tbuckley/cabot-search huggingface dataset:
ADVL1522: A phase 2 study of IMGN901 (lorvotuzumab mertansine; IND# 126953, NSC# 783609) in children with relapsed or refractory Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST), and synovial sarcoma: A Children's Oncology Group study.
Authors: James I. Geller, Joseph Gerald Pressey, Malcolm A. Smith, Rachel A. Kudgus, Renee Schoon, Renee M. McGovern, Mariana Cajaiba, Joel M. Reid, David Hall, Donald A. Barkauskas, Jeffrey Dome, Elizabeth Fox, Brenda Weigel
Journal: Journal of Clinical Oncology (2017)

10537 Background: Lorvotuzumab mertansine (IMGN901; LM) is an antibody-drug conjugate, linking anti-mitotic agent (DM1) to an anti-CD56 antibody. Preclinical data show effects in Wilms tumor (WT), rhabdomyosarcoma (RMS), and neuroblastoma (NBL). Synovial sarcoma (SS), MPNST and pleuropulmonary blastoma (PPB) also express CD56. A phase 2 trial assessing the efficacy and tolerability of LM administered at the adult recommended phase 2 dose (RP2D) was conducted in children with relapsed tumors. Methods: LM (110 mg/m 2 /dose) was administered IV on days (d) 1 and 8 of 21 d cycles, with dexamethasone pre-medication. The tolerability of LM was assessed in 6 patients prior to trial activation group-wide. Dose limiting toxicity (DLT) was assessed using CTCAE. Response was assessed by RECIST. Pharmacokinetics (PK) were obtained during cycle 1. Peripheral blood CD56-positive cells were measured d1 and d8 pre-dose. Tumor CD56 expression by immunohistochemistry in archival tissue was scored (0-3+). Results: Sixty-two patients were enrolled. The median (range) age was 14.3 y (2.8–29.9); 35 were male. Diagnoses included WT (17), RMS (17), NBL (12), SS (10), MPNST (5) and PPB (1). One patient was ineligible due to lack of measurable disease. Of 61 eligible patients, 47 were evaluable for toxicity, 50 for response, 50 for tumor CD56 expression; and 18 consented to optional PK. Five patients experienced 9 DLTs: hyperglycemia (1), colonic fistula (1) with perforation (1), nausea (1) with vomiting (1), increased ALT (2 in cycle 1; 1 in cycle 2 with increased AST (1)). Non-dose limiting toxicities (Grade ≥3) attributed to LM included lymphopenia, anemia, vomiting, dehydration, hypokalemia, hyperuricemia, hypophosphatemia. Mean DM1 C max , t 1/2 and AUC 0-∞ values were 922 ng/ml, 33 h and 27400 ng/ml*h, respectively. Tumor CD56 expression was 0 (8%), 1+(4%), 2+(12%), 3+(76%). LM and CD56 antibody PK, and response, will be reported. Conclusions: LM (110 mg/m 2 ) is tolerated in children at the adult RP2D. Clinical trial information: NCT 02452554.
Hydrodynamics of bile flow: Lessons from computational modeling
Authors: Peter L.M. Jansen
Journal: Hepatology (2017)

bench-and back" approach (Fig. 1).Also of note is the potential to use autologous cells for generation of liver organoids and cell therapy as this may obviate the need for immunosuppressive drugs, which are associated with increased risk of infections and other complications.Organoid cultures from diseased livers may further be amenable to new genome editing techniques such as CRISPR/Cas9 to correct genetic aberrations.Liver transplantation is currently the only curative option to treat end-stage biliary diseases.However, this approach is limited by the availability of healthy organs for transplantation.Using a combination of tissue engineering and regenerative medicine approaches illustrated in this article, it may one day be possible to generate bioengineered biliary tissue that could theoretically provide an adjunct therapy for certain biliary pathologies.Artificial bile ducts not only would be useful for tissue repair but also could provide a platform to model diseases of the bile duct and potentially develop and test new drug therapies.One important unanswered question is how feasible this approach will be for human therapeutic applications considering that the diseased ducts in humans might hinder collection of a homogenous population of normal cholangiocytes.Additionally, many biliary diseases are associated with a robust ductular reaction that involves hyperplasia of the peribiliary glands and expansion of a heterogeneous population of stem-like cells.In these cases, the cell isolation procedure could inadvertently select an inappropriate population of cells with unclear differentiation capacity.Another limitation of the study is that the bioengineered bile duct was implanted in a healthy mouse and not in an experimental disease model, and thus, we do not yet know if the scaffold will adapt to a pathologic environment.Furthermore, for cell replacement therapy, along with significant cell engraftment, it will also be important to ascertain whether ECOs can form functional connections with hepatocytes upon engraftment.Maintenance of physiological properties in vivo for a prolonged period of time will also be vital.Other questions include, but are not limited to, the genomic and phenotypic stability in vivo and whether this approach can be used for gene correction and autologous therapy of genetic biliary diseases.Certainly, further study is now warranted to clarify the regenerative medicine approaches that will most optimally improve human biliary disease in various clinical settings.The present studies highlight biliary organoids and biodegradable scaffolds as one potentially important approach to be considered further for translation to human disease.
TCT-217 Fractional Flow Reserve after Percutaneous Coronary Intervention in Patients with Stable Angina, Non ST Elevation Myocardial Infarction and ST Elevation Myocardial Infarction
Authors: Rutger van Bommel, Roberto Diletti, Miguel Lemmert, Jeroen Wilschut, Peter P.T. De Jaegere, Felix Zijlstra, Joost Daemen, Nicolas Van Mieghem
Journal: Journal of the American College of Cardiology (2017)
Reducing antibiotic prescriptions for childhood upper respiratory tract infections
Authors: Gary W K Wong
Journal: The Lancet Global Health (2017)

Resistance to antibiotics has become a major health threat worldwide, and one of the most important contributing factors is the widespread overuse of antimicrobials. This problem is most severe in low-income and middle-income countries (LMICs), where physicians have few resources for investigations and diagnosis, along with inherent concerns about missing an underlying bacterial infection. A young child usually develops between four and six episodes of upper respiratory tract infection per year.
PS02.19 Systematic Literature Review to Assess Role of KRAS Mutations as Prognostic Factors/Treatment Effect Modifiers in Advanced/Metastatic in NSCLC
Authors: R.E. Goulding, G. Cuyun Carter, A. Rojubally, M. Boye, K. Sheffield, W. John, C. Muehlenbein, L. Li, M. Jen, J. Jansen, E. Druyts
Journal: Journal of Thoracic Oncology (2017)
Mild Elevation of Pulmonary Arterial Pressure as a Predictor of Mortality
Authors: Philipp Douschan, Gabor Kovacs, Alexander Avian, Vasile Foris, Fabian Gruber, Andrea Olschewski, Horst Olschewski
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Normal mean pulmonary arterial pressure (mPAP) is 14.0 ± 3.3 mm Hg (mean ± SD). The prognostic relevance of mildly elevated mPAP not fulfilling the definition of pulmonary hypertension (PH; mPAP ≥ 25 mm Hg) has not been prospectively evaluated in a real-world setting.To assess the association of resting mPAP with all-cause mortality in a retrospective and a prospective cohort of patients with unexplained dyspnea and/or at risk of PH.Prognostic cutoffs were calculated by means of 1) classification and regression tree (CART) analysis without any preset thresholds, and 2) preset thresholds on the basis of literature data defining mPAP as lower-normal (≤mean + 1 SD), upper-normal (between mean + 1 SD and mean + 2 SD), borderline (between mean + 2 SD and 25 mm Hg), and manifest PH (≥25 mm Hg). We performed univariate and multivariate survival analysis adjusted for age and comorbidities.We enrolled 547 patients, of whom 137, 56, 64, and 290 presented with lower-normal, upper-normal, or borderline mPAP, and manifest PH, respectively. The CART analysis on mPAP discriminated three prognostic groups: mPAP less than 17 mm Hg, 17 to 26 mm Hg, and greater than 26 mm Hg, with significantly decreasing survival. The univariate analysis on the basis of preset thresholds showed that upper-normal mPAP, borderline mPAP, and manifest PH were significantly associated with poor survival compared with lower-normal mPAP. In the multivariate model, considering age and comorbidities, only borderline mPAP (hazard ratio, 2.37; 95% confidence interval, 1.14-4.97; P = 0.022) and manifest PH (hazard ratio, 5.05; 95% confidence interval, 2.79-9.12; P < 0.001) were significantly associated with poor survival.In patients at risk for PH and/or with unexplained dyspnea, CART analysis detects prognostic thresholds at a resting mPAP of 17 mm Hg and 26 mm Hg, and values between 20 mm Hg and 25 mm Hg represent an independent predictor of poor survival. Clinical trial registered with www.clinicaltrials.gov (NCT 01607502).
Impact du vaccin antiméningococcique C conjugué en Espagne : une décision épidémiologique et microbiologique
Authors: R Cano, A Larrauri, S Mateo, B Alcalá, C Salcedo, J A Vázquez
Journal: Eurosurveillance (2004)

En Espagne, le nouveau vaccin conjugue antimeningococcique C a ete mis sur le marche et inclu dans le programme de vaccination des nourrissons en 2000. Une campagne de rattrapage a ete mise en place pour les enfants de moins de six ans. Il en est resulte une forte baisse de l'incidence de l'infection a meningocoque de serogroupe C au cours des trois dernieres annees epidemiologiques en Espagne. Le risque de contracter la maladie de serogroupe C en 2002/2003 a chute de 58%, si l'on compare avec la saison precedant l'introduction du vaccin conjugue. Une forte baisse de la mortalite a egalement ete enregistree. Trois deces dus au meningocoque de serogroupe C sont survenus dans les tranches d'âge ciblees pour la vaccination en 2002/2003 par rapport a 30 deces dans les memes tranches d'âge la saison precedant le lancement de la campagne de vaccination. Lors des campagnes de rattrapage, la couverture vaccinale a depasse 92%. En 2001, 2002 et 2003, la couverture des programmes de vaccination a atteint des valeurs entre 90% et 95%. Les trois dernieres annees, 111 cas d'infections a meningocoque de serogroupe C ont ete declares chez des patients appartenant au groupe cible pour les vaccinations. La plupart des echecs de vaccination ont eu lieu au cours de l'annee epidemiologique 2002/2003. Huit (53%) echecs, survenus chez des enfants vaccines en routine lorsqu'ils etaient nourrissons, pourraient etre dus a une baisse de la protection avec le temps apres la vaccination. Il importe de noter l'isolement de plusieurs souches B:2a:P1.5 (lignee ST-11) pouvant avoir un fort potentiel epidemique. Il est possible que ces souches soient issues de souches C:2a:P1.5 apres recombination genetique au niveau de l'operon capsulaire conduisant a une expression de la capsule de serogroupe B.
TCT-802 Impact of diabetes mellitus on 1-year outcomes of Absorb Bioresorbable vascular scaffold vs. Everolimus-eluting Metallic stent: a propensity matched Analysis of COMPARE II, RAI and MAASSTAD-ABSORB Prospective Registries
Authors: Giuseppe Tarantini, Marco Mojoli, Giulia Masiero, Bernardo Cortese, Gaetano di Palma, Giuseppe Steffenino, Attilio Varricchio, Alfonso Ielasi, Bruno Loi, Daisuke Ueshima, Paola Tellaroli, Valeria Paradies, Georgios Vlachojannis, Pieter Smits
Journal: Journal of the American College of Cardiology (2017)
Adding trimethoprim–sulfamethoxazole to cephalexin did not increase clinical cure in uncomplicated cellulitis
Authors: Fred Arthur Zar
Journal: Annals of Internal Medicine (2017)

Source Citation Moran GJ, Krishnadasan A, Mower WR, et al. Effect of cephalexin plus trimethoprim–sulfamethoxazole vs cephalexin alone on clinical cure of uncomplicated cellulitis: a randomized clinical trial. JAMA. 2017;317:2088-96. 28535235
Raccomandazioni europee sulla sorveglianza della resistenza ai farmaci antitubercolari
Authors: V Schwoebel, C S B Lambregts, M. L. Moro, F Drobniewski, S. E. Hoffner, M. C. Raviglione, H. L. Rieder
Journal: Eurosurveillance (2000)

La resistenza ai farmaci antitubercolari, la cui entita in Europa non e ben documentata, e un seria minaccia per il controllo della tubercolosi. Lo scopo delle recenti raccomandazioni europee sulla sorveglianza della resistenza ai farmaci antitubercolari, formulate da un gruppo di lavoro composto da rappresentanti dell’OMS, della IUATLD e di 35 paesi della Regione Europea dell’OMS, e quello di migliorare la standardizzazione delle definizioni e dei metodi. Queste raccomandazioni enfatizzano l’importanza del controllo di qualita e del linkage tra i risultati di laboratorio sui test di suscettibilita ai farmaci e i dati clinici. La sorveglianza della resistenza ai farmaci antitubercolari dovrebbe diventare una componente fondamentale della sorveglianza della tubercolosi.
TCT-626 Long-term mortality of vasospastic angina with documented ST-segment depression during ergonovine provocation: Data form Asan Vasospastic Angina Registry
Authors: Hanbit Park, Minsoo Kim, Sang Yong Om, Yong-Hoon Yoon, Sang-Cheol Cho, Osung Kwon, Ungjeong Do, Kyusup Lee, Do-yoon Kang, Cheol Hyun Lee, Pil Hyung Lee, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2017)
Le contrôle de la rubéole en France
Authors: D Lévy-Bruhl, C Six, I Parent du Châtelet
Journal: Eurosurveillance (2004)

L'introduction en 1983 de la vaccination contre la rubeole dans le calendrier de vaccination du nourrisson a conduit a une reduction spectaculaire de l'incidence des infections rubeoleuses durant la grossesse et des rubeoles congenitales. Cette reduction a ete attestee par les donnees de la surveillance realisee aupres de l'ensemble des laboratoires de biologie medicale realisant la recherche d'Ig M anti-rubeoleuses. Cependant les couvertures vaccinales insuffisantes chez les enfants et les femmes en âge de procreer conduisent respectivement au maintien de la circulation du virus et a la survenue, chaque annee, de plusieurs dizaines d'infections rubeoleuses durant la grossesse. Les efforts actuellement entrepris pour ameliorer la couverture vaccinale doivent etre poursuivis si l'on veut eviter les epidemies dues au taux important de susceptibilite chez les femmes jeunes.
P3.02b-120 EGFR T790M, L792F, and C797S Mutations as Mechanisms of Acquired Resistance to Afatinib
Authors: Yoshihisa Kobayashi, Koichi Azuma, Hiroki Nagai, Young Kim, Yosuke Togashi, Yuichi Sesumi, Masaya Nishino, Masato Chiba, Masaki Shimoji, Katsuaki Sato, Kenji Tomizawa, Toshiki Takemoto, Kazuto Nishio, Tetsuya Mitsudomi
Journal: Journal of Thoracic Oncology (2017)
Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer
Authors: Caroline M. Curtin, Irene Mencía Castaño, Fergal J. O'Brien
Journal: Advanced Healthcare Materials (2017)

Abstract microRNA‐based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industry‐sponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold‐mediated miRNA therapies translates know‐how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to‐date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA‐activated scaffolds in the future of RM and cancer treatments.
Clinical efficacy of mTOR inhibitor for Kaposiform hemangioendotheliomas with Kasabach-Merritt phenomenon
Authors: Michio Ozeki, Akifumi Nozawa, Tomohiro Hori, Kaori Kanda, Norio Kawamoto, Harumi Kadota, Toshiyuki Fukao
Journal: Annals of Oncology (2017)
Salvage Use of Ibrutinib after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) for B Cell Malignancies: A Study of the French Cooperative Group for CLL, the French Soceity for Blood and Marrow Transplantation (SFGM-TC), and the European Society for Blood and Marrow Transplantation (EBMT) Chronic Malignancy and Lymphoma Working Parties
Authors: Mauricette Michallet, Peter Dreger, Mohamad Sobh, Jennifer Hoek, Ariane Boumendil, Lutz Muller, Paolo Corradini, Wolfgang Bethge, Domenico Russo, Nadira Durakovic, Michel van Gelder, Nicolaas PM Schaap, Nicolaus Kroger, Johannes Schetelig
Journal: Blood (2016)
P3.04-013 The Role of Extent of Surgical Resection and Lymph Node Assessment for Clinical Stage I Pulmonary Lepidic Adenocarcinoma
Authors: Morgan Cox, Chi-Fu Yang, Paul Speicher, Zachary Fitch, Lin Gu, Robert Davis, Thomas D'Amico, Matthew Hartwig, David Harpole, Mark Berry
Journal: Journal of Thoracic Oncology (2017)
O sarampo na Alemanha
Authors: E Gericke, Gernot Rasch, A Tischer, S Santibanez
Journal: Eurosurveillance (1997)

Apos uma reuniao de peritos, realizada em Copenhaga de 19 e 20 de Novembro de 1996, acerca da erradicacao do Sarampo na Europa, os paises europeus foram classificados em quatro categorias com base num estudo recente efectuado pelo gabinete da Organizacao Mundial da Saude para a Europa (1). A Alemanha foi colocada no terceiro grupo (quadro 1) que compreende os paises onde o sarampo e endemico, com surtos e ondas epidemicas importantes, baixa cobertura vacinal e onde a vigilância nao e realizada sistematicamente.
Abstract 15492: Spontaneous Coronary Artery Dissection: Characterizing Presentation, Management, and Outcomes at a Large Referral Cardiovascular Center
Authors: Daniel M Shivapour, Phillip Erwin, Heather L Gornik, Esther S Kim
Journal: Circulation (2015)

Introduction: Non-atherosclerotic spontaneous coronary artery dissection (SCAD) primarily affects women and may be associated with arteriopathies such as fibromuscular dysplasia (FMD). We aimed to describe patient characteristics, management, and outcome of SCAD at a large referral center. Methods: We queried our institutional cardiac cath database for SCAD diagnoses from 2000-2014. The electronic medical record was also queried for consecutive SCAD patients seen in a specialty arteriopathy clinic from 2010-2015. Details regarding presentation, treatment, and outcome of SCAD were collected. Trends in management over two time periods (2000-2009, 2010-2015) were compared. Results: There were 96 SCAD events in 75 patients (16 patients had one recurrence, one had three events, and one had four distinct events). Mean age at presentation was 47 years, 83% were female, and 84% presented with ACS. The LAD was the most commonly affected vessel (54%). Most SCAD events were treated medically (52%). Of 41 events treated with PCI, 19 were complicated by hematoma extension. Four PCI patients required subsequent CABG. Imaging of other arterial beds increased over time, with 2/3 patients receiving vascular ultrasound to evaluate for renal or carotid FMD in the more recent time period (Table). Of those evaluated for FMD, 45% had imaging findings compatible with multifocal FMD. Significant carotid tortuosity was present in 38%, with four demonstrating a classic “S surve” appearance recently shown to be a variant presentation of FMD. All patients survived to index hospitalization discharge, however, 24% of patients had at least one recurrence. Conclusions: SCAD affects predominantly young females and often manifests as ACS. Findings of FMD or carotid tortuosity are frequent and recognition of SCAD as a potential manifestation of FMD is increasing in our institution. In support of other reports, recurrence of SCAD is not rare and PCI attempts are complicated nearly half of the time.
Abstract 13299: Cross Talk Between Hyper Permeability and Autophagy in Endothelial Cells With Persistent Inflammation
Authors: Saheli Samanta, Sheeja Rajasingh, Lei Chen, Thuy Cao, Nicholas Drosos, Buddhadeb Dawn, Johnson Rajasingh
Journal: Circulation (2016)

Introduction: Lipopolysaccharide (LPS) is known to induce endothelial dysfunction causing an increase in permeability and damage intra cellular signaling as well as known to induce autophagy. However, few studies have suggested that autophagy might interrupt cell-cell interaction through adherens junction protein, which leads to endothelial barrier dysfunction. Here we demonstrated that LPS induces autophagy, and hyper permeability of lung endothelial cells and this can be prevented by the combinatorial treatment with 5-Aza 2 deoxycytidine and Tubastatin A (HDAC6 inhibitor) (referred as Aza+TBSA). Hypothesis: We hypothesize that treatment with the combination of Aza+TBSA inhibits autophagy and restores vascular integrity after LPS induced vascular hyper permeability. Methods and Results: In this study, we have used LPS to induce hyper permeability and autophagy and mTOR inhibitor Rapamycin used as a positive control for autophagy in mouse lung endothelial cells (MLECs). Our Western analysis data showed that LPS and Rapamycin induce autophagy, which is indicated by the increased level of known autophagy markers LC3 and beclin-1, and decreased VE-cadherin expression in MLECs induced with LPS or Rapamycin. Where as treatment with Aza+TBSA significantly reduced the effect of LPS induced autophagy markers and increased VE-cadherin expression (Fig. 1A). Our immunofluorescence analysis also showed a decreased expression of LC3 when the LPS induced MLECs was treated with Aza+TBSA ( Fig. 1B ). Conclusions: These data suggest that Aza+TBSA treatment can rescue endothelial barrier dysfunction and prevent autophagy in LPS-induced MLECs, indicating that LPS-induced vascular leakage is dependent on autophagy. These results support a therapeutic potential of Aza+TBSA combination for patients with acute lung injury.
Government must “get its act together” over cyberattacks on NHS, says watchdog
Authors: Adrian O’Dowd
Journal: BMJ (2017)

The NHS was warned more than once about a likely cyberattack on its IT systems but was unprepared when an actual attack struck earlier this year, the public spending watchdog the National Audit Office has said.

In a new report the NAO said that the Department of Health for England was warned by the national data guardian and by the regulator the Care Quality Commission about the risks of cyberattacks on the NHS a year before the attack,1 and although it had work under way it did not formally respond until July this year.

In May the WannaCry “ransomware,” which encrypts data on infected computers and demands a ransom payment to allow users access, was released worldwide.2 …