tbuckley/cabot-search huggingface dataset:
Autologous Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction
Authors: Binod Dhakal, Aniko Szabo, Saurabh Chhabra, Mehdi Hamadani, Anita D’Souza, Saad Z. Usmani, Rita Sieracki, Bishal Gyawali, Jeffrey L. Jackson, Fotis Asimakopoulos, Parameswaran N. Hari
Journal: JAMA Oncology (2018)

The role of high-dose therapy with melphalan followed by autologous stem cell transplant (HDT/ASCT) in patients with multiple myeloma continues to be debated in the context of novel agent induction.To perform a systematic review, conventional meta-analysis, and network meta-analysis of all phase 3 randomized clinical trials (RCTs) evaluating the role of HDT/ASCT.We performed a systematic literature search of Cochrane Central, MEDLINE, and Scopus from January 2000 through April 2017 and relevant annual meeting abstracts from January 2014 to December 2016. The following search terms were used: "myeloma" combined with "autologous," "transplant," "myeloablative," or "stem cell."Phase 3 RCTs comparing HDT/ASCT with standard-dose therapy (SDT) using novel agents were assessed. Studies comparing single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone consolidation and tandem transplantation were included for network meta-analysis.For the random effects meta-analysis, we used hazard ratios (HRs) and corresponding 95% CIs.The primary outcome was progression-free survival (PFS). Overall survival (OS), complete response, and treatment-related mortality were secondary outcomes.A total of 4 RCTs (2421 patients) for conventional meta-analysis and 5 RCTs (3171 patients) for network meta-analysis were selected. The combined odds for complete response were 1.27 (95% CI, 0.97-1.65; P = .07) with HDT/ASCT when compared with SDT. The combined HR for PFS was 0.55 (95% CI, 0.41-0.74; P < .001) and 0.76 for OS (95% CI, 0.42-1.36; P = .20) in favor of HDT. Meta-regression showed that longer follow-up was associated with superior PFS (HR/mo, 0.98; 95% CI, 0.96-0.99; P = .03) and OS (HR/mo, 0.90; 95% CI, 0.84-0.96; P = .002). For PFS, tandem HDT/ASCT had the most favorable HR (0.49; 95% CI, 0.37-0.65) followed by single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone (HR, 0.53; 95% CI, 0.37-0.76) and single HDT/ASCT alone (HR, 0.68; 95% CI, 0.53-0.87) compared with SDT. For OS, none of the HDT/ASCT-based approaches had a significant effect on survival. Treatment-related mortality with HDT/ASCT was minimal (<1%).The results of the conventional meta-analysis and network meta-analysis of all the phase 3 RCTs showed that HDT/ASCT was associated with superior PFS with minimal toxic effects compared with SDT. Both tandem HDT/ASCT and single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone were superior to single HDT/ASCT alone and SDT for PFS, but OS was similar across the 4 approaches. Longer follow-up may better delineate any OS benefit; however, is likely to be affected by effective postrelapse therapy.
Gene Therapy with pCCLchimP47 -phox Lentiviral Vector Achieves Long-term Reconstitution of NADPH Oxidase Activity in p47 -phox Chronic Granulomatous Disease (CGD) Mouse Model
Authors: Walmir Cutrim Aragao Filho, Andrea Shejtman, Marta Zinicola, Ulrich Siler, Janine Reichenbach, Gaspar Bobby, Adrian J. Thrasher, Giorgia Santilli, Antonio Condino-Neto
Journal: Journal of Allergy and Clinical Immunology (2018)
Progression of undiagnosed cutaneous lymphoma after anti–tumor necrosis factor-alpha therapy
Authors: Maria Estela Martinez-Escala, Alba L. Posligua, Heather Wickless, Audrey Rutherford, Kimberly A. Sable, Belen Rubio-Gonzalez, Xiaolong A. Zhou, Jason B. Kaplan, Barbara Pro, Jaehyuk Choi, Christiane Querfeld, Steven T. Rosen, Joan Guitart
Journal: Journal of the American Academy of Dermatology (2018)
Mast Cell Density and Its Clinical Relevance in Waldenstrom's Macroglobulinemia
Authors: Richard Lemal, Stephanie Poulain, Albane Ledoux Pilon, Lauren Veronese, Andrei Tchirkov, Benjamin Lebecque, Jacques-Olivier Bay, Frederic Charlotte, Marc G. Berger, Catherine Godfraind, Loic Ysebaert, Frederic Davi, Veronique Leblond, Olivier Hermine, Romain Guieze, Franck Pages, Olivier Tournilhac
Journal: Blood (2017)
Macrolides, mucoactive drugs and adherence for the management of bronchiectasis
Authors: Wei-jie Guan, Yan Huang, Chun-lan Chen, Rong-chang Chen, Nan-shan Zhong
Journal: European Respiratory Journal (2018)

The publication of the first European Respiratory Society guidelines for management of bronchiectasis [1] is a landmark of recent advancement in the field. Whilst the British Thoracic Society guidelines [2] delineated mechanisms of pathogenesis and offered recommendations for management of bronchiectasis, the latest document specifically addressed nine clinically important questions that may better inform clinical decisions. Although it is likely that these recommendations can be extrapolated to patients in Asian countries such as China, we have some further suggestions and/or recommendations for refinement. Macrolides, mucoactive drugs and adherence are crucial for the management of bronchiectasis <http://ow.ly/H4oq30fZArC> W-J. Guan, Y. Huang and C-L. Chen drafted the manuscript; R-C. Chen and N-S. Zhang critically reviewed the manuscript and approved final submission.
Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy
Authors: Kamron N. Khan, Melissa Kasilian, Omar A.R. Mahroo, Preena Tanna, Angelos Kalitzeos, Anthony G. Robson, Kazushige Tsunoda, Takeshi Iwata, Anthony T. Moore, Kaoru Fujinami, Michel Michaelides
Journal: Ophthalmology (2018)

To describe the earliest features of ABCA4-associated retinopathy.Case series.Children with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy.The retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients.Visual acuity, OCT, FAF, electroretinography, and AOSLO results.Eight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave-to-A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results.In childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.
Abstract 12629: Endothelial Prolyl-4 hydroxylase 2 Deletion Induces Cardiac Hypertrophy and Heart Failure via Hypoxia Inducible Factor-2α Activation
Authors: Zhiyu Dai, Maggie M. Zhu, Chen Gao, Xianming Zhang, You-Yang Zhao
Journal: Circulation (2016)

Background: Cardiac hypertrophy is a common adaptive response to injury and stress, and can eventually lead to heart failure. The role of endothelial Prolyl-4 hydroxylase 2 (PHD2)/hypoxia inducible factors (HIFs) signaling in the pathogenesis of heart failure is unclear. We hypothesize that endothelial PHD2/HIF signaling dysfunction contributes to cardiac hypertrophy and heart failure. Methods: Mice with Tie2-Cre-mediated deletion of Egln1 (encoding PHD2) ( Egln1 Tie2-Cre ), as well as double knockout mice with both Egln1 and Hif1a or Egln1 and Hif2a were generated. Egln1 f/f bone marrow cells were transplanted to lethally irradiated Egln1 Tie2-Cre mice to determine the contribution of bone marrow cells in cardiac hypertrophy. Mice carrying Egln1 f/f were bred into Endo SCL- Cre- ER(T) mice containing tamoxifen-inducible Cre to generate mice with Egln1 deletion only in endothelial cells in adult mice ( Egln1 SCL-Cre ) after tamoxifen injection. Echocardiography were measured to study cardiac size and function. Histological examination was also performed. Results: Egln1 Tie2-Cre mice exhibited left ventricular hypertrophy evident by increased thickness of anterior and posterior wall and left ventricular mass, as well as cardiac fibrosis. Egln1 deletion in bone marrow cells did not contribute to cardiac hypertrophy. Tamoxifen induced endothelial Egln1 deletion in adult Egln1 SCL-Cre mice also induced left ventricular hypertrophy and heart failure. Genetic ablation of Hif2a but not Hif1a in Egln1 Tie2 mice normalized cardiac size and function. Additionally, we observed a marked decrease of PHD2 expression in heart tissues from patients with dilated cardiomyopathy. Conclusion: This studies define for the first time an unexpected role of endothelial PHD2 deficiency in inducing cardiac hypertrophy and heart failure in a HIF-2α dependent manner. Thus, targeting PHD2/HIF-2α signaling represents a novel therapeutic approach for the treatment of heart failure.
Pomalidomide (POM) + Low-Dose Dexamethasone (LoDEX) Safety and Efficacy in Patients (pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM) Previously Treated with a Proteasome Inhibitor (PI) and in Whom Last Prior Therapy with Lenalidomide (LEN) Failed
Authors: David Siegel, Gary J. Schiller, Kevin W Song, Richy Agajanian, Ketih Stockerl-Goldstein, Hakan Kaya, Michael Sebag, Christy Samaras, Ehsan Malek, Giampaolo Talamo, Christopher S. Seet, Jorge Mouro, Faiza Zafar, Weiyuan Chung, Shankar Srinivasan, Max Qian, Amit Agarwal, Anjan Thakurta, Nizar J. Bahlis
Journal: Blood (2017)
Purtscher-like retinopathy as a first manifestation of systemic lupus erythematosus
Authors: Ye Dai, Wei Chi
Journal: BMJ (2018)

A 23 year old man developed sudden painless visual loss in both eyes. There was no history of trauma. His best corrected visual acuity was 20/40 (right) and 20/667(left). Funduscopy showed bilateral …
Seifem 2016 Study: Incidence of Probable and Proven Invasive Aspergillosis in Patients with Acute Myeloid Leukemia during Consolidation Therapy
Authors: Maria Ilaria Del Principe, Roberta di Blasi, Verga Luisa, Candoni Anna, Ballanti Stelvio, Potenza Leonardo, Cattaneo Chiara, Delia Mario, Decembrino Nunzia, Lorella Ma Melillo, Castagnola Carlo, Gianpaolo Nadali, Fanci Rosa, Ferrari Antonella, Fracchiolla Nicola, Orciuolo Enrico, Lessi Federica, Chierichini Anna, Offidani Massimo, Picardi Marco, Prezioso Lucia, Rambaldi Benedetta, Marchesi Francesco, Annibali Ombretta, Zama Daniele, Mancini Valentina, Salutari Prassede, Maria Grazia Garzia, Vacca Adriana, Simone Cesaro, Invernizzi Rosangela, Perruccio Katia, Maria Enza Mitra, Angela Maria Quinto, Maria Chiara Tisi, Martino Bruno, Venditti Adriano, Busca Alessandro, Franco Aversa, Livio Pagano
Journal: Blood (2017)
Atopy Modifies the Effect of Mouse Allergen Reduction on Asthma Outcomes in Low-income, Urban Children with Persistent Asthma
Authors: Ammara G. Ahmed, Torie L. Grant, Wanda Phipatanakul, Matthew Perzanowski, Susan L. Balcer-Whaley, Roger Peng, Jean Curtin-Brosnan, Michelle Newman, Amparito Cunningham, Adnan Divjan, Mary Beth Bollinger, Robert A. Wise, Rachel L. Miller, Ginger L. Chew, Elizabeth C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2018)
Anatomical Wiring and Functional Networking Changes in the Visual System Following Optic Neuritis
Authors: Yael Backner, Joseph Kuchling, Said Massarwa, Timm Oberwahrenbrock, Carsten Finke, Judith Bellmann-Strobl, Klemens Ruprecht, Alexander U. Brandt, Hanna Zimmermann, Noa Raz, Friedemann Paul, Netta Levin
Journal: JAMA Neurology (2018)

Clinical outcome in multiple sclerosis was suggested to be driven by not only remyelination but also adaptive reorganization. This mechanism needs to be further understood.To explore anatomical and functional visual networks in patients with optic neuritis (ON) to assess the relative weight of each connectivity modality to expedite visual recovery.Between March 11, 2011, and May 26, 2014, 39 patients with either clinically isolated syndrome (CIS) ON (n = 18) or other CIS (non-ON) (n = 21) were recruited 1 to 28 months following an initial clinical event. These patients enrolled in an ongoing prospective cohort study (107 participants at the time of this present study) about the disease course of CIS and multiple sclerosis. Inclusion criteria were an age of 18 to 65 years, the suggestive clinical and paraclinical diagnosis of CIS or multiple sclerosis after relevant differential diagnoses have been ruled out, the existence of complete imaging data, and no ocular comorbidities. Anatomical connectivity was evaluated by diffusion tensor imaging, and functional connectivity was evaluated by resting-state functional magnetic resonance imaging. The visual pathways, including optic tracts, optic radiations, and splenial fibers, were delineated, and the resting-state visual networks were detected. Data analysis took place from September 1, 2015, to December 1, 2015.Connectivity changes were quantified and compared to determine the association of ON with the visual network.This study included 18 patients with CIS ON, 11 (61%) of whom were women with a mean (SD) age of 32.83 (8.53) years, and 21 patients with CIS non-ON (11 [52%] of whom were women with a mean [SD] age of 30.86 [7.54] years). With the use of diffusion tensor imaging, reduced diffusivity (mean [SD] fractional anisotropy, 0.35 [0.03] vs 0.38 [0.03]; P < .01) was evident along the optic tracts of patients with ON, suggesting the extension of axonal injury from the damaged optic nerve. Neither the optic radiations nor the splenial fibers showed evidence of loss of integrity. Yet, in the presence of an intact postgeniculate anatomical network, the functional connectivity within the visual network was higher in the ON cohort. Functional connectivity observed in cortical motion-related areas was inversely correlated with the visual evoked potential-measured conduction velocity (r = -0.59; P < .05).In this cohort, local optic nerve demyelinating damage does not affect distant wiring, but even in the presence of an intact anatomical network, functional modification may occur. These functional network changes may be part of the recovery process, but further research is needed to elucidate this process.
Curcumin suppresses AP1 factor-dependent differentiation and activates apoptosis in human epidermal keratinocytes
Authors: Richard Eckert, Sivaprakasam Balasubramanian
Journal: Cancer Research (2007)

4196   The dietary agent, curcumin, has been shown to inhibit skin cancer cell proliferation and tumor formation. However, the effect of curcumin on normal human keratinocyte differentiation, proliferation and apoptosis has not been adequately studied. Involucrin (hINV) is a marker of keratinocyte differentiation. We show that curcumin suppresses the 12-O-tetradeconylphorbol-13-acetate (TPA)-dependent activation of hINV gene expression and that an AP1 site is required for this regulation. A nPKC, Ras, MEKK1, MEK3 signaling cascade that controls hINV expression by regulating AP1 factor function. Curcumin treatment inhibits nPKC-, Ras-and MEKK1-dependent activation of hINV promoter activity. We further show that curcumin treatment also regulates downstream events - specifically curcumin treatment suppresses the TPA-dependent increase in AP1 factor level and DNA binding. Moreover, the curcumin-dependent suppression of AP1 factor level requires proteasome function. In addition, curcumin treatment reduces cell number which is associated with a reduced cyclin A, D1, and E, and cdk1 levels. Curcumin treatment also suppresses Bcl-xL level, leading to reduced mitochondrial membrane potential, and increased cleavage of procaspase and PARP. These studies provide important insights regarding the potential mechanisms whereby curcumin may act as a chemopreventive agent in normal human  epidermis.
Inconsistency between Danish incidence and prevalence data about psoriatic arthritis (PsA)
Authors: Philipp Sewerin, Annika Hoyer, Matthias Schneider, Benedikt Ostendorf, Ralph Brinks
Journal: Annals of the Rheumatic Diseases (2018)

We are grateful to Egeberg and Kristensen for presenting the detailed data about the prevalence and incidence of psoriatic arthritis (PsA).1 Based on these detailed information, we tried to estimate the excess mortality of people with diagnosed PsA by uising a mathematical relation between incidence, prevalence and mortality.2 3 During analysis of the incidence and prevalence data, we have made the following observation: if we assume that — on population average — people with PsA do not have a better survival than those without PsA, we can compute a lower …
Paracrine wnt-β-catenin signaling inhibition as a strategy to enhance the efficacy of anti-PD-1 antibody (Ab) therapy in a transgenic model of melanoma.
Authors: Nicholas C. DeVito, Christine Xiao, Fei Zhao, Kathy S. Evans, Bala Theivanthiran, John Lewicki, Tim Hoey, Herbert Hurwitz, John H. Strickler, Brent Allen Hanks
Journal: Journal of Clinical Oncology (2017)

3053 Background: Activation of the Wnt-β-catenin signaling pathway is associated with poor T cell infiltration of tumors. We have previously demonstrated that paracrine Wnt5a-β-catenin signaling is a critical trigger of dendritic cell (DC) tolerization and regulatory T cell (Treg) differentiation in the melanoma microenvironment. In a transgenic BRAF V600E PTEN -/- model, the genetic silencing of melanoma-derived Wnt5a potently enhances infiltrating CD8 + T cell effector function and promotes responses to anti-PD-1 Ab therapy. Ipafricept (IPA) is a recombinant Wnt decoy receptor and Vantictumab (VAN) is a Fzd receptor monoclonal Ab. Both molecules inhibit Wnt-β-catenin signaling and have been well-tolerated in ongoing phase I/Ib clinical trials. We explored the ability of IPA/VAN to reverse tumor-mediated immune tolerance and enhance the efficacy of anti-PD-1 Ab immunotherapy in a pre-clinical model that closely recapitulates human melanoma. Methods: Both IPA and VAN were utilized to investigate Wnt-β-catenin inhibition as a strategy for suppressing melanoma-induced DC indoleamine 2,3-dioxygenase (IDO) expression and Treg differentiation in vitro. These agents were further tested for their ability to enhance anti-tumor T cell responses and to augment the efficacy of anti-PD-1 Ab therapy in syngeneic and autochthonous models of BRAF V600E PTEN -/- melanoma. Results: IPA and VAN effectively inhibit Wnt5a and melanoma-induced DC IDO expression and Treg differentiation in vitro. Further studies demonstrate that IPA and VAN significantly augment anti-PD-1 Ab-mediated suppression of primary and metastatic tumor progression in both syngeneic and autochthonous BRAF V600E PTEN -/- melanoma models. These anti-tumor effects correlated with suppressed IDO enzymatic activity, enhanced tumor-infiltrating CD8 + T cell/Treg ratios, and increased activation of TRP2 antigen-specific effector T cells. Conclusions: The pharmacological inhibition of paracrine Wnt-β-catenin signaling with IPA and VAN augment the anti-tumor efficacy of anti-PD-1 Ab therapy and represent a promising strategy for further phase I testing in melanoma and other solid tumors.
Results from Ongoing Phase 2 Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD)
Authors: Andrew A. Lane, Kendra L. Sweet, Eunice S. Wang, William B. Donnellan, Roland B. Walter, Anthony S. Stein, David A Rizzieri, Hetty E. Carraway, Ioannis Mantzaris, Thomas Prebet, Michael B. Maris, Stefan Faderl, Dale L. Bixby, Janice Chen, Ross Lindsay, Shay Shemesh, Christopher L. Brooks, Richard M. Stone, Hagop M. Kantarjian, Elias J. Jabbour, Marina Konopleva
Journal: Blood (2016)
Side-effect analysis of sunitinib (S) in patients treated with metastatic renal cell cancer (mRCC): Single center experience in the National Institute of Oncology, Hungary—Influence of dose reduction/modification and application schedule on the efficacy of S.
Authors: Krisztian Nagyivanyi, Krisztina Biro, Istvan Bodrogi, Fruzsina Eva Gyergyay, Zsofia Kuronya, Hajnalka Nemeth, Lajos Geczi
Journal: Journal of Clinical Oncology (2013)

e15530 Background: S, an active and relatively well tolerated treatment for mRCC, based on the result of a global phase III study. Methods: Retrospectively, 383 patient’s data with clear cell mRCC were collected, who were treated with S in our department between 01/nov/2005 and 31/dec/2012. S was used in 1st or 2 nd line setting. The first few dozen subjects were involved in a clinal trial after progression on first line INF therapy. In Hungary S became reimbursed by the public health insurence from 01/jan/2008 in second line, and from 01/feb/2010 in first line. All patients had definitely favorable or intermediate risk based on MSKCC risk group criteria. The starting dose of S was mostly 50 mg (schedule 4 weeks on followed by 2 weeks off). Results: We investigated the prevalence of necessity of dose reduction/modification or pretence to follow an out of ordinary application form. We registered the frequency and modality of the different types of side effects, we also studied the outcome of patients. Incidence of grade 3+4 side effects was nearly 60%. The most common side effects were fatigue (63%), mucositis/stomatitis (40,2%), hand-foot syndome (16,1%), diarrhea (34%), hypertension (34%), nausea (2%), anaemia (8,6%), leukopenia (4,6%), thrombopenia (20%) and hypothyreosis (20%). Objective response rate based on RECIST and progression-free survival (PFS) were also recorded. The efficacy of treatment was nearly similar to the global clinical trial results. CR was rare (4,2%), most of our patients had PR (31,1%) or SD (51,2%) as best response. In first line setting the results were even better (CR 10,5%, PR 44% and SD 57,5). Conclusions: S is effective and safe agent to treat patients with mRCC. Due to side effects, dose reduction / modification is often needed but rarely requires treatment discontinuation. The early detection and right management of side effects is crucial to maintain the patients on the treatment. Unfortunately the deviation from the standard care may bias the efficacy.
No Sustainable Effects of an Internet-Based Relapse Prevention Program over 24 Months in Recurrent Depression: Primary Outcomes of a Randomized Controlled Trial
Authors: Nicola S. Klein, Gemma D. Kok, Huibert Burger, Evelien van Valen, Heleen Riper, Pim Cuijpers, Jack Dekker, Filip Smit, Colin van der Heiden, Claudi L.H. Bockting
Journal: Psychotherapy and Psychosomatics (2018)
Clinical, Endoscopic and Histopathological Characteristics of Pediatric Patients with Eosinophilic Digestives Diseases attending the Gastroenterology Department of the National Institute Of Pediatrics in Mexico City
Authors: Amyra Ali Azamar Jacome, Josefina Monserrat Cazares Mendez, David Alejandro Mendoza Hernandez, Jose G. Huerta Lopez
Journal: Journal of Allergy and Clinical Immunology (2018)