tbuckley/cabot-search huggingface dataset:
A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer
Authors: Yen-Shen Lu, Keun Seok Lee, Tsu-Yi Chao, Ling-Ming Tseng, Imjai Chitapanarux, Shin-Cheh Chen, Chien-Ting Liu, Joohyuk Sohn, Jee Hyun Kim, Yuan-Ching Chang, Youngsen Yang, Kanjana Shotelersuk, Kyung Hae Jung, Roberta Valenti, Cassandra Slader, Melissa Gao, Yeon Hee Park
Journal: Clinical Cancer Research (2020)

Abstract Purpose: This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor–positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC). Patients and Methods: This study enrolled premenopausal women with HR+, HER2− ABC. Patients received tamoxifen (20 mg once daily) and goserelin acetate (3.6 mg every 28 days) with either alpelisib (350 mg once daily; n = 16) or buparlisib (100 mg once daily; n = 13) in 28-day cycles until MTD was observed. Results: The criteria for MTD were not met for both alpelisib and buparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. Both combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group. Conclusions: The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HR+, HER2− ABC. See related commentary by Clark et al., p. 371
Ibrutinib for Chronic Lymphocytic Leukemia with <i>TP53</i> Alterations
Authors: Inhye E. Ahn, Xin Tian, Adrian Wiestner
Journal: New England Journal of Medicine (2020)

Ibrutinib in CLL with TP53 Alterations Patients with chronic lymphocytic leukemia with chromosome 17 abnormalities have a worse prognosis than those without such alterations. In this phase 2 study,...
Exposure to bisphenols and asthma morbidity among low-income urban children with asthma
Authors: Lesliam Quirós-Alcalá, Nadia N. Hansel, Meredith McCormack, Antonia M. Calafat, Xiaoyun Ye, Roger D. Peng, Elizabeth C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2020)
Nivolumab-Induced Periaortitis Demonstrated by FDG PET/CT
Authors: Masatoshi Hotta, Go Naka, Ryogo Minamimoto, Yuichiro Takeda, Masayuki Hojo
Journal: Clinical Nuclear Medicine (2020)

Abstract A 66-year-old man with a history of non–small cell lung cancer treated with nivolumab underwent contrast-enhanced CT and FDG PET/CT. No recurrence was demonstrated; however, soft-tissue thickening that showed delayed contrast enhancement and FDG uptake was detected around an abdominal aortic aneurysm. After discontinuation of nivolumab, the periaortic lesion disappeared within 2 months, indicating nivolumab-induced periaortitis. Immune checkpoint inhibitors such as nivolumab can cause vasculitis and periaortitis, a potentially fatal condition, as immune-related adverse events. The underlying aortic aneurysm may have contributed to genesis of periaortitis. FDG PET/CT can be useful for detecting periaortitis and excluding other forms of vasculitis.
Trusting the process and myself
Authors: Emily Potter
Journal: British Journal of Sports Medicine (2020)

I went to my first Canada Basketball National Team camp when I was 16 years old, which is an opportunity that I never thought would present itself. When I was in grade 9, I tried out for the provincial team (Basketball Manitoba), and the director sent my name to Canada Basketball. I hopped on a plane by myself, for the first time, with no idea what to expect. It was definitely a little overwhelming; I was out of my comfort zone, surrounded by people I didn’t know. I just tried to be a sponge. I got cut from the team that first year, but the experience motivated me and opened my eyes to 1 day wearing the Canada jersey as an Olympian. I didn’t think it was a possibility, and it never crossed my mind until I went to that first identification camp (figure 1).



Figure 1 
Emily Potter.



We had lots of great off-court sessions about nutrition, recovery and mental health at that camp. It was the first time I realised that I needed to do more besides just play basketball when I got home. I went back to Winnipeg and was connected through Basketball Manitoba and Canada Basketball to a bunch of resources through the Centre for Sport Performance (eg, nutrition …
ABC score: a new risk score that accurately predicts mortality in acute upper and lower gastrointestinal bleeding: an international multicentre study
Authors: Stig Borbjerg Laursen, Kathryn Oakland, Loren Laine, Vered Bieber, Riccardo Marmo, Eduardo Redondo-Cerezo, Harry R Dalton, Jeffrey Ngu, Michael Schultz, Marco Soncini, Ian Gralnek, Vipul Jairath, Iain A Murray, Adrian J Stanley
Journal: Gut (2020)

Existing scores are not accurate at predicting mortality in upper (UGIB) and lower (LGIB) gastrointestinal bleeding. We aimed to develop and validate a new pre-endoscopy score for predicting mortality in both UGIB and LGIB.International cohort study. Patients presenting to hospital with UGIB at six international centres were used to develop a risk score for predicting mortality using regression analyses. The score's performance in UGIB and LGIB was externally validated and compared with existing scores using four international datasets. We calculated areas under receiver operating characteristics curves (AUROCs), sensitivities, specificities and outcome among patients classified as low risk and high risk.We included 3012 UGIB patients in the development cohort, and 4019 UGIB and 2336 LGIB patients in the validation cohorts. Age, Blood tests and Comorbidities (ABC) score was closer associated with mortality in UGIB and LGIB (AUROCs: 0.81-84) than existing scores (AUROCs: 0.65-0.75; p≤0.02). In UGIB, patients with low ABC score (≤3), medium ABC score (4-7) and high ABC score (≥8) had 30-day mortality rates of 1.0%, 7.0% and 25%, respectively. Patients classified low risk using ABC score had lower mortality than those classified low risk with AIMS65 (threshold ≤1) (1.0 vs 4.5%; p<0.001). In LGIB, patients with low, medium and high ABC scores had in-hospital mortality rates of 0.6%, 6.3% and 18%, respectively.In contrast to previous scores, ABC score has good performance for predicting mortality in both UGIB and LGIB, allowing early identification and targeted management of patients at high or low risk of death.
Transradial Versus Transfemoral Approach for Chronic Total Occlusion of Coronary Arteries: Feasibility and Predictors of Success
Authors: Andres Iñiguez Romo, Antonio Alejandro De Miguel Castro, Guillermo Bastos Fernández, José Antonio Baz Alonso, Alberto Ortiz Saez, Ivan Tomas Gómez Blázquez, Victor Alfonso Jiménez Díaz
Journal: Journal of the American College of Cardiology (2011)
THU0636-HPR REMS TECHNOLOGY APPLIED TO RHEUMATIC DISEASE
Authors: M. D. Tomai Pitinca, C. Caffarelli, S. Gonnelli
Journal: Annals of the Rheumatic Diseases (2020)

Background: Many Rheumatic disease such as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, dermatomyositis/polymyositis and vasculitis are characterised by osteoporosis and fragility fractures. Inflammatory cytokines, steroid treatment, immobilization and reduced physical activity due to joint pain and muscle weakness are considered the major risk factors for the development of low bone mineral density in these diseases.Many evidences have highlighted the role of pro-inflammatory cytokines (TNF-a, IL-1, IL-6, IL-7, IL17) in bone homeostasis regulation.Chronic inflammation is often characterized by an imbalance between bone formation and resorption, with a clear prevalence of osteoclastogenesis which is a strong determinant in rheumatic diseases bone loss. Objectives: The aim of this study is to evaluate the REMS (Radiofrequency Echographic Multi-Spectrometry) technology in rheumatologic patients, compared to DEXA currently recognised as the gold standard for the evaluation of bone mineral density. Methods: Twenty female patients (mean age 60.6 ±14.41 years) with different rheumatologic diseases were considered. Each patient underwent a lumbar spine and hip examination performed by DEXA and REMS technology. In particular, after a quality control to assess that both the exams were performed correctly, 18 lumbar and 20 femoral exams (DEXA vs REMS) were compared. Results: As Expected the exams performed show a good diagnostic match (&gt;60%LS and &gt;85% FEMORE). The tests that didn’t show diagnostic concordance were those affected by arthrosis processes (greater on the Spine). The REMS T-score values were lower than those obtained with the DXA method. Conclusion: These results show how REMS technology can discriminate patients with osteoporosis as much as DEXA technology. The REMS technology can be a diagnostic option especially in patients with rheumatologic diseases that cause alterations in the spine reducing the diagnostic sensitivity of DXA technology. Disclosure of Interests: None declared
Should We Be for ASCT?
Authors: Barry H. Trachtenberg, Rammurti Kamble, Arvind Bhimaraj, Jerry D. Estep
Journal: JACC Heart Failure (2020)

We were pleased to see the paper by Barrett et al. ([1][1]) regarding “Outcomes in Patients with Cardiac Amyloidosis Undergoing Heart Transplantation”. Among 31 patients who underwent orthotopic heart transplantation (OHT), 13 patients underwent transplantations for light-chain amyloidosis (AL
Apical Sparing Strain Pattern in Danon Disease
Authors: Quan M. Bui, Kimberly N. Hong, Megan Kraushaar, Gary S. Ma, Michela Brambatti, Andrew M. Kahn, Chrystelle Bougault, Kylie Boynton, Luisa Mestroni, Matthew R.G. Taylor, Eric Adler
Journal: JACC. Cardiovascular imaging (2020)
SAT0052 Colombian guidelines for the treatment of hip, knee and hand osteoarthritis
Authors: E Diaz, JL Rueda-Cifuentes, HL Gonzalez-Medina, MA Chalem-Iglesias, FE Rondon-Reyes, JY Forero-Muñoz, GJ Ramirez-Manrique, LO Ramirez-Uribe, LJ Pinto-Molina, RJ Sierra-Salas
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The highest burden of rheumatic disease in Colombia according to the Ministry of Health is due to Osteoarthritis (OA) and Rheumatoid Arthritis (RA). Currently we don´t have guidelines for the treatment of OA in our country. <h3>Objectives</h3> To propose recommendations for treatment (medical and surgical) of hip, knee and hand OA based on both Evidence Based Medicine (EBM) and expert consensus approach. <h3>Methods</h3> A task force of experts in Clinical Epidemiology and in OA research and management was created. The first stage was to assist a two-day course of guideline methodology. The second stage was the selection of treatment modalities and principal clinical questions to be considered. The third stage was a systematic literature review that permitted the ranking of the recommendations from A (based on results of meta-analyses) to E (negative recommendations based on results of meta-analyses). The final stage was recopilation and review of the consensus by an internal/external pair. <h3>Results</h3> Different non-pharmacological and surgical modalities were evaluated. Medical: Acetaminophen, NSAIDS and COXIBS were similar in efficacy to relieve pain (A). Gastrointestinal safety improves with COXIBS rather than the comparators (A). Hialuronate acid, glucosamine sulfate and NSAIDS were similar in efficacy to relieve pain (A-B). Alternative: Yoga and acupuncture lessened pain and improved functional capacity (B-C). Surgery: There is no recommendation for knee and hip artroplasty. <h3>Conclusion</h3> The recommendations of this task force (1) the best evidence is in the treatment of pain; (2) currently there is no evidence for drugs modified disease; (3) certain alternative medicines are useful as coadyuvants and (4) this consensus is the base for new research.
Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis
Authors: Jaekyung Cheon, Hong Jae Chon, Yeonghak Bang, Neung Hwa Park, Jung Woo Shin, Kang Mo Kim, Han Chu Lee, Jooho Lee, Changhoon Yoo, Baek-Yeol Ryoo
Journal: Liver Cancer (2020)

Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed.We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed.Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1-6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8-16.5) months for patients treated with first-line lenvatinib (n = 57). With second- or later-line lenvatinib (n = 17), median PFS and OS were 4.1 (95% CI 3.1-5.1) and 6.4 (95% CI 5.1-7.7) months, respectively. In the Child-Pugh B group (n = 18), median PFS and OS were 2.6 (95% CI 0.6-4.6) and 5.3 (95% CI 2.0-8.5) months, respectively. The most common grade 3-4 toxicities were hyperbilirubinemia (n = 8; 8.7%), AST elevation (n = 6; 6.5%), and diarrhea (n = 5; 5.4%) across all study patients.In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.
Consideration of Adolescent Pain in Responses to the Opioid Crisis
Authors: Marco Battaglia, Patrick D. Quinn, Cornelius B. Groenewald
Journal: JAMA Psychiatry (2020)

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 Psychiatry 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 Psychiatry journal
A novel role of adenomatous polyposis coli (APC) in DNA repair and carcinogenesis
Authors: Satya Narayan, Aruna S. Jaiswal, Ramesh Balusu
Journal: Cancer Research (2005)

1627  Mutations in the adenomatous polyposis coli (APC) gene have been identified in many intestinal and extra-intestinal tumors. At least, in colon, mutations in the APC gene are considered to be one of the earliest events in the cancer development. However, in other cases, mutations in the APC gene have been identified in later stages of cancer development. Although a great deal has been learnt about the role of mutations in APC gene in various cellular functions and cancer development, its role in normal cells, especially when they are challenged with DNA-damaging agents is not known. In the present investigation, we report a novel and previously unsuspected function of APC in DNA repair involving base excision repair (BER) pathway. We identified a proliferating cell nuclear antigen (PCNA)-interacting protein (PIP)-like box sequence in APC that binds DNA polymerase β (pol-β) and blocks pol-β-mediated strand-displacement synthesis in long-patch BER without affecting short-patch BER. We further showed that the colon cancer cell line expressing the wild-type APC gene was more sensitive to a DNA-methylating agent due to decreased DNA repair by long-patch BER than the cell line expressing the mutant APC gene lacking the PIP-like box. Experiments based on RNA interference showed that the wild-type APC gene expression is required for DNA methylation-induced sensitivity of colon cancer cells. Thus, APC may play a critical role in determining utilization of long- versus short-patch BER pathways and affect the susceptibility of colon cancer cells to carcinogenic and chemotherapeutic agents. These studies were partially supported to S.N. by the grants from NCI-NIH (RO1-CA 097031, RO1-CA 100247) and Flight Attendants Medical Research Institute.
Activation of NRF2 ameliorates oxidative stress and cystogenesis in autosomal dominant polycystic kidney disease
Authors: Yi Lu, Yongzhan Sun, Zhiheng Liu, Yumei Lu, Xu Zhu, Bingxue Lan, Zeyun Mi, Lin Dang, Na Li, Wenlei Zhan, Lu Tan, Jingbo Pi, Hui Xiong, Lirong Zhang, Yupeng Chen
Journal: Science Translational Medicine (2020)

Pharmacological induction of NRF2 restores redox homeostasis and slows cystogenesis in mouse models of polycystic kidney disease.
Graft-Versus-Host Disease Presenting as a Myositis and Myonecrosis
Authors: Dhruv M. Patel, Domnique S. Newallo, Bruce Barron
Journal: Clinical Nuclear Medicine (2020)

Abstract Graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation. Polymyositis with myonecrosis is a rare manifestation of GVHD. Here, we report the case of a 32-year-old man with acute myeloid leukemia who developed GVHD after transplant. He subsequently developed polymyositis, which was diagnosed on PET/CT and confirmed on pathology. Treatment with corticosteroids resulted in the resolution of the symptoms. Abnormal muscular FDG uptake resolved on the follow-up PET/CT.
Regulatory Considerations for Contribution of Effect of Drugs Used in Combination Regimens: Renal Cell Cancer Case Studies
Authors: Jamie R. Brewer, Elaine Chang, Sundeep Agrawal, Harpreet Singh, Daniel L. Suzman, James Xu, Chana Weinstock, Laura L. Fernandes, Joyce Cheng, Lijun Zhang, Diqiong Xie, Kirsten B. Goldberg, Erik W. Bloomquist, Shenghui Tang, Rajeshwari Sridhara, Marc R. Theoret, Richard Pazdur, Amna Ibrahim, Julia A. Beaver
Journal: Clinical Cancer Research (2020)

The development and review of combination drug regimens in oncology may present unique challenges to investigators and regulators. For regulatory approval of combination regimens, it is necessary to demonstrate the contribution of effect of each monotherapy to the overall combination. Alternative approaches to traditional designs may be needed to accelerate oncology drug development, for example, when combinations are substantially superior to available therapy, to reduce exposure to less effective therapies, and for drugs that are inactive as single agents and that in combination potentiate activity of another drug. These approaches include demonstration of activity in smaller randomized trials and/or monotherapy trials conducted in a similar disease setting. This article will discuss alternative approaches used in the development of approved drugs in combination, based on examples of recent approvals of combination regimens in renal cell carcinoma.
Results of a nation-wide cohort study suggest favorable long-term outcomes of clone-targeted chemotherapy in immunotactoid glomerulopathy
Authors: Vincent Javaugue, Léa Dufour-Nourigat, Estelle Desport, Audrey Sibille, Bruno Moulin, Pierre Bataille, Pascal Bindi, Cyril Garrouste, Christophe Mariat, Lionel Karlin, Mathilde Nouvier, Jean-Michel Goujon, Viviane Gnemmi, Jean-Paul Fermand, Guy Touchard, Frank Bridoux
Journal: Kidney International (2020)
A Radiomics Model for Predicting the Response to Bevacizumab in Brain Necrosis after Radiotherapy
Authors: Jinhua Cai, Junjiong Zheng, Jun Shen, Zhiyong Yuan, Mingwei Xie, Miaomiao Gao, Hongqi Tan, Zhongguo Liang, Xiaoming Rong, Yi Li, Honghong Li, Jingru Jiang, Huiying Zhao, Andreas A. Argyriou, Melvin L.K. Chua, Yamei Tang
Journal: Clinical Cancer Research (2020)

Bevacizumab is considered a promising therapy for brain necrosis after radiotherapy, while some patients fail to derive benefit or even worsen. Hence, we developed and validated a radiomics model for predicting the response to bevacizumab in patients with brain necrosis after radiotherapy.A total of 149 patients (with 194 brain lesions; 101, 51, and 42 in the training, internal, and external validation sets, respectively) receiving bevacizumab were enrolled. In total, 1,301 radiomic features were extracted from the pretreatment MRI images of each lesion. In the training set, a radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm. Multivariable logistic regression analysis was then used to develop a radiomics model incorporated in the radiomics signature and independent clinical predictors. The performance of the model was assessed by its discrimination, calibration, and clinical usefulness with internal and external validation.The radiomics signature consisted of 18 selected features and showed good discrimination performance. The model, which integrates the radiomics signature, the interval between radiotherapy and diagnosis of brain necrosis, and the interval between diagnosis of brain necrosis and treatment with bevacizumab, showed favorable calibration and discrimination in the training set (AUC 0.916). These findings were confirmed in the validation sets (AUC 0.912 and 0.827, respectively). Decision curve analysis confirmed the clinical utility of the model.The presented radiomics model, available as an online calculator, can serve as a user-friendly tool for individualized prediction of the response to bevacizumab in patients with brain necrosis after radiotherapy.