tbuckley/cabot-search huggingface dataset:
Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study
Authors: An S. De Vriese, Rogier Caluwé, Lotte Pyfferoen, Dirk De Bacquer, Koen De Boeck, Joost Delanote, Didier De Surgeloose, Piet Van Hoenacker, Bruno Van Vlem, Francis Verbeke
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Functional vitamin K deficiency, exacerbated by the use of vitamin K antagonists (VKAs), is thought to contribute to the rapid progression of vascular calcifications in patients on dialysis. We randomized patients receiving chronic hemodialysis with atrial fibrillation to VKAs, rivaroxaban, or rivaroxaban with high-dose vitamin K2 supplements. During 18 months of follow-up, vitamin K status improved significantly by withdrawal of VKAs and vitamin K2 supplementation. Nevertheless, changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not different among the treatment arms. Replacement of VKAs by rivaroxaban was safe and potentially associated with less life-threatening and major bleeding. Further studies should determine whether earlier and multitargeted intervention can halt the progression of vascular calcifications in dialysis. Background Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation. Methods Patients were randomized to VKAs with target INR 2–3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000 µ g thrice weekly during 18 months. Systemic dp-ucMGP levels were quantified to assess vascular vitamin K status. Cardiac and thoracic aorta calcium scores and pulse wave velocity were measured to evaluate VC progression. Results Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm. Conclusions Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs.
A Prospective Disease Registry of Patients with Mantle Cell Lymphoma Treated with Novel Agents: Treatment Patterns, Outcomes, and Patient-Reported Health-Related Quality of Life
Authors: Chaitra Ujjani, Anthony R. Mato, Jonathon B. Cohen, Jakub Svoboda, David Andorsky, Andre Goy, Michael L. Wang, Anita Kumar, Peggy Ann Torney, Michelle Dawson, Cynthia Elesinmogun, Shaum M Kabadi, Brian Seal, John M. Pagel, Scott D Ramsey
Journal: Blood (2019)
ACTR-22. INITIAL TREATMENT OF GBM WITH A KETOGENIC DIET ALONG WITH RADIATION AND CHEMOTHERAPY: CLINICAL OUTCOMES
Authors: Kenneth Schwartz, Mary Noel, Michele Nikolae, Karl Olson, Micheal Zakem, Mohamed Elnabtity, Justin Clark, Bryan Figueroa, Howard Chang
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Combining an adjuvant ketogenic diet (KD) with standard therapy of radiation and chemotherapy right after tissue diagnosis is feasible and safe. We report outcomes of a pilot clinical trial study using a KD combined with radiation and chemotherapy as initial therapy for glioblastoma (GBM). METHODS Eligibility criteria included: 1. Tissue diagnosis; 2. Age over 18; 3. ECOG performance status of 2 or better; and 4. Not having diabetes or being pregnant. An isocaloric KD diet with 3:1 weight ratio of fat to combined weight of carbohydrate and protein was supervised by an experienced dietitian and maintained with initial radiation and chemotherapy for 6 weeks. RESULTS 9 patients (8M, 1F, mean age 45) completed the prescribed 6 week trial. Blood counts, chemistries, lipid profiles and uric acids were not markedly changed. Ketosis was maintained for the 6 week study period with blood ketone and glucose levels checked twice daily. 3 younger patients (mean age 28 at diagnosis) are working and show no progression of their gliomas at 49 (IDH +), 31 (IDH WT with methylated MGMT), and 32 (IDH WT) months since diagnosis. 6 older male patients (mean age 54) have died at 25, 25, 13, 12, 9 and 9 months after diagnosis. A recent report of 6 additional older male pts mean age 53 tx with a KD with daily checks of blood ketones showed limited survival ranging from 12–19 mo. (van der Louw accepted for pub in “Therapeutic Advances in Medical Oncology”). CONCLUSION KD may be a helpful in initial treatment of GBM patients, especially in younger patients. Additional studies are needed. However, since 12 older male patients have not substantially benefited from the KD, we suggest that future evaluations of the efficacy of KD for GBM be focused towards younger patients.
Perforated Gastric Ulcer
Authors: W. Broadbent
Journal: BMJ (1897)

appearance.Therei is no consti-Lutional disturbance.The contents of the vesicles are not acid, so that they are not simply full of retained sweat.Moreover, it differs from hvdroadenitis, inasmuch as it is a much more superficial disease.These vesicular rashes were chiefly observed in the earlier cases, not when the disease had become a regular epidemic.The third variety occurs in persona who have not suffered from prickly heat, or at any rate not to any great extent; the spots are vesicular or pustular, and, when coming out, are accompanied by a sharp stinging pain, like in herpes zoster, another point of similarity to this disease being that they
Monotherapy Activity with the First CD20-Targeted Immunotoxin, MT-3724, in Subjects with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Paul A. Hamlin, Vasile Musteata, Mamia Zodelava, Steven I Park, Christine Burnett, Kristina Dabovic, Eric T Williams, Jack P Higgins, Daniel O. Persky
Journal: Blood (2019)
Proof of Concept for Repair of Sickle Cell Disease By Non-Myeloablative MHC Disparate T Cell Depleted HSCT Combined with Donor-Derived Veto Cells
Authors: Aloukick Kumar Singh, Elias Schetzen, Esther BACHAR Lustig, Wei-Hsin Liu, Raj Kumar Yadav, Sandeep Kumar Yadav, Kathryn McGinnis, Yair Reisner
Journal: Blood (2019)
The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus
Authors: Sheng-Xiao Zhang, Jia Wang, Jun-Wei Chen, Ming-Xing Zhang, Yi-Fan Zhang, Fang-Yuan Hu, Zhi-Qin Lv, Chong Gao, Ya-Feng Li, Xiao-Feng Li
Journal: Annals of the Rheumatic Diseases (2019)

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder mainly mediated by lymphocytes and autoantibodies, which have a pervasive negative impact on the majority of organs.1 2 It deserves more attention to further explore the pathogenesis because of the unclear complex pathogenesis and the limited clinical efficacy of SLE treatment.

Recently, a cross-sectional discovery cohort in the USA conducted by Azzouz et al , published in Annals of Rheumatic Diseases, suggested that specific gut commensal strains, especially Ruminococcus gnavus , may contribute to the disease activity and autoantibody production in SLE patients,3 which put forward a novel concept for the immune pathogenesis of SLE. Their study was well performed and analysed the abundance of intestinal flora and sera profiled for antibacterial and autoantibody responses between SLE patients with the different disease activity index scores and matched healthy controls. However, the faecal microbiota is lacking a precise link with lymphocytes in peripheral blood of the patients, which are the important participants …
Efficacy and Tolerance of Interferon-α in Hypereosinophilic Syndromes. a Retrospective Multicenter Study on 29 Patients
Authors: Pauline De Malglaive, Matthieu Groh, Guillaume Lefèvre, Chafika Morati Hafsaoui, Magda Alexis, Mathilde Hunault, Julien Seneschal, Hilaire Charlanne, Claude Preudhomme, Bernard Bonnotte, Jean Emmanuel Kahn
Journal: Blood (2019)
Evaluation of Pulmonary Function in Patient with Transfusion Dependent Beta Thalassemia with Severe Iron Overload
Authors: Mohamed A Yassin, Mushtaq Ahmad, Shehab Mohamed, Khadra S Yassin, Abdulqadir Jeprel Nashwan, Vincenzo Desanctis, Ashraf Tawfiq Soliman
Journal: Blood (2019)
SURG-21. STEREOTACTIC BIOPSY FOR DEEP SEATED BRAIN LESIONS USING THE LEKSELL STEREOTACTIC FRAME SYSTEM
Authors: Takamitsu Fujimaki, Sachiko Hirata, Naruhiko Terano, Kenji Wakiya, Jun-ichi Adachi, Ryo Nishikawa, Atsushi Sasaki, Masahito Kobayashi
Journal: Neuro-Oncology (2019)

Abstract PURPOSE To evaluate the results of stereotactic biopsies. PATIENTS AND METHODS Fifty-two patients with intraaxial lesions suspected of brain tumor. The locations of lesions includes, 19 deep cerebral white matter, 9 basal ganglia, 10 thalamus, 4 midbrain and 6 pons. Patients age ranged from 9 to 86 years (median 65 years), 33 were men and 19 were women. Under local anesthesia the Leksell stereotactic frame was fixed and the MRI were taken. Neuroimages such as enhanced CT scan or PET study were also used as references. After MRI patients were transferred to OR and under general anesthesia, several samples were taken with 2.1mm diameter needle by aspiration. Most of the cases the biopsy was done through frontal lobe, but in some cases through temporal lobe or through cerebellum. The samples were taken deeper and nearer regions of the designed targets with same trajectory, also. If there were cysts, aspiration of the cyst was performed as much as possible. The trajectory should avoid sulci, cortical veins or ventricular system. After biopsy inside the needle were irrigated repeatedly with 0.1 - 0.2 ml saline using thin plastic tube until the fluid does not contain bloody fluids to ensure hemostasis. RESULTS In all patients appropriate samples for pathological diagnosis were obtained. The diagnoses were 28 gliomas (pilocytic 1, grade II 8, grade III 11, grade VI (GBM) 6, high grade 1, glial tumor 1), 17 lymphomas, 3 germinoma and 2 were non-tumorous pathology. There were no symptomatic bleeding nor neurological complications. CONCLUSION With detailed planning, stereotactic biopsy was safely performed even from basal ganglia or brainstem. Trajectories other than from frontal can be also considered for some lesions. Repeated irrigation with saline might effective to prevent symptomatic bleeding and this case series shows lower complication rates compared to the published literatures.
Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non–Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study
Authors: Yukio Hosomi, Satoshi Morita, Shunichi Sugawara, Terufumi Kato, Tatsuro Fukuhara, Akihiko Gemma, Kazuhisa Takahashi, Yuka Fujita, Toshiyuki Harada, Koichi Minato, Kei Takamura, Koichi Hagiwara, Kunihiko Kobayashi, Toshihiro Nukiwa, Akira Inoue
Journal: Journal of Clinical Oncology (2019)

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations; however, little is known about the efficacy and safety of this combination compared with that of standard therapy with EGFR- tyrosine kinase inhibitors alone.We randomly assigned 345 patients with newly diagnosed metastatic NSCLC with EGFR mutations to gefitinib combined with carboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially analyzed as primary end points according to a hierarchical sequential testing method. Secondary end points were objective response rate (ORR), safety, and quality of life.The combination group demonstrated a better ORR and PFS than the gefitinib group (ORR, 84% v 67% [P < .001]; PFS, 20.9 v 11.9 months; hazard ratio for death or disease progression, 0.490 [P < .001]), although PFS2 was not significantly different (20.9 v 18.0 months; P = .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9 v 38.8 months; hazard ratio for death, 0.722; P = .021). The rate of grade ≥ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3% v 31.0%); there were no differences in quality of life. One treatment-related death was observed in the combination group.Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.
Dysregulation of Hemostatic Biomarkers, Inflammatory Biomarkers, and Alteration of Cellular Indices As Predictors of Adverse Outcomes in Pulmonary Embolism Patients
Authors: Iman Darwish, Yevgeniy Brailovsky, Amir Darki, Debra Hoppensteadt, Brett Slajus, Emily Bontekoe, Frank De Stefano, Jawed Fareed
Journal: Blood (2019)
Multicentre trials on specialised exercise training and rehabilitation are useful in patients with pulmonary hypertension
Authors: Ekkehard Grünig, Nicola Benjamin, Christina A. Eichstaedt, Andrew J. Peacock
Journal: European Respiratory Journal (2019)

<b>Multicentre trials on specialised exercise training and rehabilitation in patients with pulmonary hypertension are needed to provide further evidence on its haemodynamic effects and to show implementation in different healthcare systems is possible.</b>http://bit.ly/2L4Mrgt
Impact of a Tailored Nutritional and Physical Exercise Programme on Efficacy and Functional Outcomes in Older Patients with Hematological Malignancies Classified By Frailty Profile
Authors: Maite Antonio, Montserrat Arnan Sangerman, Eva Domingo-Domenech, Eva González-Barca, Casimiro Javierre, Laura Hurtos, Judit Sola, Anna Sureda, Josep Maria Borras
Journal: Blood (2019)
Efficacy and Safety of the Glucagon Receptor Antagonist RVT-1502 in Type 2 Diabetes Uncontrolled on Metformin Monotherapy: A 12-Week Dose-Ranging Study
Authors: Jeremy H. Pettus, David D’Alessio, Juan P. Frias, Eric G. Vajda, James D. Pipkin, Julio Rosenstock, Gretchen Williamson, Miriam A. Zangmeister, Lin Zhi, Keith B. Marschke
Journal: Diabetes Care (2019)

OBJECTIVE Evaluate the safety and efficacy of RVT-1502, a novel oral glucagon receptor antagonist, in subjects with type 2 diabetes inadequately controlled on metformin. RESEARCH DESIGN AND METHODS In a phase 2, double-blind, randomized, placebo-controlled study, subjects with type 2 diabetes (n = 166) on a stable dose of metformin were randomized (1:1:1:1) to placebo or RVT-1502 5, 10, or 15 mg once daily for 12 weeks. The primary end point was change from baseline in HbA1c for each dose of RVT-1502 compared with placebo. Secondary end points included change from baseline in fasting plasma glucose (FPG) and safety assessments. RESULTS Over 12 weeks, RVT-1502 significantly reduced HbA1c relative to placebo by 0.74%, 0.76%, and 1.05% in the 5-, 10-, and 15-mg groups (P &amp;lt; 0.001), respectively, and FPG decreased by 2.1, 2.2, and 2.6 mmol/L (P &amp;lt; 0.001). The proportions of subjects achieving an HbA1c &amp;lt;7.0% were 19.5%, 39.5%, 39.5%, and 45.0% with placebo and RVT-1502 5, 10, and 15 mg (P ≤ 0.02 vs. placebo). The frequency of hypoglycemia was low, and no episodes were severe. Mild increases in mean aminotransferase levels remaining below the upper limit of normal were observed with RVT-1502 but were reversible and did not appear to be dose related, with no other liver parameter changes. Weight and lipid changes were similar between RVT-1502 and placebo. RVT-1502–associated mild increases in blood pressure were not dose related or consistent across time. CONCLUSIONS Glucagon receptor antagonism with RVT-1502 significantly lowers HbA1c and FPG, with a safety profile that supports further clinical development with longer-duration studies (NCT02851849).
EPID-27. OCCURRENCE OF SYSTEMIC CANCER IN PATIENTS WITH ASTROCYTOMA: POPULATION CHARACTERIZATION AND COMPLICATIONS
Authors: Erika Horta, James Snyder, Tobias Walbert
Journal: Neuro-Oncology (2019)

Abstract It is unclear how the diagnosis of a second cancer influences the treatment and complications of patients with astrocytoma. A chart review of patients with astrocytoma and a second systemic cancer was performed to understand the possible complications that a systemic cancer diagnosis might bring to the treatment of the patient. Inclusion criteria was the histological diagnosis of diffuse or anaplastic astrocytoma and another non-skin systemic cancer. Exclusion criteria was the diagnosis of any genetic syndrome that predisposes tumorigenesis. A total of 17 patients were identified. The most common systemic cancer was thyroid (22) followed by colon and breast cancer (each one 17%). Men were 59% of the patients (p= 0.38), but older (60 +14 years, p=0.003) when compared to CBTRUS data. Systemic cancer was diagnosed before astrocytoma in 61% of the cases. Age at the diagnosis of systemic cancer was 48 +14 years. Only 9% of the patients who had systemic cancer before astrocytomas survived 5 years, what is less than expected when compared with literature, (p=0.02). Those also survived less than the patients that had systemic cancer after the diagnosis of astrocytomas (8.1+6.4 years). Thromboembolism was seen in 12.5% (p=0.8), always after the astrocytoma diagnosis. Thrombocytopenia was not related to prior chemotherapy. In patients with systemic cancer diagnosed while on treatment for astrocytoma, a delay or shortened course of the treatment was seen in rare cases, and one patient had their course of treatment for astrocytoma shortened. The conclusion of this chart review of patients with the diagnosis of astrocytoma and a systemic cancer identifies that this population is older than expected and the diagnosis of systemic cancer before astrocytoma might predict a shorter survival.
An Ongoing Global, Longitudinal, Observational Study of Patients with Pyruvate Kinase Deficiency: The PEAK Registry
Authors: Rachael F. Grace, Paola Bianchi, Bertil Glader, Andreas Glenthøj, Bryan Jones, Hitoshi Kanno, Kevin H. M. Kuo, D. Mark Layton, Eduard J. van Beers, Joan-Lluis Vives Corrons, Tu Xu
Journal: Blood (2019)
Eye Injuries and Their Treatment.
Journal: JAMA (1907)

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Induction Treatment and Feasibility of Allogeneic Hematopoietic Stem Cell Transplantation in Young Patients (&lt;65 years) with High-Risk Cytogenetic and Secondary Acute Myeloid Leukemia (AML): A Single Center Experience in Argentina with CLAG-M and 7+3
Authors: Maria Lucia Fuente, Maria Del Rosario Custidiano, Santiago Cranco, Laura Korin, Paola Ochoa, Adriana Vitriu, Evelina Babuin, Andrea Novoa, Paula Tempra, Maria Belen Venegas, Fernando Diaz Couselo, Norma Elisabeth Tartas, Julio Cesar Sanchez Avalos, Maria Cecilia Foncuberta
Journal: Blood (2019)
CBMT-48. TARGETING METABOLIC REPROGRAMMING WITH NANOCURCUMIN IN GLIOBLASTOMA MULTIFORME
Authors: Hamid Suhail, Rattan Ramandeep, Giri Shailendra, Ana deCarvalho, Steven Kalkanis, Meser Ali
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is a highly glycolytic aggressive brain tumor characterized by increased proliferation and resistance to chemotherapy and radiotherapy. AMPK has been reported as tumor suppressor and reprograms the cellular metabolic pathways and produces a metabolic checkpoint on the cell cycle though mTORC1, p53 and other modulators involved in cell proliferation, growth, survival and autophagy. The AMPK activity is diminished in gastric, breast and ovarian tumor cells by activated PI3K-AKT pathways. Cancer cells are able to reprogram their energy metabolism to compensate their high bioenergetic demands needed for their aggressive growth and survival. Curcumin exhibits pleiotropic properties and activate MAPK and leads to suppress p53, Wnt/β-catenin, SHH and PI3K-AKT signaling pathways. Curcumin or diferuloylmethane is a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa). The absorption, biodistribution, metabolism, and elimination studies of curcumin have, unfortunately, shown only poor absorption, rapid metabolism, and elimination of curcumin as major reasons for poor bioavailability of this interesting polyphenolic compound. We have engineered a curcumin-based nanoparticle (Curc-NP) which demonstrates high water solubility. Curc-NP was effectively transported into the cells by nanoparticles through endocytosis and localized around the nuclei in the cytoplasms. In vitro studies proved that the cytotoxicity of Curc-NP is more effective against U-251 cell line in a dose-dependent manner. Systemic delivery of Curc-NP led to preferentially accumulation in an orthotopic preclinical glioma model minimizing systemic toxic effect. Multicolor microscopy images of the tumor tissue showed that Curc-NP particles were internalized inside tumor cells selectively and localized within nuclei. Curc-NP demonstrated to restore the dysregulated AMPK activity in glioma cells. Curc-NP-induced AMPK activation resulted in inhibition of oncogenic signalling pathways in glioma. Curc-NP-induced metabolic reprograming in glioma cells will be examined and the in vivo therapeutic efficacy of Curc-NP in an experimental rat model of GBM will also be evaluated.