tbuckley/cabot-search huggingface dataset:
Brodalumab in patients who had inadequate response to ustekinumab
Authors: R.G. Langley, A.W. Armstrongi, M.G. Lebwohl, A. Blauvelt, S. Hsu, S. Tyring, S. Rastogi, R. Pillai, R. Israel
Journal: British Journal of Dermatology (2019)

Psoriasis is a chronic condition that causes red, scaly patches on the surface of the skin. Treatments may include topical (applied to the skin) creams and oral and injectable medications. Psoriasis can be caused by an autoimmune reaction in which the body's own immune system attacks healthy cells and tissues. To treat moderate‐to‐severe psoriasis, doctors sometimes use specialized medicines called antibodies, which block different parts of the autoimmune reaction that can lead to psoriasis. Although these antibody treatments can be very effective, they do not work in every patient. This study looked at data from two clinical studies of patients with moderate‐to‐severe psoriasis. In each study, patients were initially given one of two antibody treatments: ustekinumab or brodalumab. Some patients initially given ustekinumab or brodalumab did not have adequate skin clearance at week 16; these patients either started taking brodalumab (if they were initially given ustekinumab) or continued taking brodalumab (if they were initially given brodalumab) through to week 52. Patients who experienced inadequate response to their initial treatment after week 16 continued to receive their initial treatment until week 52. At week 52, patients who switched to brodalumab after an inadequate response to ustekinumab showed improvement in skin clearance. Skin clearance in patients who continued taking ustekinumab following inadequate response after week 16 was not as complete as skin clearance in those who switched to brodalumab after an inadequate response at week 16. Additionally, side effects were similar between patients who switched to brodalumab and those who remained on ustekinumab. The results of this study suggest brodalumab may be a successful treatment in patients with moderate‐to‐severe psoriasis who do not experience adequate skin clearance with other psoriasis treatments.
The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogue Cessation Among Asian Chronic Hepatitis B Patients: Friend or Foe?
Authors: Chia‐Chi Wang, Jia‐Horng Kao
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article by Liu et al.1 They found that hepatitis B surface antigen (HBsAg) level <100 IU/mL at end of treatment (EOT) seemed to be a useful marker to decide when to stop nucleos(t)ide analogue (NA) therapy because it was associated with a low incidence (20%‐30%) of virological or clinical relapse and high probability (20%‐60%) of HBsAg loss for chronic hepatitis B (CHB) patients. Although this systemic review provided a practical and attainable cessation criterion instead of infinite NA treatment, several issues deserve discussion and further investigations. First, "when to stop NA treatment" is a clinical dilemma because of the low rate of HBsAg seroclearance under NA treatment, especially in chronic hepatitis B (CHB) patients with genotype B and C.2 Although long‐term NA treatment can reverse fibrosis progression and even cirrhosis,3 it carries the concerns of drug compliance, safety issues, and economic burden. Cessation of NA treatment before HBsAg loss will expose patients to risk of clinical relapse, decompensation, or even mortality. Second, the systemic review suggested that HBsAg level <100 IU/mL at EOT seemed to be an optimal cut‐off value to discontinue NA treatment, which is consistent with the findings of our previous prospective study.4 In our study population, 13.6% achieved sustained viral response (SVR), which was defined as undetectable hepatitis B virus DNA levels at off‐therapy 12 months. No clinical relapse was observed in all of them during a median off‐therapy follow‐up period of 24.8 months. Using multivariate analysis, EOT HBsAg level was the only factor associated with SVR. Furthermore, cumulative incidence of SVR was significantly higher in patients with EOT quantitative (q)HBsAg <100 IU/mL compared with those with EOT qHBsAg 100‐1,000 or >1000 IU/mL, suggesting that serum qHBsAg <100 IU/mL can serve as a surrogate endpoint of the existing treatment guideline. Unfortunately, our prospective study was not included in the systematic review by Liu et al.; otherwise, their results will be more convincing. Finally, patients with rebound hepatitis complicated by liver failure or even death were occasionally observed in Asian CHB patients after cessation of NA treatment. It is thus imperative to remind practicing physicians of such catastrophic complications. Accordingly, if this systemic review could provide the incidence of off‐therapy liver decompensation or death in patients with EOT qHBsAg <100 IU/mL, we could understand more about the risk and benefit of discontinuing NA treatment on the basis of this cut‐off value.
Prognostic restaging at the time of second-line therapy in patients with AL amyloidosis
Authors: Yi L. Hwa, Morie A. Gertz, Shaji K. Kumar, Martha Q. Lacy, Francis K. Buadi, David Dingli, Prashant Kapoor, Steve R. Zeldenrust, Nelson Leung, Susanne R. Hayman, Wilson I. Gonsalves, Taxiarchis V. Kourelis, Rahma Warsame, Ronald S. Go, Eli Muchtar, Miriam A. Hobbs, Amie L. Fonder, Stephen Russell, Robert A. Kyle, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Leukemia (2019)
Association between Patient Profile and Outcomes of Best Responders to Carfilzomib: A Post-Hoc Sub-Group Analysis of Aspire and Endeavor
Authors: Katja Weisel, Maria-Victoria Mateos, Francesca Marianatal Gay, Michel Delforge, Gordon Cook, Lucy DeCosta, Renaud Desgraz, Zsolt Szabo, Philippe Moreau
Journal: Blood (2018)
NHS long term plan is just one part of the picture
Authors: Ryan C Swiers
Journal: BMJ (2019)

In recognising that the NHS 10 year plan “seeks to contribute what is within its compass,” Chapman and Middleton explain why any plan constrained by organisational boundaries cannot be a comprehensive plan for “health, wellbeing, equality, and care.”1

Although the plan is limited in tackling upstream determinants,2 much of the secondary prevention proposed, such as in-hospital support for smokers, should be welcomed. This comes as shrinking …
Abstract 16028: Differential Effects of Antiplatelet Therapy on Toll-Like Receptor (TLR)-Mediated Platelet Activation
Authors: Kathryn Hally, Scott Harding, Anne La Flamme, Peter Larsen
Journal: Circulation (2017)

Introduction: Platelet activation in the setting of coronary artery disease (CAD) is pathological and antiplatelet therapy is a mainstay of therapeutic intervention to limit this. Platelets express...
Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma
Authors: Peter A. Forsberg, Adriana C. Rossi, Angelique Boyer, Linda Tegnestam, Roger N. Pearse, Arthur Perry, Karen A. Pekle, David Jayabalan, Scott Ely, Leora Boussi, Daniel W. Sherbenou, Colt Williams, John N. Allan, Morton Coleman, Ruben Niesvizky, Tomer M. Mark
Journal: American Journal of Hematology (2019)

Carfilzomib and dexamethasone (Kd) has significant activity in relapsed and refractory multiple myeloma. Kd has not previously been evaluated in newly diagnosed multiple myeloma (NDMM). We report a single-arm phase 2 study of 72 patients with NDMM to evaluate the efficacy and tolerability of Kd induction. Carfilzomib was administered in two dosing cohorts with dosing of 20/45 mg/m2 in the first 25 patients and 20/56 mg/m2 in the subsequent 47 patients. Carfilzomib was administered on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle, dexamethasone 20 mg was administered orally on days 1, 2, 8, 9, 15, 16, 22 and 23. Treatment was continued to maximum response, progression of disease, or regimen intolerability. Endpoints included overall response rate (ORR), regimen toxicity and impact of carfilzomib on CD34+ stem cell collection yield. Sixty-five pts achieved at least a partial response (PR) for an ORR of 90%. The maximum response achieved was complete response or better in 5 (7%), very good partial response (VGPR) in 42 (58%), PR in 18 (25%) and stable disease in 7 pts (10%). Toxicities were predominantly low grade with 547 grade 1/2 adverse events and 44 grade ≥3 events. The rate of grade ≥3 cardiovascular adverse events was 11.1% with eight observed events. The activity of Kd described represents the highest rate of overall response and ≥VGPR for any 2-agent combination in NDMM reported to date. Kd demonstrated a safety profile consistent with previously reported carfilzomib studies.
Study cites austerity as factor in stalling of life expectancy in rich countries
Authors: Bryan Christie
Journal: BMJ (2019)

Progress made through the 20th century in adding years to life is now stalling and, in some countries, going into reverse, finds research carried out by Scotland’s Public Health Observatory. It looked at trends in life expectancy across 24 high income countries over periods of five years from 1992 to 2016.1 The stalling was evident in several countries across western Europe and North America.

The research report cites austerity measures introduced in many of the world’s richest countries after the 2008 economic recession as one of the possible causes of a slowing improvement in life …
Abstract 11727: Long-term Fenofibrate Therapy Increases Fibroblast Growth Factor 21 and Retinol-binding Protein 4 in Subjects With Type 2 Diabetes
Authors: Kwok Leung Ong, Kerry-Anne Rye, Rachel O'Connell, Alicia J Jenkins, Chris Brown, Aimin Xu, David R Sullivan, Philip J Barter, Anthony C Keech
Journal: Circulation (2012)

Introduction: Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-alpha agonist which showed beneficial effects on lipid profile and total cardiovascular risk in patients with type 2...
Haploidentical Transplantation with Regulatory and Conventional T Cells Improves Outcome of Patients Affected By Acute Myeloid Leukemia with Complex Karyotype and/or Monosomy 7/Del(7q)
Authors: Antonio Pierini, Andrea Marra, Alessandra Carotti, Loredana Ruggeri, Adelmo Terenzi, Franca Falzetti, Sara Piccinelli, Valeria Cardinali, Antonella Mancusi, Cecilia Tardioli, Rita Felicini, Amico Lucia, Genni Casarola, Sara Tricarico, Samanta Bonato, Matteo Paradiso, Mario Griselli, Barbara Crescenzi, Roberta La Starza, Cristina Mecucci, Brunangelo Falini, Massimo Fabrizio Martelli, Maria Paola Martelli, Andrea Velardi
Journal: Blood (2018)
Combination of Enasidenib and Venetoclax Shows Superior Anti-Leukemic Activity Against IDH2 Mutated AML in Patient-Derived Xenograft Models
Authors: Severine Cathelin, David Sharon, Amit Subedi, Dan Cojocari, Darren C. Phillips, Joel D. Leverson, Kyle MacBeth, Brandon Nicolay, Rohini Narayanaswamy, Sebastien Ronseaux, Guowen Liu, Steven M Chan
Journal: Blood (2018)
Abstract 14045: Reperfusion Therapy With Recombinant Human Relaxin (Serelaxin) Attenuates Myocardial Inflammasome Formation and Ischemic Injury in Mice via eNOS-dependent Mechanism
Authors: Juan Valle Raleigh, Adolfo G Mauro, Carlo Marchetti, Jun He, Stefano Toldo, Antonio Abbate, Fadi N Salloum
Journal: Circulation (2015)

Background: The preconditioning-like infarct-sparing and anti-inflammatory effects of the peptide hormone relaxin following ischemic injury have been studied in the heart. Whether reperfusion therapy with recombinant human relaxin (serelaxin, SRLX) reduces myocardial infarct size and attenuates NLRP3 inflammasome formation/caspase-1 activation and subsequent loss of functional myocardium following ischemia/reperfusion (I/R) injury is unknown. Methods and Results: After baseline echocardiography, adult male C57BL (WT) or eNOS knockout (KO) mice underwent myocardial infarction (MI) by coronary artery ligation for 30 minutes followed by 24 h reperfusion. Mice were treated with either SRLX (10 μg/Kg; sc) or saline 5 minutes before reperfusion. SRLX improved survival at 24 h post MI in WT mice (79%) as compared with controls (42%), whereas there was no difference in survival between SRLX- and saline-treated eNOS KO mice. Moreover, SRLX significantly reduced infarct size, measured with TTC staining, and preserved LV fractional shortening (FS) and end-systolic diameter (LVESD) in WT mice as compared with controls. Interestingly, cardiac caspase-1 activity was markedly reduced in SRLX-treated mice compared with controls at 24 h post MI (Figure A-D). Genetic deletion of eNOS abolished the infarct-sparing and anti-inflammatory effects of SRLX as well as functional preservation. SRLX plasma levels were assessed 5 min. after treatment using ELISA and the results demonstrate therapeutic levels comparable to plasma relaxin during the first trimester of pregnancy (Figure E). Conclusion: Reperfusion therapy with SRLX attenuates myocardial I/R injury and NLRP3 inflammasome formation via eNOS-dependent mechanism. We propose that SRLX possesses an anti-inflammatory effect preventing caspase-1 activation and inflammatory complications following MI, which may shed some light on the mechanism behind the survival benefit observed in the RELAX-AHF trial.
Methodology Flaws and Implications of a Complementary Medicine Study—In Reply
Authors: Skyler B. Johnson, Cary P. Gross, James B. Yu
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
Intravascular Mesenchymal Stromal/Stem Cell Therapy Product Diversification: Time for New Clinical Guidelines
Authors: Guido Moll, James A. Ankrum, Julian Kamhieh-Milz, Karen Bieback, Olle Ringdén, Hans-Dieter Volk, Sven Geissler, Petra Reinke
Journal: Trends in Molecular Medicine (2019)

Intravascular infusion is the most popular route for therapeutic multipotent mesenchymal stromal/stem cell (MSC) delivery in hundreds of clinical trials. Meta-analysis has demonstrated that bone marrow MSC infusion is safe. It is not clear if this also applies to diverse new cell products derived from other sources, such as adipose and perinatal tissues. Different MSC products display varying levels of highly procoagulant tissue factor (TF) and may adversely trigger the instant blood-mediated inflammatory reaction (IBMIR). Suitable strategies for assessing and controlling hemocompatibility and optimized cell delivery are crucial for the development of safer and more effective MSC therapies.
High-serum blood sugar level significantly enhances oxaliplatin resistance in stage III colorectal cancer patients.
Authors: Jaw-Yuan Wang
Journal: Journal of Clinical Oncology (2019)

532 Background: FOLFOX4 chemotherapy is one of the most widely used adjuvant therapies in patients with stage III colon cancer after surgical resection. However, chemotherapy resistance is associated with a poor prognosis. The prognostic impact of high blood sugar levels on oxaliplatin resistance in CRC patients is an unexplored topic. Methods: A total of 157 patients with stage III CRC were classified according to their serum blood sugar level (≥ 126 or &lt; 126 mg/dL). Clinicopathological features and clinical outcomes (oxaliplatin resistance) of the two groups were analyzed. Results: Through multivariate analysis, both disease-free and overall survival of CRC patients was found to be significantly associated with serum blood glucose levels (both P &lt; 0.05) but not DM history. In vitro cell proliferation assay was performed through D-(+)-glucose administration. After metformin administration, enhanced proliferation of CRC cells with D-(+)-glucose administration could be reversed and oxaliplatin sensitivity considerably increased ( P &lt; 0.05). Furthermore, phosphorylation of two glycolysis-related target proteins, SMAD3 and MYC, notably increased with high glucose concentration. Conclusions: In summary, hyperglycemia could affect clinical outcomes in CRC patients receiving adjuvant chemotherapy, with the underlying oxaliplatin resistance mechanism possibly associated with increasing phosphorylation of SMAD3 and MYC and upregulation of G9A expression.
Abstract P5-04-19: Withdrawn
Authors: S Ghassemifar, G Finn, H Zhang, J Richardson, G Kuesters, S Santillana, M Pipas
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Ghassemifar S, Finn G, Zhang H, Richardson J, Kuesters G, Santillana S, Pipas M. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-04-19.
The need for improvement in the management of fatigue, depression and pain in pancreatic cancer.
Authors: Amy Westermann, Lynn McCormick Matrisian, Lola Rahib
Journal: Journal of Clinical Oncology (2019)

429 Background: Pancreatic cancer (PC) and its treatment(s) results in symptom and side effect burden and can impact patient’s overall quality of life (QOL). Methods: Patient reported information on management of side effects and symptoms were collected using PanCAN’s Patient Registry (01/2016 – 07/2018). Results: Patient reported information on side effects, pain and depression is detailed in the table. Side effects: 94% reported fatigue and 8% reported taking anti-fatigue medication. 72% reported nausea or vomiting during treatment and 83% reported taking anti-nausea medication. Pain: Of the 90% of patients who reported pain related to PC, 27% did not take pain medication, 47% visited the ER and 32% were hospitalized due to pain. Depression: Of the 83% of users reported feeling depressed during PC, 46% were diagnosed with depression, 37% prescribed anti-depressant, and 48% did not see a therapist. Conclusions: Nausea was reported as most managed. Fatigue, pain and depression were generally unmanaged. ER visits and hospitalizations due to pain were frequently reported. An improvement in the management of these side effects and symptoms is needed as it can affect patient’s ability to tolerate treatment, improve overall QOL, and may lower overall healthcare costs. [Table: see text]
The correlation between DPYD*9A (c.85T &gt; C) genotype and dihydropyrimidine dehydrogenase deficiency phenotype in patients with gastrointestinal malignancies treated with fluoropyrimidines: Updated analysis.
Authors: Anu Singh Maharjan, Gwendolyn A. McMillin, Girijesh K. Patel, Saad Awan, William R. Taylor, Sachin Pai, Arthur E. Frankel, Cindy Nelson, Bin Wang, Peter Joel Hosein, Ajay Singh, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2019)

544 Background: The correlation between DPYD*9A (c.85T &gt; C) genotype and dihydropyrimidine dehydrogenase (DPD) deficiency phenotype is controversial. In our cohort of 28 patients with gastrointestinal malignancies (GI) treated with fluoropyrimidines, DPYD*9A was the most commonly diagnosed variant (46%) and there was a noticeable genotype-phenotype correlation (Khushman et al). In this updated analysis, a larger cohort of a mixed racial background was genotyped for DPYD*9A variant to confirm the incidence and genotype-phenotype correlation. Methods: Between 2011 and 2018, in addition to genotyping for high risk DPYD variants (DPYD*2A, DPYD*13 and DPYD*9B), genotyping for DPYD*9A variant was performed on 113 patients. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v 5.0). Results: DPYD variants were identified in 61 patients. DPYD*2A was identified in 3 patients and DPYD*9B was identified in 2 patients (one patient had double heterozygous *9A and *9B). Heterozygous DPYD*9A was identified in 46 patients (41%) and homozygous DPYD*9A was identified in 11 patients (10%). Among patients with DPYD*9A variant, Caucasians represented 51% and African Americans represented 46%. 27 patients (47%) were females. Grade 3-4 toxicities were experienced in 26 patients with mutant DPYD*9A (3 patients had homozygous DPYD*9A) and in 20 patients with no identified DPYD mutation (P = 0.7035). In patients who received full dose fluoropyrimidines (N = 85), grade 3-4 toxicities were experienced in 22 patients with mutant DPYD*9A (2 patients had homozygous DPYD*9A) and in 17 patients with no identified DPYD mutation (P = 0.8275). Conclusions: In our updated analysis, DPYD*9A variant was the most commonly diagnosed variant. The correlation between DPYD*9A variant and DPD clinical phenotype was not reproduced. The noticeable correlation that we previously reported is likely due to small sample size and patients’ selection and testing bias.
Material Need Insecurity and Its Concurrent Barriers to Diabetes Management Among Low-Income Latino Adults Receiving Medical Care
Authors: Briga Mullin, Brett S. Cervantes, John Billimek
Journal: Diabetes Care (2019)

Material need insecurity—limited or uncertain ability to access or pay for basic needs such as food, housing, or energy (1)—is reported by 18.9% of older adults with chronic health conditions (2). The association between material need insecurity and health is likely bidirectional (1,3). The sacrifices and trade-offs made to meet material needs lead to exacerbation of chronic conditions, and poor health creates circumstances that precipitate insecurity (3).

Material need insecure (MNI) individuals receiving treatment for diabetes tend to be no less likely than material need secure (MNS) individuals to receive recommended health care services (4). However, upstream challenges leading to insecurities (such as unstable employment, family, and housing situations) likely undermine patients’ ability to manage health conditions for reasons that extend beyond access to medical services (1). This problem is especially relevant in Latino patients who face higher rates of material deprivation and worse diabetes outcomes than non-Latino individuals, even after accounting for access to care (5). As efforts to screen for and respond to material need insecurity in clinical settings expand, it is important for providers to consider correlates of insecurity that extend beyond a patient’s lack of resources.

The current study uses secondary analysis of cross-sectional observational data from low-income Latino …
Gamaglobulin infusion in patients with severe atopic dermatitis
Authors: Marina Medeiros Caputo, Pamela Pittelkow Silva, Pâmela Pittelkow, Patricia Guerzet Ayres Bastos, Patrícia Guerzet, Laís Gomes Japiassú, Laís Japiassú, Marcia C. Mallozi, Carolina S. Aranda, Beatriz Tavares Costa-Carvalho, Juliana Themudo Lessa Mazzucchelli, Dirceu Sole
Journal: Journal of Allergy and Clinical Immunology (2019)