tbuckley/cabot-search huggingface dataset:
Continuous versus interruption of imatinib (IM) in responding patients with advanced GIST after three years of treatment: A prospective randomized phase III trial of the French Sarcoma Group
Authors: A. Le Cesne, I. Ray-Coquard, B. Bui, M. Rios, A. Adenis, F. Bertucci, F. Duffaud, V. Bourne Branchu, D. Perol, J. Y. Blay
Journal: Journal of Clinical Oncology (2007)

10005 Background: IM the first-line targeted therapy for advanced GIST, must not be interrupted after one year (yr) in responding patients (pts) and has to be given continuously until disease progression (PD) or intolerance (Blay, Le Cesne et al, ASCO 2004 and 2005). The impact on progression free survival (PFS) of IM discontinuation in long lasting responding pts is unknown. Methods: This prospective national multicenter BFR14 study was initiated in June 2002. After 3 yrs of IM 400mg/day, pts free from progression were randomly offered to continue (C arm) or interrupt (I arm) IM, with the exception of pts initially randomized in the I arm after 1 yr of IM (32 pts). Pts allocated to the I arm could restart IM (same dose) in case of PD. Primary endpoint was PFS. Pts declining randomization proceed with IM. Results: As of december 2006, 286 pts were included in this trial and up to date, 35 non progressive pts at 3 yrs were randomized, 19 and 16 in the I anc C arm respectively. Pt characteristics were well balanced between the two arms. Nine progressions were reported after a median follow-up of 5.3 months (range 0–14) in this cohort of patients. IM reintroduction in the I arm after a re-progression allowed again a tumor control (OR or SD) in all evaluable pts so far. Conclusions: An increase in the rate of PD was observed in patients randomized after 3 years of IM. The final analysis will be performed after the randomization of 50 pts. Updated results including mutational analysis will be presented at the meeting. No significant financial relationships to disclose.
Autistic people may lack social motivation, without being any less human
Authors: Sue Fletcher-Watson, Catherine J. Crompton
Journal: Behavioral and Brain Sciences (2019)

Abstract In arguing that autistic people are socially motivated, Jaswal &amp; Akhtar miss the opportunity to puncture the notion that social motivation is a prerequisite for humanity. Instead, we contend that some autistic people may indeed find social interactions to be unmotivating and that this doesn't have to be seen as a problem.
Outcomes of patients with endometrial cancer and aggressive histology.
Authors: Samed Rahatli, Nadire Kucukoztas, Omer Dizdar, Polat Dursun, Selim Yalcin, Nihan Haberal, Ozlem Ozen, Cagla Tarhan, Ozden Altundag, Ferah Yildiz, Ali Ayhan
Journal: Journal of Clinical Oncology (2013)

e16536 Background: To present patterns of practice and outcomes of patients with early stage poor histology endometrial cancer. Methods: Records of the patients with FIGO stage I-II serous papillary, clear cell, mixed or undifferentiated endometrial cancer were retrospectively evaluated. All patients were initially treated surgically by the same surgeon with comprehensive staging lymphadenectomy, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy, bilateral pelvic and paraaortic lymph node dissection and omentectomy. Adjuvant chemotherapy was offered to all patients and given unless the patient refused. Results: 38 patients with early stage poor histology were identified Median age was 61 and 86.8 % of the patients were post menopausal. Median BMI was 31.2 kg/m2. 28 patients (73.7%) received chemotherapy (90% with paclitaxel and carboplatin for 6 cycles). 5 patients (13.2 %) received external radiotherapy 3 patients (7.9%) received brachytherapy. Median follow up was 19 mos. Totally 3 patients (7.9%) had relapse on follow up; Among those who received adjuvant chemotherapy, only one patient had recurrence on vaginal cuff and was treated with radiotherapy and currently disease free for 4 years. Among those who did not receive adjuvant chemotherapy, 2 patients had widespread abdominal and distal recurrence and died on follow up. 2 patients died without recurrence. Conclusions: Complete surgical staging and adjuvant chemotherapy results in excellent prognosis in our patient series. [Table: see text]
Inhibition of Bcl-2 Synergistically Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia
Authors: Jun Ma, Shoujing Zhao, Xinan Qiao, Tristan Knight, Holly Edwards, Lisa Polin, Juiwanna Kushner, Sijana H. Dzinic, Kathryn White, Guan Wang, Lijing Zhao, Hai Lin, Yue Wang, Jeffrey W. Taub, Yubin Ge
Journal: Clinical Cancer Research (2019)

To investigate the efficacy of the combination of the FLT3 inhibitors midostaurin or gilteritinib with the Bcl-2 inhibitor venetoclax in FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) and the underlying molecular mechanism.Using both FLT3-ITD cell lines and primary patient samples, Annexin V-FITC/propidium iodide staining and flow cytometry analysis were used to quantify cell death induced by midostaurin or gilteritinib, alone or in combination with venetoclax. Western blot analysis was performed to assess changes in protein expression levels of members of the JAK/STAT, MAPK/ERK, and PI3K/AKT pathways, and members of the Bcl-2 family of proteins. The MV4-11-derived xenograft mouse model was used to assess in vivo efficacy of the combination of gilteritinib and venetoclax. Lentiviral overexpression of Mcl-1 was used to confirm its role in cell death induced by midostaurin or gilteritinib with venetoclax. Changes of Mcl-1 transcript levels were assessed by RT-PCR.The combination of midostaurin or gilteritinib with venetoclax potently and synergistically induces apoptosis in FLT3-ITD AML cell lines and primary patient samples. The FLT3 inhibitors induced downregulation of Mcl-1, enhancing venetoclax activity. Phosphorylated-ERK expression is induced by venetoclax but abolished by the combination of venetoclax with midostaurin or gilteritinib. Simultaneous downregulation of Mcl-1 by midostaurin or gilteritinib and inhibition of Bcl-2 by venetoclax results in "free" Bim, leading to synergistic induction of apoptosis. In vivo results show that gilteritinib in combination with venetoclax has therapeutic potential.Inhibition of Bcl-2 via venetoclax synergistically enhances the efficacy of midostaurin and gilteritinib in FLT3-mutated AML.See related commentary by Perl, p. 6567.
Addressing the Cardiovascular Disease Burden in China—Is It Possible Without Surgery?—Reply
Authors: Shiwei Liu, Yichong Li, Maigeng Zhou
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Therapeutic and Diagnostic Implications of T Cell Scarring in Celiac Disease and Beyond
Authors: Asbjørn Christophersen, Louise F. Risnes, Shiva Dahal-Koirala, Ludvig M. Sollid
Journal: Trends in Molecular Medicine (2019)

Few therapeutic and diagnostic tools specifically aim at T cells in autoimmune disorders, but are T cells a narrow target in these diseases? Lessons may be learned from celiac disease (CeD), one of the few autoimmune disorders where the T cell driving antigens are known, i.e. dietary gluten proteins. T cell clonotypes specific to gluten are expanded, persist for decades and express a distinct phenotype in CeD patients. Cells with this phenotype are increased also in other autoimmune conditions. Accordingly, disease-specific CD4+ T cells form an immunological scar in CeD and probably other autoimmune disorders. We discuss approaches how such T cells may be targeted for better treatment and diagnosis via their antigen specificity or via their expression of characteristic phenotypic markers.
Deep learning predicts hip fracture using confounding patient and healthcare variables
Authors: Marcus A. Badgeley, John R. Zech, Luke Oakden-Rayner, Benjamin S. Glicksberg, Manway Liu, William Gale, Michael V. McConnell, Bethany Percha, Thomas M. Snyder, Joel T. Dudley
Journal: npj Digital Medicine (2019)

Hip fractures are a leading cause of death and disability among older adults. Hip fractures are also the most commonly missed diagnosis on pelvic radiographs, and delayed diagnosis leads to higher cost and worse outcomes. Computer-aided diagnosis (CAD) algorithms have shown promise for helping radiologists detect fractures, but the image features underpinning their predictions are notoriously difficult to understand. In this study, we trained deep-learning models on 17,587 radiographs to classify fracture, 5 patient traits, and 14 hospital process variables. All 20 variables could be individually predicted from a radiograph, with the best performances on scanner model (AUC = 1.00), scanner brand (AUC = 0.98), and whether the order was marked "priority" (AUC = 0.79). Fracture was predicted moderately well from the image (AUC = 0.78) and better when combining image features with patient data (AUC = 0.86, DeLong paired AUC comparison, p = 2e-9) or patient data plus hospital process features (AUC = 0.91, p = 1e-21). Fracture prediction on a test set that balanced fracture risk across patient variables was significantly lower than a random test set (AUC = 0.67, DeLong unpaired AUC comparison, p = 0.003); and on a test set with fracture risk balanced across patient and hospital process variables, the model performed randomly (AUC = 0.52, 95% CI 0.46-0.58), indicating that these variables were the main source of the model's fracture predictions. A single model that directly combines image features, patient, and hospital process data outperforms a Naive Bayes ensemble of an image-only model prediction, patient, and hospital process data. If CAD algorithms are inexplicably leveraging patient and process variables in their predictions, it is unclear how radiologists should interpret their predictions in the context of other known patient data. Further research is needed to illuminate deep-learning decision processes so that computers and clinicians can effectively cooperate.
Roxadustat and Anemia of Chronic Kidney Disease
Authors: Joshua Kaplan
Journal: New England Journal of Medicine (2019)

Until 1989, when recombinant erythropoietin therapy was first approved, anemia of chronic kidney disease could be treated only symptomatically with blood transfusions. Erythropoiesis-stimulating agents were able to increase patients' hemoglobin levels to between 9 and 11 g per deciliter, resulting in improved quality of life and decreased left ventricular hypertrophy and mortality.1,2 Since that time, erythropoiesis-stimulating agents along with oral and intravenous iron have been the linchpin of treatment for chronic kidney disease accompanied by profound anemia. With the proof that erythropoietin and iron could markedly correct anemia, the next obvious question was addressed some years ago: Would full reversal . . .
Next of Kin
Authors: Pavlos Theodorou
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Melanoma Extracellular Vesicles Generate Immunosuppressive Myeloid Cells by Upregulating PD-L1 via TLR4 Signaling
Authors: Viktor Fleming, Xiaoying Hu, Céline Weller, Rebekka Weber, Christopher Groth, Zeno Riester, Laura Hüser, Qian Sun, Vasyl Nagibin, Carsten Kirschning, Vincenzo Bronte, Jochen Utikal, Peter Altevogt, Viktor Umansky
Journal: Cancer Research (2019)

Tumor cell-derived extracellular vesicles (EV) convert normal myeloid cells into myeloid-derived suppressor cells (MDSC), inhibiting antitumor immune responses. Here, we show that EV from Ret mouse melanoma cells upregulate the expression of programmed cell death ligand 1 (PD-L1) on mouse immature myeloid cells (IMC), leading to suppression of T-cell activation. PD-L1 expression and the immunosuppressive potential of EV-generated MDSC were dependent on the expression of Toll-like receptors (TLR). IMC from Tlr4-/- mice failed to increase T-cell PD-L1 expression and immunosuppression with Ret-EV treatment, and this effect was dependent on heat-shock protein 86 (HSP86) as HSP86-deficient Ret cells could not stimulate PD-L1 expression on normal IMC; IMC from Tlr2-/- and Tlr7-/- mice demonstrated similar results, although to a lesser extent. HSP86-deficient Ret cells slowed tumor progression in vivo associated with decreased frequency of tumor-infiltrating PD-L1+CD11b+Gr1+ MDSC. EV from human melanoma cells upregulated PD-L1 and immunosuppression of normal monocytes dependent on HSP86. These findings highlight a novel EV-mediated mechanism of MDSC generation from normal myeloid cells, suggesting the importance of EV targeting for tumor therapy. SIGNIFICANCE: These findings validate the importance of TLR4 signaling in reprogramming normal myeloid cells into functional myeloid-derived suppressor cells.
James Denis Fair Lockhart
Authors: Andrew Lockhart
Journal: BMJ (2019)

James Denis Fair Lockhart (“Denis”) was born in February 1932 at the European Hospital in Tabora, Tanganyika (now Tanzania), where his father, also a doctor, was a colonial medical officer (he was later, during the second world war, director of health at Nairobi). After schooling in Africa and then at Stowe School, Denis followed his parents into the medical profession. He studied at Trinity College Dublin, where his mother had qualified as a doctor in 1925.

Denis completed his national service with the Royal …
Plastic fantastic innate lymphoid cells
Authors: Lewis L. Lanier
Journal: The Journal of Experimental Medicine (2019)

In this issue of JEM, Nagasawa et al. (https://doi.org/10.1084/jem.20190490) have undertaken a detailed study of the cell surface phenotype, transcriptional profile, and cytokine secretion of ILC progenitor populations in human peripheral blood and tissues and describe markers that highlight the heterogeneity of these chameleons.
Harms From Uninformative Clinical Trials
Authors: Deborah A. Zarin, Steven N. Goodman, Jonathan Kimmelman
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
What’s New in Understanding the Risk Associated With Body Size and Shape?
Authors: Lilian Golzarri-Arroyo, Luis M. Mestre, David B. Allison
Journal: JAMA Network Open (2019)

Yangbo Sun, MD, PhD; Buyun Liu, MD, PhD; Linda G. Snetselaar, PhD; Robert B. Wallace, MD; Bette J. Caan, DrPH; Thomas E. Rohan, MBBS, PhD, DHSc; Marian L. Neuhouser, PhD; Aladdin H. Shadyab, PhD; Rowan T. Chlebowski, MD, PhD; JoAnn E. Manson, MD, DrPH; Wei Bao, MD, PhD
Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice
Authors: Clea Bárcena, Rafael Valdés-Mas, Pablo Mayoral, Cecilia Garabaya, Sylvère Durand, Francisco Rodríguez, María Teresa Fernández-García, Nuria Salazar, Alicja M. Nogacka, Nuria Garatachea, Noélie Bossut, Fanny Aprahamian, Alejandro Lucia, Guido Kroemer, José M. P. Freije, Pedro M. Quirós, Carlos López-Otín
Journal: Nature Medicine (2019)
Prognostic factors in malignant pleural mesothelioma (MPM): A mono-institutional evaluation of Bologna Malignant Pleural Mesothelioma Group.
Authors: Daniela Adua, Francesca Sperandi, Paolo Castellucci, Barbara Melotti, Stefania Giaquinta, Stefano Fanti, Carmine Pinto
Journal: Journal of Clinical Oncology (2013)

e18509 Background: The prognostic systems currently in use in MPM, such as the EORTC and CALGB score, include the clinical and histological parameters, excluding the FDG-PET (PET) evaluation and the possibility of surgery. The aim of our study was to investigate the role of PET baseline SUV-max and surgery as prognostic factors in MPM. Methods: From April 2002to December 2012, 48 pts with a certain histological diagnosis of MPM underwent staging by PET scan before peri-operative (multimodality treatment) or palliative first-line chemotherapy (CT). Surgery was performed in 22(45.8%) pts. Pt characteristics: males 44(91.7%), females 4(8.3%); median age 65 (51-77) years; ECOG PS 0-1 45(93.7 %), PS 2 3(6.3 %); IMIG stage I-II 18(37.5%), III-IV 30(62.5%); histological subtype epithelial 40(83.3%), mixed 5(10.4%), sarcomatoid 3(6.3%); extrapleural pneumonectomy 8(16.8%), pleurectomy/decortication 14(29.2%), 17 (35.4%) VATS plus pleurodesis, 19(39.6%) no surgical procedures. Platinum based CT was performed in combination with pemetrexed in 39(81.3%) pts and with gemcitabine in 9(18.7%). According to the EORTC score 30(62.5%) pts were classified in the good prognosis group and 18(37.5%) as poor prognosis. The cut-off value of PET baseline SUV-max calculated by ROC analysis was 9; SUV-max at baseline PET was ≤ 9 in 32(66.7%) pts and &gt;9 in 16(33.3%). Median overall survival (OS) was 12 (3-60) months. Results: Upon validating the impact of individual factors on OS using the Kaplan-Meier analysis, we found statistical significance was reached by histology (p=0.0038) and surgery (p=0.0027). In a multivariate analysis using the Cox regression system, considering OS as a dependent variable, according to age, histology, stage, PET baseline SUV-max and surgery, epithelial histology (p =0.002) and surgery (p=0.012) achieved a statistical significance. SUV-max at baseline PET was not statistically significant (p = 0.290), excluding it as a possible independent prognostic factor in MPM. Conclusions: This analysis does not indicate any prognostic value for baseline PET in MPM, confirming the importance of histological subtype and introducing surgery as a possible prognostic factor.
Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens
Authors: Sara Pedron, Gabrielle L. Wolter, Jee-Wei E. Chen, Sarah E. Laken, Jann N. Sarkaria, Brendan A.C. Harley
Journal: Biomaterials (2019)
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis
Authors: Nan Chen, Chuanming Hao, Xiaomei Peng, Hongli Lin, Aiping Yin, Li Hao, Ye Tao, Xinling Liang, Zhengrong Liu, Changying Xing, Jianghua Chen, Laimin Luo, Li Zuo, Yunhua Liao, Bi-Cheng Liu, Robert Leong, Chunrong Wang, Cameron Liu, Thomas Neff, Lynda Szczech, Kin-Hung P. Yu
Journal: New England Journal of Medicine (2019)

Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis.
Consultants and SAS doctors in England to get 2.5% pay rise
Authors: Abi Rimmer
Journal: BMJ (2019)

Consultants and specialty and associate specialist (SAS) doctors in England will receive a 2.5% pay rise backdated to April 2019, the government has said.

The announcement came after the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) published its 2019 recommendations for increases to doctors’ pay.1

In line with the DDRB’s recommendations the health and social care secretary, Matt Hancock, said that consultants would receive a 2.5% general uplift in pay backdated to April 2019.2 He said that the value of national and the old style local clinical excellence awards would be frozen.

In its report the …
NHS is spending more on private providers despite government pledges
Authors: Adrian O’Dowd
Journal: BMJ (2019)

The NHS in England is spending increasing amounts of money in the private sector to provide services for its patients despite government promises to roll back on the role of the independent sector in the NHS.

The recently published annual accounts of the Department of Health and Social Care show that the NHS spent £9.18bn ($11.5bn; €10.2bn) on the independent sector in 2018-19,1 up from £8.76bn the previous year.

The BMA has criticised what it sees as “record amounts” of taxpayers’ money being diverted out of the NHS, despite comments made by health secretary Matt Hancock to MPs in January during an evidence session of the health and social care …