tbuckley/cabot-search huggingface dataset:
Presentation of a Case for Diagnosis
Journal: Circulation (1955)

This conference was presented at the Fourth Annual Heart Symposium sponsored by the Indiana Heart Foundation at the Indiana University School of Medicine, Indianapolis, Ind. on Jan. 20, 1955. Participating were members of the Research Committee of the American Heart Association and members of the Faculty of the School of Medicine. Participants from the Research Committee were: Dr. Robert H. Bayley of the University of Oklahoma College of Medicine, Oklahoma City; Dr. Howard Burchell, Mayo Clinic, Rochester; Dr. Howard Sprague, Harvard Medical School, Boston. Participants from the Indiana University School of Medicine Faculty were: Dr. James O. Ritchey, Department of Medicine, Moderator; Dr. Warren Coggeshall, Department of Medicine; Dr. John A. Campbell, Department of Radiology; Dr. Edward Smith, Department of Pathology; Edited by: Dr. Roy H. Behnke, Department of Medicine.
Clinical Classification In Pediatric Pulmonary Arterial Hypertension Associated With Congenital Heart Disease
Authors: W. M. H. Zijlstra, J. M. Douwes, M. J. Ploegstra, U. Krishnan, M. T. Roofthooft, H. L. Hillege, D. Ivy, E. B. Rosenzweig, R. M. Berger
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Congenital heart disease (CHD) is a frequent cause of pediatric pulmonary arterial hypertension (PAH), with diverse etiology and outcome. We aimed to describe phenotypic heterogeneity in pediatric PAH associated with CHD (PAH-CHD), assess the applicability of the Nice CHD classification, and explore whether this classification accurately reflects patient/disease characteristics and survival. All children with CHD from a contemporary cohort of consecutive pediatric PAH patients followed in three major referral centers (Denver, New York, the Netherlands) were characterized and classified on the basis of the latest proposed clinical classification for PAH-CHD (World Symposium on Pulmonary Hypertension, Nice, 2013). According to this classification, 24% of 134 children were classified into group 1, 14% into group 2, 19% into group 3, and 30% into group 4; 11% could not be classified. Types of CHD and hemodynamic profile differed between groups, with the highest right atrial pressure in group 4 (P < 0.040). Group 3 children had Down syndrome less frequently (P = 0.011) but other (un)defined syndromes most frequently (P = 0.063) and received most intense PAH-targeted therapy (P = 0.003). With 15 deaths and one lung transplant (12%; median follow-up: 4.3 years), survival differences could not be demonstrated between the groups in the Nice CHD classification. Pediatric PAH-CHD is a heterogeneous condition frequently associated with extracardiac, developmental factors that are believed to affect disease development. The Nice CHD classification identifies groups with specific patient/disease characteristics. However, a substantial proportion of children could not be classified. Group 3 forms a distinct disease entity. Its prognostic value could not be determined because of the low number of events. The Nice CHD classification supports clinical characterization of PAH-CHD; however, further refinement is needed to classify all children with PAH-CHD.
Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100 nm Particles
Authors: Yu Sakurai, Tomoya Hada, Shoshiro Yamamoto, Akari Kato, Wataru Mizumura, Hideyoshi Harashima
Journal: Molecular Therapy (2016)

A number of nano drug delivery systems have recently been developed for cancer treatment, most of which are based on the enhanced permeability and retention effect. The advantages of the enhanced permeability and retention effect can be attributed to immature vasculature. Herein we evaluated the intratumoral distribution of lipid nanoparticles when the VEGF receptor 2 on tumor endothelial cells was inhibited by liposomal siRNA. VEGF receptor 2 inhibition resulted in an increase in intratumoral distribution and therapeutic efficacy despite the maturation of the tumor vasculature. A small molecule inhibitor against matrix metalloproteinase and macrophage depletion cancelled the improvement in the distribution of the lipid nanoparticles, suggesting that remodeling of tumor microenvironment played a role in the facilitated intratumoral distribution via the down-regulation of VEGF receptor 2. Accordingly, our results suggest that the enhanced permeability and retention effect is dependent, not only on the structure of the tumor vasculature, but also on the dynamics of the tumor microenvironment including extracellular matrix remodeling. Regulating the tumor microenvironment and the extracellular matrix by delivering tumor endothelial cell-targeting siRNA could potentiate the enhanced permeability and retention effect-based strategy. A number of nano drug delivery systems have recently been developed for cancer treatment, most of which are based on the enhanced permeability and retention effect. The advantages of the enhanced permeability and retention effect can be attributed to immature vasculature. Herein we evaluated the intratumoral distribution of lipid nanoparticles when the VEGF receptor 2 on tumor endothelial cells was inhibited by liposomal siRNA. VEGF receptor 2 inhibition resulted in an increase in intratumoral distribution and therapeutic efficacy despite the maturation of the tumor vasculature. A small molecule inhibitor against matrix metalloproteinase and macrophage depletion cancelled the improvement in the distribution of the lipid nanoparticles, suggesting that remodeling of tumor microenvironment played a role in the facilitated intratumoral distribution via the down-regulation of VEGF receptor 2. Accordingly, our results suggest that the enhanced permeability and retention effect is dependent, not only on the structure of the tumor vasculature, but also on the dynamics of the tumor microenvironment including extracellular matrix remodeling. Regulating the tumor microenvironment and the extracellular matrix by delivering tumor endothelial cell-targeting siRNA could potentiate the enhanced permeability and retention effect-based strategy.
Senior doctors must support junior colleagues, say medical royal colleges
Authors: Tom Moberly
Journal: BMJ (2016)

Senior doctors must ensure that their junior colleagues feel supported while the dispute over the junior doctor contract continues, leaders of the medical royal colleges have said.

Last week the Royal College of Anaesthetists issued a statement saying that it was “crucial that trainees are, and feel, supported at this time.”1 The college said that doctors who felt “overwhelmed” should talk to fellow trainees, family, and friends, meet their supervisors, tutors, or mentors, and use available support schemes. “It is important that as a profession we remain united in caring for each other,” it said. “Look after yourselves and each other.”

The statement was signed by Liam Brennan, president of the Royal College of Anaesthetists, along with other senior members of the college, the Faculty of Intensive Care Medicine, and the Association of Anaesthetists of Great Britain and …
Incorporation of rituximab and liposomal doxorubicin into CODOX-m/IVAC for HIV-negative and HIV-positive adult patients (pts) with untreated Burkitt's lymphoma (BL): Preliminary results of a multicenter phase II study.
Authors: S. A. Gregory, P. M. Barr, C. Nabhan, A. Nukala, L. Gallot, A. Larsen, M. Z. Moll, S. E. Smith, L. I. Gordon, A. M. Evens
Journal: Journal of Clinical Oncology (2010)

8033 Background: The survival of adult BL has improved with intensification of multiagent chemotherapy, although 2-year survival rates remain <65%. Efforts to improve survival and decrease treatment related toxicities are needed. Methods: We report results of the first stage of the Simon 2 stage investigator initiated trial (planned analysis). Low risk (LR) pts were defined as normal LDH, stage I/II, ECOG <2, and no mass >10 cm. All other pts were high risk (HR). LR pts received 3 CODOX-M cycles, while HR pts received 4 alternating cycles of CODOX-M and IVAC. Liposomal doxorubicin (40 mg/m2) was used in lieu of doxorubicin (day 1 CODOX-M) and rituximab (500 mg/m2) was added days 0 + 8 of CODOX-M and days 0 + 6 of IVAC. Methotrexate dose was 3,000 mg/m2 iv. Results: 18 pts have enrolled, of whom 12 were in the first stage. The median age was 43 years (23-70), 3/12 pts had HIV+ disease, and 9/12 had HR disease. Similar to previous CODOX-M/IVAC data, myelosuppression was common (83% grade 4 neutropenia and thrombocytopenia, while only 8% had grade 4 anemia). Incidence of mucositis also appeared similar to prior reports (42% grade 3, 8% grade 4). Other grade 3 toxicities included infection (42%), transaminitis (33%), diarrhea (17%), elevated creatinine (17%) and hypokalemia (17%). One grade 3 cardiac event occurred in a 69yo M with history of myocardial infarction. Of all pts, the median ejection fraction at study end vs entry was: -7% (-13% to +11%). 11 pts were evaluable for response. The overall response rate after 2 cycles was 100% (11/11) with a complete remission rate (CRR) of 82% (9/11). The 2 non-CR pts were otherwise in CR, but restaging bone marrows were deferred/not performed (both pts had widespread/bulky adenopathy at study entry). The 2-year PFS and OS rates are 73%, while the cause-specific survival is 82%. One pt died in CR from unknown causes, while 2 pts died due to progressive disease. Conclusions: In preliminary analysis, the incorporation of rituximab and liposomal doxorubicin to CODOX-M/IVAC for BL appears safe. The prerequisite interim CRR (>70%) was met and accrual has continued to the second stage of the clinical trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech, Ortho Biotech
Axe Beam: Encouraging Early Results of a Neo-Adjuvant Bevacizumab, Capecitabine +/- Oxaliplatin and Radiation Multimodality Regimen for Locally Advanced Rectal Cancer
Authors: G. Chiritescu, K. Dumon, P. Vergauwe, J. Arts, A. D'Hoore, A. Debucquoy, M. Verstraete, X. Sagaert, K. Haustermans, E. Van Cutsem
Journal: Annals of Oncology (2012)
Cost-effectiveness of adjuvant systemic therapy in early-stage breast cancer patients with isolated tumor cells or micrometastases in regional lymph nodes.
Authors: M. De Boer, E. M. Adang, K. C. Van Dycke, J. A. Van Dijck, G. F. Borm, C. H. Van Deurzen, P. J. Van Diest, P. Bult, A. T. Donders, V. C. Tjan-Heijnen
Journal: Journal of Clinical Oncology (2010)

614 Background: The MIRROR study has shown a negative prognostic impact of isolated tumor cells and micrometastases in regional lymph nodes in early-stage breast cancer patients who had not received adjuvant systemic therapy (endocrine and/or chemotherapy) compared to those who had received adjuvant therapy. The goal of the present study was to evaluate whether administering AST in those patients is cost-effective. Methods: The primary objective of this cost-effectiveness analysis was to determine the incremental cost-effectiveness ratio (ICER), expressed as the investment necessary to prevent one percent of events after 5 years of follow-up. The median costs of the adjuvant and nonadjuvant therapy cohort of the MIRROR study were compared using a log regression taking into account possible confounders. The costs of every treatment delivered for primary breast cancer, follow-up, and recurrence of disease were included in the analyses. The 5- year disease free survival was assessed using Cox regression analysis. To assess the robustness of the study results, we carried out one-way sensitivity analyses for several parameters. Results: In the non-adjuvant therapy cohort, 22.7% of patients with complete follow-up or an event (n = 366) had an event within 5 years, and the estimated mean costs per patient were €15,528 (95% CI, €13,832-€17,223). In the adjuvant therapy cohort, 15.3% of patients with complete follow-up or an event (n = 483) had an event within 5 years, and the estimated mean costs per patient were €17,773 (95% CI, €16,957-€18,588). The costs of the adjuvant therapy cohort were significantly higher (p < 0.0001), after correction for age, log tumor size, tumor grade, and axillary treatment. The ICER was €304 per % events prevented. Sensitivity analyses resulted in ICERs ranging from €31 and €406 per % event prevented. Conclusions: In the adjuvant therapy cohort with complete follow-up after 5 years, the disease event rate was 7.4% lower as compared to the nonadjuvant therapy cohort. To obtain this, €2,250 had to be invested per patient with early-stage breast cancer and isolated tumor cells or micrometastases in regional lymph nodes. No significant financial relationships to disclose.
The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index
Authors: Gabriele Valentini, Michele Iudici, Ulrich A Walker, Veronika K Jaeger, Murray Baron, Patricia Carreira, László Czirják, Christopher P Denton, Oliver Distler, Eric Hachulla, Ariane L Herrick, Otylia Kowal-Bielecka, Janet Pope, Ulf Müller-Ladner, Gabriela Riemekasten, Jerome Avouac, Marc Frerix, Suzana Jordan, Tünde Minier, Elise Siegert, Voon H Ong, Serena Vettori, Yannick Allanore
Journal: Annals of the Rheumatic Diseases (2016)

Validity of European Scleroderma Study Group (EScSG) activity indexes currently used to assess disease activity in systemic sclerosis (SSc) has been criticised.Three investigators assigned an activity score on a 0-10 scale for 97 clinical charts. The median score served as gold standard. Two other investigators labelled the disease as inactive/moderately active or active/very active. Univariate-multivariate linear regression analyses were used to define variables predicting the 'gold standard', their weight and derive an activity index. The cut-off point of the index best separating active/very active from inactive/moderately active disease was identified by a receiver-operating curve analysis. The index was validated on a second set of 60 charts assessed by three different investigators on a 0-10 scale and defined as inactive/moderately active or active/very active by other two investigators. One hundred and twenty-three were investigated for changes over time in the index and their relationships with those in the summed Medsger severity score (MSS).A weighted 10-point activity index was identified and validated: Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease. Changes in the index paralleled those of MSS (p=0.0001).A preliminarily revised SSc activity index has been developed and validated, providing a valuable tool for clinical practice and observational studies.
Phase II study of short course CHOP-rituximab followed by 90-y ibritumomab tiuxetan as first-line treatment for follicular lymphoma: Extended follow-up and predictors of relapse.
Authors: D. R. Mehta, R. C. Jankowitz, D. E. Lenzner, S. R. Land, S. A. Jacobs
Journal: Journal of Clinical Oncology (2010)

8066 Background: We previously reported complete response rate (CR) of 89% in 60 patients with stage II-IV symptomatic or bulky follicular lymphoma(FL) who received a short-course CHOP-rituximab (R) × 3 cycles followed by ibritumomab tiuxetan (IT) and extended R as first-line treatment. (Clin Cancer Rsrch. 2008;14(21):7088-7094) This abstract will update the response rate at median follow-up of 45 months (range 30-60 months). Methods: Determination of response and duration of response included a fusion [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET)-computed tomography (CT) imaging performed at baseline, after the third cycle of CHOP-R, 12 weeks after RIT, then at 6-month intervals for the first three years, and then yearly or at physicians' discretion. Results: Of the 60 enrolled patients, 55 completed all protocol therapy. 54 patients are available for evaluation. The CR rate for all enrolled patients by PET-CT is 59%. To date, 22(41%) patients have relapsed at 7.8-55 months. Of the 32 patients with bone marrow involvement, 17 patients had relapses, while of the 22 patients with no bone marrow involvement, only 5 relapsed. 20 of 36 patients with bulky disease have relapsed compared to 2 of 18 patients with non-bulky disease. 9 of 18 patients (50%) with a positive PET scan after CHOP-R have relapsed compared to 13 relapses of 36(36%) patients with a negative PET scan after CHOP-R. 12 of 25 (48%) patients with FLIPI score ≥3 have relapsed compare to 10 of 29 patients (34%) with FLIPI score <3. Six patients have been diagnosed with a second malignancy. None of the patients developed myelodysplastic syndrome or acute myeloid leukemia. Conclusions: Short course CHOP-R followed by IT and extended R results in high CR rate. After median follow up of 45 months, 59% patients still remain in clinical remission. However, despite achieving a CR after initial therapy, positive bone marrow involvement (p=0.03) and bulky disease (p<0.001) at baseline are predictive of relapse. Further evaluation of the molecular marker, Fc gamma receptor genotyping, is planned as potential predictor of outcome. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Zevalin
IL-17 enhances the migration of B cells during asthma by inducing CXCL13 chemokine production in structural lung cells
Authors: Roua Al-Kufaidy, Alejandro Vazquez-Tello, Ahmed S. BaHammam, Saleh Al-Muhsen, Qutayba Hamid, Rabih Halwani
Journal: Journal of Allergy and Clinical Immunology (2016)
Rules of attraction: endothelial Notch signalling controls leucocyte homing in atherosclerosis via VCAM1
Authors: Jaba Gamrekelashvili, Florian P. Limbourg
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Endothelial Jag1-RBPJ signalling promotes inflammatory leucocyte recruitment and atherosclerosis’ by M. Nus et al. , pp. 568–580 

Notch signalling is an evolutionary conserved regulator of vascular and immune cell development and homeostasis.1,2 In this issue of Cardiovascular Research , Nus et al. 3 now report a new role of endothelial Notch signalling in regulating vascular homeostasis by regulating vascular inflammation in atherosclerosis.

Activation of Notch receptors is controlled by membrane-bound Notch ligands consisting of the Jagged (Jag) and Delta-like (Dll) gene families.2 Notch signalling regulates endothelial cell proliferation, migration, and sprouting angiogenesis and thereby critically regulates vascular morphogenesis and function.1,4,5 In response to ischaemic vascular injury, Notch activation mediates vascular repair and regeneration, which ensures neovascularization of tissues, organs, and recovery of their function.6,7 In this issue of Cardiovascular Research , Nus et al. 3 now report that endothelial Notch signalling regulates homing of leucocytes to the vascular wall during atherosclerosis. They demonstrate that the Notch ligand Jag1 and Notch signalling are upregulated in atherosclerotic human and mouse arteries. Furthermore, …
Systems biology—opportunities and challenges: the application of proteomics to study the cardiovascular extracellular matrix
Authors: Javier Barallobre-Barreiro, Marc Lynch, Xiaoke Yin, Manuel Mayr
Journal: Cardiovascular Research (2016)

Systems biology approaches including proteomics are becoming more widely used in cardiovascular research. In this review article, we focus on the application of proteomics to the cardiac extracellular matrix (ECM). ECM remodelling is a hallmark of many cardiovascular diseases. Proteomic techniques using mass spectrometry (MS) provide a platform for the comprehensive analysis of ECM proteins without a priori assumptions. Proteomics overcomes various constraints inherent to conventional antibody detection. On the other hand, studies that use whole tissue lysates for proteomic analysis mask the identification of the less abundant ECM constituents. In this review, we first discuss decellularization-based methods that enrich for ECM proteins in cardiac tissue, and how targeted MS allows for accurate protein quantification. The second part of the review will focus on post-translational modifications including hydroxylation and glycosylation and on the release of matrix fragments with biological activity (matrikines), all of which can be interrogated by proteomic techniques.
Myeloablative Double-Unit Cord Blood Transplantation (CBT) in Pediatric Patients with High-Risk Acute Leukemia Demonstrates Encouraging Disease-Free Survival with Both TBI and Chemotherapy-Only-Based Conditioning
Authors: Andromachi Scaradavou, Marissa N Lubin, Patrick Hilden, Farid Boulad, Kevin J. Curran, Rachel Kobos, Susan E. Prockop, Richard J. O'Reilly, Jo-Ann Tonon, Courtney Byam, Peter G Steinherz, Neerav Shukla, Aisha Hasan, Thomas M. Renaud, Nicole Zakak, Nancy A. Kernan, Juliet N. Barker
Journal: Blood (2014)
Safety and efficacy of daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients
Authors: Stanislas Pol, Marc Bourliere, Sandy Lucier, Christophe Hezode, Céline Dorival, Dominique Larrey, Jean-Pierre Bronowicki, Victor D.E. Ledinghen, Fabien Zoulim, Albert Tran, Sophie Metivier, Jean-Pierre Zarski, Didier Samuel, Dominique Guyader, Patrick Marcellin, Anne Minello, Laurent Alric, Dominique Thabut, Olivier Chazouilleres, Ghassan Riachi, Valérie Bourcier, Philippe Mathurin, Véronique Loustaud-Ratti, Louis D’Alteroche, Isabelle Fouchard-Hubert, François Habersetzer, Xavier Causse, Claire Geist, Isabelle Rosa, Jérôme Gournay, Eric Saillard, Eric Billaud, Ventzislava Petrov-Sanchez, Alpha Diallo, Hélène Fontaine, Fabrice Carrat
Journal: Journal of Hepatology (2016)