tbuckley/cabot-search huggingface dataset:
Secukinumab efficacy in patients with PsA is not dependent on patients’ body mass index
Authors: Ilenia Pantano, Daniela Iacono, Ennio Giulio Favalli, Giuseppe Scalise, Luisa Costa, Francesco Caso, Giuliana Guggino, Raffaele Scarpa, Francesco Ciccia
Journal: Annals of the Rheumatic Diseases (2020)

Figure 1 Correlation between BMI and DAPSA and serum IL-17 levels in PsA obese and non-obese patients.(A) Correlation between BMI and DAPSA by Kendall's tau coefficient and Spearman's rho tests (*statistical significance is for values of 0.05, one tail).(B) Graphical representation of correlation between BMI and DAPSA by Spearman test.(C) Analysis of serum levels of IL-17 in 20 obese and 20 obese and 20 non-obese patients compared to 30 healthy controls.BMI, body mass index; HC, health control; IL, interleukin; PsA, psoriatic arthritis.
25P Development of new therapeutic drugs for pancreatic cancer targeting choline transporter-like protein 1 (CTL1/SLC44A1)
Authors: M. Inazu, K. Hirai, S. Watanabe, N. Nishijima, K. Shibata, A. Hase, R. Gido, T. Yamanaka
Journal: Annals of Oncology (2020)
Dose increases in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate (IM): Estimated using administrative claims data in a US managed care population
Authors: C. C. Davis, P. Hines, G. Devercelli, S. Ray, S. Cheng, J. E. Cortes
Journal: Journal of Clinical Oncology (2006)

16014 Background: Dose increase is often the first step when resistance is encountered in CML patients treated with IM. The primary objective of this study is to determine the proportion of CML patients who experienced a dose increase from their starting dose within one year after initiation of IM therapy. Methods: Patients ≥18 years of age diagnosed with CML (ICD-9-CM code = 205.1) between 2001 and 2003 and treated with IM were identified in the Pharmetrics Integrated Claims Database which covers a US managed care population. Eligible patients had at least two claims for IM and were continuously enrolled for at least six months following their first IM prescription. Follow-up was one year after their first IM prescription. Results: A total of 113 CML patients using IM were identified. Eighty-four percent of these patients started IM at 400 mg/day; eight percent started at doses ≥ 600 mg/day; remaining started at doses &lt; 400 mg/day The mean daily dose of IM used by the study group was 419 mg (SD = 91). Nineteen percent of users required at least one dose increase from their starting dose within one year. The first dose increase was most frequently 200 mg/day (mean daily dose = 574 mg (SD = 199). The median maximum daily dose reached by patients experiencing dose increases was 600 mg/day (25 th – 75 th percentile: 500, 750 mg). The median ending dose in these patients was 600 mg/day (25 th –75 th percentile: 400, 600 mg). Median time to first dose increase was 5.8 (25 th –75 th percentile: 2.0, 7.4 months). Median time to maximum dose from initial IM dose was 6.5 (25 th –75 th percentile: 2.7, 7.4 months). Conclusions: Nearly 20% of all IM-treated CML patients required a dose increase of approximately 200 mg/day within one year. Of those dose increases, 50% occurred within the first 6 months. No significant financial relationships to disclose.
Misdiagnosis, Mistreatment, and Harm — When Medical Care Ignores Social Forces
Authors: Seth M. Holmes, Helena Hansen, Angela Jenks, Scott D. Stonington, Michelle Morse, Jeremy A. Greene, Keith A. Wailoo, Michael G. Marmot, Paul E. Farmer
Journal: New England Journal of Medicine (2020)

The Case Studies in Social Medicine demonstrate that when physicians use only biologic or individual behavioral interventions to treat diseases that stem from or are exacerbated by social factors, we risk harming the patients we seek to serve.
Abstract 14898: Comparative Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants versus Warfarin Among Patients With Non-Valvular Atrial Fibrillation and Diabetes: ARISTOPHANES Diabetes Subgroup Analysis
Authors: S Deitelzweig, A Keshishian, X Li, A Dhamane, X Luo, N Balachander, L Rosenblatt, J Mardekian, X Pan, A Nadkarni, M Di Fusco, Alessandra Garcia Reeves, H Yuce, Gyh Lip
Journal: Circulation (2018)

Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs) have been shown to be at least as effective and safe versus warfarin in non-valvular atrial fibrillation (NVAF) patients. However,...
α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer
Authors: Thai Q. Tran, Eric A. Hanse, Amber N. Habowski, Haiqing Li, Mari B. Ishak Gabra, Ying Yang, Xazmin H. Lowman, Amelia M. Ooi, Shu Y. Liao, Robert A. Edwards, Marian L. Waterman, Mei Kong
Journal: Nature Cancer (2020)
Management of ANCA associated vasculitis
Authors: Zachary S Wallace, Eli M Miloslavsky
Journal: BMJ (2020)

ABSTRACT Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a small to medium vessel vasculitis associated with excess morbidity and mortality. This review explores how management of AAV has evolved over the past two decades with pivotal randomized controlled trials shaping the management of induction and maintenance of remission. Contemporary AAV care is characterized by approaches that minimize the cumulative exposure to cyclophosphamide and glucocorticoids, increasingly use rituximab for remission induction and maintenance, and consider therapies with less toxicity (for example, methotrexate, mycophenolate mofetil) for manifestations of AAV that do not threaten organ function or survival. Simultaneously, improvements in outcomes, such as renal and overall survival, have been observed. Additional trials and observational studies evaluating the comparative effectiveness of agents for AAV in various patient subgroups are needed. Prospective studies are necessary to assess the effect of psychosocial interventions on patient reported outcomes in AAV. Despite the expanding array of treatments for AAV, little guidance on how to personalize AAV care is available to physicians.
SAFETY AND EFFICACY OF TICAGRELOR IN CAROTID ARTERY ANGIOPLASTY IN PATIENTS WITH CLOPIDOGREL RESISTANCE: REAL LIFE EXPERIENCE
Authors: Dor Lotan, Zeev Itsekzon-Hayosh, Eduard Itelman, Yishai Wasserstrum, Shlomi Matetzky, Jason Perlmutter, Amit Segev, Paul Fefer, David Orion, Victor Guetta
Journal: Journal of the American College of Cardiology (2020)
Cellular Adhesion Molecules in Young Adulthood and Cardiac Function in Later Life
Authors: Ravi B. Patel, Laura A. Colangelo, Alexander P. Reiner, Myron D. Gross, David R. Jacobs, Lenore J. Launer, Joao A.C. Lima, Donald M. Lloyd-Jones, Sanjiv J. Shah
Journal: Journal of the American College of Cardiology (2020)
Cardiologist is awarded £870 000 after he was sacked for raising safety concerns
Authors: Clare Dyer
Journal: BMJ (2020)

A consultant cardiologist has won £870 000 (€980 000; $1 100 000) in compensation from the NHS trust that sacked him after he raised safety concerns after a patient’s death.

Kevin Beatt, 68, who joined Croydon Health Services NHS Trust in 2005 and specialised in interventional cardiology, was dismissed in September 2012 after telling managers, a coroner, and a commissioning general practitioner that the catheterisation laboratory that he had set up was unsafe because there were too few specialist nurses.

He was fired after making a report to the coroner on the death of a 63 year old patient who suffered a cardiac arrest during an angioplasty in June 2011. Beatt told the coroner that he learned only when part way through the procedure that trust managers had suspended the head nurse on whom he relied in the middle of a working day, which he blamed for …
Effectiveness of D2 gastrectomy for lymph node positive and advanced gastric cancer: Survival results of the Italian Gastric Cancer Study Group (IGCSG) randomized surgical trial on D1 versus D2 dissection for gastric carcinoma.
Authors: Maurizio Degiuli
Journal: Journal of Clinical Oncology (2013)

4027 Background: It is still unclear whether D2 lymphadenectomy can significantly improve survival of gastric cancer and therefore should be applied routinely or performed in selected cases. We conducted a multicenter randomized trial to compare the efficacy of D2 and D1 lymphadenectomy for gastric cancer. Primary outcome was overall survival; secondary endpoints were disease specific survival, morbidity and in-hospital mortality. Methods: Between June 1998 and December 2006 patients with gastric adenocarcinoma were randomly assigned to either D1 or D2 lymphadenectomy. Intraoperative randomization was implemented centrally by telephone. Results: A total of 267 eligible patients were allocated to either D1 (133) or D2 group (134). Morbidity (12·0% vs 17·9%, p=0·18) and mortality (3·0% vs 2·3%; p=0·72) were similar. There was no difference in the overall 5-year survival (66·5% vs 64·2%, p = 0.70). Subgroups analyses showed a 5-years disease specific survival benefit for pT1 cases treated with D1 dissection (98.0% vs 82.9%, p = 0.01) and of pT&gt;1 LN+ patients treated with D2 resection (38·4% vs 59·5%, p = 0.05 at five years). Conclusions: In intention to treat analysis we observed no overall 5-year survival benefit from D2 resection. The trial showed a survival benefit of D1 procedure in early stages. On the opposite, despite evidence of contamination in the D1 arm, a survival advantage was documented in patients with advanced disease and lymph node metastases submitted to D2 procedure. Clinical trial information: ISRCTN11154654. [Table: see text]
Immunotherapy as a Downstaging Therapy for Liver Transplantation
Authors: Birgit Schwacha‐Eipper, Iulia Minciuna, Vanessa Banz, Jean François Dufour
Journal: Hepatology (2020)

Schwacha‐Eipper, Birgit; Minciuna, Iulia; Banz, Vanessa; Dufour, Jean François Author Information
HSR20-101: Real-World Chemoradiotherapy Use Among Unresectable Stage III Non-Small Cell Lung Cancer Patients: A Retrospective Observational Study
Authors: Meghan J. Mooradian, Kenneth Shermock, David Merola, Brian Seal, Candice Yong, Lance Brannman
Journal: Journal of the National Comprehensive Cancer Network (2020)

"HSR20-101: Real-World Chemoradiotherapy Use Among Unresectable Stage III Non-Small Cell Lung Cancer Patients: A Retrospective Observational Study" published on 20 Mar 2020 by National Comprehensive Cancer Network.
Visualising improved peritoneal perfusion at lower intra-abdominal pressure by fluorescent imaging during laparoscopic surgery: A randomised controlled study
Authors: Kim I Albers, Fatih Polat, Tom Loonen, Leon J Graat, Jan P Mulier, Marc Mj Snoeck, Ivo F Panhuizen, Ad A Vermulst, Gert-Jan Scheffer, Michiel C Warlé
Journal: International Journal of Surgery (2020)
Assessment of cancer patients of the local patient’s support organizations and the available sources of the patient’s health education: Local perspectives from Saudi Arabia.
Authors: Ravichandran Kandasamy, Abdelmuniem Al-Dalee, Ali Husain Aljubran
Journal: Journal of Clinical Oncology (2012)

e19526 Background: Few Local patients’ support organizations are available for cancer patients in Saudi Arabia. These non governmental organizations NGOs were recently founded to provide social, financial, logistic and educational support to cancer patients. Their role and participation to the cancer patient’s care is not well estimated. On the other hand, Health education is imperative. However, there is yet no clear estimation of the adequacy and quality of the available local sources for cancer health education. This study was intended to show the cancer patient’s assessment of the available resources of support and health education to cancer patients. Methods: The subjects were adult cancer patients who attended the outpatient clinics at King Faisal cancer center in Riyadh, Saudi Arabia. They completed a validated questionnaire of six sections. In this abstract, we only present the data of the fifth and sixth sections. The fifth is regarding patient’s impression about the support provided by the family and society. The sixth is about the patient’s sources of information and education about their diseases. Results: 234 patients participated. Age range: 15-86, median: 40.5 y. Males: 61.5%. 12.4% from suburban areas. 41.5% had higher than high school education, and 76% had annual income &lt;$32,000. 90% of the participating patients evaluated the family support as full support. However, 92% did not receive any support from the NGOs, and 54% were not aware that such organizations exist. Only 20% of those who suffered psychological/ psychiatric changes actually did ask for help. Regarding the patient’s use of the available sources of health education, 77% received education other than that provided directly by physicians. 45% had more information about their conditions from educational brochures and health magazines and only 33% sought more information from the internet. Conclusions: The cancer patient’s assessment of the role and participation of the NGOs is generally poor. Majority of patients were able to have more information about their conditions through different means. The use of internet is relatively inadequate.
When to suspect a non-melanoma skin cancer
Authors: H Smith, A Wernham, A Patel
Journal: BMJ (2020)

### What you need to know

Assessing non-melanocytic skin lesions is a routine part of general practice. The key concern for patient and doctor is often whether the lesion may be a basal cell carcinoma or squamous cell carcinoma, collectively termed non-melanoma skin cancer (NMSC). This article aims to help primary care clinicians, who may not routinely have access to dermoscopy and biopsy, to identify possible NMSC lesions, which require further specialist assessment or monitoring.

### How this article was made

We searched for relevant journal articles in the British Journal of Dermatology , BMJ , and British Association of Dermatology guidelines. A secondary literature search was conducted using Google Scholar with the key words “basal cell carcinoma,” “squamous cell carcinoma,” “non-melanoma skin cancer” associated with “risk factors,” “treatment,” “management,” “follow-up.”

Non-melanoma skin cancer is more commonly diagnosed than all other malignancies combined,1 and the incidence of skin cancer is rising, with rates of NMSC predicted to reach almost 400 000 per year in the UK by 2025.2 This is thought to be due to a combination of people living longer, increased exposure to ultraviolet (UV) light, and improved data collection and diagnostic tools.34 Risk factors are summarised in table 1, with the key environmental risk being UV exposure from tan-seeking behaviour and outdoor activities without adequate sun protection.12 Both basal cell carcinomas and cutaneous squamous cell carcinomas are more common with increasing age, with incidence of cutaneous squamous cell carcinomas peaking at 66 years of age.

View this table:

Table 1 
Risk factors for non-melanoma skin cancer



Box 1 summarises the procedure …
The gut microbiota and genetic risk for rheumatoid arthritis in the absence of disease: a TwinsUK association study
Authors: Philippa Wells, Adewale Adebayo, Ruth Bowyer, Maxim Freidin, Axel Finckh, Till Strowig, Till Robin Lesker, Deshire Alpizar-Rodriguez, Benoit Gilbert, Bruce Kirkham, Andrew Cope, Claire Steves, Frances Williams
Journal: The Lancet Rheumatology (2020)
FEASIBILITY OF THREE-DIMENSIONAL CARDIAC MAGNETIC RESONANCE IMAGING (3D-CMR) FOR PREOPERATIVE PLANNING OF TRANS-CATHETER AORTIC VALVE IMPLANTATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Tushar Acharya, Muhammad Ajmal, Toshinobu Kazui, Neil Gheewala, Kapildeo Lotun, Ranjith Shetty
Journal: Journal of the American College of Cardiology (2020)
THE HEMATOPOIETIC TRANSCRIPTION FACTOR GATA2 IS A NOVEL REGULATOR OF APOPTOTIC CELL CLEARANCE BY MACROPHAGES IN ATHEROSCLEROSIS
Authors: Charles Yin, Angela M. Vrieze, James Akingbasote, Emily N. Pawlak, Rajesh A. Jacob, Jonathan Hu, Neha Sharma, Garth Blackler, Jimmy D. Dikeakos, Lillian Barra, Dave Nagpal, Bryan Heit
Journal: Journal of the American College of Cardiology (2020)
Nfkbie-deficiency leads to increased susceptibility to develop B-cell lymphoproliferative disorders in aged mice
Authors: Veronique Della-Valle, Damien Roos-Weil, Laurianne Scourzic, Enguerran Mouly, Zakia Aid, Walaa Darwiche, Yann Lecluse, Frederik Damm, Sylvie Mémet, Thomas Mercher, Said Aoufouchi, Florence Nguyen-Khac, Olivier A. Bernard, Hussein Ghamlouch
Journal: Blood Cancer Journal (2020)

Abstract Aberrant NF-κB activation is a hallmark of most B-cell malignancies. Recurrent inactivating somatic mutations in the NFKBIE gene, which encodes IκBε, an inhibitor of NF-κB-inducible activity, are reported in several B-cell malignancies with highest frequencies in chronic lymphocytic leukemia and primary mediastinal B-cell lymphoma, and account for a fraction of NF-κB pathway activation. The impact of NFKBIE deficiency on B-cell development and function remains, however, largely unknown. Here, we show that Nfkbie -deficient mice exhibit an amplification of marginal zone B cells and an expansion of B1 B-cell subsets. In germinal center (GC)-dependent immune response, Nfkbie deficiency triggers expansion of GC B-cells through increasing cell proliferation in a B-cell autonomous manner. We also show that Nfkbie deficiency results in hyperproliferation of a B1 B-cell subset and leads to increased NF-κB activation in these cells upon Toll-like receptor stimulation. Nfkbie deficiency cooperates with mutant MYD88 signaling and enhances B-cell proliferation in vitro. In aged mice, Nfkbie absence drives the development of an oligoclonal indolent B-cell lymphoproliferative disorders, resembling monoclonal B-cell lymphocytosis. Collectively, these findings shed light on an essential role of IκBε in finely tuning B-cell development and function.
Differences of protein expression of renal cell carcinoma (RCC) by tumor location and treatment.
Authors: Anneliese Gonzalez, Rabih Said, Robert E Brown, Yufeng Zhang, Robert J. Amato
Journal: Journal of Clinical Oncology (2013)

e15556 Background: Resistance to targeted therapy in RCC is primarily related to tumor and environmental changes. We assessed the difference of morphology and protein analyte expression by metastatic site and treatment types. Methods: Archival tissues from primary and metastatic RCC biopsies were studied. Immunohistochemical probes included antibodies for the protein analytes: phospholipase D2; fatty acid synthase; phosphorylated (p)-Akt (Ser 473); p-mTOR [Ser 2448]); p-p70S6K (Thr 389); p-extracellular signal-regulated kinase (ERK) 1/2 (Thr 202/Tyr 204); p-signal transducer and activator of transcription (STAT)3 (Tyr 705); vascular endothelial growth factor (VEGF)-A; stem cell markers CD44 and CD56; and intratumoral FOXP3 vs. CD8 lymphocytes. Results: A total of 66 patients with available tissue biopsies were assessed. Fourteen patients had additional biopsy at progression. Morphoproteomics was assessed on a total of 81 specimens. The nuclear distribution of phospholipase D2 was statistically significant different by biopsy site (p=0.0046) with highest expression in bone and lung. Similarly, the cytoplasmic expression fatty acid synthase was significantly different by biopsy site (p=0.0167) with highest expression in lymph node and adrenal. More importantly, nuclear mTOR activity was different by tumor biopsy site (p=0.001) with predominant expression in lung, lymph nodes and brain. Compared to mTORC1, which was more expressed in primary tumors, mTORC2 is more expressed in lung and bone metastasis. None of the other protein analytes expression was different based on tumor location. Further analysis on patients with multiple biopsies showed that the plasmalemmal CD56 expression increased with therapy but none of the other protein expression. Conclusions: This analysis emphasized the role of the microenvironment in tumor biology. Prospective treatment trial is underway based on the different molecular fingerprints.
Recombinant Adenosine Deaminase Ameliorates Inflammation, Vascular Disease, and Fibrosis in Preclinical Models of Systemic Sclerosis
Authors: Yun Zhang, Honglin Zhu, Florian Layritz, Hui Luo, Thomas Wohlfahrt, Chih‐Wei Chen, Alina Soare, Christina Bergmann, Andreas Ramming, Florian Groeber, Christian Reuter, GianFranco Fornasini, Nadejda Soukhareva, Brian Schreiber, Santosh Ramamurthy, Kerstin Amann, Georg Schett, Jörg H. W. Distler
Journal: Arthritis & Rheumatology (2020)

Systemic sclerosis (SSc) is characterized by fibrosis, vascular disease, and inflammation. Adenosine signaling plays a central role in fibroblast activation. We undertook this study to evaluate the therapeutic effects of adenosine depletion with PEGylated adenosine deaminase (PEG-ADA) in preclinical models of SSc.The effects of PEG-ADA on inflammation, vascular remodeling, and tissue fibrosis were analyzed in Fra-2 mice and in a B10.D2→BALB/c (H-2d ) model of sclerodermatous chronic graft-versus-host disease (GVHD). The effects of PEG-ADA were confirmed in vitro in a human full-thickness skin model.PEG-ADA effectively inhibited myofibroblast differentiation and reduced pulmonary fibrosis by 34.3% (with decreased collagen expression) (P = 0.0079; n = 6), dermal fibrosis by 51.8% (P = 0.0006; n = 6), and intestinal fibrosis by 17.7% (P = 0.0228; n = 6) in Fra-2 mice. Antifibrotic effects of PEG-ADA were also demonstrated in sclerodermatous chronic GVHD (reduced by 38.4%) (P = 0.0063; n = 8), and in a human full-thickness skin model. PEG-ADA treatment decreased inflammation and corrected the M2/Th2/group 2 innate lymphoid cell 2 bias. Moreover, PEG-ADA inhibited proliferation of pulmonary vascular smooth muscle cells (reduced by 40.5%) (P < 0.0001; n = 6), and prevented thickening of the vessel walls (reduced by 39.6%) (P = 0.0028; n = 6) and occlusions of pulmonary arteries (reduced by 63.9%) (P = 0.0147; n = 6). Treatment with PEG-ADA inhibited apoptosis of microvascular endothelial cells (reduced by 65.4%) (P = 0.0001; n = 6) and blunted the capillary rarefication (reduced by 32.5%) (P = 0.0199; n = 6). RNA sequencing demonstrated that treatment with PEG-ADA normalized multiple pathways related to fibrosis, vasculopathy, and inflammation in Fra-2 mice.Treatment with PEG-ADA ameliorates the 3 cardinal features of SSc in pharmacologically relevant and well-tolerated doses. These findings may have direct translational implications, as PEG-ADA has already been approved by the Food and Drug Administration for the treatment of patients with ADA-deficient severe combined immunodeficiency disease.