tbuckley/cabot-search huggingface dataset:
Long term toxicity and fatigue after treatment for non-Hodgkin lymphoma (NHL): An analysis of twelve collaborative lymphoma study association (LYSA) trials, the Simonal Study.
Authors: Nicolas Mounier, Sabine Anthony, Raphael Busson, Catherine Thieblemont, Virginie Nerich, Vincent Ribrag, Marie Castera, Herve Tilly, Corinne Haioun, Rene-Olivier Casasnovas, Franck Morschhauser, Pierre Feugier, Richard Delarue, Loic Ysebaert, Catherine Sebban, Florence Broussais, Gandhi Damaj, Jean-Philippe Jais, Michel Henry-Amar, Gilles A. Salles
Journal: Journal of Clinical Oncology (2016)

7518 Background: NHL survivors are at high risk for second cancers (SC) and late toxicities such as cardiovascular (CV) or neuro-psychiatric (NP) disorders. Little is known about new agents such as rituximab (RITUX). The impact of treatment regimens on late morbidity was analyzed in a large cohort of survivors with long follow-up (FU). Methods: In 2015, a fatigue (MFI-20) and a self-assessment Life Situation Questionnaire (LSQ) were mailed to survivors treated in 12 successive LYSA randomized trials (1993-2007) for Diffuse Large B cell (DLBCL) and follicular (FL) lymphomas. Of 8113 pts enrolled into trials, 5247 were alive at last FU. Addresses were obtained for 3317 survivors of whom 1671 (50%) returned the questionnaires. Responders more often came from recent trials and were more often treated with RITUX than non-responders. NHL prognostic factors and chemotherapy were similar in both groups. Linear regression models were used to assess factors linked to increased fatigue level. Results: There were 906 males and 765 females (median age 64 yrs; 24 to 95). 28% had FL and 72% DLBCL. 811 pts received CHOP-like chemotherapy, 518 high-dose CHOP and 342 up-front autograft consolidation (ASCT). RITUX was combined to chemotherapy in 829 pts (50%). Median FU was 11 yrs (5 to 23). 583 pts (35%) reported no morbidity. For the remaining, late events (1 to 7) were: CV in 20%, NP in 17%, infections in 12%, musculoskeletal (MSk) disorders in 11%, pulmonary (Pulm) diseases in 8%, digestive diseases in 5% and SC in 8%. RITUX was associated with less SC (6 vs 9%, p = 0.02) and less CV (17 vs 23%, p = 0.006). Up-front ASCT was associated with more infections (17 vs 11%, p = 0.002) and more Pulm (12 vs 7%, p = 0.005). Age above 75 (20%) was only associated with more CV and more SC. 1036 pts (64%) expressed persistent fatigue (MFI score ≥ 40). There were no significant impact of any treatments. Increased fatigue level was associated (p < 0.001) with age, obesity, CV, Pulm, MSk and NP. Conclusions: This first study reporting on long-term NHL survivors confirmes an altered health status. Initial combination of chemotherapy and RITUX does not increase late morbidity and fatigue. Clinical trial information: pooled trials already registred.
Abstract 222: Combination of Blood Cardioplegic and Strategic Reperfusion Period Leucodepletion During Cardiopulmonary Bypass Preserves the Cardiac and Pulmonary Function: A Prospective Randomized Controlled Study
Authors: Qiang Chen, Amir Sheikh, Stuart Sheppard, Roslyn Gibbs, David Smith, Marcus Haw
Journal: Circulation Research (2012)

Objectives: Leucocytes activation during cardiopulmonary bypass (CPB) contributes to postoperative organ dysfunction. We compared the outcomes of various leucodepletion strategies in patients undergoing coronary artery bypass grafting (CABG). Methods: One hundred-twenty low-risk patients undergoing first time CABG were prospectively randomized to six groups: 1 non-leucodepletion arterial filtration; 2 continuous arterial leucodepletion; 3 reperfusion period leucodepletion; 4 leucodepletion of blood cardioplegia; 5 combination of continuous arterial and blood cardioplegic leucodepletion; 6 combination of blood cardioplegic and reperfusion period leucodepletion. Blood samples were taken 5 min before CPB, 5 and 30 min on CPB, 5, 60 min after aortic X-clamp removal and 6 h post-CPB. Activated leucocytes were identified with Nitroblue Tetrazolium staining. Exhaled nitro oxide (NO) was measured pre- and post-CPB using real-time chemiluminescense analyzer. Respiratory index (alveolar-arterial oxygenation index, AaOI) was calculated 5 min before CPB and 5 min on CPB, 1, 2, 4, 8 and 18 h post-CPB. Results: Activated white cell counts were similar before CPB in all groups, but reduced significantly 5, 60 min following aortic X-clamp removal, and 6 h post-CPB in groups 2, 3, 5 and 6, compared with group 1 (ANOVA p=0.02). Post-CPB, NO increased in all groups (p&lt;0.05) except in Group 6 (3.17±0.64 vs. 3.63±0.79 ppb/s, p=0.22). Group 6 exhibited a lower AaOI than group 1 over all time points post-CPB (ANOVA, p=0.02). Postoperatively, there was a significant reduction in inotropic requirement, ventilation time and atrial fibrillation in group 6 (p=0.045, 0.04 and 0.043, respectively). There was no difference in chest drain output, length of ICU and hospital stay among all groups. Conclusions: Combination of blood cardioplegic and reperfusion period leucodepletion appeared to be most effective in attenuating activated leucocytes during CPB, which was associated with better preservation of cardiac and pulmonary function compared with other leucodepletion strategies.
A changing natural history of HER2-positive breast cancer metastatic to the brain in the era of new, targeted therapies.
Authors: Louisa Mounsey, Allison Mary Deal, Julia M. Benbow, Kevin Keith, Timothy Zagar, Elizabeth Claire Dees, Lisa A. Carey, Matthew G. Ewend, Carey K. Anders
Journal: Journal of Clinical Oncology (2016)

584 Background: The prognosis of advanced HER2+ breast cancer has evolved with the wide adoption of HER2-targeted therapies. Given the frequency and clinical importance of breast cancer brain metastases (BCBM) in HER2+ breast cancer, we studied how prognosis of BCBM has varied over time. Methods: Patients with HER2+ BCBM were identified from a prospectively-maintained database at the University of North Carolina Chapel Hill. Patients were divided into 3 cohorts defined by year of BCBM diagnosis. Cohort time intervals were selected by year of HER2-targeted therapy FDA approvals (1998-2007, trastuzumab; 2008-2012, lapatinib; 2013-2015, pertuzumab and trastuzumab-emtansine [TDM1]). Overall survival (OS), time to non-brain metastatic diagnosis, time to BCBM, and survival after BCBM were evaluated using the Kaplan-Meier method. Results: 123 patients were identified for analysis: mean age 51.6 years (yrs), 61% Caucasian, and 32% African American. 64% of patients received systemic therapy after BCBM diagnosis, 86% received radiation to the brain (60% WBRT, 21% SRS, 19% both), and 27% underwent neurosurgical resection. IHC subtype illustrated hormone receptor (HR) positivity in 56%. 30% of patients were diagnosed with BCBM between the years 1998-2007, 37% 2008-2012, and 33% 2013-2015. OS from initial breast cancer diagnosis improved over time (3.6 yrs [CI 2.8-6.1] 1998-2007, 6.6 yrs [CI 4.5- 8.6] 2008-2012, 7.6 yrs [CI 4.4-9.6] 2013-2015, p = 0.05). While the time to non-brain metastatic diagnosis did not differ by cohort (p = 0.09), time to BCBM improved over time (2.6 yrs [CI 1.3-3.5] 1998-2007, 2.6 yrs [CI 2.1-4.3] 2008-2012, 3.4 yrs [CI 2.2-6] 2013-2015, p = 0.04). Although survival following BCBM diagnosis was not significantly different by cohort (p = 0.24), patients who received HER2-targeted therapy after BCBM lived longer than those who did not (2.1 yrs [CI 1.6-2.6] vs. 0.65 yrs [CI 0.4-1.3], p = .0014). Conclusions: OS from primary breast cancer diagnosis for patients with HER2+ breast cancer who develop BCBM has significantly improved over time, now exceeding 7 years; survival from brain metastasis diagnosis may now exceed 2 years.
The emergence of Clostridium difficile PCR ribotype 027 in Denmark – a possible link with the increased consumption of fluoroquinolones and cephalosporins?
Authors: L Søes, K Mølbak, S Strøbæk, K Truberg Jensen, M Torpdahl, S Persson, M Kemp, K E Olsen
Journal: Eurosurveillance (2009)

Increasing rates of Clostridium difficile infection (CDI) with an unusual, severe course have been reported in several countries; this rise has partly been ascribed to the emergence of a virulent strain, C. difficile PCR ribotype 027 (CD027). An intriguing question is whether this could be related to increasing consumption of broadspectrum antibiotics. From 1997 to 2007, the number of hospital discharges in Denmark with the diagnosis enterocolitis caused by C. difficile increased from eight to 23 per 100,000 hospital discharges. This increase was proportional to a concomitant rise in the consumption of fluoroquinolones and cephalosporins. The first outbreak of CD027 in Denmark occurred from October 2006 to August 2007 and included 13 patients, most of them elderly, admitted to three hospitals in the same region. Most of the patients had overlapping periods of admission. All patients had been treated with broadspectrum antibiotics, in particular cephalosporins and fluoroquinolones, prior to positive culture of CD027. 30 days after confirmation of diagnosis, three of the 13 patients had died. Taken together, the data support the hypothesis that the increasing use of certain broadspectrum antibiotics may be related to a possible increase of C. difficile infection, and show that the specific contribution by CD027 in its emergence needs to be determined.
Abstract P028: The Effect of Cotransplantation of Human Embryonic Stem Cell--Derived Cardiomyocytes and Mesenchymal Stem Cells on Ventricular Function and Remodeling After Myocardial Infarction in Nude Rats
Authors: Wangde Dai, Mary Kearns-Jonker, Paul Gerczuk, Mirja Gunthart, Nandini Girish, Martin Pera, Christine Mummery, Robert A Kloner
Journal: Circulation Research (2011)

We determined whether co-transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and mesenchymal stem cells (MSCs) had additive effects on left ventricular (LV) function and remodeling compared with hESC-CMs treatment alone in a rat myocardial infarction model. One week after myocardial infarction induced by left coronary ligation, nude rats received hESC-CMs (n=15), hESC-CMs + MSCs (n=16), hESC-CMs + MSCs transduced to over-express hemeoxygenase 1(HO-1) (n=14), or saline (n=19). At 4 weeks after treatment, LV function was assessed by left ventriculography, echocardiography and Millar catheter. Some hearts were processed for histology. The LV ejection fraction (LVEF) in sham noninfarcted hearts was 78.1±1.8% (n=5) in the nude rat model. LVEF in the 3 cell treated groups (hESC-CMs: 67.6±1.4%; hESC-CMs + MSCs: 67.2±1.6%; and hESC-CMs + MSCs with HO-1: 66.3±1.7%) were comparable, and significantly higher than in the saline group (60.6±1.2%, n=19; p=0.0022). There was a trend for less left ventricular akinesis and dyskinesis (expressed as % of LV circumference) assessed by left ventriculography at 8.96±1.9% in hESC-CMs group, 8.37±1.67% in hESC-CMs + MSCs group and 4.57±1% in hESC-CMs + MSCs with HO-1 group compared to 10.73±1.76% in the control group (p=0.056). There was a nonsignificant trend for LV fractional shortening assessed by echocardiography to be greater in the 3 cell groups (32.1±3.9% in hESC-CMs; 30.2±2% in hESC-CMs + MSCs; 31.0±1.9% in hESC-CMs + MSCs with HO-1) compared to 24.8±2.2% in the saline group (p=0.18). Expansion index reflecting thinning and dilatation of the infarct was significantly worse in the control group at 0.71±0.05 versus the other 3 groups at 0.32±0.05 (p=0.0039). Thus, cell therapy by hESC-CMs alone or combination transplantation of hESC-CMs and MSCs (with or without HO-1) significantly improved LV function assessed by left ventriculography and reduced expansion index. However, co-transplantation of hESC-CMs and MSCs did not provide better functional improvement compared with hESC-CMs treatment alone after left coronary artery occlusion in nude rats over a period of 4 weeks, suggesting that there may be a ceiling effect above which LV function can not further improve after cell therapy.
Combination of Ibrutinib and BCL-2 or SYK Inhibitors in Ibrutinib Resistant ABC-Subtype of Diffuse Large B-Cell Lymphoma
Authors: Hsu-Ping Kuo, Richard Crowley, Ling Xue, Karl J. Schweighofer, Leo WK. Cheung, Sidney Hsieh, Karl Eckert, Matthias Versele, Betty Y. Chang
Journal: Blood (2014)
Association of dietary fiber intake and gut microbiota in healthy adults.
Authors: Daniel Lin, Brandilyn Peters, Rashmi Sinha, James J. Goedert, Richard Hayes, Jiyoung Ahn
Journal: Journal of Clinical Oncology (2017)

1569 Background: Increasing evidence has shown that gut microbiota alterations may play a role in colorectal cancer risk. Diet, particularly fiber intake, may modify gut microbiota composition, which may consequently impact cancer risk development. We investigated the relationship between dietary fiber intake and gut microbiota in healthy humans. Methods: Using 16S rRNA gene sequencing, we assessed gut microbiota in fecal samples from 151 healthy adults in two independent study populations: Study A, n = 75 (healthy controls from a colorectal cancer case-control study), and Study B, n = 76 (polyp-free subjects from a cross-sectional colonoscopy study). We calculated energy-adjusted total dietary fiber intake of participants based on food frequency questionnaires. For each study population, we evaluated the relationship between quartiles of higher fiber intake as a continuous ordinal variable, and global gut microbiota community composition (via PERMANOVA of weighted UniFrac distance) and specific taxon abundance (via DESeq2). Results: We found that fiber intake was significantly associated with overall microbial community composition in Study B (p = 0.003) but not Study A (p = 0.68), after adjustment for age, sex, race, body mass index, and cigarette smoking. In a taxonomy-based meta-analysis of these two study populations, higher fiber intake was associated with lower abundance of genus Actinomyces (fold change [FC] = 0.769, p = 0.003), and higher abundance of genera Faecalibacterium (FC = 1.153, p = 0.03), Lachnospira (FC = 1.167, p = 0.04), and SMB53 (FC = 1.201, p = 0.05). A species-level meta-analysis showed an association between higher fiber intake and higher abundance of Faecalibacterium prausnitzii (FC = 1.165, p = 0.03) and lower abundance of Ruminococcus bromii (FC = 0.828, p = 0.08). Conclusions: Our results suggest that higher intake of dietary fiber may alter gut microbiota in healthy adults. Given the potentially modifiable nature of the gut microbiota through diet, these findings warrant further study of diet-microbiota based colorectal cancer prevention strategies.
Aspects morphologiques pancréatiques et biliaires de la pancréatite auto-immune en IRM et en échoendoscopie
Authors: D O'Toole, MP Vullierme, V Rebours, L Palazzo, A Aubert, P Ponsot, K Nahon-Uzan, A Couvelard, P Lévy, P Ruszniewski, V Vilgrain, P Hammel
Journal: Endoscopy (2006)

En absence d'histologie ou de maladie dysimmunitaire associée, le diagnostic demeure difficile. Des anomalies parenchymateuses ou canalaires évocatrices ont été suggérées en IRM et échoendoscopie (EE), mais les données sont limitées.
European Post-Approval Safety Study (Registry) of Relapsed/Refractory Multiple Myeloma (RRMM): Safety of Patients Treated with Pomalidomide
Authors: Francesco Di Raimondo, Charalampia Kyriakou, Martin Schmidt-Hieber, Marie-Christiane Vekemans, Ángel Ramírez Payer, Pal Tore Bentsen, Birgitta Lauri, Elisabeth Kueenburg, Frederik Lersch, Barbara Rosettani, Pamela Bacon, Torben Plesner
Journal: Blood (2016)
Initial experience with molecular testing for HNPCC
Authors: K Sheahan, D Keegan, E Fox, D Leahy, R Geraghty, A Green, J Hyland, DP O'Donoghue
Journal: Endoscopy (2005)

Aims: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) accounts for 1–3% of all colorectal cancer (CRC) cases. Diagnosis can lead to appropriate screening of patients and affected family members. Identification of the causative mutation allows for predictive testing of family members. Microsatellite instability (MSI) detection & immunohistochemistry (IHC) for mismatch repair proteins (MMR) may help identify cases and focus the search for the mutation.
Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy.
Authors: Chantale Bernatchez, Cara L. Haymaker, Michael E. Hurwitz, Harriet M. Kluger, Michael T. Tetzlaff, Natalie Jackson, Ivan Gergel, Mary Ann Tagliaferri, Jonathan Zalevsky, Ute Hoch, Christie Fanton, Ernesto Iacucci, Sandra Aung, Michael Imperiale, Ej Liao, Salah E Bentebibel, Nizar M. Tannir, Patrick Hwu, Mario Sznol, Adi Diab
Journal: Journal of Clinical Oncology (2017)

2545 Background: NKTR-214 is a CD122-biased agonist designed to provide sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2Rβɣ) to preferentially activate and expand effector CD8+ T and NK cells over T regulatory cells in the tumor microenvironment. Immune changes in the tumor microenvironment after NKTR-214 treatment was assessed in patients with locally advanced or metastatic solid tumors. Methods: NKTR-214 was administered IV in an outpatient setting q2w or q3w. Serial blood and tumor tissue samples were collected to measure immune activation using immunophenotyping including flow cytometry, immunohistochemistry (IHC), T cell clonality and gene expression analyses. Results: 26 patients (pts) have been treated with NKTR-214 at q3w, 4@0.003, 9@0.006, 6@0.009 and 1@0.012 mg/kg. Six pts received 0.006 mg/kg q2w. 58% of pts had prior immunotherapy. The most common Gr1-2 TRAEs were fatigue (73%) and pruritus (65%), and decreased appetite (46%). One pt experienced Gr3 syncope and hypotension at the highest dose tested and continued treatment at a lower dose. No drug-related AEs led to study discontinuation. No immune-related AEs or capillary leak syndrome were observed. 6 pts (23%) experienced tumor shrinkage from 10-30%. Three immunotherapy naïve pts receiving sequential anti-PD1 therapy, after ending treatment with NKTR-214, experienced significant tumor regression at first scan. In all pts evaluated, blood samples showed increases in newly proliferating (Ki67+) T and NK cells 8 days post dose. Flow cytometry and/or IHC revealed an up to 10-fold increase from baseline in tumor CD8+T and NK cells in the tumor microenvironment, with minimal changes to Tregs. PD-1 expression increased 2-fold in TILs. Gene expression analysis of tumor tissue showed increases in several immune checkpoint genes, cytotoxic markers (IFNg, PRF1, and GZMB), as well as a dynamic change in T cell clonality. Conclusions: Based on a favorable safety profile and strong correlative biomarker data, a phase 1/2 trial combining NKTR-214 and nivolumab is currently enrolling. Clinical trial information: NCT02869295.
Apport de la cytométrie en flux par brossage cytologique dans la prise en charge de l'endobrachyoesophage
Authors: YH Lam, A Chassevent, V Quentin, V Le Tallec, A Maurin, J Boyer
Journal: Endoscopy (2006)

Actuellement il est recommandé de surveiller l'endobrachyoesophage par le protocole biopsique de la Société Francaise d'Endoscopie Digestive (SFED). Il est cependant limité d'une part par le risque d'échantillonnage car il n'explore environ que 5% de la muqueuse et d'autre part par la mauvaise concordance inter observateurs pour le diagnostic anatomopathologique des dysplasies.
BMA annual meeting: UK government must act to avert future medical workforce crises, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

Delegates at the BMA’s annual representative meeting in Bournemouth on Monday 26 June voted in favour of a motion demanding that the UK government should take action to bolster the workforce. As part of this work it should review its shortage occupation list and invest in particular medical specialties at risk of shortages, the motion said.

The shortage occupation list is an official list of occupations for which there are not enough UK workers to fill vacancies. …
Questions remain over implementing Scottish scheme to curb harmful drinking
Authors: Bryan Christie
Journal: BMJ (2017)

GPs in Scotland have an important role in helping patients curb excessive alcohol consumption, but lessons need to be learnt on the best way to support interventions, say two research reports.12

Scotland introduced a national programme of delivering alcohol brief interventions for heavy drinkers in 2008. From then till 2015 more than 560 000 such interventions were delivered, more than half of them in primary care.

The evidence based interventions, comprising short, structured conversations, aimed to motivate people to change their drinking habits. The two new reports, funded by Scottish Health Action on Alcohol Problems …
Characteristics of Prostate Cancer Found at Fifth Screening in the European Randomized Study of Screening for Prostate Cancer Rotterdam: Can We Selectively Detect High-grade Prostate Cancer with Upfront Multivariable Risk Stratification and Magnetic Resonance Imaging?
Authors: Arnout R. Alberts, Ivo G. Schoots, Leonard P. Bokhorst, Frank-Jan H. Drost, Geert J. van Leenders, Gabriel P. Krestin, Roy S. Dwarkasing, Jelle O. Barentsz, Fritz H. Schröder, Chris H. Bangma, Monique J. Roobol
Journal: European Urology (2017)
Prévalence de l'endobrachyoesopahe au cours de la sclérodermie systémique
Authors: J Wipff, Y Allanore, F Soussi, B Terris, V Abitbol, A Kahan, S Chaussade
Journal: Endoscopy (2005)

L'atteinte oesophagienne est fréquente (70 à 90% des cas) au cours de la sclérodermie systémique (ss) conduisant à la survenue d'un RGO quasi constant. L'Endobrachyoesophage (EBO) est une complication fréquente du RGO, exposant les patients à un risque d'adenocarcinome. Les facteurs de risque reconnus de l'EBO, en dehors du RGO, sont le sexe masculin, une origine caucasienne, l'obésité, un alcoolo tabagisme. Le rôle des IPP dans la prévention de la survenue de l'EBO ou d'une dysplasie est discuté.