tbuckley/cabot-search huggingface dataset:
FRI0265 Angiogenic t cells in primary sjÖgren’s syndrome: a double-edged sword
Authors: A. Alunno, M. Manetti, O. Bistoni, S. Cipriani, L. Ibba Manneschi, R. Gerli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Angiogenic T cells (Tang) have been recently identified within colonies of endothelial progenitor cells (EPCs) as mediators of endothelial repair. Both Tang and EPCs are reduced in rheumatoid arthritis and this contributes to persistent endothelial damage and eventually increased cardiovascular risk. In primary Sjögren's syndrome (pSS), EPCs are expanded but no data are currently available about Tang. <h3>Objectives</h3> Aim of this study was to assess Tang (CD3 +CD31+CXCR4+) in peripheral blood (PB) and target organs of pSS as well as the association with EPCs (CD34 +CD133+VEGFR-2+) and clinical and serological features of the disease. <h3>Methods</h3> Thirty-six pSS patients and 20 sex- and age-matched healthy donors (HD) were enrolled. Phenotipic analysis of peripheral blood mononuclear cells was performed by flow cytometry using FITC, Pe, Pe-Cy7 or AlexaFluor647 labelled anti-human CD3, CD31, CXCR4, CD4, CD8, CD28, CD34, CD133, VEGFR-2, and IL-17 antibodies. Minor salivary gland (MSG) biopsies from 8 pSS patients were studied and compared to samples from 12 patients with sicca symptoms and either non-specific chronic sialadenitis (NSCS) or normal parenchyma (n=6 each). MSG sections were subjected to immunofluorescence staining to assess the presence of CD3 +CD31+CXCR4+Tang cells and the expression of the CXCR4-ligand CXCL12/SDF-1 chemokine. <h3>Results</h3> Circulating Tang were expanded in pSS compared to HD and were directly correlated to EPCs. Both Tang and EPCs directly correlated with disease activity as calculated with the EULAR Sjögren's syndrome disease activity index (ESSDAI). Over 60% of Tang lacked CD28 revealing a senescent phenotype. Only a small proportion of Tang displayed either CD4 or CD8, the majority of Tang being therefore CD4-CD8- double negative (DN). A subset of Tang produced IL-17 and the highest proportion of IL-17-producing cells was observed among DN cells. Immunofluorescence analyses revealed the exclusive presence of infiltrating Tang cells along with increased expression of CXCL12/SDF-1 in pSS MSGs compared to either NSCS or normal MSGs. <h3>Conclusions</h3> Circulating Tang cells are expanded in pSS, display a senescent phenotype, are mainly CD4-CD8- DN and produce IL-17. Moreover, Tang cells home to and infiltrate MSGs in pSS, presumably through the SDF-1/CXCR4 chemotactic axis. Our data suggest that besides their positive effect together with EPCs in endothelial repair, Tang cells may contribute to disease pathogenesis. <h3>Disclosure of Interest</h3> None declared
Clinical and genetic risk factors for AI-induced arthralgia.
Authors: Karin Paige Miller, Xueliang Jeff Pan, Cynthia Dawn Timmers, Robert Pilarski, Charles L. Shapiro, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2014)

e20601 Background: Aromatase Inhibitors (AIs) are associated with arthralgia development, leading to therapy non-adherence and premature discontinuation. Clinical and genetic risk factors have been investigated including polymorphisms in four SNPs near the T-cell leukemia 1A (TCL1A) gene (Ingle et al, 2010). We aimed to characterize the prevalence of AI-induced arthralgia and further evaluate clinical and genomic risk factors. Methods: Patient charts from the Columbus Breast Cancer Tissue Bank Registry were reviewed for arthralgia development in women diagnosed with stage I-III breast cancer, treated with anastrozole, exemestane, and/or letrozole. Data was collected and analyzed on patient demographics, past medical history, and AI usage. DNA samples were tested for genetic polymorphisms in SNPs, rs11849538, rs2369049, rs7159713 and rs7158782, as well as Cyp19. Results: Of 286 patients, 114 (39.9%) developed arthralgia (cases) on the first AI while the rest did not (controls). 75.43% of cases and 90.70% of controls are currently on or have completed therapy with their first, second, or third AI (P=0.001). Women with a BMI≥30 kg/m2 carried a non-significant trend toward developing arthralgia (Odds Ratio=1.55, CI=0.96-2.50, P=0.073), and women with a time since LMP≥10 years carried a non-significant trend against developing arthralgia (Odds Ratio=0.54, CI=0.29-1.02, P=0.056). Cases had a higher frequency of minor alleles than controls for the SNPs: rs11849538 (14.9% cases, 9.8% controls, P=0.08), rs2369049 (18.9% cases, 13.2% controls, P=0.08), rs7159713 (18.9% cases, 13.5% controls, P=0.1) and rs7158782 (18.9% cases, 13.5% controls, P=0.1). This was not statistically significant, likely due to small sample size. There was no significant difference of Cyp19 with 3bp deletion (33.3% vs 34.9%, p>0.5). The current sample size provided about 80% power to detect a 13-18% difference of allele frequency between the two groups at a significance level of 0.05. Conclusions: AI-induced arthralgia was a prevalent occurrence. Women who experienced arthralgia were less likely to complete or continue ongoing AI therapy. The phenomenon of AI-induced arthralgia requires further study due to its high prevalence and unknown pathophysiologic mechanism.
Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: nested case-control study within Lung Cancer Cohort Consortium
Authors: David C Muller, Tricia L Larose, Allison Hodge, Florence Guida, Arnulf Langhammer, Kjell Grankvist, Klaus Meyer, Qiuyin Cai, Alan A Arslan, Anne Zeleniuch-Jacquotte, Demetrius Albanes, Graham G Giles, Howard D Sesso, I-Min Lee, J Michael Gaziano, Jian-Min Yuan, Judith Hoffman Bolton, Julie E Buring, Kala Visvanathan, Loic Le Marchand, Mark P Purdue, Neil E Caporaso, Øivind Midttun, Per M Ueland, Ross L Prentice, Stephanie J Weinstein, Victoria L Stevens, Wei Zheng, William J Blot, Xiao-Ou Shu, Xuehong Zhang, Yong-Bing Xiang, Woon-Puay Koh, Kristian Hveem, Cynthia A Thomson, Mary Pettinger, Gunnar Engström, Hans Brunnström, Roger L Milne, Meir J Stampfer, Jiali Han, Mikael Johansson, Paul Brennan, Gianluca Severi, Mattias Johansson
Journal: BMJ (2019)

Abstract Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. Setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. Participants 5299 patients with incident lung cancer, with individually incidence density matched controls. Exposure Circulating hsCRP concentrations in prediagnostic serum or plasma samples. Main outcome measure Incident lung cancer diagnosis. Results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P&lt;0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. Conclusions Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.
Impact of an interventional counseling procedure in BRCA families: Efficacy and safety.
Authors: Erica Sermijn, Liesbeth Delesie, Ellen Deschepper, Ingrid Pauwels, Maryse Bonduelle, Erik Teugels, Jacques De Greve
Journal: Journal of Clinical Oncology (2014)

1552 Background: Predictive genetic testing has high impact on cancer prevention for BRCA carriers. Passing information in BRCA families on the availability of testing is important. In most countries this is mainly proband - mediated, but this path is defective, and denies relatives lifesaving information.This study assessed the safety/ efficacy of an intervention, aiming at actively informing relatives. Methods: Sequential prospective study in new BRCA families. First the proband told relatives about the hereditary trait/predictive testing (standard procedure; phase I). After 6 months a letter was sent to adult relatives, who had not been reached (study; phase II). The letter provided vital information, preserving the probands’ anonymity. Contact info and an inquiry form probing the acceptability were provided. After the letter a phone call was made to obtain a final notion of their wishes. All subjects received a psychometric test (State - Trait Anxiety Inventory, STAI), an interview, and routine counseling. Results: Twenty families were included. Of 172 relatives at risk, 89 participated: 47 by the proband, 42 by the letter as the major trigger to seek counseling. Nearly all of these subjects (98 %) opted for predictive testing, of which 30 were mutation carriers. Subjects were satisfied with the intervention. Twenty-four of the eligible relatives could not be reached; 59 were ‘decliners’. Reasons for not participating were: age, being male, having no child, prevention elsewhere, no interest. The intervention is psychologically safe: the 95 % CI for the estimated mean difference in STAI DY1 between phase II/I subjects, ( mean difference - 1.07, 95 % CI (-4.48;2.35), p=0.53), shows that the mean STAI DY1 score for phase II is at most 2.35 units higher than for phase I, which is not relevant. Conclusions: The practice of proband - based information tranfer in BRCA families is highly defective. A protocol in which relatives are directly informed by the counselor nearly doubles the number of relatives tested. This approach is psychologically safe and allows more carriers to adopt effective prevention. These results should lead to a change in counseling guidelines in families with a strong germline predisposition for cancer. Clinical trial information: 2005/087.
Analysis of apoptotic processes in bone marrow cell culture of lymphoma (L) patients (pts).
Authors: Kristina A. Novoselova, Elena Yurievna Zlatnik, Irina B. Lysenko, Liubov Yu Vladimirova, Inna Arnoldovna Novikova, Larisa V. Peredreeva, Nadezhda V. Nikolaeva, Elena A. Kapuza, Olga V. Kozyuk, Tatyana A. Snezhko, Olga N. Shatokhina, Viktoriya V. Dmitrieva
Journal: Journal of Clinical Oncology (2014)

e14018 Background: Apoptosis is important process in the tumor cell death and is poorly studied in L pts. Methods: An analysis ofapoptosis was made with an annexin test in vitro in bone marrow cell culture. The effect of pentoxyphyline low concentrations on bone marrow cells was studied in 40 pts with newly diagnosed L and in 40 pts with L relapses. Bone marrow samples (2 ml) were placed into test-tubes with heparinized medium and treated with pentoxyphyline diluted with isotonic sodium chloride solution in a concentration of 10-6/ml. Bone marrow aspirate with the equivalent volume of heparinized medium was used as the control. The analysis was carried out in dependence of mts to bone marrow. Results: The Table presents the data on spontaneous and induced apoptosis and necrosis of bone marrow cell culture in the L pts. Conclusions: Decrease of the cells in early apoptosis was revealed in the pts with L relapses in comparison to pts with newly diagnosed L, р<0,05. This testifies to the poor prognosis in case of L relapses. Apoptotic properties of pentoxyphyline (the drug not meant for apoptosis induction) were revealed. This leads to the necessity of L chemotherapy individualization, as well as the possibility of pentoxyphyline usage in order to increase cytostatics effectiveness. Pts with newly diagnosed L Pts with L relapses Without bone marrow mts n=20 Without bone marrow mts n=20 With bone marrow mts n=14 Without bone marrow mts n=26 Early apoptosis Late apoptosis Necrosis Early apoptosis Late apoptosis Necrosis Early apoptosis Late apoptosis Necrosis Early apoptosis Late apoptosis Necrosis Control n=80 9,9±0,8 3,3±0,8 0 7,6±1,0 6±0,7 1,4±0,3 7,8±1,5b 4,5±0,7 1,8±1,1 5,5±1,8 b 2,8±0,5 0 Pentoxyphyline n=80 15,5±0,5a 18±2,0a 7,5±0,5a 12±1,9a 13±1,6a 2,7±0,5 8,2±1,4 7,3±0,4 2,3±0,8 16,3±2,0a 13,3±1,3a 7,3±1,3a a Statistically valid to the control, р<0,05. b Statistically valid to the group of newly diagnosed L pts, р<0,05.
Exploration of Potential Relationships between CD22 and Selected Safety Outcomes in the Inotuzumab Ozogamicin Phase 3 INO-VATE Study
Authors: Partow Kebriaei, Daniel J. DeAngelo, Anjali S. Advani, Susan M. O'Brien, David Marks, Hagop M. Kantarjian, Elias J. Jabbour, Tao Wang, Erik Vandendries, A. Douglas Laird, Sonja Nick, Matthias Stelljes
Journal: Blood (2018)
GPs think that lack of mental health services is putting young people at risk
Authors: Abi Rimmer
Journal: BMJ (2018)

UK general practitioners think that mental health services for children and young people are inadequate, a survey has found.

The survey of 1000 UK GPs found that 99% feared that young people may come to harm while waiting for specialist mental health treatment from Child and Adolescent Mental Health Services (CAMHS).

The survey, conducted on behalf of mental health charity stem4, found …
A virtual consult service to optimize clinical trial participation in patients with metastatic breast cancer.
Authors: Karen Anne Cadoo, Payal Deepak Shah, Alexandra Snyder Charen, Jacqueline Bromberg, Elizabeth Anne Comen, Gabriella D'Andrea, Chau T. Dang, Teresa Gilewski, Ayca Gucalp, Diana Lake, Andrew David Seidman, Maria Theodoulou, Tiffany A. Traina, Clifford A. Hudis, Larry Norton, Mary Ellen Moynahan, Shanu Modi, Maura N. Dickler, Jose Baselga, Sarat Chandarlapaty
Journal: Journal of Clinical Oncology (2014)

6601 Background: With an increasing complexity and number of endocrine, molecularly-targeted and immunotherapeutic clinical trial and standard-of-care therapies available for patients with metastatic breast cancer (MBC), rapidly identifying appropriate options is a challenge for physicians. We designed and piloted an email-based virtual consult system to facilitate matching of patients to appropriate studies. Methods: We assembled eligibility criteria and slot availability for 10 therapeutic Phase Ib/II clinical trials in the Breast Cancer Medicine Service at a tertiary referral center. Service physicians emailed patient details to a centralized address, one of three consulting fellows reviewed the patient’s chart and responded within 24 hours with a ranked list of relevant studies. Results: 56 unique consults were received in 4 months. Median age was 56 (21-83), median ECOG performance status 0 (0-3). Reflecting the trials available, the majority (96%) of patients had estrogen receptor positive, human epidermal growth factor receptor 2 (HER2) negative disease. Mutational analysis of PIK3CA, AKT and HER2 was available for 35 tumors (62.5%); 21 had an actionable mutation, all of these tumors harbored PIK3CA mutations, one had a concurrent AKT mutation. 44/56 patients (79%) were eligible for at least one trial, of which 24 (55%) are enrolled onto or waitlisted for a specific study. Of the 20 eligible patients who did not pursue a trial, reasons included: the attending recommended alternate therapy with cause (9, 45%) patient declined (4, 20%), trial slot was unavailable (2, 10%), or unknown (5, 25%). 12 patients (21%) were ineligible due to site of progressive disease, second active malignancy, number of prior therapies or declining performance status. Conclusions: This virtual consult system is a potential strategy to assist physicians in identifying clinical trial options for patients. This process can be performed by supervised non-professional personnel with defined criteria, which will be the next phase of the pilot, incorporating prespecified metrics to ascertain the benefit.
FOLFIRI regimen as second- and third-line chemotherapy for metastatic biliary tract or pancreatic cancer.
Authors: Fernanda Navarro Loiola, Marcos Pedro Guedes Camandaroba, Viviane Teodoro Oliveira Fernandes, Augusto Akikubo Rodrigues Pereira
Journal: Journal of Clinical Oncology (2014)

e15122 Background: Currently, there is no standard treatment after progression in the first-line therapy with gemcitabine-based regimens for pancreatic and biliary tract carcinomas. Methods: We retrospectively analyzed, from January 2010 to January 2014, patients with metastatic pancreatic or biliary tract cancer treated with FOLFIRI as second and third-line therapy, in a single institution, to evaluate toxicity and efficacy of this regimen. FOLFIRI consisted of irinotecan 180 mg/m2 IV on D1, leucovorin 200 mg/m2 IV on D1, 5-FU 400 mg/m2 bolus on D1 and 5-FU 2400 mg/m2IV by continuous infusion for 46 hours, repeated every 2 weeks until progression. Results: Of 21 patients, 9 (42.9%) had pancreatic and 12 (57.1%) had biliary tract cancer. Eleven (52.3%) patients were treated in the second-line and 10 (47.6%) in the third-line. Median age was 57 years-old (range:39-74). Median number of cycles was 7 (range:3-26). Overall response (ORR) and disease control rates (DCR=ORR+SD) were 19.0% and 57.1%, respectively. In the second-line treatment, ORR and DCR were 36.3% and 63.0%, respectively. There were none responses on the third-line, but 50.0% had stable disease as best response. Patients with pancreatic and biliary cancer had DCR of 33.3% and 75.0% (p=0,087), respectively. Most common G3-4 adverse events were neutropenia (33.4%), febrile neutropenia (14.3%), anemia (9.5%) and diarrhea (4.8%). In the entire population, median OS was 11.59 months (95%CI, 8.02-15.17) and median PFS was 5.06 months (95%CI, 2.56-7.55). Median OS in the second-line was 9.75 vs. 7.63 months in the third-line (p=0,71). Median PFS in the second-line and third-line was 5.06 vs. 2.36 months, respectively (p=0,14). Patients with DCR had significant improved OS (13.24 vs. 5.02 months; p=0,002) and PFS (7.68 vs. 2.36 months; p<0.0001) compared with patients who had progressive disease. Conclusions: FOLFIRI regimen had an acceptable toxicity profile and a good activity, mainly in the second-line treatment. Improved OS and PFS were found in patients who achieved partial response or stable disease.
Sorafenib with or without everolimus in patients with unresectable hepatocellular carcinoma (HCC): A randomized multicenter phase II trial (SAKK 77/08 and SASL 29).
Authors: Dieter Koeberle, Jean-Francois Dufour, Gyula Demeter, Panagiotis Samaras, Piercarlo Saletti, Qiyu Li, Arnaud Roth, Daniel Horber, Michael Buehlmann, Anna Dorothea Wagner, Michael Montemurro, Gabor Lakatos, Karin Ribi, Jonas Feilchenfeld, Markus Peck-Radosavljevic, Daniel Rauch, Ivana Cvijetic, Britta Tschanz, Gyorgy Bodoky
Journal: Journal of Clinical Oncology (2014)

4099 Background: Sorafenib (S), a multitargeted tyrosine kinase inhibitor, has become standard of care for first-line systemic treatment of advanced HCC. Everolimus (E) is a potent inhibitor of the mTOR, a pathway frequently up-regulated in HCC. In preclinical HCC-models, S+E has additive effects compared to S. The objective of this trial was to investigate the antitumor activity of combined treatment with S+E. Methods: Patients (pts) with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomly assigned to receive daily S 800 mg alone or S 800 mg + E 5 mg until progression or unacceptable toxicity. The primary endpoint was progression free survival at 12 weeks (PFS12). In the S+E arm a PFS12 of ≤ 55% was considered uninteresting and promising if ≥ 75% using a Fleming`s single-stage design with 90% power and 5% significance level. The S arm was used for calibration. Secondary endpoints included response rate, PFS, TTP, OS, duration of disease stabilization (DS), safety and quality of life (QoL) assessments. Results: 106 pts were randomized;46 pts received S and 60 pts S+E. 93 pts are evaluable for the primary endpoint, 105 pts for the safety analysis. Main reasons for stopping therapy were: progressive disease (S: 64%; S+E: 51%), toxicity (S: 21%; S+E: 28%), or death 5% (both arms). PFS12 rate was 70% in S (95% CI: 54-83) and 68% in S+E (95% CI: 53-81). Response rate was 0% in S arm and 10% in S+E arm. Median PFS was 6.6 vs. 5.7, median TTP was 7.6 vs. 6.3, median DS 6.7 vs. 6.7, and median OS 10 vs. 12 months in the S vs. S+E arm. Activation of Hepatitis C virus was observed in 3 pts in each arm. No re-activation of Hepatitis B virus infection occurred. Grade 3 and 4 adverse events occurred in 72% (S) and in 86% (S+E). Pts receiving S+E had worse QoL scores over time compared to pts receiving S with significant differences for physical well-being and mood. Conclusions: Addition of a reduced dose of E to full doses of S is feasible, equally effective, but more toxic than S alone. Phase III testing of S 800 mg + E 5 mg daily appears not warranted in patients with unselected advanced HCC. Clinical trial information: NCT01005199.
Abstract 17788: Heart Failure With Mid-Range Ejection Fraction: Clinical Characteristics and Survival Comparing With Heart Failure With Reduced and Preserved Ejection Fraction
Authors: Dan L Li, Renato Quispe, Nidhi Madan, Cynthia C Taub
Journal: Circulation (2017)

Introduction: Definitions of heart failure (HF) with preserved ejection fraction (HFpEF) and with reduced EF (HFrEF) are variable in prior literature. There is significant overlap of left ventricul...
Epidemiologic profile of colorecto-anal cancer in Oncologos del Occidente from Colombia 1997-2012.
Authors: Carlos Raul Villegas Mejia, Jose Arnoby Chacon Cardona, Tomas Sanchez Villegas
Journal: Journal of Clinical Oncology (2014)

e14653 Background: Colorectal cancer is the third leading cause of cancer death in the Western world and the fourth leading cause in Colombia, being the East the regions with the highest mortality rates. There are many prognostic factors described in the literature, but the clinical stage is the most important but the pattern of occurrence of this neoplasm has been little studied. Methods: A descriptive study of patients with Colon, Rectum and Anal cancer who attended to Oncólogos del Occidente of eastern Colombia (Caldas, Risaralda, Quindío, and North of Valle) from 1997 to 2013 was performed. Results: 2279 patients were analyzed with 50 % of colon, rectum 41 % and 9% of anal cancer; 56 % female; 38% of 41-60 years old and 43% from 61-80 years, 7% over 81 years old; 41 % in right colon , middle rectum 49 % and 43 % low rectum; 44% localized clinical stage, 43% in advanced stage and 10% metastatic state; Caldas State 34%, Risaralda state 33%, Quindío state 23% and North of Valle state 9%; 93% Urban Area; chemotherapy regimens applied like XELOX 13.4%, 4.4% Capecitabine alone, FOLFOX 4 in 6%, 5-FU as monotherapy in 4% and LF on 45%. The distribution of diagnoses per year was 2% in 1997, 8 % in 2009 increased to 15% in 2013; prognostic factors were Obstruction ( 29%), Ulceration ( 25%) and 30% without any factor; 33% had 12 or more lymph nodes retrieved; 27 % had liver metastases. Conclusions: To our knowledge, this is the first study and represents a report that will reveal the epidemiological profile of this neoplasm in a specific area of Colombia (Coffee Triangle) in order to understand their pattern of occurrence, so subsequent analytic studies should be made based on this work.