tbuckley/cabot-search huggingface dataset:
Pancreatic Islets: Functionalization of Alginate with Extracellular Matrix Peptides Enhances Viability and Function of Encapsulated Porcine Islets (Adv. Healthcare Mater. 9/2020)
Authors: Juan D. Medina, Michael Alexander, Michael D. Hunckler, Marc A. Fernández‐Yagüe, María M. Coronel, Alexandra M. Smink, Jonathan R. Lakey, Paul de Vos, Andrés J. García
Journal: Advanced Healthcare Materials (2020)

Interactions between pancreatic islets and extracellular matrix (ECM) have regulative effects on pancreatic islet survival and function. These interactions are lost during the islet isolation process necessary for islet transplantation. In article number 2000102, Jonathan R. Lakey, Paul de Vos, Andrés J. García, and co-workers show that incorporation of a specific adhesion peptide sequence promotes islet health and function in vitro. The cover image shows a healthy pancreas (top), which is digested to extract islets. Isolation results in islet damage, evidenced by their necrotic core and loss of adhesion substrate (middle). Encapsulation of isolated islets into biomimetic microcapsules restores islet-adhesion connections and enhances the islet's health and function (bottom).
Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus
Authors: E. Salvador, M. Oualha, E. Bille, A. Beranger, F. Moulin, S. Benaboud, S. Boujaafar, I. Gana, S. Urien, Y. Zheng, J. Toubiana, C. Briand, O. Bustarret, G. Geslain, S. Renolleau, J.-M. Treluyer, D. Hirt
Journal: Clinical Microbiology and Infection (2020)
COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options
Authors: Tomasz J Guzik, Saidi A Mohiddin, Anthony Dimarco, Vimal Patel, Kostas Savvatis, Federica M Marelli-Berg, Meena S Madhur, Maciej Tomaszewski, Pasquale Maffia, Fulvio D’Acquisto, Stuart A Nicklin, Ali J Marian, Ryszard Nosalski, Eleanor C Murray, Bartlomiej Guzik, Colin Berry, Rhian M Touyz, Reinhold Kreutz, Dao Wen Wang, David Bhella, Orlando Sagliocco, Filippo Crea, Emma C Thomson, Iain B McInnes
Journal: Cardiovascular Research (2020)

Abstract The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) —a homologue of ACE—to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.
Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors
Authors: Erica Banks, Michael Grondine, Deepa Bhavsar, Evan Barry, Jason G. Kettle, Venkatesh Pilla Reddy, Crystal Brown, Haiyun Wang, Jerome T. Mettetal, Teresa Collins, Oladipupo Adeyemi, Ross Overman, Deborah Lawson, Alexander R. Harmer, Corinne Reimer, Lisa Drew, Martin J. Packer, Sabina Cosulich, Rhys DO. Jones, Wenlin Shao, David Wilson, Sylvie Guichard, Stephen Fawell, Rana Anjum
Journal: Science Translational Medicine (2020)

AZD3229 demonstrates pan-KIT/PDGFRα activity in several preclinical models and is a promising agent for the treatment of GIST.
PTH-052 A retrospective analysis of endoscopic management of post liver transplant biliary anastomotic strictures
Authors: Jonathan Potts, Leonardo Eusebi, Olivia Greenham, Margaret Keane, George Goodchild, Kalpesh Besherdas, Michael Chapman, Gavin Johnson, Steve Pereira, George Webster, Douglas Thorburn
Journal: Endoscopy (2018)

<h3>Introduction</h3> Biliary anastomotic strictures (AS) occur in 5%–15% of liver transplant (LT) recipients and cause graft dysfunction and morbidity. The main alternative to surgical reconstruction is stenting at endoscopic retrograde cholangiopancreatography (ERCP), using plastic polyethylene or fully-covered self-expanding metal stents (fcSEMS). We retrospectively reviewed outcomes after ERCP for biliary AS, aiming to assess rates of success and complications. <h3>Methods</h3> Records for all patients undergoing ERCP post LT between 2013–16 were reviewed. AS were classified as early or late (&lt;3 or≥3 mths post LT) and cases of diffuse cholangiopathy excluded. Data collected included graft characteristics, timing/nature of ERCPs and complications. Stricture resolution was determined from graft function, imaging and ERCP findings. <h3>Results</h3> In total 252 ERCPs were performed (median 4/patient, range 2–10) in 62 patients, 72.6% male, age at LT 54 years (range 20–71). 48 grafts (77.4%) were donations after brain death, 13 (21.0%) after cardiac death and 1 live donor. At first endoscopy 53 (85.4%) had a native papilla. Median time from LT was 28 days (4–75) in early AS (n=29, 46.7%, 9 presenting with bile leak) vs 11.5 mths (3.4–251) in late AS (n=33, 53.2%). Biliary stents were placed in 172 ERCPs (63.4% plastic vs 36.6% fcSEMS) and AS dilated in 68 (27.0%; 60 in conjunction with stenting). Stricture resolution was achieved endoscopically in 47/55 patients with complete outcome data (85.5%). Plastic stents were placed at index ERCP in 23/26 of early AS, in whom sequential plastic 'upstenting' was ultimately successful in 9 (39.1%) and 12 (52.2%) proceeded to fcSEMS (stricture remodelled in all). Of late AS, 9/29 were managed with fcSEMS (88.8% successfully), 8 plastic 'upstenting' (75% success), 8 fcSEMS after initial plastic stent (all successful) and 2 resolved with dilatation only. The overall rate of post-ERCP pancreatitis (PEP) was 7.1% (none severe by Cotton criteria) and was higher after fcSEMS (15.9%) than plastic stenting (5.5%, p=0.024), despite similar use of NSAID prophylaxis. Compared with plastic stents, fcSEMS were more likely to migrate (36.5% vs 12.8%, p&lt;0.001) and embed (6.3% vs 0%, p=0.008) but stent occlusion was numerically lower (0% vs 4.6%, p=0.084). Of 8 endoscopic failures (14.5%), 3 (5.5%) required percutaneous stenting and 2 (3.6%) biliary reconstruction, one after duodenal perforation by a migrated plastic stent. <h3>Conclusions</h3> Endoscopic management is effective in treating 85% of biliary AS. fcSEMS appear superior to sequential plastic 'upstenting' but are associated with higher rates of PEP and migration.
Prognostic factors, therapeutic approaches, and distinct immunobiologic features in patients with primary mediastinal large B-cell lymphoma on long-term follow-up
Authors: Hui Zhou, Zijun Y. Xu-Monette, Ling Xiao, Paolo Strati, Fredrick B. Hagemeister, Yizi He, Huan Chen, Yajun Li, Ganiraju C. Manyam, Yong Li, Santiago Montes-Moreno, Miguel A. Piris, Ken H. Young
Journal: Blood Cancer Journal (2020)

Abstract Primary mediastinal large B-cell lymphoma (PMBCL) is a rare and distinct subtype of diffuse large B-cell lymphoma (DLBCL) without prognostic factors or a single standard of treatment clearly defined. In this study we performed retrospective analysis for clinical outcomes of 166 patients with PMBCL. In overall PMBCL, higher International Prognostic Index, stage, Ki-67 proliferation index, and positron emission tomography (PET) maximum standardized uptake values (SUVmax) at diagnosis were significantly associated with poorer survival, whereas MUM1 expression and higher peripheral blood lymphocyte/monocyte ratios were significantly associated with better survival. Patients who received R-HCVAD or R-EPOCH had better clinical outcome than did those who received the standard treatment R-CHOP. Treatment response and end-of-treatment PET SUVmax had remarkable correlations with survival outcome. In patients with refractory or relapsed PMBCL, stem cell transplant significantly improved overall survival. PMBCL had distinct gene expression signatures compared with overall DLBCL–NOS but not with DLBCL with PD-L1 / PD-L2 amplification. PMBCL also showed higher PD-L2 expression in B-cells, lower PD-1 expression in T-cells, and higher CTLA-4 expression in T-cells and distinct miRNA signatures compared with DLBCL-NOS. The prognostic factors, effectiveness of treatment, transcriptional and epigenetic signatures, and immunologic features revealed by this study enrich our understanding of PMBCL biology and support future treatment strategy.
Cardiovascular Considerations in Caring for Pregnant Patients: A Scientific Statement From the American Heart Association
Authors: Laxmi S. Mehta, Carole A. Warnes, Elisa Bradley, Tina Burton, Katherine Economy, Roxana Mehran, Basmah Safdar, Garima Sharma, Malissa Wood, Anne Marie Valente, Annabelle Santos Volgman
Journal: Circulation (2020)

Cardio-obstetrics has emerged as an important multidisciplinary field that requires a team approach to the management of cardiovascular disease during pregnancy. Cardiac conditions during pregnancy include hypertensive disorders, hypercholesterolemia, myocardial infarction, cardiomyopathies, arrhythmias, valvular disease, thromboembolic disease, aortic disease, and cerebrovascular diseases. Cardiovascular disease is the primary cause of pregnancy-related mortality in the United States. Advancing maternal age and preexisting comorbid conditions have contributed to the increased rates of maternal mortality. Preconception counseling by the multidisciplinary cardio-obstetrics team is essential for women with preexistent cardiac conditions or history of preeclampsia. Early involvement of the cardio-obstetrics team is critical to prevent maternal morbidity and mortality during the length of the pregnancy and 1 year postpartum. A general understanding of cardiovascular disease during pregnancy should be a core knowledge area for all cardiovascular and primary care clinicians. This scientific statement provides an overview of the diagnosis and management of cardiovascular disease during pregnancy.
The Role of Imaging in the Detection and Management of COVID-19: A Review
Authors: Di Dong, Zhenchao Tang, Shuo Wang, Hui Hui, Lixin Gong, Yao Lu, Zhong Xue, Hongen Liao, Fang Chen, Fan Yang, Ronghua Jin, Kun Wang, Zhenyu Liu, Jingwei Wei, Wei Mu, Hui Zhang, Jingying Jiang, Jie Tian, Hongjun Li
Journal: IEEE Reviews in Biomedical Engineering (2020)

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly around the world, resulting in a massive death toll. Lung infection or pneumonia is the common complication of COVID-19, and imaging techniques, especially computed tomography (CT), have played an important role in diagnosis and treatment assessment of the disease. Herein, we review the imaging characteristics and computing models that have been applied for the management of COVID-19. CT, positron emission tomography - CT (PET/CT), lung ultrasound, and magnetic resonance imaging (MRI) have been used for detection, treatment, and follow-up. The quantitative analysis of imaging data using artificial intelligence (AI) is also explored. Our findings indicate that typical imaging characteristics and their changes can play crucial roles in the detection and management of COVID-19. In addition, AI or other quantitative image analysis methods are urgently needed to maximize the value of imaging in the management of COVID-19.
Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response
Authors: Wendy Béguelin, Matt Teater, Cem Meydan, Kenneth B. Hoehn, Jude M. Phillip, Alexey A. Soshnev, Leandro Venturutti, Martín A. Rivas, María T. Calvo-Fernández, Johana Gutierrez, Jeannie M. Camarillo, Katsuyoshi Takata, Karin Tarte, Neil L. Kelleher, Christian Steidl, Christopher E. Mason, Olivier Elemento, C. David Allis, Steven H. Kleinstein, Ari M. Melnick
Journal: Cancer Cell (2020)
A Surgeon Reflects
Journal: JAMA (1941)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Noninvasive measurement of femoral blood flow and portal pressure response to propranolol in patients with cirrhosis*1
Authors: A LUCA
Journal: Hepatology (1995)

This study investigated the correlation between changes in hepatic and systemic hemodynamics and femoral blood flow (FBF), measured by dual-beam pulsed wave Doppler, in 58 portal hypertensive patients receiving propranolol (0.15 mg/Kg intravenously; n = 44) or placebo (n = 14) under double-blind conditions. Placebo administration had no effects. Propranolol caused significant reductions (P < .0001) in hepatic venous pressure gradient (HVPG; from 19.1 ± 4.1 to 16.2 ± 4.2 mm Hg), azygos blood flow (from 563 ± 204 to 387 ± 176 mL/ min), cardiac index (CI; from 4.4 ± 1.0 to 3.3 ± 0.8 L/m2/min), and FBF (from 237 ± 79 to 176 ± 58 mL/m2/min). In 17 patients HVPG decreased below 12 mm Hg and/or more than 20% of the baseline value (good response; mean change, −26 ± 8%); in the remaining 27 patients (poor response) the mean change in HVPG was less: −9 ± 6%. Patients with a good response had bled less often from varices, had significantly higher FBF (272 ± 73 vs. 215 ± 76 mL/m2/min) and lower baseline HVPG (16.8 ± 3.9 vs. 20.6 ± 3.6 mm Hg) than those with poor response in HVPG. The good response was also associated with greater decreases in FBF (−33 ± 12 vs. −19 ± 13% in poor responders), CI (−30 ± 9 vs. −19 ± 12%), and heart rate (−19 ± 5 vs. −16 ± 6%). A decrease in FBF of >20% predicted a good response in 16 of 28 patients (positive predictive value, 57%). A negative test (decrease in femoral blood flow of <20%) predicted a lack of response in HVPG in 15 of 16 patients (negative predictive value, 94%). This study suggests that the noninvasive measurements of FBF allow the identification of patients with a poor response of HVPG to propranolol. However, measurements of HVPG would still be needed for patients whose FBF decreased >20%, half of whom have an insufficient decrease in HVPG.
Assessment of germ-line and somatic alterations in main candidate genes among patients with multiple primary melanoma.
Authors: Giuseppe Palmieri, MariaCristina Sini, Vincenzo De Giorgi, Amelia Lissia, Daniela Massi, Corrado Rubino, Antonio Cossu, Ignazio Stanganelli, Grazia Palomba, Gerardo Botti, Corrado Caraco, Nicola Mozzillo, Paolo Antonio Ascierto, Maria Colombino
Journal: Journal of Clinical Oncology (2012)

8581 Background: We have studied a series of patients with multiple primary melanoma (MPM) for the involvement of the key-regulator genes in susceptibility (CDKN2A) and pathogenesis (BRAF, cKIT, CyclinD1) of such a disease. Methods: Genomic DNA from peripheral blood of 63 MPM patients (54 cases with two primary melanomas, 8 with three, and 1 with four) were screened for germline mutations in p16 CDKN2A and p14 CDKN2A genes by automated DNA sequencing. Melanoma families were identified according to standardized criteria: 9 (14%) patients were classified as familial cases. Paired synchronous and/or asynchronous MPM tissues (N=100) from same patients (N=46) were analyzed for somatic mutations in BRAF gene and FISH-based amplifications in cKIT and CyclynD1 genes. Results: Overall, 6 (10%) different CDKN2A germline mutations were identified: 5 in p16 CDKN2A and 1 in p14 CDKN2A . The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were significantly more frequent in patients with familial history of melanoma (5/9; 56%) compared with patients without (1/54; 2%) (P&lt;0.001), and in patients with more than two melanomas (3/9; 33%) compared with patients with only two melanomas (3/54; 6%) (P=0.012). The debated A148T polymorphism was found at low level (2/54; 4%) in our series. Regarding genetic alterations at somatic level, BRAF mutations were identified in 36/100 (36%) primary melanoma tissues, whereas amplification of cKIT and CyclinD1 genes was observed in 2/88 (2%) and 10/88 (11%) analyzed tissue samples, respectively. Considering all types of genetic events, paired samples presented a poorly consistent distribution of somatic alterations in same patients (52% consistency). Conclusions: Coexistence of MPM and familial recurrence of melanoma as well as the presence of more than two melanomas seem to be strong indications to address patients to CDKN2A mutational screening. The low consistency in genetic patterns of primary tumors from the same patients provide additional evidence that pathogenetic mechanisms of melanomagenesis are heterogeneous and molecularly different cell types may be generated in multiple primary melanoma.
Phase I Trial of Adenovirus-Mediated p53 Gene Therapy for Recurrent Glioma: Biological and Clinical Results
Authors: Frederick F. Lang, Janet M. Bruner, Gregory N. Fuller, Kenneth Aldape, Michael D. Prados, Susan Chang, Mitchel S. Berger, Michael W. McDermott, Sandeep M. Kunwar, Larry R. Junck, William Chandler, James A. Zwiebel, Richard S. Kaplan, W.K. Alfred Yung
Journal: Journal of Clinical Oncology (2003)

Purpose: Advances in brain tumor biology indicate that transfer of p53 is an alternative therapy for human gliomas. Consequently, we undertook a phase I clinical trial of p53 gene therapy using an adenovirus vector (Ad-p53, INGN 201). Materials and Methods: To obtain molecular information regarding the transfer and distribution of exogenous p53 into gliomas after intratumoral injection and to determine the toxicity of intracerebrally injected Ad-p53, patients underwent a two-stage approach. In stage 1, Ad-p53 was stereotactically injected intratumorally via an implanted catheter. In stage 2, the tumor-catheter was resected en bloc, and the postresection cavity was treated with Ad-p53. This protocol provided intact Ad-p53–treated biologic specimens that could be analyzed for molecular end points, and because the resection cavity itself was injected with Ad-p53, patients could be observed for clinical toxicity. Results: Of fifteen patients enrolled, twelve underwent both treatment stages. In all patients, exogenous p53 protein was detected within the nuclei of astrocytic tumor cells. Exogenous p53 transactivated p21 CIP/WAF and induced apoptosis. However, transfected cells resided on average within 5 mm of the injection site. Clinical toxicity was minimal and a maximum-tolerated dose was not reached. Although anti-adenovirus type 5 (Ad5) titers increased in most patients, there was no evidence of systemic viral dissemination. Conclusion: Intratumoral injection of Ad-p53 allowed for exogenous transfer of the p53 gene and expression of functional p53 protein. However, at the dose and schedule evaluated, transduced cells were only found within a short distance of the injection site. Although toxicity was minimal, widespread distribution of this agent remains a significant goal.
A Phase 1b Dose Escalation Trial of NC-6300 (Nanoparticle Epirubicin) in Patients with Advanced Solid Tumors or Advanced, Metastatic, or Unresectable Soft-tissue Sarcoma
Authors: Sant P. Chawla, Sanjay Goel, Warren Chow, Fadi Braiteh, Arun S. Singh, Juneko E. Grilley Olson, Atsushi Osada, Iulian Bobe, Richard F. Riedel
Journal: Clinical Cancer Research (2020)

NC-6300 is a novel nanoparticle formulation of epirubicin that has a pH-sensitive linker conjugated to epirubicin. It exhibits selective tumor accumulation owing to enhanced permeability and retention effect. We conducted a phase 1b trial to determine MTD and recommended phase II dose (RP2D) of NC-6300 monotherapy in advanced, metastatic, or unresectable solid tumors, including soft-tissue sarcomas.This phase 1b dose-escalation trial of NC-6300 monotherapy employed a Bayesian continuous reassessment method design. NC-6300 was administered on day 1 of every 21-day cycle, with epirubicin-equivalent dose increments from 125 to 215 mg/m2. Safety, efficacy, quality of life, and pharmacokinetic profile of NC-6300 monotherapy were evaluated.Twenty-nine subjects (16 male) were enrolled: 17 with soft-tissue sarcoma, one with osteosarcoma, and 11 with other solid tumors. Observed dose-limiting toxicities included thrombocytopenia, stomatitis, lung infection, and febrile neutropenia. The most common grade 3/4 adverse events were neutropenia (59%), anemia (24%), thrombocytopenia (24%), and febrile neutropenia (21%). MTD and RP2D were determined to be 185 mg/m2 and 150 mg/m2, respectively. The objective response rate in the evaluable population was 11%. Partial response was observed in angiosarcoma and endometrial stromal sarcoma. A dose-dependent increase was observed in both total and released epirubicin concentrations.NC-6300 was well tolerated with a manageable side effect profile, despite the MTD and RP2D being higher than conventional epirubicin doses. A signal of preliminary activity was observed in angiosarcoma. NC-6300 warrants further investigation in patients with advanced solid tumors, including sarcoma.