tbuckley/cabot-search huggingface dataset:
OP0133 Cardiovascular safety profile of rofecoxib: a meta-analysis
Authors: DR Shapiro, E Barr, AS Reicin
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> COX-1 inhibition compromises GI homeostasis; however, by inhibiting platelet aggregation, COX-1 blockade is cardioprotective. COX-2 inhibitor therapy results in marked reductions in GI events relative to non-selective NSAID (COX-1/COX-2 inhibitor) therapy. Because COX-2 inhibitors do not have antiplatelet properties, chronic use of COX-2 inhibitors or non-selective NSAIDs may result in differential risks of platelet-mediated vascular events. Evaluation of the impact of these agents on vascular events is complicated by the variable effects of NSAIDs on platelet aggregation. NSAIDs that mediate near complete inhibition of platelet function throughout their entire dosing cycle may be similar to aspirin and reduce the risk of vascular events; other compounds with less substantial platelet inhibition may have no impact on vascular events. <h3>Objectives</h3> To evaluate the cardiovascular (CV) safety profile of rofecoxib, a selective COX-2 inhibitor. <h3>Methods</h3> A meta-analysis of all Phase IIb-V clinical trials was conducted using individual patient data and focusing on the relative risk of CV thrombotic serious adverse experiences in patients taking rofecoxib as compared to placebo, naproxen (an NSAID with near complete inhibition of platelet function throughout its dosing interval), and non-selective NSAIDs that lack potent sustained inhibition of platelet function (diclofenac, ibuprofen, and nabumetone). The primary metric utilised was the Antiplatelet Trialists' Collaboration (APTC) combined endpoint of cardiovascular or unknown death, stroke, or myocardial infarction. <h3>Results</h3> Over 28,000 patients in 19 studies (Osteoarthritis, Rheumatoid Arthritis, Alzheimer's, and Chronic Low Back Pain trials) representing over 14,000 patient-years at risk were included in the meta-analysis. The relative risk (95% CI) for an APTC combined endpoint was: 0.59 (0.37, 0.94) when comparing naproxen (n = 7870) vs. rofecoxib (n = 9083); 1.27 (0.64, 2.50) when comparing non-naproxen NSAIDs (n = 2755) vs. rofecoxib (n = 4549); 1.19 (0.73, 1.96) when comparing placebo (n = 3482) vs. rofecoxib (n = 6290); and, 1.31 (0.86, 2.01) when comparing non-naproxen NSAIDs or placebo (n = 6017) vs. rofecoxib (n = 7675). <h3>Conclusion</h3> (1) The risk of sustaining a thrombotic cardiovascular event was similar in patients treated with rofecoxib, placebo, or non-selective NSAIDs without sustained effects on platelet function and, (2) the risk of sustaining a thrombotic cardiovascular event was reduced in patients treated with naproxen compared to rofecoxib. This reduction in events on naproxen is likely due to its ability to maintain near complete inhibition of platelet function throughout its dosing interval.
Incidence of Retinoblastoma Has Increased: Results from 40 European Countries
Authors: Andrew W. Stacey, Richard Bowman, Allen Foster, Tero T. Kivelä, Francis L. Munier, Nathalie Cassoux, Ido Didi Fabian, Lamis Al Harby, Silvia Alarcón Portabella, Donjeta B. Alia, Charlotta All-Eriksson, Romanzo Antonino, Nicholas J. Astbury, Julia Balaguer, Walentyna Balwierz, Honorio Barranco, Covadonga Bascaran, Maja Beck Popovic, Eva M. Biewald, Nadia Bobrova, Norbert Bornfeld, Bénédicte G. Brichard, Sharon Blum, Michael Capra, Guilherme Castela, Jaume Català-Mora, Guillermo L. Chantada, Violeta S. Chernodrinska, Krzysztof Cieslik, Codruta Comsa, Maria G. Correa Llano, Monika Csóka, Patrick De Potter, Laurence Desjardins, Monica D. Dragomir, Ana Fernández-Teijeiro, David García Aldana, Pernille A. Gregersen, Nir Gomel, Theodora Hadjistilianou, Stanislava Hederova, Marlies Hummlen, Kristina Husakova, Russo Ida, Vesna R. Ilic, Helen Jenkinson, Noa Kapelushnik, Tamar Kardava, Naama Keren-Froim, Tomas Kepak, Zaza Khotenashvili, Artur Klett, Dalia Krivaitiene, Slobodanka Latinović, Livia Lumbroso, Lesia Lysytsia, Erika Maka, Nieves Martín Begue, Edoardo Midena, Annette C. Moll, Gabriela Murgoi, Larisa Naumenko, Vladimir Neroev, Marina Nikitovic, Andrzej Olechowski, Ruzanna Papyan, Raffaele Parrozzani, Manoj V. Parulekar, Katarzyna Pawinska-Wasikowska, Sanja Perić, Pavel Pochop, Vladimir G. Polyakov, M. Ashwin Reddy, Petra Ritter-Sovinz, Svetlana Saakyan, Mandeep S. Sagoo, Sonsoles San Román Pacheco, Stefan Seregard, Sónia Silva, Tetyana Sorochynska, Christina Stathopoulos, Branka Stirn Kranjc, Karel Svojgr, Gevorg Tamamyan, Alketa Tandili, Bekim Tateshi, Manca Tekavcic Pompe, Steen F. Urbak, Tatiana L. Ushakova, Sandra Valeina, Milo van Hoefen Wijsard, Nevyana V. Veleva-Krasteva, Maris Viksnins, Werner Wackernagel, Charlotte Wolley Dod, Vera A. Yarovaya, Andrey A. Yarovoy, Katsiaryna Zhilyaeva, Marcia Zondervan
Journal: Ophthalmology (2021)
AB0150 Effects of glucosamine sulfate and nimesulide on the progresssion of knee osteoarthritis
Authors: CI Chirieac, E Rezus, D Stratan, R Chiriac
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of this study was to assess the clinical, radiological and biological efficacy and tolerability of oral glucosamine sulfate associated with a selective COX 2 inhibitor, nimesulide, in patients suffering from Knee osteoarthritis (OA). <h3>Methods</h3> There was a 6 month randomised, double blind study which included 35 patients of both sexes, aged between 45 and 72 years, with symptomatic knee OA, with Kellgren and Lawerence radiological scores I-II. Patients were treated only with oral glucosamine sulfate and 100 mg nimesulide daily or with a placebo (PBO) associated with 100 mg nimesulide per day. The main outcome criteria were the degree of spontaneous joint pain and the overall mobility capacity; secondary outcome criteria included the joint space measurement and the levels of biochemical markers of bone and joint metabolism (osteocalcin, deoxypyridoline, nitric oxyde, matrix-metalloproteinases). <h3>Results</h3> The results of this study confirm that the association glucosamine sulfate- nimesulide was well tolerated and both reduces significantly pain and increase overall joint mobility; a stabilisation of the femoro-tibial joint narrowing (measured with a digitised image analyzer) was noted in these patients, whereas joint narrowing space increased in placebo-treated patients. in addition, the metabolism of bone and joint assessed by different biochemical parameters also stabilised in patients receiving glucosamine sulfate and nimesulide combination, while remained unchanged in the PBO patients. <h3>Conclusion</h3> The association glucosamine sulfate – nimesulide is effective and safe; glucosamine sulfate is an effective symptomatic and structure modifying slow acting drug for the treatment of knee OA, that may be able to stabilise the joint space width and to modulate bone and joint metabolism.
Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome
Authors: Larry Nichols
Journal: Annals of Internal Medicine (2021)

LettersJanuary 2021Pulmonary Arterial Thrombosis in COVID-19 With Fatal OutcomeLarry Nichols, MDLarry Nichols, MDMercer University School of Medicine, Macon, GeorgiaAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-1275 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Lax and colleagues (1) have done a great service in their thorough study of 11 patients who died of coronavirus disease 2019 (COVID-19). However, they may have overreached in concluding that thrombosis was present in small and medium pulmonary arteries in all 11 patients. In some cases, they may have overinterpreted blood in these arteries, clotted after death, as antemortem thrombosis in situ.Panel C of Figure 2 purports to show a pulmonary artery with thrombosis, but the blood in the artery has 2 components: a denser eosinophilic component and a lighter eosinophilic one, which is characteristic ...References1. Lax SF, Skok K, Zechner P, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med. 2020;173:350-61. doi:10.7326/M20-2566 LinkGoogle Scholar2. Wichmann D, Sperhake JP, Lütgehetmann M, et al. Autopsy findings and venous thromboembolism in patients with COVID-19. A prospective cohort study. Ann Intern Med. 2020;173:268-77. doi:10.7326/M20-2003 LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Larry Nichols, MDAffiliations: Mercer University School of Medicine, Macon, GeorgiaDisclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-1275. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome Sigurd F. Lax , Kristijan Skok , Peter Zechner , Harald H. Kessler , Norbert Kaufmann , Camillo Koelblinger , Klaus Vander , Ute Bargfrieder , and Michael Trauner Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome Sigurd F. Lax , Kristijan Skok , Peter M. Zechner , and Michael Trauner Metrics Cited byVascular Implications of COVID-19: Role of Radiological Imaging, Artificial Intelligence, and Tissue Characterization: A Special ReportImpairing RAGE signaling promotes survival and limits disease pathogenesis following SARS-CoV-2 infection in miceDetection methods for SARS-CoV-2 in tissueNachweismethoden von SARS-CoV-2 in Gewebe January 2021Volume 174, Issue 1Page: 139KeywordsBloodBlood vesselsCOVID-19OxygenPulmonary arteriesPulmonary embolismPulmonary vascular diseasesThrombosisVascular diseasesViral diseases ePublished: 19 January 2021 Issue Published: January 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
RAINBOW-Asia: A randomized, multicenter, double-blind, phase III study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line chemotherapy with platinum and fluoropyrimidine.
Authors: Rui-hua Xu, Yan-Qiao Zhang, Hongming Pan, Ji Feng Feng, Tao Zhang, Tianshu Liu, Yanru Qin, Rubing Han, Wanli Zhang, Lin Shen
Journal: Journal of Clinical Oncology (2021)

199 Background: Ramucirumab (RAM), a fully human IgG1 monoclonal antibody targeting vascular endothelial growth factor receptor 2, has been approved in combination with paclitaxel (PTX) in patients with advanced gastric cancer in the second-line setting outside of China in around 80 countries based on the significant overall survival (OS) benefit in the global phase 3 RAINBOW study. RAINBOW-Asia was a bridging study of RAINBOW to evaluate the efficacy and safety of RAM in a predominantly Chinese population. Methods: Patients with advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who experienced disease progression on first-line chemotherapy (platinum plus fluoropyrimidine with or without an anthracycline) were randomized at a 2:1 ratio to receive RAM (8 mg/kg) on day 1 and 15 plus PTX (80 mg/m²) on day 1, 8, and 15 of a 28-day cycle or placebo (PL) plus PTX. Randomization was stratified by ECOG Performance Status (0 versus 1) and peritoneal metastases (yes versus no). The co-primary endpoints were PFS and OS. Results: From Mar 2017 to Jun 2020, 440 pts were randomized (RAM+PTX: 294; PL+PTX: 146). Median PFS was significantly improved with RAM+PTX compared to PL+PTX (4.14m vs. 3.15m; HR = 0.765 [95% CI: 0.613 to 0.955]; p = 0.0184). Median OS was 8.71m with RAM+PTX and 7.92m with PL+PTX (HR = 0.963 [95% CI: 0.771 to 1.203]; p = 0.7426). Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurring in &gt; 5% of patients with RAM+PTX were: neutrophil count decreased (54.3% RAM+PTX; 38.6% PL+PTX), white blood cell count decreased (43.3% vs. 29.0%), anaemia (15.7% vs. 16.6%), hypertension (7.2% vs. 6.2%), and febrile neutropenia (6.1% vs. 0.7%). Conclusions: The combination of RAM+PTX as 2nd-line therapy demonstrated a statistically significant PFS benefit, and OS benefit consistent with RAINBOW study in a predominantly Chinese population with advanced gastric and GEJ cancer. The safety profile of RAM was consistent with previous studies. No new safety signal was observed. Clinical trial information: NCT02898077.
Human Aged Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection
Authors: E. Lazzarini, J. Marcandalli, A. M. Lodrini, V. Biemmi, C. Balbi, S. Bolis, C. Altomare, G. Vassalli, S. Bollini, M. Rocchetti, L. Perez, L. Barile
Journal: Circulation Research (2020)

Introduction: Growing evidences suggest that cardiac complications in COVID19 patients, including ischemic heart disease and atrial fibrillation, may involve direct mechanism of heart infection and damage by the circulating SARS-CoV-2 virus  Angiotensin-converting enzyme 2 (ACE2), which serves as gateway for coronavirus entry, is expressed in cardiomyocytes (CM)  Its expression can increase in failing hearts at both mRNA and protein levels and it is specifically upregulated in CM during dilated and hypertrophic cardiomyopathy  Very recently, RNA-sequencing analysis performed on isolated CM reveled that ACE2 is highly expressed in CM of aged individuals as compared to young ones  Methods: We used human induced pluripotent stem-cells derived cardiomyocytes (hiPS-CM) to develop a model of human senescent CM by sub-lethal concentration of doxorubicin (Doxo) exposure  Pseudotype lentiviral particles with SARS-CoV-2 Spike and encoding the mCherry reporter was used to evaluate CM susceptibility to virus entry  Real time PCR and flow cytometry were used to evaluate expression of exogenous construct  The proximity ligation assay (PLA) was performed to directly visualize Spike-ACE2 interaction on the surface of CM  Results: Cellular senescence occurs in CM as a result of exposure to Doxo, as cells with senescence-associated β-galactosidase activity were significantly more over untreated ones (control)  Senescent profile in CM was associated with overexpression of the host-cell surface ACE2 protein, suggesting an enhanced SARS-CoV-2 pseudovirions tropism for aged CM  Indeed, PLA assay showed increased efficiency in virions binding (fluorescent signal) onto surface of senescent-like CM  PCR evaluation of mCherry mRNA revealed augmented viral transduction in senescent-like hiPS CM by 2-fold increase compared to control group;FACS analysis further confirmed fluorescent reporter expression in infected cells  Conclusion: Our preliminary results suggest that human aged cardiomyocytes are more susceptible to SARS-CoV-2 infection then their young counterpart, with PLA assay being shown a suitable tool to directly visualize occurred interaction between spike and ACE2 proteins on the surface of CM
An Unbiased Response to the Open Peer Commentaries on “Does Consent Bias Research?”
Authors: Mark A. Rothstein, Abigail B. Shoben
Journal: The American Journal of Bioethics (2013)

Click to increase image sizeClick to decrease image size Notes For the sake of these consent calculations and to match the numbers given by Groenwold and colleagues, we imagined a population twice as big as the original study (so that a consent rate could be calculated for having more than 50 people who donated blood and did not exercise).
Trajectory of Serum Bilirubin Predicts Spontaneous Recovery in a Real-World Cohort of Patients With Alcoholic Hepatitis
Authors: Richard Parker, Joaquin Cabezas, Jose Altamirano, Juan Pablo Arab, Meritxell Ventura-Cots, Ashish Sinha, Ashwin Dhanda, Marco Arrese, C. Anne McCune, Ian A. Rowe, Bernd Schnabl, Phillipe Mathurin, Debbie Shawcross, Juan G. Abraldes, Michael R. Lucey, Guadalupe Garcia-Tsao, Elizabeth Verna, Robert S. Brown, Francisco Bosques-Padilla, Victor Vargas, Alexandre Louvet, Andrew P. Holt, Ramon Bataller
Journal: Clinical Gastroenterology and Hepatology (2021)
Real-world outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma.
Authors: Laura Miotke, Christopher Duane Nevala-Plagemann, Jian Ying, Vaia Florou, Benjamin Haaland, Ignacio Garrido-Laguna
Journal: Journal of Clinical Oncology (2021)

387 Background: Optimal management of patients with recurrent pancreatic ductal adenocarcinoma (PDAC) is unknown. In the clinical trials that established a survival benefit with combination chemotherapy compared to single agent gemcitabine, patients with recurrent PDAC were either excluded (PRODIGE-4) or severely underrepresented (MPACT). In this study, we evaluated clinical outcomes of recurrent PDAC patients who receive systemic therapy and compared outcomes to patients with de novo advanced PDAC. Methods: Patients diagnosed with advanced PDAC between 2014 and October of 2019 were included using the nationwide Flatiron Health EHR-derived de-identified database. Patients without a clinic visit or initiation of treatment within 90 days of diagnosis were excluded. Patients were characterized as either de novo or recurrent PDAC based on stage at diagnosis and history of surgery. Patients with recurrent PDAC were further stratified based on time to recurrent disease. Overall survival (OS) was summarized within groups via Kaplan-Meier survival estimates, and compared between groups in the context of univariable and multivariable Cox proportional hazards models. The covariates adjusted for were gender, age, race, ECOG, smoking status, primary site, CA199, albumin, lymphocytes, neutrophils and monocytes. Results: We included 5170 patients with advanced PDAC, of which 1101 (21.3%) met criteria for recurrent disease. Patients with recurrent PDAC were more likely to have tumors in the head of the pancreas (71% vs 40%, p &lt; 0.001) and had lower median CA19-9 (92.8 vs 617, p &lt; 0.001), compared to the de novo PDAC patients. Median OS for the recurrent group was 10.8 m (95% CI = 9.9-11.7) vs. 7.3 m (95% CI = 7.0-7.7) in the de novo group (p &lt; 0.001, both univariate and multivariable adjusted analyses). The most common first line palliative chemotherapy in patients with recurrent disease was Nab-paclitaxel plus gemcitabine (41%) or FOLFIRINOX (21%). Patients who recurred within six months of surgery (28%) had an OS of 10.0 m (95% CI = 8.7 -11) vs. 11.6 m (95% CI 10-12, p = 0.256) in those who recurred greater than six months from surgery. Conclusions: Our data suggest that patients with recurrent disease have significantly better survival outcomes compared to patients with de novo metastatic disease. We did not observe a significant difference in survival of patients who recurred within 6 months of resection compared to those who recurred greater than six months after surgery. These data support the inclusion of patients with recurrent PDAC in clinical trials, including those who develop recurrent disease within 6 months of surgery, with appropriate stratification for these variables.
Endoscopic ultrasound-directed transgastric ERCP (EDGE): a systematic review describing the outcomes, adverse events, and knowledge gaps
Authors: Shaurya Prakash, B. Joseph Elmunzer, Erin M. Forster, Gregory A. Cote, Robert A. Moran
Journal: Endoscopy (2021)

Abstract Background Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) has emerged as a viable completely endoscopic method for performing pancreaticobiliary interventions in patients with Roux-en-Y gastric bypass anatomy. The aims of this systematic review were: (1) to describe the indications, outcomes, and complications of EDGE; and (2) to identify deficiencies in our knowledge of important technical approaches and clinical outcomes. Methods A systematic review was conducted via comprehensive searches of Medline, Scopus, CINAHL, and Cochrane to identify studies focusing on EDGE outcomes. Simple descriptive statistics were derived from case series only. Case reports were only included to qualitatively describe additional indications, techniques, and adverse events. Results The initial search identified 2143 abstracts. Nine case series and eight case reports were included. In the nine case series, 169 patients underwent EDGE. The technical success rate was 99 % (168 /169) for gastrogastrostomy/jejunogastrostomy creation and 98 % (166 /169) for subsequent ERCP. Minor adverse events specifically related to EDGE occurred in 18 % (31/169) and included intraprocedural stent migration/malposition (n = 27) and abdominal pain (n = 4). Moderate adverse events specific to EDGE occurred in 5 % (9/169): including bleeding (2 %), persistent fistula (1 %), and perforation (1 %). Severe adverse events occurred in one patient with a perforation requiring surgery. Deficiency in reporting on the clinical significance of adverse events was identified. Conclusion Based on limited observational data, in expert hands, EDGE has a high rate of technical success and an acceptable rate of adverse events. As a novel procedure, many knowledge gaps need to be addressed to inform the design of meaningful comparative studies and guide informed consent.
Alarming spread of vancomycin resistant enterococci in Sweden since 2007
Authors: T Söderblom, O Aspevall, M Erntell, G Hedin, D Heimer, I Hökeberg, K Kidd-Ljunggren, Å Melhus, B Olsson-Liljequist, I Sjögren, J Smedjegård, J Struwe, S Sylvan, K Tegmark-Wisell, M Thore
Journal: Eurosurveillance (2010)

The total number of persons infected or colonised with vancomycin-resistant enterococci mandatorily reported to the Swedish Institute for Infectious Disease Control increased dramatically during 2007 and 2008. During a period of twenty months from 1 July 2007 to 28 February 2009, a total of 760 cases were reported compared with 194 cases reported during the entire period from 2000 to 2006. This rise was mainly attributed to a wide dissemination of vancomycin resistant enterococci which started in a number of hospitals in Stockholm in the autumn of 2007 and was followed by dissemination in various healthcare facilities (hospitals and homes for the elderly) in a further two Swedish counties in 2008. The majority of the cases (97%) were acquired in Sweden and among these, healthcare-acquired E. faecium vanB dominated (n=634). The majority of these isolates had identical or closely related pulsed-field gel electrophoresis patterns indicating clonal dissemination in the affected counties. The median minimum inhibitory concentration of vancomycin was 32 mg/L (ranging from 4 to >128 mg/L) and of teichoplanin 0.12 mg/L (ranging from 0.06 to 0.25 mg/L). Particular emphasis was placed on countermeasures such as screening, contact tracing, cleaning procedures, education in accurate use of infection control practices as well as increasing awareness of hygiene among patients and visitors. With these measures the dissemination rate decreased substantially, but new infections with the E. faecium vanB strain were still detected.