tbuckley/cabot-search huggingface dataset:
Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms
Authors: Ajay Malhotra, Xiao Wu
Journal: Annals of Internal Medicine (2018)

Letters16 January 2018Growth and Rupture Risk of Small Unruptured Intracranial AneurysmsAjay Malhotra, MD, MMM and Xiao Wu, BSAjay Malhotra, MD, MMMYale University, New Haven, Connecticut (A.M., X.W.)Search for more papers by this author and Xiao Wu, BSYale University, New Haven, Connecticut (A.M., X.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0524 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:A substantial number of ruptured aneurysms are reported to be small. However, rupture is uncommon given the prevalence of unruptured intracranial aneurysms in the general population. In our study, we found poor correlation between growth and rupture risk in small aneurysms. This finding has implications for subsequent management after detection of incidental unruptured intracranial aneurysms: Should they be routinely treated? Should they undergo imaging surveillance? If so, for how long and how frequently? The literature has relatively poor evidence addressing these questions, and practice varies substantially. Author, Article, and Disclosure InformationAffiliations: Yale University, New Haven, Connecticut (A.M., X.W.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0246. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGrowth and Rupture Risk of Small Unruptured Intracranial Aneurysms Ajay Malhotra , Xiao Wu , Howard P. Forman , Holly K. Grossetta Nardini , Charles C. Matouk , Dheeraj Gandhi , Christopher Moore , and Pina Sanelli Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms Mark S. Roberts Metrics Cited byThe potential biomarkers for the formation and development of intracranial aneurysm 16 January 2018Volume 168, Issue 2Page: 159KeywordsAneurysmsDisclosure ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Endoscopic ultrasound-guided sclerosant injection and coil embolization of bleeding gastric varices
Authors: Bhavtosh Dedania, Keshav Kukreja, Tomas Davee, Manoop Bhutani
Journal: Endoscopy (2018)

The usefulness of endoscopic ultrasound (EUS) as a diagnostic tool is well known; however, its therapeutic implications are upcoming. There are data for the use of cyanoacrylate glue (CYA) as a temporary measure to control bleeding in gastric varices, followed either by a transjugular intrahepatic portosystemic shunt (TIPS) procedure or by balloon-occluded retrograde transvenous obliteration (BRTO).
Murine chronic graft-versus-host disease proteome profiling discovers CCL15 as a novel biomarker in patients
Authors: Jing Du, Ryan Flynn, Katelyn Paz, Hong-Gang Ren, Yuko Ogata, Qing Zhang, Philip R. Gafken, Barry E. Storer, Nathan H. Roy, Janis K. Burkhardt, Wendy Mathews, Jakub Tolar, Stephanie J. Lee, Bruce R. Blazar, Sophie Paczesny
Journal: Blood (2018)
Erratum: “Urinary Concentrations of Organophosphate Flame Retardant Metabolites and Pregnancy Outcomes among Women Undergoing <i>in Vitro</i> Fertilization”
Authors: Courtney C. Carignan, Lidia Mínguez-Alarcón, Craig M. Butt, Paige L. Williams, John D. Meeker, Heather M. Stapleton, Thomas L. Toth, Jennifer B. Ford, Russ Hauser
Journal: Environmental Health Perspectives (2017)

[This corrects the article DOI: 10.1289/EHP1021.].
Hematologic safety data of single-agent ponatinib from a phase I and phase II trial in Philadelphia chromosome-positive (Ph+) CML/ALL patients.
Authors: Devon M Greer, Susanne Liewer, Mojtaba Akhtari
Journal: Journal of Clinical Oncology (2014)

e18021 Background: Ponatinib is a tyrosine kinase inhibitor (TKI) indicated for the treatment of Ph+ chronic myeloid leukemia (CML) or acute lymphocytic leukemia (ALL) in the absence of other appropriate TKI therapies or presence of the T315I BCR-ABL mutation. Hematologic toxicity can result in dose reductions, interruptions and discontinuation of drug therapy. In the following analysis, we summarize the hematologic safety profile of single agent ponatinib reported in 468 patients from 2 trials. The primary objective is to evaluate the number and percent of patients with hematologic toxicities based on previously published data. Methods: Data reported from patients treated with ponatinib in trials 10-201 and 07-101 was included in the analysis. Ponatinib was dosed at 45 mg orally once daily. Hematologic adverse effects analyzed included thrombocytopenia, neutropenia, anemia and arterial thrombotic events. Results: See Table below for summary of events. Thrombocytopenia, neutropenia and anemia were more frequently associated with patients in blast or accelerated phase CML and Ph+ ALL. Dose reductions and interruptions secondary to any adverse reaction were measured in 449 patients with an incidence of 55% (n=247) and 67% (n=301). Arterial thrombotic events were measured in 449 patients and had a frequency of 16% (n=70). Of these patients, the majority had a history of ischemic disease or a minimum of one risk factor prior to enrollment. Conclusions: The frequency of hematologic toxicities was comparable to previously approved TKIs, with the exception of arterial thrombotic events. These occurred in a larger number of patients although the significance of ponatinib's role is difficult to interpret due to the high number of cardiovascular risk factors. In summary, this analysis supports the use of ponatinib in heavily pre-treated CML or Ph+ALL or patients with the T315I BCR-ABL mutation with stringent monitoring and safety measures for arterial thrombotic events. Thrombocytopenia N=468, n (%) Neutropenia N=468, n (%) Anemia N=468, n (%) Arterial Thrombotic Events N=449, n (%) Any AE 173 (37) 85 (18) 61 (13) 70 (16) Grade 3/4 AE 136 (29) 76 (16) 41 (9)
<i>IDH1/2</i> Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is Reversed by IDH1/2-Mutant Inhibitors
Authors: Remco J. Molenaar, Tomas Radivoyevitch, Yasunobu Nagata, Mohammed Khurshed, Bartolomiej Przychodzen, Hideki Makishima, Mingjiang Xu, Fonnet E. Bleeker, Johanna W. Wilmink, Hetty E. Carraway, Sudipto Mukherjee, Mikkael A. Sekeres, Cornelis J.F. van Noorden, Jaroslaw P. Maciejewski
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Somatic mutations in IDH1/2 occur in approximately 20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increased DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2MUT AML is not known. Experimental Design: Well-characterized primary IDH1MUT, IDH2MUT, and IDH1/2WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation, and PARP inhibitors. Results: IDH1/2MUT caused increased DNA damage and sensitization to daunorubicin, irradiation, and the PARP inhibitors olaparib and talazoparib in AML cells. IDH1/2MUT inhibitors protected against these treatments. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2MUT AML cells. We provide evidence that the therapy sensitivity of IDH1/2MUT cells was caused by D2HG-mediated downregulation of expression of the DNA damage response gene ATM and not by altered redox responses due to metabolic alterations in IDH1/2MUT cells. Conclusions: IDH1/2MUT AML cells are sensitive to PARP inhibitors as monotherapy but especially when combined with a DNA-damaging agent, such as daunorubicin, whereas concomitant administration of IDH1/2MUT inhibitors during cytotoxic therapy decrease the efficacy of both agents in IDH1/2MUT AML. These results advocate in favor of clinical trials of PARP inhibitors either or not in combination with daunorubicin in IDH1/2MUT AML. Clin Cancer Res; 24(7); 1705–15. ©2018 AACR.
Inhaled corticoids in asthmatic patients: effect on body mass index and spirometry
Authors: Rosilane dos Reis Pacheco, Mayra Coutinho Andrade, Natalia falci Pedroso, Priscila Takejima, Marcelo V. Aun, Jorge Elias Kalil Filho, Pedro Giavina-Bianchi, Rosana C. Agondi
Journal: Journal of Allergy and Clinical Immunology (2018)
A New Secretory Peptide of Natriuretic Peptide Family, Osteocrin, Suppresses the Progression of Congestive Heart Failure After Myocardial Infarction
Authors: Takahiro Miyazaki, Kentaro Otani, Ayano Chiba, Hirohito Nishimura, Takeshi Tokudome, Haruko Takano-Watanabe, Ayaka Matsuo, Hiroyuki Ishikawa, Keiko Shimamoto, Hajime Fukui, Yugo Kanai, Akihiro Yasoda, Soshiro Ogata, Kunihiro Nishimura, Naoto Minamino, Naoki Mochizuki
Journal: Circulation Research (2018)

Rationale: An increase of severe ischemic heart diseases results in an increase of the patients with congestive heart failure (CHF). Therefore, new therapies are expected in addition to recanalization of coronary arteries. Previous clinical trials using natriuretic peptides (NPs) prove the improvement of CHF by NPs. Objective: We aimed at investigating whether OSTN (osteocrin) peptide potentially functioning as an NPR (NP clearance receptor) 3-blocking peptide can be used as a new therapeutic peptide for treating CHF after myocardial infarction (MI) using animal models. Methods and Results: We examined the effect of OSTN on circulation using 2 mouse models; the continuous intravenous infusion of OSTN after MI and the OSTN-transgenic (Tg) mice with MI. In vitro studies revealed that OSTN competitively bound to NPR3 with atrial NP. In both OSTN–continuous intravenous infusion model and OSTN-Tg model, acute inflammation within the first week after MI was reduced. Moreover, both models showed the improvement of prognosis at 28 days after MI by OSTN. Consistent with the in vitro study binding of OSTN to NPR3, the OSTN-Tg exhibited an increased plasma atrial NP and C-type NP, which might result in the improvement of CHF after MI as indicated by the reduced weight of hearts and lungs and by the reduced fibrosis. Conclusions: OSTN might suppress the worsening of CHF after MI by inhibiting clearance of NP family peptides.
Abstract 13850: Achievement of Target Systolic Blood Pressure for Lowering the Risk of Major Adverse Cardiovascular Events: From the Action to Control Cardiovascular Risk in Diabetes Blood Pressure Trial
Authors: Briain O Hartaigh, Jackie Szymonifka, Peter M Okin
Journal: Circulation (2016)

Background: Prior epidemiologic studies have documented deleterious effects of more intensive systolic blood pressure (SBP) lowering in persons with diabetes mellitus (DM). Yet, whether the risk of adverse cardiovascular events might improve, as a function of achieving target SBP goals, remains to be elucidated. Objective: To test the efficacy of achieving target SBP less than 120 mm Hg, or below 140 mm Hg (versus those unable to achieve target SBP), for offsetting the risk of major adverse cardiovascular events (MACE). Methods: Data from the ACCORD BP trial were utilized, which comprised 4,732 (mean±SD age: 63±7 years; 2,258 [48%] women) persons presenting with advanced DM. Participants were randomly assigned to achieve either intensive (&lt;120 mm Hg) or standard (&lt;140 mm Hg) SBP control in an effort to offset the risk of MACE - defined as a composite of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular causes. Results: During a median follow-up of 5.0 (interquartile range: 4.2-5.7) years, 1,939 (82%) and 2,038 (86%) persons achieved SBP targets below 120 mm Hg and 140 mm Hg in each treatment arm, respectively. In total, 208 (9%) and 237 (10%) persons belonging to the intensive and standard treatment arms experienced the composite endpoint. Multivariable Cox regression analyses revealed no significant reduction in risk of MACE for those in the intensive treatment arm, who achieved a target SBP below 120 mm Hg. Conversely, those in the standard treatment arm who achieved a target SBP of less than 140 mm Hg displayed a substantial reduction in risk of MACE (HR = 0.65, 95% CI: 0.48-0.88, P =0.005), all-cause death (HR = 0.64, 95% CI: 0.43-0.94, P =0.02), and non-fatal stroke (HR = 0.47, 95% CI: 0.26-0.87, P =0.02). Conclusion: Achieving a standard SBP goal between 120-140 mm Hg may prove useful for lowering the burden of cardiovascular risk in persons with DM, whereas achieving a target SBP &lt;120 mm Hg does not appear to reduce risk.
Exploratory responder analyses of greatest depth of response (DepOR) and survival in patients with metastatic non-small cell lung cancer (mNSCLC) treated with a targeted therapy or immunotherapy.
Authors: Dickran Gano Kazandjian, Gideon Michael Blumenthal, Lijun Zhang, Caroline Elizabeth McCoach, Shenghui Tang, Rajeshwari Sridhara, Robert Charles Doebele, Patricia Keegan, Richard Pazdur
Journal: Journal of Clinical Oncology (2016)

2590 Background: RECIST criteria as a binary output may not fully capture the clinical benefit of targeted therapy and immunotherapy in mNSCLC. We sought to determine the association between the maximum reduction in tumor target lesions from baseline (DepOR) with overall survival (OS) for two drugs, an ALK inhibitor (ALKi) and a PD-1 inhibitor (PD-1i), which represent the targeted and immune therapy drug classes. Methods: Data from two randomized trials were pooled for each drug for exploratory analyses. Data from patients with any tumor shrinkage were grouped into 4 quartiles based on the greatest percent shrinkage in tumor target lesions from baseline and compared to data from patients with no tumor shrinkage. A retrospective exploratory responder analysis was performed to evaluate the association between the DepOR quartiles and OS for each drug using hazard ratios (HR, Cox proportional hazards model) Results: The exploratory responder analysis suggested that patients with the highest percentages of tumor shrinkage experienced the longest survival for both drugs. Specifically, pooled analysis of ALKi trials suggested incrementally larger HR for OS with increased tumor shrinkage by quartile. Pooled analysis of PD-1i trials suggested that greater than 50% tumor shrinkage was associated with more favorable OS HR compared to subgroups with 1-50% tumor shrinkage and with no tumor shrinkage (Table). Conclusions: Our analysis suggests that a positive association between the percentage of maximal tumor shrinkage with increasing effects on survival as measured by HR for both ALKi and PD-1i. These exploratory retrospective analyses results are hypothesis generating and further evaluation is necessary to understand these relationships. Crizotinib DepOR Subgroups N = 305 OS HR (95% CI) No tumor shrinkage (n = 12) 1-25% (n = 39) 0.98 (0.36, 2.69) 26-50% (n = 70) 0.66 (0.25, 1.75) 51-75% (n = 144) 0.38 (0.15, 0.96) 76-100% (n = 40) 0.06 (0.01, 0.33) Nivolumab DepOR Subgroups N = 355 No tumor shrinkage (n = 168) 1-25% (n = 70) 0.54 (0.38, 0.76) 26-50% (n = 44) 0.50 (0.32, 0.78) 51-75% (n = 45) 0.09 (0.04, 0.21) 76-100% (n = 28) 0.14 (0.06, 0.31)
Human Olfactory Mucosa-Derived Mesenchymal Stem Cells Suppress Cytotoxic Functions of CD8+ T-Lymphocytes and Natural Killer Cells
Authors: N. Antonevich, Andrei Hancharou, O. Buschik, A. Rydna, V. Chekan, E. Strinkevich, Lawrence Dubuske
Journal: Journal of Allergy and Clinical Immunology (2018)
Animal models of obesity and diabetes mellitus
Authors: Maximilian Kleinert, Christoffer Clemmensen, Susanna M. Hofmann, Mary C. Moore, Simone Renner, Stephen C. Woods, Peter Huypens, Johannes Beckers, Martin Hrabe de Angelis, Annette Schürmann, Mostafa Bakhti, Martin Klingenspor, Mark Heiman, Alan D. Cherrington, Michael Ristow, Heiko Lickert, Eckhard Wolf, Peter J. Havel, Timo D. Müller, Matthias H. Tschöp
Journal: Nature Reviews Endocrinology (2018)
Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury
Authors: Enrico Velardi, Jennifer J Tsai, Stefan Radtke, Kirsten Cooper, Kimon V Argyropoulos, Shieh Jae-Hung, Lauren F Young, Amina Lazrak, Odette M Smith, Sophie Lieberman, Fabiana Kreines, Yusuke Shono, Tobias Wertheimer, Robert R Jenq, Alan M Hanash, Prema Narayan, Zhenmin Lei, Malcolm A Moore, Hans-Peter Kiem, Marcel R M van den Brink, Jarrod A Dudakov
Journal: Nature Medicine (2018)
Comprehensive molecular characterization and analysis of muscle-invasive urothelial carcinomas.
Authors: Seth P. Lerner, Gordon Robertson, Jaegil Kim, Andrew Cherniack, Guangwu Guo, Rehan Akbani, Rupa S Kanchi, Katherine A. Hoadley, Toshinori Hinoue, Peter W. Laird, Hikmat Al-Ahmadie, Joaquim Bellmunt, Mauro Castro, Dmitry Gordenin, Gordon B. Mills, Francisco Sanchez-Vega, Sachet A Shukla, Ewan A Gibb, John N. Weinstein, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2017)

4500 Background: We reported the integrated molecular analysis of 131 tumors in 2014 (Nature 507:315, 2014) and now report on the entire cohort of 412 tumors from the TCGA project in chemotherapy-naïve, muscle-invasive urothelial bladder cancer. Methods: Following strict clinical and pathologic quality control, tumors were analyzed for DNA copy number variants, somatic mutations (WES), DNA methylation, mRNA, non-coding RNA (lncRNA and miRNA) and (phospho-) protein expression, gene fusions, viral integration, pathway perturbation, clinical correlates, outcomes, and histopathology. Results: There was a high overall somatic mutation rate (8.2/Mb), as previously reported. There were 58 significantly mutated genes (SMGs) (MutSig_2CV), increased from 32 in the original report. We identified 5 mutation signatures including APOBEC-a and b, ERCC2, C &gt; T_CpG, and a single ultra-mutated sample with a functional POLE mutation. APOBEC mutagenesis explained 70% of the mutation burden and was associated with survival (p = 0.0013). High mutation burden and neoantigen load were also associated with improved outcome (p = 0.00014 and 0.00078). The previously identified four mRNA subtypes were predicted on the larger set and also identified a novel poor-survival ‘neuronal’ subtype that nevertheless lacked small cell or neuroendocrine histology. Clustering converged for mRNA, lncRNA and miRNA expression, and for inferred activity of gene sets associated with regulator expression. We identified subsets with differential epithelial-mesenchymal transition scores, carcinoma-in-situ scores, and survival, with implications for distinct therapeutic potential. Conclusions: This integrated analysis of 412 TCGA patient samples validates and extends observations from the first 131 patients and significantly increases our power to detect additional low-frequency aberrations. The results provide unique insights into mechanisms of bladder cancer development, and identify novel subsets of MIBC that may benefit from differential treatment approaches.
Kindlin-1 Promotes Pulmonary Breast Cancer Metastasis
Authors: Sana Sarvi, Hitesh Patel, Jun Li, Georgia L. Dodd, Helen Creedon, Morwenna Muir, Jocelyn Ward, John C. Dawson, Martin Lee, Jayne Culley, Donald M. Salter, Andrew H. Sims, Adam Byron, Valerie G. Brunton
Journal: Cancer Research (2018)

Abstract In breast cancer, increased expression of the cytoskeletal adaptor protein Kindlin-1 has been linked to increased risks of lung metastasis, but the functional basis is unknown. Here, we show that in a mouse model of polyomavirus middle T antigen–induced mammary tumorigenesis, loss of Kindlin-1 reduced early pulmonary arrest and later development of lung metastasis. This phenotype relied on the ability of Kindlin-1 to bind and activate β integrin heterodimers. Kindlin-1 loss reduced α4 integrin–mediated adhesion of mammary tumor cells to the adhesion molecule VCAM-1 on endothelial cells. Treating mice with an anti–VCAM-1 blocking antibody prevented early pulmonary arrest. Kindlin-1 loss also resulted in reduced secretion of several factors linked to metastatic spread, including the lung metastasis regulator tenascin-C, showing that Kindlin-1 regulated metastatic dissemination by an additional mechanism in the tumor microenvironment. Overall, our results show that Kindlin-1 contributes functionally to early pulmonary metastasis of breast cancer. Significance: These findings provide a mechanistic proof in mice that Kindin-1, an integrin-binding adaptor protein, is a critical mediator of early lung metastasis of breast cancer. Cancer Res; 78(6); 1484–96. ©2018 AACR.
Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial
Authors: Emma Guttman-Yassky, Patrick M. Brunner, Avidan U. Neumann, Saakshi Khattri, Ana B. Pavel, Kunal Malik, Giselle K. Singer, Danielle Baum, Patricia Gilleaudeau, Mary Sullivan-Whalen, Sharon Rose, Shelbi Jim On, Xuan Li, Judilyn Fuentes-Duculan, Yeriel Estrada, Sandra Garcet, Claudia Traidl-Hoffmann, James G. Krueger, Mark G. Lebwohl
Journal: Journal of the American Academy of Dermatology (2018)

BackgroundInterleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function.ObjectiveEvaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD).MethodsWe performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point.ResultsAt 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections.LimitationsThe limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD.ConclusionFezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.
Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation into Ly6c+CD103+ Monocytic Antigen-Presenting Cells in Tumors
Authors: Madhav D. Sharma, Paulo C. Rodriguez, Brent H. Koehn, Babak Baban, Yan Cui, Gang Guo, Michiko Shimoda, Rafal Pacholczyk, Huidong Shi, Eun-Joon Lee, Hongyan Xu, Theodore S. Johnson, Yukai He, Taha Mergoub, Christopher Venable, Vincenzo Bronte, Jedd D. Wolchok, Bruce R. Blazar, David H. Munn
Journal: Immunity (2018)