heavy drinking days and 58.47% drinking days (heavy drinking days: odds ratio=0.14, 95% CI=0.058, 0.333; drinking days: odds ratio=0.265, 95% CI=0.146, 0.481). No such benefit of prazosin was observed in those reporting low or no alcohol withdrawal symptoms. Individuals with high alcohol withdrawal symptoms on prazosin compared with placebo also showed significantly improved anxiety, depression, and alcohol craving over the course of the trial. Conclusions: The findings indicate that alcohol withdrawal symptoms are a significant moderator of prazosin treatment response for alcohol use outcomes and for associated symptoms of alcohol craving, anxiety, and mood symptoms. These data support further evaluation of alcohol withdrawal symptoms as a prognostic indicator of prazosin’s efficacy in the treatment of AUD.
Abstract 13718: Automatic Microvolt-level Measurement of ST Level at J-point on 12-lead Electrocardiography Can Distinguish Takotsubo Syndrome and Acute Anterior Myocardial Infarction
Authors: Masato Shimizu, shummo cho, Yoshiki Misu, Mari Ohmori, Ryo Tateishi, Toshio Kaneda, Yosuke Yamakami, Hiroshi Shimada, Tomoko Manno, Ami Isshiki, Shigeki Kimura, Hiroyuki Fujii, Makoto Suzuki, Mitsuhiro Nishizaki, Tetsuo Sasano
Journal: Circulation (2020)

Introduction: ST elevation/depression on 12-leads electrocardiography (ECG) at onset was recognized difficult to distinguish Takotsubo syndrome (TTS) and acute anterior myocardial infarction (ant AMI). Diagnostic performance of automatic microvolt-level measurement of the ST levels was not elucidated. Hypothesis: Microvolt-level differences of ST level at J-point on ECG can distinguish TTS and ant AMI in acute phase. Methods: We firstly enrolled consecutive 40 patients of TTS, and among 500 ant AMI patients, one to two random matching was done by their age and gender. Finally, 40+80 patients (74.5±11.2 years, 87 females) were enrolled. ECG at onset of both group was measured by automated system (ECAPs12c: Nihon-Koden). Results: ST level of TTS at J-point in I/II/V4-6 lead was significantly elevated comparing to that of ant AMI. Conversely, Conversely, significant ST depression in aVR and no ST elevation in V1 of TTS was observed in TTS. Logistic regression analysis revealed that ST elevation in I lead and no ST elevation in V1 lead showed high odds ratio and low P value. Conclusions: Automated measurement of microvolt-level difference of ST level at J-point was a powerful tool to distinguish TTS and ant AMI at onset.
Abstract 16183: Role of Anticoagulation in the Management of Atrial Fibrillation Post Catheter Ablation in Patients With Moderate Chadsvasc
Authors: Aneesh Dhore-Patil, Muhammad Umer Butt, Soufian Almahameed, Amit Arbune, David Hoffman, Ohad Ziv
Journal: Circulation (2019)

Background: Recent data has suggested that catheter ablation (CA) for atrial fibrillation (AF) may reduce stroke risk. The long term risks and benefits of anticoagulation (AC) in patients with succ...
Case 36-2020: A 72-Year-Old Woman with Dark Urine and Weakness
Authors: Rajeev Malhotra, Mayooran Namasivayam, Brian B. Ghoshhajra, Jonathan J. Passeri, Peter A. Hoenig, James R. Stone
Journal: New England Journal of Medicine (2020)

A 72-year-old woman who had undergone mechanical mitral-valve and aortic-valve replacements 25 years earlier presented to the hospital with weakness and dark urine. Cardiac ultrasonography revealed normal biventricular function, no pericardial effusion, and a possible clot on the mitral valve. Diagnostic tests were performed.
Abstract 14586: Variability in Indicated Left Ventricular Function Reassessment After Mi: The Acute Myocardial Infarction Quality Assurance (AMIQA) Canada Multicenter Prospective Study
Authors: Stephen Wilton, Matthew Bennett, Ratika Parkash, Katherine M KAVANAGH, Marc Jolicoeur, Frank Halperin, Umjeet Jolly, Peter Leong-Sit, Rozsa Sas, Derek Chew, Sarah Singh, Stephanie J Frisbee, Robert MacLachlan, Jaimie Manlucu
Journal: Circulation (2020)

Introduction: Persistently reduced LVEF after acute MI predicts adverse prognosis and directs use of evidence-based treatments to prevent sudden death (SCD) and/or progressive heart failure. We conducted a multicentre, prospective, observational study to assess adherence with guideline recommendations to repeat imaging assessment post-MI in those with initially depressed LVEF. Methods: We enrolled 501 patients with type 1 acute MI and LVEF ≤45% during the index hospitalization, from 14 Canadian sites. Outcomes were the proportion having a repeat LVEF assessment by 6 months and the proportion with an actionable reduced LVEF in follow-up: &lt;35%, prompting referral for ICD therapy; &lt;40%, prompting consideration of additional heart failure therapy; or 36% to 50%, prompting referral for participation in SCD risk reduction research Results: Mean age was 63.3 ± 13.0, and 113 (22.6%) were female. Overall, 370 (73.4%) presented with STEMI, and 454 (91.6%) had one or more in-hospital revascularization procedures. The mean baseline LVEF was 36.9% ± 6.7%. Over a median follow-up of 198 days, 18 (3.6%) patients died and 27 (5.3%) were lost to follow-up. Of 456 remaining patients, 303 (66.5%) had LVEF reassessment and significant variation was observed across sites (range 46.7-90.0%; p=0.035). Patients from community vs academic hospitals were more likely to undergo LVEF reassessment (73.6% vs. 63.2%, p=0.034), as were those with worse LVEF at baseline ( Figure, panel A ). In those with follow-up LVEF (n=302), 61.6% had an actionable persistent LVEF reduction: 13.9% had LVEF &lt;35%, 28.8% had LVEF &lt;40%, and 47.7% had LVEF between 36 and 50%, with significant variation based on initial LVEF ( Figure, Panel B ). Conclusions: One in three patients with at least mild LVEF reduction after acute MI did not undergo indicated LVEF reassessment within 6 months. In those with follow-up imaging, clinically actionable persistent LVEF reduction was identified in over one quarter of patients.
SAT0198 How normal are the hands of normal controls? a study with dedicated magnetic resonance imaging
Authors: M Parodi, G Dazzi, E Silvestri, G Garlaschi, E Poggi, MA Cimmino
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Imaging of the joints is an invaluable technique for rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is increasingly used to visualise joint lesions in RA.<sup>1</sup> MRI is a very sensitive technique, which is able to show subtle changes of the joints. However, little is known about MRI findings in normal subjects. <h3>Objectives</h3> Our study evaluated bone lesions, articular space and thickness of the synovial membrane in normal controls. <h3>Methods</h3> 50 hands of 25 controls (19 women) with age range 31–88 years were studied. Four subjects had slight osteoarthritis of the first carpometacarpal joint: this joint was excluded from further evaluation. MRI of the hand was performed using a 0.2T dedicated device (Artoscan, Esaote, Genova, Italy). GE T1 and STIR sequences were used on the coronal and axial planes. Evaluated lesions included a) bone oedema; b) erosions; c) tenosynovitis, and d) thickness of the synovial membrane and effusion in 6 different areas of the wrist, as well as in the MCP and PIP joints. <h3>Results</h3> Bone oedema was seen in one subject only. Bone erosions were seen in 9/25 controls (36%). They were more frequent in subjects older than 65 years (50% vs. 23%; ns). The localization of erosions in the normal hand was not different from that observed in RA. Tenosynovitis of the extensor and flexor tendons was seen in 2/25 (8%) and 4/25 (16%) of controls, respectively. It was more frequent in subjects older than 65 years (41.7% vs. 7.7%; p = 0.07). Erosions and tenosynovitis were not associated with manual labour. Joint space range was calculated in 14 different locations of the hand. No differences were found according to gender. In contrast, subjects aged more than 65 years showed an increased thickness of the synovial membrane at the radio-ulnar joint (p = 0.01) and in the intercarpal row (p = 0.002), and an increased joint space in the third (p = 0.03) and fifth (p = 0.04) MCP joints. <h3>Conclusion</h3> Bone erosions and tenosynovitis are frequent findings in normal subjects. In contrast, bone oedema was seen in only one control and seems therefore to be a specific finding of arthritic joints. Age, but not sex or manual activity, was associated with these changes. Articular space in the MCP and PIP joints, and synovial membrane thickness in 6 different locations of the wrist were increased in elderly subject. Our results indicate that caution should be used in defining MRI changes as specific for arthritis and in interpreting the data of published studies. Sufficiently large control groups should be included in studies of the arthritic joints. <h3>Reference</h3> Cimmino, <i>et al</i>. Semin Arthritis Rheum. 2000;30:180–95
Attention should be paid to what women want
Authors: K. Hinshaw, A. El-Horishy, S. Bates
Journal: BMJ (1996)

shows this adequately.The Edinburgh postnatal depression scale is a validated tool for screening for psychiatric morbidity, which is indicated by a score of ¢ 12 or 13.4 Presenting these data in the form of a mean and SD does little other than describe the range of emotional and mental states of the sample.To show the incidence of postnatal depression it would have been better to include the number or percentage of patients in each group who exceeded the threshold score and to analyse the significance of any difference between these.As the paper stands, we are left with the information that women randomised to fewer antenatal visits were more anxious, worried, and likely to have negative feeling about their babies than women randomised to traditional care, but we do not have sufficient information to determine whether more of these women are at risk of postnatal depression.
Abstract 17326: Blockade of Thrombospondin1 Attenuates Tgfβ Signaling and Enhances the Automaticity of Tbx18-Induced Pacemaker Cells
Authors: Natasha Fernandez, Jinqi Fan, Hee Cho
Journal: Circulation (2020)

Introduction: Transcription factor Tbx18 can reprogram chamber cardiomyocytes to induced pacemaker cells (iPMs). Transcriptomic analysis of Tbx18-iPMs identified Tgfβ pathway as a prominent signaling cascade in this transition. The activity of Tgfβ1 is regulated primarily in the extracellular domain where the secreted latent form must be modified to expose the active ligand. We hypothesize that thrombospondin1 (Tsp1) mediates the activation of the Tgfβ signaling by Tbx18. Methods: Neonatal rat ventricular myocytes (NRVMs) were transduced with adenoviral constructs expressing either human TBX18 or GFP. Results: Tsp1 transcript (Thbs1) level was higher in TBX18 iPMs compared to GFP-NRVMs (1.5±1.3 vs 0.6±0.6, p&lt;0.05, n=4). Tsp1 concentration was higher in the conditioned media of TBX18 iPMs than in GFP-NRVMs (1220±794 vs 138±178 pg/mL, p&lt;0.05, n=20). The population of Tsp1+ fibroblasts were significantly higher within TBX18 iPMs compared to GFP-NRVMs (45±7% vs 9±10%, p&lt;0.05, n=3). We tested for cause-and-effect relationship between Tsp1 and Tgfβ signaling. Treatment of TBX18 iPMs with 20μM LSKL, a peptide inhibitor of Tsp1, attenuated secreted Tgfβ1 ligand concentration compared to DMSO-treated TBX18 iPMs (127±70 vs 214±44 pg/mL, p&lt;0.05, n=20). Similarly, LSKL treatment reduced αSMA+ myofibroblast population in TBX18 iPMs at day 4 compared to untreated iPMs (10±6 vs 21±5%, p&lt;0.05, n=3). Transcript levels of key Tgfβ signaling genes such as of Cola1, Tgfβ1, and Thbs1 were downregulated in LSKL-treated TBX18 iPMs compared to DMSO-treated iPMs. Functionally, LSKL treatment increased rates of single cell automaticity (125±13 vs 61±6 bpm) and the percentage of spontaneously beating cells (95±7 vs 62±17%, n=6, p&lt;0.05) in TBX18-iPMs compared to DMSO-treated TBX18 iPMs at day 16 after gene transfer. The enhanced automaticity was evident by day 7 and remained stable for two weeks. Conclusions: Our data identify Tsp1 as the key mediator through which Tbx18 activates the Tgfβ pathway during iPM reprogramming. Inhibition of Tgfβ pathway may serve as a solution to attain durable pacing from TBX18-iPMs.
Silicone adhesive multilayer foam dressings as adjuvant prophylactic therapy to prevent hospital‐acquired pressure ulcers: a pragmatic noncommercial multicentre randomized open‐label parallel‐group medical device trial*
Authors: D. Beeckman, A. Fourie, C. Raepsaet, N. Van Damme, B. Manderlier, D. De Meyer, H. Beele, S. Smet, L. Demarré, R. Vossaert, A. de Graaf, L. Verhaeghe, N. Vandergheynst, B. Hendrickx, V. Hanssens, H. Keymeulen, K. Vanderwee, J. Van De Woestijne, S. Verhaeghe, A. Van Hecke, I. Savoye, J. Harrison, F. Vrijens, F. Hulstaert
Journal: British Journal of Dermatology (2020)

Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital-acquired pressure ulcers (PUs).To determine whether silicone foam dressings in addition to standard prevention reduce the incidence of PUs of category 2 or worse compared with standard prevention alone.This was a multicentre, randomized controlled medical device trial conducted in eight Belgian hospitals. At-risk adult patients were centrally randomized (n = 1633) to study groups based on a 1 : 1 : 1 allocation: experimental groups 1 (n = 542) and 2 (n = 545) - pooled as the treatment group - and the control group (n = 546). The experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on the relevant body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU of category 2 or worse at the studied body sites.In the intention-to-treat population (n = 1605), PUs of category 2 or worse occurred in 4·0% of patients in the treatment group and 6·3% in the control group [relative risk (RR) 0·64, 95% confidence interval (CI) 0·41-0·99, P = 0·04]. Sacral PUs were observed in 2·8% and 4·8% of the patients in the treatment group and the control group, respectively (RR 0·59, 95% CI 0·35-0·98, P = 0·04). Heel PUs occurred in 1·4% and 1·9% of patients in the treatment and control groups, respectively (RR 0·76, 95% CI 0·34-1·68, P = 0·49).Silicone foam dressings reduce the incidence of PUs of category 2 or worse in hospitalized at-risk patients when used in addition to standard of care. The results show a decrease for the sacrum, but no statistical difference for the heel and trochanter areas.
Abstract 16364: Effect of Social Determinants on Outcomes in a High-risk Cardio-obstetrics Population
Authors: Corinne Carland, Danielle Panelli, Christine Lee, Elizabeth Sherwin, Eleanor Levin, Shirin Zarafshar, Jennifer A Tremmel, Sandra Tsai, Katherine Bianco, Abha Khandelwal
Journal: Circulation (2020)

Introduction: Cardiovascular disease is the leading cause of maternal mortality. The hemodynamic changes that occur during pregnancy make this a particularly vulnerable time for women with heart disease. Additionally, it is known that social determinants have an effect on certain outcomes in pregnancy, although research to quantify this effect is limited. We compared demographics and outcomes for women in upper- and lower-income brackets based on zip codes. Methods: We performed a retrospective cohort study of high-risk pregnant patients with cardiac diagnoses between November 2010 and June 2019. Patients were stratified into upper- and lower-income based on median household income in their zip code (2018 U.S. census). Results: We studied 191 pregnancies. Patients were stratified by zip code into lower (&lt;$118,201/yr, N = 95) and upper median household income (N = 96) groups (Table 1). Women in the lower income bracket had more antepartum hospitalizations (38.3% vs 17.9%), were younger (30.6 vs 33.9 years), Hispanic (42.1% vs 10.4%), and more likely to have public insurance (46.8% vs 21.3%). There was a difference in cardiac diagnoses between the two groups; those with lower income had more structural heart disease (41.1% vs 17.7%) and fewer arrhythmias (25.3% vs 39.6%). In the lower income group, there were 2 maternal deaths and 1 neonatal death before discharge, while in the upper income there was 1 neonatal death. Conclusions: Our study examined the relationship between median income per zip code and pregnancy outcomes, and demographics in women with heart disease. Our observations demonstrate a significant difference in maternal age, race, distribution of cardiac diagnoses, and antepartum hospitalizations. Despite all women being treated at the same facility, antepartum hospitalizations differed based on income bracket. Social determinants of health are important factors that impact outcomes in the cardiac-obstetric population and require further investigation.