tbuckley/cabot-search huggingface dataset:
Man With Mesenteric Ulceration
Authors: Ishwarya Balasubramanian, Jarlath C. Bolger, J. Calvin Coffey
Journal: JAMA Surgery (2017)

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Afatinib in patients with advanced or metastatic urothelial carcinoma (UC) with genetic alterations in ErbB receptors 1–3 who failed on platinum-based chemotherapy: The Phase II LUX-Bladder 1 trial
Authors: A. Font, F.X. Real, J. Puente, F.J. Vazquez Mazon, N. Sala, J.A. Virizuela, A. Rodriguez-Vida, E. Grande Pulido, D. Castellano, M.A. Climent, E. Gallardo, A. González del Alba, P.L. Fernandez, P. Jares, I. Aldecoa, N. Gibson, J. Serra, E.R. Imedio, E. Ehrnrooth, B. Mellado
Journal: Annals of Oncology (2017)
Phase 1 study of E7046, an inhibitor of the PGE<sub>2</sub> receptor EP-4, that targets immunosuppressive myeloid cells in the tumor microenvironment (NCT02540291).
Authors: David S. Hong, Eunice Lee Kwak, Matthew Guo, Chean Eng Ooi, Ozlem Ataman, Aurelien Marabelle
Journal: Journal of Clinical Oncology (2016)

e14116 Background: Tumor-associated host myeloid cells can be either antitumor (eg, type 1 macrophages, mature antigen-presenting cells) or immunosuppressive pro-tumor (eg, type 2 macrophages, myeloid-derived suppressor cells). The presence or accumulation of immunosuppressive myeloid cells in tumors is associated with a poorer prognosis.E7046 is a selective prostaglandin E2 receptor-type-4 small-molecule inhibitor, designed to inhibit the differentiation and function of monocytic myeloid lineage cells in the tumor microenvironment. E7046 has demonstrated antitumor activity in preclinical syngeneic tumor models with myeloid infiltration (Mol Cancer Ther2015;14:B198). This is a first-in-human study of E7046 to determine safety/tolerability, maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D). Methods: From Aug 2015–Mar 2017, about 30–40 pts will be enrolled. Accrual has started with currently 6 pts enrolled in the first cohort. Main eligibility criteria: pts ≥ 18 years old, advanced cancers (high myeloid infiltrated tumor types), and ECOG-PS of 0 or 1. Pts previously treated with CSF1R antagonists, and pts with autoimmune diseases requiring prior treatment with immunosuppressives will be excluded. Results: The study is a modified 3+3 dose escalation design (n = 24) with 125–750 mg (once-daily, oral) doses of E7046 given to maximum 4 cohorts of 6 pts each (21-day cycle). Dose-limiting toxicity (DLT) will be assessed in cycle 1 with MTD defined as 1 dose level below DLT rate of ≥ 2/6 pts. If MTD is not reached, RP2D will be selected based on integrated evaluation of safety, clinical benefit, pharmacokinetics (PK), and pharmacodynamics (PD) data. An expansion cohort (n = 6 to 16) will be enrolled at the RP2D to confirm results. Conclusions: Primary objectives are to determine E7046 safety/tolerability, and MTD and/or RP2D. Key secondary objectives include PK, objective response rate, progression-free survival, and disease control rate. PD assessments include effect of E7046 on select immune cell populations in tumor infiltrate and 18FDG-PET as an early biomarker of response. For further information please contact Ozlem_Ataman@eisai.net. Clinical trial information: NCT02540291.
Epidemiology of Left Ventricular Systolic Dysfunction and Heart Failure in the Framingham Study
Authors: Ramachandran S. Vasan, Vanessa Xanthakis, Asya Lyass, Charlotte Andersson, Connie Tsao, Susan Cheng, Jayashri Aragam, Emelia J. Benjamin, Martin G. Larson
Journal: JACC. Cardiovascular imaging (2017)
Thermoresponsive β-glucan-based polymers for bimodal immunoradiotherapy – Are they able to promote the immune system?
Authors: Lenka Loukotová, Jan Kučka, Mariia Rabyk, Anita Höcherl, Kristýna Venclíková, Olga Janoušková, Petr Páral, Věra Kolářová, Tomáš Heizer, Luděk Šefc, Petr Štěpánek, Martin Hrubý
Journal: Journal of Controlled Release (2017)
A phase 1b study evaluating the safety and pharmacokinetics (PK) of regorafenib (REG) in combination with cetuximab (CTX) in patients with advanced solid tumors
Authors: C. Weekes, A.C. Lockhart, H-J. Lenz, J.J. Lee, A. Cleton, F. Huang, I. Sturm
Journal: Annals of Oncology (2017)
Evolution in neutrophil-to-lymphocyte ratio (NLR) among advanced soft tissue sarcoma (STS) patients treated with pazopanib within EORTC 62043/62072 trials
Authors: E. De Maio, N. Touati, S. Litière, S. Sleijfer, W.T.A. van der Graaf, A. Le Cesne, L. D'Ambrosio, P.G. Casali, A. Italiano, I. Desar, A. Gronchi
Journal: Annals of Oncology (2017)
Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond–like features
Authors: Raphael Carapito, Martina Konantz, Catherine Paillard, Zhichao Miao, Angélique Pichot, Magalie S. Leduc, Yaping Yang, Katie L. Bergstrom, Donald H. Mahoney, Deborah L. Shardy, Ghada Alsaleh, Lydie Naegely, Aline Kolmer, Nicodème Paul, Antoine Hanauer, Véronique Rolli, Joëlle S. Müller, Elisa Alghisi, Loïc Sauteur, Cécile Macquin, Aurore Morlon, Consuelo Sebastia Sancho, Patrizia Amati-Bonneau, Vincent Procaccio, Anne-Laure Mosca-Boidron, Nathalie Marle, Naël Osmani, Olivier Lefebvre, Jacky G. Goetz, Sule Unal, Nurten A. Akarsu, Mirjana Radosavljevic, Marie-Pierre Chenard, Fanny Rialland, Audrey Grain, Marie-Christine Béné, Marion Eveillard, Marie Vincent, Julien Guy, Laurence Faivre, Christel Thauvin-Robinet, Julien Thevenon, Kasiani Myers, Mark D. Fleming, Akiko Shimamura, Elodie Bottollier-Lemallaz, Eric Westhof, Claudia Lengerke, Bertrand Isidor, Seiamak Bahram
Journal: Journal of Clinical Investigation (2017)

Shwachman-Diamond syndrome (SDS) (OMIM #260400) is a rare inherited bone marrow failure syndrome (IBMFS) that is primarily characterized by neutropenia and exocrine pancreatic insufficiency. Seventy-five to ninety percent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamond syndrome (sbds) gene. Using trio whole-exome sequencing (WES) in an sbds-negative SDS family and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent patients, each of whom carried a de novo missense variant in srp54 (encoding signal recognition particle 54 kDa). These 3 patients shared congenital neutropenia linked with various other SDS phenotypes. 3D protein modeling revealed that the 3 variants affect highly conserved amino acids within the GTPase domain of the protein that are critical for GTP and receptor binding. Indeed, we observed that the GTPase activity of the mutated proteins was impaired. The level of SRP54 mRNA in the bone marrow was 3.6-fold lower in patients with SRP54-mutations than in healthy controls. Profound reductions in neutrophil counts and chemotaxis as well as a diminished exocrine pancreas size in a SRP54-knockdown zebrafish model faithfully recapitulated the human phenotype. In conclusion, autosomal dominant mutations in SRP54, a key member of the cotranslation protein-targeting pathway, lead to syndromic neutropenia with a Shwachman-Diamond-like phenotype.
Abstract 213: Evolving Challenges in Promoting Stem Cell Based Cardiovascular Repair and Regeneration
Authors: Mani T Valarmathi, Jiang Li
Journal: Circulation Research (2016)

Introduction: Use of adult stem cells in the stimulation of mammalian cardiac muscle regeneration is in its infancy, and to date, it has been difficult to determine the efficacy of the procedures that have been employed. The outstanding question remains whether stem cells derived from the bone-marrow or some other location within or outside of the heart can populate a region of myocardial damage and transform into tissue-specific cells, and also exhibit functional synchronization. As a result, this necessitates the development of an appropriate in vitro three-dimensional (3-D) model of cardiomyogenesis and prompts the development of a 3-D cardiac muscle construct for tissue engineering purposes, especially using the adult stem cells. Hypothesis: Functioning vascularized cardiac tissue can be generated by the interaction of human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human multipotent mesenchymal stem cells (hMSCs) on a 3-D prevascularized collagen cell carrier (CCC) scaffold. Methods and Results: In order to achieve the above aim, we have developed an in vitro 3-D functioning vascularized cardiac muscle construct using hiPSC-ECMs and hMSCs. First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured on 3-D CCCs for 7 days under vasculogenic culture conditions, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of micro vessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed dramatic neo-angiogenesis and neo-cardiomyogenesis. Conclusions: Thus, our unique 3-D co-culture system provided us the apt in vitro functioning prevascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty.
Temporal trends in and predictors of receipt of contralateral breast mastectomy among U.S. men diagnosed with breast cancer.
Authors: Ahmedin Jemal, Rachel A. Freedman, Chun Chieh Lin, Helmneh Sineshaw, Carol DeSantis, Elizabeth Mary Ward
Journal: Journal of Clinical Oncology (2015)

e17522 Background: Previous studies reported marked increase in receipt of contralateral prophylactic mastectomy (CPM) among US women diagnosed with breast cancer. However, whether similar trend is occurring among US men is unknown. We used a nationwide population-based cancer database , the North American Association of Central Cancer Registries (NAACCR), to examine temporal trends in use of CPM among men diagnosed with in situ and invasive unilateral breast cancer. We also examined predictors of receipt of CPM. Methods: 9770 adult men diagnosed with American Joint Committee on Cancer (AJCC) stage 0-III unilateral breast cancer from 2004 to 2011. Temporal trends in receipt of surgical treatment were evaluated using the Cochran-Armitage test. Multivariate logistic regression was used to examine predictors of receipt of CPM. Results: Over the entire study period, 70% of men received unilateral mastectomy, 22% lumpectomy, and 4% CPM. The proportion of patients receiving CPM between 2004-05 and 2010-11 significantly increased from 3.2% to 5.2% in all ages and from 5.5% to 10.1% in age < 60 years (p-trend: 0.03). Receipt of CPM monotonically decreased with age at diagnosis from 15% in age < 40 years to 1.4% in age ≥ 70 years (p < .05). Among men age < 60 years, recent years of diagnosis (2010-2011 vs. 2004-2005; aOR = 2.03, 95%CI 1.36-3.04), advanced stage at diagnosis (stage I/II vs. 0; aOR = 2.01, 95% CI 1.13-3.58), and Southern residency (vs. Northeast; aOR = 1.92, 95%CI 1.23-2.98) were associated with higher adjusted odds of receipt of CPM, whereas Non-Hispanic Black race (vs. Non-Hispanic White; aOR = 0.58, 95%CI 0.38-0.89) and no insurance (vs. private insurance; aOR = 0.33, 95%CI 0.12-0.91)were associated with lower odds of receipt of CPM. Among men aged 60+, age ≥ 70 years (vs. 60-69 years; aOR = 0.43, 95%CI 0.3-0.62) was the only significant factor associated with likelihood of receipt of CPM. Conclusions: Receipt ofCPM is increasing in US men diagnosed with unilateral breast cancer, especially in those age < 60 years.
Prognostic effect of surgery of metastases in patients with advanced gastric cancer: Real-world data from the AGAMENON registry
Authors: P. Jiménez-Fonseca, R. Hernandez, A. Custodio, A. Ramchandani Vaswani, M. Sánchez Cánovas, R. Sánchez Bayona, C. López López, I. Echavarria Diaz-Guardamino, L. Visa, E. Buxo Orra, D. Arias, A. Viudez, A. Martin Carnicero, P. Cerdà, M. Ferrer, J.E. Lorenzo Barreto, M.L. Limón, I. MACIAS, P. Felices
Journal: Annals of Oncology (2017)
Neoadjuvant chemotherapy followed by surgery (NACT-surgery) versus concurrent cisplatin and radiation therapy (CTRT) in patients with stage IB2 to IIB squamous carcinoma of cervix: A randomized controlled trial (RCT)
Authors: S. Gupta, P. Parab, R. Kerkar, U. Mahantshetty, A. Maheshwari, S. Sastri, R. Engineer, R. Hawaldar, J. Ghosh, S. Gulia, S. Godbole, N. Kumar, J. Malliga, R. Dalvi, Y. Kembhavi, M. Gaikar, R. Ranade, H. Tongaonkar, R. Badwe, S. Shrivastava
Journal: Annals of Oncology (2017)
Impact of surveillance for hepatocellular carcinoma on survival in patients with compensated cirrhosis
Authors: Ju Dong Yang, Ajitha Mannalithara, Andrew J. Piscitello, John B. Kisiel, Gregory J. Gores, Lewis R. Roberts, W. Ray Kim
Journal: Hepatology (2017)

Surveillance for hepatocellular carcinoma (HCC) has been recommended in patients with cirrhosis. In this study, we examined the extent to which the competing risk of hepatic decompensation influences the benefit of HCC surveillance by investigating the impact of availability of liver transplantation (LTx) and the rate of progression of hepatic decompensation on survival gain from HCC surveillance. A multistate Markov model was constructed simulating a cohort of 50‐year‐old patients with compensated cirrhosis. The primary outcome of interest was all‐cause and HCC‐specific mortality. The main input data included incidence of HCC, sensitivity of screening test, and mortality from hepatic decompensation. Treatment modalities modeled included LTx, resection, and radiofrequency ablation. In the base case scenario, LTx would be available to prevent death in a certain proportion of patients. In the absence of surveillance, 68.2% of the cohort members died within 15 years; of these decedents, 25.1% died from HCC and 43.6% died from hepatic decompensation. With surveillance, the median survival improved from 10.4 years to 11.2 years. The number of subjects under surveillance needed to reduce one all‐cause and one HCC‐specific death over 15 years was 28 and 18, respectively. In sensitivity analyses, incidence of HCC and progression of cirrhosis had the strongest effect on the benefit of surveillance, whereas LTx availability had a negligible effect. Conclusion: HCC surveillance decreases all‐cause and tumor‐specific mortality in patients with compensated cirrhosis regardless of LTx availability. In addition, incidence of HCC and sensitivity of surveillance test also had a substantial impact on the benefits of surveillance. (Hepatology 2018;68:78‐88).
Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome
Authors: Andreas Goebel, Jatinder Bisla, Roy Carganillo, Bernhard Frank, Rima Gupta, Joanna Kelly, Candy McCabe, Caroline Murphy, Nick Padfield, Ceri Phillips, Mark Sanders, Mick Serpell, Nick Shenker, Karim Shoukrey, Lynne Wyatt, Gareth Ambler
Journal: Annals of Internal Medicine (2017)

Background: Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. Objective: To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. Design: 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756) Setting: 7 secondary and tertiary care pain management centers in the United Kingdom. Participants: 111 patients with moderate or severe CRPS of 1 to 5 years' duration. Intervention: IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. Measurements: The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. Results: The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, −0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of −1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Limitations: Results do not apply to patients who have had CRPS for less than 1 year or more than 5 years and do not extend to full-dose treatment (for example, 2 g/kg). The study was inadequately powered to detect subgroup effects. Conclusion: Low-dose immunoglobulin treatment for 6 weeks was not effective in relieving pain in patients with moderate to severe CRPS of 1 to 5 years' duration. Primary Funding Source: Medical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Program, Pain Relief Foundation, and Biotest United Kingdom.
Randomized controlled trial comparing radiotherapy +/- endocrine therapy versus endocrine therapy alone for PSA failure after radical prostatectomy: Japan Clinical Oncology Group Study JCOG0401
Authors: A. Yokomizo, T. Satoh, K. Hashine, T. Inoue, K. Fujimoto, S. Egawa, T. Habuchi, K. Kawashima, O. Ishizuka, N. Shinohara, M. Sugimoto, Y. Yoshino, M. Wakabayashi, K. Nihei, H. Fukuda, K-I. Tobisu, Y. Kakehi, S. Naito
Journal: Annals of Oncology (2017)
Brote de parotiditis en una comunidad religiosa
Authors: C A van den Bosch, B J Cohen, T Walters, L Jin
Journal: Eurosurveillance (2000)

Entre julio de 1998 y abril de 1999, se declararon ciento cuarenta y cuatro casos de parotiditis en una comunidad religiosa de Londres, confirmandose la infeccion en el 82% de las personas a las que se analizo una muestra de saliva (51/62). El cincuenta por ciento de los casos clinicos y la misma proporcion de casos confirmados habian recibido una dosis de la vacuna triple virica (SPR). Se esta investigando la eficacia de la vacuna.
Concussion is associated with altered preparatory postural adjustments during gait initiation
Authors: C Doherty, John Ryan, Yusuke Komaba, Akihiro Inomata, Liang Zhao, Brian Caulfield
Journal: British Journal of Sports Medicine (2017)

Objective To quantify the preparatory postural adjustments (PPAs) during gait initiation (GI) in a group with concussion compared with a ‘healthy’ control group. Design Case-control study Setting University Biomechanics Laboratory. Outcome measures Centre of pressure (COP) trajectory computed from a force plate and centre of mass (COM) trajectory as computed from an inertial measurement unit placed on the sacrum. Results Concussed patients exhibited decreased COP excursion in the posterior direction on their dominant foot, both when it was the stepping limb (9.71mm [95% CI: 8 to 11mm] vs 15mm [95%CI: 12 to 17mm]) and when it was the support limb (10mm [95% CI: 8 to 12mm] vs 18mm [95%CI: 14 to 21mm]). This was reflected in the trajectory of the COM, wherein concussion patients exhibited lower posterior displacement (19mm [95%CI: 19.4mm to 19.7mm]) compared with controls (23mm [95%CI: 23 to 24]). Conclusions : Individuals with concussion display deficits during a GI task comparable to those which have previously been established in populations with supraspinal impairments in motor control. Competing interests None.
Smart electrical bi-layers lipopeptides: Novel peptidic chains like zigzag map esterified with phospho-glyceride as mono-layer moieties capable in forming a meso-sphere- envelop with scaffold- ability to cellular impurities
Authors: Sami Saadi, Nazamid Saari, Mohammed Sabo Abdulkarim, Hasanah Mohd Ghazali, Farooq Anwar
Journal: Journal of Controlled Release (2017)
Fairness and Transparency in an Expanded Access Program: Allocation of the Only Treatment for SMA1
Authors: Alyssa M. Burgart, Julie Collier, Mildred K. Cho
Journal: The American Journal of Bioethics (2017)

This article refers to:Expanded Access for Nusinersen in Patients With Spinal Muscular Atropy: Negotiating Limited Data, Limited Alternative Treatments, and Limited Hospital Resources
Economic Evaluation of the Direct Oral Anticoagulants Compared to Vitamin K Antagonists in the Treatment of Deep Venous Thrombosis and Pulmonary Embolism in the Outpatient Setting: Analysis from the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia
Authors: Abdullah S. Al Saleh, Patrick Berrigan, David Anderson, Sudeep Shivakumar
Journal: Blood (2016)
Multimodal Imaging in Klippel-Trénaunay-Weber Syndrome
Authors: Su Wan Kim, Heesung Song
Journal: Clinical Nuclear Medicine (2017)

We report the case of a 19-year-old man who presented with a 12-year history of progressive fatigue, feeling hot, excessive sweating, and numbness in the left arm. He had undergone multimodal imaging and was diagnosed as having Klippel-Trénaunay-Weber syndrome (KTWS). This is a rare congenital disease, defined by combinations of nevus flammeus, venous and lymphatic malformation, and hypertrophy of the affected limbs. Lower extremities are affected mostly. Conventional modalities for evaluating KTWS are ultrasonography, CT, MRI, lymphoscintigraphy, and angiography. There are few reports on multimodal imaging of upper extremities of KTWS patients, and this is the first report of an infrared thermography in KTWS.