tbuckley/cabot-search huggingface dataset:
Treatment of epithelial ovarian cancer
Authors: Lindsay Kuroki, Saketh R Guntupalli
Journal: BMJ (2020)

ABSTRACT Ovarian cancer is the third most common gynecologic malignancy worldwide but accounts for the highest mortality rate among these cancers. A stepwise approach to assessment, diagnosis, and treatment is vital to appropriate management of this disease process. An integrated approach with gynecologic oncologists as well as medical oncologists, pathologists, and radiologists is of paramount importance to improving outcomes. Surgical cytoreduction to R0 is the mainstay of treatment, followed by adjuvant chemotherapy. Genetic testing for gene mutations that affect treatment is the standard of care for all women with epithelial ovarian cancer. Nearly all women will have a recurrence, and the treatment of recurrent ovarian cancer continues to be nuanced and requires extensive review of up to date modalities that balance efficacy with the patient’s quality of life. Maintenance therapy with poly ADP-ribose polymerase inhibitors, bevacizumab, and/or drugs targeting homologous recombination deficiency is becoming more widely used in the treatment of ovarian cancer, and the advancement of immunotherapy is further revolutionizing treatment targets.
Abstract 14112: Apabetalone (RVX-208) Reduces ACE2 Expression in Human Cell Culture Systems, Which Could Attenuate SARS-CoV-2 Viral Entry
Authors: Dean Gilham, Li Fu, Laura M Tsujikawa, Brooke Rakai, Sylwia Wasiak, Stephanie Stotz, Christopher Sarsons, Michael Sweeney, Jan JOHANSSON, Norman Wong, Ewelina Kulikowski
Journal: Circulation (2020)

Introduction: Apabetalone is an orally available small molecule that affects gene transcription by inhibiting BET protein interactions with acetylated histones and transcription factors. Apabetalone is in late stage clinical development for the treatment of cardiovascular disease (CVD). Clinical trials show apabetalone is well tolerated and has a favorable safety profile. Recent evidence indicates this drug could be repurposed to treat COVID-19 by reducing expression of the angiotensin converting enzyme 2 (ACE2) receptor that is essential for SARS-CoV-2 viral entry and/or disrupting viral protein E interaction with BET proteins. The spike protein of SARS-CoV-2 engages with human ACE2 expressed in multiple organs such as lung, liver, kidney, heart and intestine to initiate infection in host cells. Ultimately, the infection leads to life threatening complications in COVID-19 patients. Hypothesis: Apabetalone downregulates ACE2 expression to protect human cells from SARS-CoV-2. Methods: Primary human kidney tubular epithelial cells (RPTEC) were stimulated with TNFα and co-treated with apabetalone overnight. Primary human hepatocytes (PHH) and the hepatoma cell line, HepG2, were treated up to 96 h with apabetalone or other BET inhibitors (BETi). Gene expression was analyzed by microarray or RT-PCR. Human aortic endothelial cells (HAEC) were pretreated with apabetalone for 1 h followed by TNFα stimulation for another 1h. Chromatin occupancy of the BET protein BRD4 was examined by ChIP-seq. Results: In RPTEC, 5μM apabetalone downregulated ACE2 mRNA by 50%. Apabetalone dose dependently reduced ACE2 gene expression in HepG2 or PHH from 3 independent donors by up to 90%. JQ1 is a pan BET inhibitor, whereas MZ1 promotes BET protein degradation. Both JQ1 and MZ1 treatments downregulated ACE2 in liver cells, indicating an on target BETi effect. In HAEC, apabetalone abolished BRD4 occupancy at an enhancer in proximity to the ACE2 gene. Conclusions: Apabetalone reduces ACE2 gene expression in multiple human cell types. ACE2 expression may be regulated by adjacent BRD4 enhancer occupancy. The impact of apabetalone on SARS-CoV-2 life cycle is under investigation. The results will provide mechanistic support for potential COVID-19 clinical trials.
Abstract 14164: Trends in U.S. Spending on Diabetes Therapies by Insurance Payer From 2007 to 2017
Authors: Nicholas Chiu, Rahul Aggarwal, Rishi Wadhera, Changyu Shen, Robert W Yeh, Dhruv Kazi
Journal: Circulation (2020)

Importance: Diabetes mellitus is an important cardiovascular risk factor, and diabetes therapies are among the most commonly prescribed medications in the U.S. While the introduction of new, high-cost therapies has increased costs, recent trends in national spending on diabetes medications by insurance payer have not been examined. Understanding the burden of costs amongst all payers may help inform strategies to optimize drug expenditures in the US. Objective: To produce nationally representative estimates of US spending on diabetes therapies from 2007 to 2017, stratified by insurance payers (Medicare, Medicaid, Private, VA, and TRICARE—a program for civilian health benefits for US Armed Forces). Trends in out-of-pocket costs were also examined. Design/Setting: Retrospective analysis of patient-level data from the Medical Expenditure Panel Survey, a nationally representative survey that is the most complete source of data on healthcare costs in the US, from 2007 to 2017. Participants: All patients receiving one or more classes of diabetes therapies. Outcomes: Inflation-adjusted total national expenditures on all diabetes therapies. Results: There were substantial increases in total expenditures on diabetes therapies for all payers during the study period, ranging from +165.6% for VA &amp; TRICARE ($380.6 million to $1.0 billion) to +460.4% for Medicaid ($1.1 to $6.1 billion). Private insurers increased spending by +346.6% ($5.7 to $25.5 billion), and Medicare increased spending by +389.9% ($5.4 to $25.2 billion). Out-of-pocket spending increased more modestly (+15.7%, from $4.7 to $5.7 billion). Conclusions/Relevance: Spending on diabetes therapies increased dramatically between 2007-2017, with Medicare spending increasing by 389.9%. In contrast, increases in out-of-pocket costs have been more modest. Reasons for the rapid rate of rise in Medicare and private spending compared to out-of-pocket spending should be examined in future studies.
Population-based case-finding to identify airflow obstruction in symptomatic adults at high risk for asthma and COPD
Authors: George A. Whitmore, Shawn D. Aaron
Journal: European Respiratory Journal (2020)

We appreciate the interest of the correspondents in our article and their thoughtful comments about methodological considerations that affect the interpretation of our results [1]. We are pleased to have this opportunity to reply to the questions posed by J.L. Perret and colleagues. Reply to J.L. Perret and co-workers <https://bit.ly/3jMx5wX>
PTU-006 Time to polypectomy competency in the uk: retrospective analysis of 1633 dopys from 131 trainees
Authors: A Rajendran, S Thomas-Gibson, P Bassett, P Dunckley, N Sevdalis, A Haycock
Journal: Gut (2017)

Introduction  Directly Observed Polypectomy Skills (DOPyS) is a validated tool used to assess polypectomy technique (1). In the UK, trainees are certified as competent in Level 1 (  Method  Data were extracted from the JETS database (Jan 2009 to Sept 2015) on 131 trainees (1633 DOPyS) from the time of their first DOPyS (1 st DOPyS) up to achieving provisional and full certification. As not all trainees achieved certification, the analysis was performed using survival analysis methods. Cox regression was used to examine PI association with the time to achieving certification. Kaplan-Meier graphs were used to show the proportion of trainees who achieved certification at different points in time.  Results  The analysis demonstrates that 38% of trainees had reached provisional certification by one year, 74% by two years, 94% by three years, and 99% by four years of the 1 st DOPyS. 5% of endoscopists had reached full certification after one year, 33% after two years, 50% by three years and 87% by four years from 1 st DOPyS. There was some evidence that PI at 1 st DOPyS (baseline PI) was associated with time to provisional (p=0.06) and time to full certification (p=0.08). A higher baseline PI was associated with a higher probability of obtaining polypectomy competency/certification in a shorter timescale. A five-unit increase in baseline PI was associated with a 25% increase in the chance of obtaining provisional and 17% increase in obtaining full status at any time. A graphical illustration of the results is shown in Image 1  Conclusion  In the UK, the majority (94%) of trainees achieve Level 1 polypectomy competency within 3 years of 1 st DOPyS, but only 50% achieve Level 2 polypectomy competency in the same time. Increasing PI to an average of >10 procedures/month may shorten the learning curve to polypectomy competency/full certification. Current data collection only allows the estimation of learning curve by time and DOPyS documented and not the number of polypectomies performed. There is ongoing work to establish the learning curve based on number of polypectomies.  References  . Gupta, et al. GIE2012.  . JAG 2011.  Disclosure of Interest  None Declared
Abstract 14432: Myocardial Work in Stage I and II Hypertensive Patients
Authors: Akshar Jaglan, Sarah Roemer, Ana C Perez Moreno, Bijoy K Khandheria
Journal: Circulation (2020)

Introduction: Myocardial work is a novel parameter that can be used in a clinic setting to assess left ventricular (LV) pressures and deformation. This study sought to distinguish patterns of global myocardial work index in hypertensive vs. non-hypertensive patients. Methods: Fifty (25 male, mean age 60±14 years) hypertensive patients and 15 (7 male, mean age 38±12 years) control patients underwent transthoracic echocardiography at rest. Hypertensive patients were divided into stage 1 (26 patients) and stage 2 (24 patients) based on the 2017 American College of Cardiology guidelines. We excluded patients with suboptimal image quality for myocardial deformation analysis, reduced ejection fraction (EF), valvular heart disease, and arrhythmia. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were estimated from LV pressure strain loops utilizing proprietary software from speckle-tracking echocardiography. LV systolic and diastolic pressures were estimated using a noninvasive brachial artery cuff. Results: Global longitudinal strain (GLS) and EF were preserved between the two groups with no statistically significant difference whereas there was a statistically significant difference in the GWI (p&lt;0.01), GCW (p=0.03), GWW (p&lt;0.01), and GWE (p=0.03) (Figure and Table). Conclusions: Myocardial work gives us a closer look at the relationship between LV pressure and contractility in settings of increased load dependency whereas LVEF and GLS cannot. We show how myocardial work is an advanced assessment of LV systolic function in hypertensive patients.
Abstract 16344: Pericardial Complications in Patients With COVID-19: A Systematic Review of Published Cases
Authors: Sandeep Singh, Akhil Jain, Priyanka Chaudhari, Faizan Ahmad Malik, Virmitra Desai, falah abu hassan, Vraj Shah, Viral Patel, Rupak Desai
Journal: Circulation (2020)

Introduction: COVID-19 has been linked to cardiac damage and life-threatening pericardial complication on which data are trivial which incited us to perform this review of published case reports. Methods: PubMed/Medline, Web of Science and SCOPUS were searched until June 2020 for case reports on COVID-19-associated pericarditis, cardiac tamponade or pericardial effusion. Results: We identified 8 articles reporting 11 COVID-19 positive cases [mean age: 51.4±14.3 (34-78 yrs) 5 male/6 female)] with pericardial complications. All (100%) cases were COVID-19 positive at the presentation with ~80% having dyspnea, chest pain and cough. Time interval from first symptom to pericardial effusion was 7±8 (1-26) days. Five patients reported heart failure with reduced EF on echocardiography with mean LVEF 36.25%±8.54%. All patients showed nearly normal Troponin-I without angiographically significant stenosis except one. Out of 8 cases on echocardiography 4 cases reported with diffuse hypokinesia, 2 reported inferior and inferolateral walls hypokinesia and 2 reported signs of pericardial tamponade. Out of 11 patients, cardiovascular risk factors in the form of diabetes or hypertension or obesity were present in 5 patients. Cardiovascular comorbidities such as heart failure with low ejection fraction, non-ischemic cardiomyopathy and prior myocarditis were present in 3 patients. ST-segment elevation in 3, sinus tachycardia in 2, T wave inversion in 1 case were noted. Four patients developed cardiac tamponade, 1 developed takotsubo syndrome and 3 patients died. Conclusions: COVID-19 patients had signs of a high burden of cardiac injury. Pericardial complications (pericardial effusion and cardiac tamponade) remain infrequent complications which may require prompt care to avoid mortality.
Assessment of a circular powered stapler for creation of anastomosis in left-sided colorectal surgery: A prospective cohort study
Authors: Daniel O. Herzig, James W. Ogilvie, Allen Chudzinski, Andrea Ferrara, Shazad Q. Ashraf, Rosa M. Jimenez-Rodriguez, Kurt Van der Speeten, James Kinross, Hendrik Schimmelpenning, Peter M. Sagar, Jamie A. Cannon, Michael L. Schwiers, David W. Singleton, Jason R. Waggoner, Raymond Fryrear, Patricia Sylla
Journal: International Journal of Surgery (2020)
Abstract 68: Trends in Postresuscitation Care: A 7-Year Experience After Implementation of Therapeutic Hypothermia
Authors: Claudius Jacobshagen, Stephan Schmidt-Schweda, Theresa Pelster, Anja Pax, Bernhard Unsoeld, Tim Seidler, Gerd Hasenfuss, Lars S Maier
Journal: Circulation (2011)

Background: The 2010 AHA guidelines for CPR emphasize the crucial importance of patient care in the early post-resuscitation period. In particular, therapeutic hypothermia and adequate treatment of the post-cardiac arrest syndrome are of utmost importance. Methods: In a single center retrospective registry analysis, the data from all resuscitated patients treated in the cardiology ICU between 2003 and 2009 were evaluated systematically. All data on hemodynamics, respiration, hypothermia, diagnostic and therapeutic procedures and outcome were analyzed. Results: 436 consecutive post-cardiac arrest patients were included. The proportion of patients treated with mild hypothermia could be increased from 56% (2003) to &gt;80% (2006-2009). &gt;90% of the patients with out-of-hospital arrest (OHA) were cooled. Induction of therapeutic hypothermia could be accelerated significantly (time to &lt;34°C, 2003: 13h 59min, 2005: 6h 30min, 2009: 2:15min). The frequency of using cold infusions and intravascular cooling devices correlated directly with the velocity of cooling induction. The PaO2/FiO2 ratio on arrival at the ICU was 242±23 indicating an acute lung injury (ALI). The comparison of cooled and uncooled patients showed no significant differences in the parameters of respiration (in spite of significantly greater fluid intake in the hypothermia group). However, the cooled patients were significantly longer intubated than the uncooled patients (7.0±0.9 vs. 3.7±1.5 days). In patients treated with hypothermia the LVEF improved significantly from 35.4±0.7% at admission to 40.1±1.1% at hospital discharge. In contrast, in patients not treated with hypothermia there was no significant increase in LVEF. In-hospital mortality was 43%. Despite improvement in cooling measures, there was no significant improvement in the survival rates between 2003 and 2009. Conclusion: This registry provides an overview of trends in post-cardiac arrest treatment. By optimizing the post-resuscitation care cooling induction can be accelerated. An acute lung injury is part of the post cardiac arrest syndrome. Hypothermia might improve LVEF recovery in patients with post cardiac arrest syndrome.
Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD: A Swedish Population-Based Cohort Study
Authors: Johanna Rehnberg, Adina Symreng, Jonas F. Ludvigsson, Louise Emilsson
Journal: Journal of the American Society of Nephrology (2020)

Background Case reports suggest an association between inflammatory bowel disease, a chronic autoimmune condition linked to increased circulating IgA levels, and IgA nephropathy, the most common form of primary GN and a leading cause of ESKD. Methods In a Swedish population-based cohort study, we compared 3963 biopsy-verified IgA nephropathy patients with 19,978 matched controls between 1974 and 2011, following up participants until 2015. Inflammatory bowel disease data and ESKD status were obtained through national medical registers. We applied Cox regression to estimate hazard ratios (HRs) for future inflammatory bowel disease in IgA nephropathy and conditional logistic regression to assess risk of earlier inflammatory bowel disease in IgA nephropathy. We also explored whether inflammatory bowel disease affects development of ESKD in IgA nephropathy. Results During a median follow-up of 12.6 years, 196 (4.95%) patients with IgA nephropathy and 330 (1.65%) matched controls developed inflammatory bowel disease (adjusted HR, 3.29; 95% confidence interval [95% CI], 2.73 to 3.96). Inflammatory bowel disease also was more common before a confirmed IgA nephropathy diagnosis. Some 103 (2.53%) IgA nephropathy patients had an earlier inflammatory bowel disease diagnosis compared with 220 (1.09%) controls (odds ratio [OR], 2.37; 95% CI, 1.87 to 3.01). Both logistic regression (OR, 2.60; 95% CI, 2.02 to 3.35) and time-varying Cox regression (HR, 1.84; 95% CI, 1.33 to 2.55) demonstrated that inflammatory bowel disease was associated with increased ESKD risk in patients with IgA nephropathy. Conclusions Patients with IgA nephropathy have an increased risk of inflammatory bowel disease both before and after their nephropathy diagnosis. In addition, among patients with IgA nephropathy, comorbid inflammatory bowel disease elevates the risk of progression to ESKD.
SAT0201 Improvement of myositis ossificans circumscripta diagnosis by magnetic resonance imaging
Authors: AJ Weber, M Wybier, JD Laredo, T Bardin
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Myositis ossificans circumscripta (MOC) is a focal benign heterotopic ossification in musculoskeletal tissues, often occurring in young adults. Early stages of MOC may be mistaken for infection or malignancy. Since magnetic resonance (MR) imaging has now a key role in the diagnosis of soft tissue masses, MR features of MOC have to be recognised. <h3>Objectives</h3> To compare the different features of MOC, as shown by the different imaging modalities (plain radiographs, computed tomography (CT) and MR examinations). <h3>Methods</h3> 19 cases (M/F: 0.9, mean age: 32 years) of MOC from several hospitals in Paris were retrospectively studied with a special focus on imaging features. Diagnosis of MOC was based upon clinical and radiological criteria. Pathological examination was also obtained for 6 patients. The lesions were analysed for margin definition, MR signal intensity, surrounding oedema and contrast enhancement. <h3>Results</h3> Post contrast enhancement was observed in the peripheral typical rim-like ossification, whatever the stage of the MOC. Enhancement of the calcified rim in mature lesions was an unexpected finding, since, to our knowledge, no mature calcified or ossified musculoskeletal lesions disclose such enhancement. The surrounding oedema was frequently observed on CT or RM examinations. It appeared in 3 patients as uncommon concentric intramuscular streaks. Oedema extension did not correlate with the early or mature stage of MOC. Synovitis or articular effusion were seen for 4 patients when MOC was located close to a joint. <h3>Conclusion</h3> In this study, imaging patterns of MOC, specially MR imaging, could be analysed. Interestingly, original findings could be observed, which could help early diagnosis, thus avoid needless invasive procedures. <h3>References</h3> De Smet AA, Norris MA, Fisher DR. Magnetic resonance imaging of myositis ossificans: analysis of seven cases. Skeletal Radiol. 1992;21:503–7 Shirkhoda A, Armin AR, Bis KG, Makris J, Irwin RB, Shetty AN. MR imaging of myositis ossificans, variable patterns at different stages. J Magn Reson Imaging 1995;5:287–92
Preoperative diagnosis of multiple intraductal tubulopapillary neoplasms of the pancreas: dynamic imaging features from endoscopic ultrasound
Authors: Wei-hui Liu, Xiao-ju Su, Xu Fang, Hui Jiang, Shi-wei Guo, Kai-xuan Wang
Journal: Endoscopy (2020)

A 60-year-old man with recurrent pancreatitis was admitted to our hospital for further examination and treatment. Abdominal computed tomography highlighted multiple cystic lesions in the pancreas ([Fig. 1 a]). Magnetic resonance imaging revealed atrophic pancreatic parenchyma and segmentally dilated pancreatic duct ([Fig. 1 b]). The diagnosis of intraductal papillary mucinous neoplasm (IPMN) or intraductal tubulopapillary neoplasm (ITPN) was proposed. Subsequent endoscopic ultrasound (EUS) showed multiple cystic lesions with solid tumors inside extending along the dilated main pancreatic duct ([Fig. 1 c]). The intraductal tumor was surrounded by pancreatic fluid in the head of the pancreas, representing the “cork-of-wine-bottle sign;” however, the hypoechoic tumors connecting with anechoic fluids were displayed as two different colors in the dilated duct, indicating the “2-tone duct sign” ([Video 1]). Based on the above two typical imaging findings [1] [2], ITPN was reliably diagnosed preoperatively using EUS; thus, surgery was recommended.
OP0082 Central sensitisation and clinical pain severity in cyp2d6 phenotyped fibromyalgia (fm) patients
Authors: JA Desmeules, C Cedraschi, E Baumgartner, A Finckh, P Cohen, P Dayer, TL Vischer
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Nociceptive processing in fibromyalgia (FM) patients could be altered by aberrant central mechanisms. <h3>Objectives</h3> R-III nociceptive reflex can be used to assess nociceptive processing and to provide indirect evidence of central pain sensitisation. <h3>Methods</h3> 95 of 150 FM included in an ongoing RCT of an exercise program vs 40 matched controls (C) were evaluated. Pain severity was assessed by number of tender points (TP), myalgic score (MS) and physician global impression (PGI). Patient's ratings included a VAS and the regional pain score (RPS). FM and C were assessed by central (R-III) and peripheral (thermotests) quantitative sensory testing (QST). QST and clinical parameters were correlated to CYP2D6 phenotypes. <h3>Results</h3> Nearly all FM were female (98%); main reason for exclusion was the inability to interrupt drugs with analgesic properties for &gt;10 days. Age [FM mean 49(SEM1) vs C 46(2) y.], gender and socio-demographic characteristics were similar in both groups. Mean duration of symptoms was 8 y (range 0.4–49). RPS was 64(13–98), VAS was 5.7 (SD 2). Means for clinical examination were: TP 16(0.3), MS 29(0.9) and PGI 2.7(0.1). R-III reflex threshold was reduced in FM [26(2) vs 38(2) mA, p &lt; 0.01]. Thermal perceptions (hot and cold) were similar in both groups, whereas thermal pain thresholds and latency (hot, cold, and cold pressure test) were drastically decreased in FM(p &lt; 0.001). Correlation analysis showed a significant relationship between PGI, and central QST(Pearson r = -0.28; p = 0.02) and between PGI, MS and TP(r = 0.34 and r = 0.66, respectively p &lt; 0.01). Correlation with CYP2D6 activity is under analysis. <h3>Conclusion</h3> Physician global impression, but not the other clinical scores, correlates with the extent of central sensitisation. Supported by the SNSF (3200–056028.98).