tbuckley/cabot-search huggingface dataset:
SAINT: Results of a phase 1/2 study of safety/efficacy using safe amounts of ipilimumab, nivolumab, and trabectedin as first-line treatment of advanced soft tissue sarcoma.
Authors: Erlinda Maria Gordon, Victoria S. Chua-Alcala, Katherine Kim, Seiya Liu, Nicole Angel, Rekha Baby, Don Brigham, William W. Tseng, Seth Pollack, Robin Lewis Jones, Noah Federman, Amor M. Srikureja, John Jalas, Sant P. Chawla
Journal: Journal of Clinical Oncology (2019)

11016 Background: Sarcoma cells are most immunogenic earlier in the disease course and prior to treatment when the immune system can recognize and destroy them. Hypothesis: Immune checkpoint inhibitors would be most effective when given as first line therapy. Methods: This is an IRB-approved dose-seeking Phase 1/2 protocol using defined doses of I (1 mg/kg i.v. q 12 weeks), N (3 mg/kg i.v. q 2 weeks) and escalating doses of T (1.0, 1.2, 1.5 mg/m2 i.v. q 3 weeks), employing the “Cohort of Three” design, followed by a Phase 2 using the MTD of trabectedin. Results: Nine subjects were treated in Phase 1 of the study, and 31 subjects in Phase 2. Safety analysis: at Dose 1: Grade 3 treatment-related adverse events (TRAEs) included fatigue (n = 1), increased TSH (n = 1). At Dose 2, Grade 4 TRAEs included thrombocytopenia with bleeding, DLT (n = 1), increased CK (n = 1); Grade 3 TRAEs included anemia (n = 1), myalgia (n = 1), increased TSH (n = 1), decreased TSH (n = 1), increased AST (n = 1). Efficacy analysis (evaluable patients): At Dose 1: Disease Control Rate (DCR = CR, PR, SD) was 67%, median PFS, 18 weeks; median OS, 50 weeks; At Dose 2: PR (n-1), DCR 60%, median PFS, 24 weeks; median OS, &gt; 46 weeks. At Phase 2, MTD Dose 2 (PUPs): Safety analysis (n = 31): Grade 3 TRAEs included fatigue (n = 2), increased ALT (n = 6), increased AST (n = 4), hypernatremia (n = 1), hyponatremia (n = 1), dehydration (n = 1), rash (n = 1), port cellulitis (n = 1), psoriasis exacerbation (n = 1), increased TSH (n = 1), decreased hemoglobin (n = 2), neutropenia (n = 1). Efficacy analysis (N = 23 evaluable): PR (n-5; 2 UPS, 1 synovial sarcoma, 1 liposarcoma, 1 leiomyosarcoma,), BORR 22%, DCR 96%. Median PFS and OS not yet reached. After 4 treatment cycles, one resected tumor showed 80% necrosis and a greater number (30%) of CD8+ killer T cells, in the TME compared to archived pre-treatment tumor. Conclusions: These data suggest that the SAINT protocol (1) is safe with manageable adverse events, with no additive toxicity, and (2) may control tumor growth. Phase 2 of the study is on-going. Clinical trial information: NCT03138161.
<i>Vital Signs</i>: Surveillance for Acute Flaccid Myelitis — United States, 2018
Authors: Adriana Lopez, Adria Lee, Angela Guo, Jennifer L. Konopka-Anstadt, Amie Nisler, Shannon L. Rogers, Brian Emery, W. Allan Nix, Steven Oberste, Janell Routh, Manisha Patel
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Acute flaccid myelitis (AFM), a serious paralytic illness, was first recognized as a distinct condition in 2014, when cases were reported concurrent with a large U.S. outbreak of severe respiratory illness caused by enterovirus D-68 (EV-D68). Since 2014, nationwide outbreaks of AFM have occurred every 2 years in the United States; the cause for the recent change in the epidemiology of AFM in the United States, including the occurrence of outbreaks and a biennial periodicity since 2014, is under investigation. This report updates clinical, laboratory, and outcome data for cases reported to CDC during 2018.Clinical data and specimens from persons in the United States who met the clinical criterion for AFM (acute onset of flaccid limb weakness) with onset in 2018 were submitted to CDC for classification of the illnesses as confirmed, probable, or non-AFM cases. Enterovirus/rhinovirus (EV/RV) testing was performed on available specimens from persons meeting the clinical criterion. Descriptive analyses, laboratory results, and indicators of early recognition and reporting are summarized.From January through December 2018, among 374 reported cases of AFM, 233 (62%) (from 41 states) were classified as confirmed, 26 (7%) as probable, and 115 (31%) as non-AFM cases. Median ages of patients with confirmed, probable, and non-AFM cases were 5.3, 2.9, and 8.8 years, respectively. Laboratory testing identified multiple EV/RV types, primarily in respiratory and stool specimens, in 44% of confirmed cases. Among confirmed cases, the interval from onset of limb weakness until specimen collection ranged from 2 to 7 days, depending on specimen type. Interval from onset of limb weakness until reporting to CDC during 2018 ranged from 18 to 36 days, with confirmed and probable cases reported earlier than non-AFM cases.Identification of risk factors leading to outbreaks of AFM remains a public health priority. Prompt recognition of signs and symptoms, early specimen collection, and complete and rapid reporting will expedite public health investigations and research studies to elucidate the recent epidemiology of AFM and subsequently inform treatment and prevention recommendations.
Beyond Parity and Toward Socially Owned Anticancer Drug Research
Authors: Ian Neff
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Randomized phase II study of cladribine with simultaneous or delayed rituximab in patients with untreated hairy cell leukemia.
Authors: Dai Chihara, Evgeny Arons, Maryalice Stetler-Stevenson, Constance Yuan, Hong Zhou, Mark Raffeld, Liqiang Xi, Seth M. Steinberg, Laura Wisch, Julie Feurtado, Lacey James-Echenique, Raul Braylan, Katherine R. Calvo, Irina Maric, Alina Dulau, Robert J. Kreitman
Journal: Journal of Clinical Oncology (2019)

7003 Background: Single-agent purine analog therapy, usually cladribine, has been the standard 1 st -line therapy of hairy cell leukemia (HCL) for ~30 years. Relapse is attributed to minimal residual disease (MRD) persisting despite complete remission (CR). Rituximab can clear MRD, but there are no long-term data for how frequently and for how long this happens, or even how frequently MRD remains after cladribine. We therefore conducted a randomized phase II trial of 1st-line cladribine with concurrent vs delayed rituximab. Methods: The primary endpoint was to determine if 8 weekly doses of rituximab (375 mg/m 2 iv) begun the same day as 5 daily doses of cladribine (0.15 mg/kg iv) reduce HCL MRD 6 months later compared to cladribine alone. Secondary endpoints included testing delayed rituximab, 8 weekly doses beginning if/when MRD is detected in blood (or if HCL-related cytopenias persist preventing consideration of CR) ≥ 6 months after cladribine. Both groups could receive a 2 nd course of rituximab if the same situation recurred ≥ 6 months after starting the 1 st course of rituximab. MRD was assessed in blood (PB) and bone marrow (BM) using flow cytometry (FC), consensus PCR, and immunohistochemistry. Results: Sixty-eight patients were randomized 1:1 to concurrent vs delayed arms. At 6 months after cladribine, 97% concurrent vs 24% delayed (p &lt; 0.0001) patients were MRD-free by all tests. 100% concurrent vs 41% delayed patients were MRD-free by all tests except BMA FC (p &lt; 0.0001). At a median follow-up of 87.3 months, delayed rituximab was required by 1 concurrent patient vs 27 courses in 21 delayed patients. MRD-free survival after 1 st rituximab was not reached for 34 patients after concurrent rituximab, with 32 still MRD-free after a median of 72 months (94% MRD-free survival), compared to median MRD-free survival 60.1 months after delayed rituximab, with 10 (48%) of 21 remaining MRD-free (p &lt; 0.0001, hazard ratio for concurrent rituximab 0.09). Conclusions: Achievement of MRD-free CR after 1 st line cladribine for HCL is greatly enhanced by concurrent rituximab. Use of delayed rather than concurrent rituximab could achieve MRD-free CR but durability was clearly inferior to concurrent rituximab. Longer follow-up will determine if MRD-free survival leads to cures of HCL, increased CR duration, and/or less need for additional therapy. Clinical trial information: NCT00923013.
Copy number variation in longitudinal liver metastases biopsies in colorectal cancer identifies biomarker candidates of resistance to standard chemotherapy
Authors: K. Gambaro, M. Marques, S. McNamara, M. Couetoux du Tertre, C. Hoffert, A. Srivastava, B. Samson, B. Lesperance, Y. Ko, R. Dalfen, E. St-Hilaire, L. Sideris, F. Couture, R. Burkes, M. Harb, E. Camlioglu, A. Gologan, V. Pelsser, S. Tejpar, P. Kavan, C. Kleinman, G. Batist
Journal: Annals of Oncology (2019)
Safety and efficacy of nintedanib (BIBF 1120) plus pemetrexed in Japanese patients with advanced or recurrent non-small cell lung cancer (NSCLC): A phase I study.
Authors: Haruko Daga, Koji Takeda, Hideaki Okada, Masaki Miyazaki, Shinya Ueda, Hiroyasu Kaneda, Isamu Okamoto, Kiyotaka Yoh, Koichi Goto, Koichi Konishi, Akiko Sarashina, Nobutaka Yagi, Kiyomi Mera, Rolf Kaiser, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2013)

8056 Background: Nintedanib (N) is a potent, orally bio-available triple angiokinase inhibitor that targets VEGFRs, PDGFRs and FGFRs, as well as RET and Flt3. The open-label phase I part of this phase I/II study was designed to determine the maximum tolerated dose (MTD) of N when combined with standard-dose pemetrexed (PEM), and to investigate safety and efficacy in Japanese patients (pts) with advanced/recurrent NSCLC. Methods: Eligible pts had histologically/cytologically confirmed stage IIIB/IV or recurrent NSCLC (any histology) after failure of first-line chemotherapy. Pts received PEM 500 mg/m 2 iv on day 1 followed by N twice daily (bid) po on days 2–21 every 21 days using a standard 3+3 design. N was started at 100 mg bid and escalated to 200 mg bid in 50 mg bid intervals. Pts received ≥4 cycles of combination therapy with an option of continuing with single-agent N until disease progression or undue adverse events (AEs). Primary endpoints were MTD, defined as the highest dose at which incidence of dose-limiting toxicities (DLTs) was &lt;33.3%, and safety. DLTs were defined as grade 3 non-hematologic or grade 4 hematologic AEs. Secondary endpoints included objective tumor response and pharmacokinetics (PKs). Results: 18 pts (14 male) were treated: 3 at N 100 mg bid, 6 at N 150 mg bid, and 9 at N 200 mg bid. DLTs were observed in 0/3, 1/6, and 2/9 pts in each cohort, respectively; 2 of these pts had liver enzyme elevations. The MTD for N (plus PEM) was 200 mg bid. The most common drug-related AEs were increased GGT, increased AST, decreased appetite, and diarrhea. Grade 3 AEs included neutropenia (22.2%), increased AST, increased ALT, and lymphopenia (each 11.1%); no pts experienced grade 4/5 AEs. Two pts (11.1%) achieved a partial response and 12 (66.7%) had stable disease. At the MTD, N exposure after PEM administration was similar to that seen with N monotherapy in a previous Japanese study. Co-administration of N did not affect the PKs of PEM. Conclusions: The combination of N and standard-dose PEM had a manageable safety profile and showed promising signs of efficacy in previously treated Japanese pts with advanced/recurrent NSCLC. As in Caucasian pts, the MTD of N was 200 mg bid. Clinical trial information: NCT00979576.
Survival outcomes in patients with good risk acute myeloid leukemia: A single-center retrospective review.
Authors: Kathryn Bower, Sijin Wen, Aaron Cumpston, Nilay Arvind Shah
Journal: Journal of Clinical Oncology (2019)

e18519 Background: Cytogenetics and gene mutations play a significant role in determining necessity of allogeneic transplant in patients with AML. Core binding cytogenetic factors (CBF) such as t(8;21), inv 16, and t(16;16) as well as molecular mutations in nucleophosmin-1 (NPM1) and bi-allelic CCAAT/enhancer binding protein alpha (CEBPA) mutations in cytogenetically normal patients have conferred improved relapse-free survival (RFS) and overall survival (OS) rates. We report outcomes of these “good-risk” patients in an Appalachian population, to evaluate differences from previous reports. Methods: A total of 79 patients with AML diagnosed between July 2007 and July 2017 at West Virginia University (WVU) who qualified for good-risk disease per ELN 2017 criteria were retrospectively analyzed for RFS and OS. Eighteen of these patients were excluded from our final analysis: 10 for primary refractory disease and 8 for proceeding to transplant in first remission. Results: A total of 61 patients were included in our analysis, with a median age of 56 (range 11-81), 32 females, and 29 males. Good-risk features included 29 patients with NPM1, no patients with CEBPA, 19 with inv 16, 9 with t(8;21), and 1 with t(16;16). All patients received cytarabine and an anthracycline induction chemotherapy, and a median of 4 cycles (range 1 -4) of high-dose cytarabine consolidation chemotherapy. The RFS and OS at 4 years was 36% and 50%, respectively. There were no occurrences of treatment-related mortality among the patients. Among the 22 patients relapsing, 12 (55%) were able to achieve a second remission and received allogeneic transplant. Conclusions: Our outcomes appear somewhat lower than previous reports, but continuing to highlight the ability to achieve long-term remissions in this subset of patients, without the need for allogeneic transplant. Continued efforts should focus on improving outcomes in these patients, to further prevent relapses.
ICD should reflect what it’s like to live with mental illness, study concludes
Authors: Jacqui Wise
Journal: BMJ (2019)

Mental health patients want diagnostic descriptions in the World Health Organisation’s international classification of diseases (ICD) to better reflect their lived experience. This was the key finding of a study published in Lancet Psychiatry that systematically sought patients’ views on the major diagnostic guideline.1

The ICD includes 55 000 unique codes for injuries, diseases, and causes of death and is highly influential on policy and the provision of services.

The researchers, in collaboration with WHO, looked at the chapter on mental, behavioural, and neurodevelopmental disorders in the latest revision (ICD-11), which will come into effect in …
Evaluation of PQ500, a 500-plasma protein blood panel in NSCLC subjects using high-throughput MRM mass spectrometry.
Authors: Nicholas Dupuis, Sebastian Muller, Tobias Treiber, Claudia Escher
Journal: Journal of Clinical Oncology (2019)

110 Background: Monitoring of circulating proteins in cancer subjects can provide insight into the host response to the tumor. Recent studies have demonstrated the utility of circulating proteins for early detection, differential diagnosis, and predicting response to therapy. Although the utility is clear, standardization of measurement methods across a large number of proteins from plasma has remained challenging. Here, we evaluate the detection of proteins from a &gt; 500-protein plasma panel assembled from stable-isotope standard (SIS) peptides and measured in a high-throughput MRM workflow. Methods: Plasma samples from subjects with Stage III-IV non-small cell lung cancer (n = 15), Stage IV pancreatic cancer (n = 6) and healthy donors (n = 15) were prepared for analysis. Prior to analysis, a panel of SIS peptides covering 582 plasma proteins (804 peptides), was spiked into each sample enabling absolute quantification of detectable peptide species. All samples were analyzed using a capillary flow liquid chromatography (5 µl/min) with a one-hour gradient coupled to a Thermo Scientific TSQ Altis triple quadrupole mass spectrometer. Protein data was extracted and quantified for statistical analysis using SpectroDive (Biognosys). Results: Across all samples, 607 peptides representing 411 proteins were quantified at least once, with an average of 300 proteins quantified per sample. From triplicate analyses, the median CV across all proteins was 5.3%. Statistical testing identified 42 significantly regulated proteins (36 up- and 6 down-regulated; q-value &gt; 0.05 and log2 fold change &gt; 0.58). Key species that were strongly dysregulated in cancer samples included: c-reactive protein (CRP), serum amyloid a (SAA1/SAA2), complement C9, S100A8/S100A9, and leucine rich glycoprotein 1 (LRG1). Conclusions: PQ500 is a comprehensive blood-focused multiplexed biomarker panel that enables absolute quantification of plasma proteins. The dysregulated proteins identified in this study highlight that the PQ500 can monitor the host immune response through multiple pathways. Accurate monitoring these proteins offers the possibility to define molecular based markers with clinical and diagnostic utility.
Building Trust Through Punk Rock
Authors: Christopher Moriates, Mehraj Baig
Journal: Annals of Internal Medicine (2019)

On Being a Doctor16 July 2019Building Trust Through Punk RockChristopher Moriates, MD and Mehraj Baig, DOChristopher Moriates, MDDell Medical School, The University of Texas at Austin, Austin, Texas (C.M., M.B.)Search for more papers by this author and Mehraj Baig, DODell Medical School, The University of Texas at Austin, Austin, Texas (C.M., M.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-0396 Audio Reading - “Building Trust Through Punk Rock” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Building Trust Through Punk Rock” by Christopher Moriates, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail We received handoff on a patient that ran something like this: She is refusing care. She is demanding opioids. She is an injection drug user. She is difficult to deal with, and, sadly, she is likely going to die soon.She was a 30-year-old active heroin user with recently diagnosed aggressive T-cell acute lymphoblastic leukemia.When we walked into her unlit room the next morning, it looked as though at least one thing we heard was true—she definitely seemed like she was going to die. Thin. Emaciated. Her face gaunt with temporal wasting and sunken eyes. Tattoos covered her body, ... Author, Article, and Disclosure InformationAffiliations: Dell Medical School, The University of Texas at Austin, Austin, Texas (C.M., M.B.)Corresponding Author: Christopher Moriates, MD, Dell Medical School, The University of Texas at Austin, 1501 Red River Street, Health Learning Building, Room 2.323, Austin, TX 78712; e-mail, [email protected]utexas.edu. PreviousarticleNextarticle Advertisement Audio Reading - “Building Trust Through Punk Rock” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Building Trust Through Punk Rock” by Christopher Moriates, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byExamining the Dimensionality of Trust in the Inpatient Setting: Exploratory and Confirmatory Factor Analysis 16 July 2019Volume 171, Issue 2Page: 139-140KeywordsChemotherapyDrugsHealth careLungsPleural effusionPrecursor cellsRibsRiversThoraxUltrasound imaging ePublished: 16 July 2019 Issue Published: 16 July 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 454: Protein Phosphatase Pp2a Regulates Hypertrophic Response Through Hdac2 Dephosphorylation in the Heart
Authors: Hyun-Ki Min, Somy Yoon, Duk-Hwa Kwon, Hyun Kook, Gwang Hyeon Eom
Journal: Circulation Research (2016)

Rationale: Cardiac hypertrophy is an adaptive process to meet the hemodynamic demands from exogenous stresses, and histone deacetylase (HDAC) 2 plays central role in cardiac remodeling. Recently, we have suggested the importance of acetylation of HDAC2; however, specific phosphatase of HDAC2 remains unclear. Objective: We aimed to delineate the phosphatase of HDAC2 in the development of cardiac hypertrophy and to suggest therapeutic implications of those phosphatase in cardiac remodeling. Methods and Results: We performed complex-isolation assay in the heart and found that Hdac2 physically interacted with the Ppp2ca, and Hsp70. Ppp2ca kept Hdac2 unphosphorylated in the absence of hypertrophic stresses. Hypertrophic stresses-induced Hdac2 K75 acetylation, which then allowed Ppp2ca to dissociate from Hdac2, which led to phosphorylate Hdac2. The agonist-induced hypertrophy was significantly attenuated in transgenic mice heart expressing Ppp2ca. Forced expression of phosphorylation mimicking mutant of Hdac2, Hdac2 S394E, successfully overcame to antihypertrophic effects of Ppp2ca, whereas wild type of Hdac2 failed to do so. On the other hand, hypertrophic stresses induced Hsp70, one of the binding partners of Hdac2, which then preferentially bound to phosphorylated Hdac2 rather than to unphosphorylated one. The increase in expression of Hsp70 led to dissociate Ppp2ca from Hdac2. Hsp70 significantly increased phosphorylation of Hdac2 by protection from Ppp2ca. Cardiac hypertrophy was observed in the TgHsp70 mice and hyper-phosphorylation of Hdac2 was also detected. Double transgenic mice expressing both Ppp2ca and Hsp70 showed cardiac hypertrophy, which implicated that Hsp70 functioned as an endogenous regulator of Ppp2ca in the heart. TgHsp70-induced cardiac hypertrophy was significantly inhibited by adeno-Ppp2ca in a dose response fashion. Conclusion: Taken together, HDAC2 forms a complex with PP2A in the absence of hypertrophic stresses and remains inactivated. HDAC2 acetylation results in dissociation of PP2A and thereby phosphorylation, which is maintained by the association with HSP70 during development of cardiac hypertrophy. Hyun-Ki Min and Somy Yoon contributed equally to this work.