tbuckley/cabot-search huggingface dataset:
Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer
Authors: Athanassios Argiris, Shuli Li, Panayiotis Savvides, James P. Ohr, Jill Gilbert, Marshall A. Levine, Arnab Chakravarti, Missak Haigentz Jr, Nabil F. Saba, Chukwuemeka V. Ikpeazu, Charles J. Schneider, Harlan A. Pinto, Arlene A. Forastiere, Barbara Burtness
Journal: Journal of Clinical Oncology (2019)

We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved.The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy (P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy (P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy.The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.
Infectious Complications in Advanced Relapsed/Refractory Multiple Myeloma Patients Treated with Lenalidomide (Revlimid +/- Corticosteroids).
Authors: Vishal Kukreti, Esther Masih-Khan, Saima Dean, Deepali Kumar, Joseph R. Mikhael, Suzanne Trudel, Donna E. Reece, Christine Chen
Journal: Blood (2009)
PWE-121 Faecal Calprotectin Levels of 50–200: Endoscopic Findings and Subsequent Diagnoses
Authors: S Sartain, A Stone
Journal: Gut (2016)

<h3>Introduction</h3> Faecal calprotectin (FC) is a marker of intestinal inflammation, used to investigate gastrointestinal symptoms for inflammatory bowel disease (IBD). The normal range and significance of mild elevations in FC remains under debate. This study aimed to determine endoscopic findings and conditions associated with levels of 50–200. <h3>Methods</h3> Data was collected retrospectively. Details of patients with FC of 50–200 received by St Richard’s Hospital pathology department over an 11 month period were obtained. Results were reviewed with clinical information from clinic letters and investigations that were available 9 months after the FC collection period. <h3>Results</h3> 189 patients had a FC of 50–200, with 109 having clinical information available. The remaining 80 not seen in secondary care were excluded. Of the 109 patients included, mean FC was 102.7, 73 were female and mean age 47.3 years. The most prevalent symptoms were abdominal pain (46.8%) and diarrhoea (64.2%). 82 (75.2%) patients underwent endoscopy, (54 colonoscopies, 32 flexi-sigmoidoscopies), with 10 procedures done before. 47 (57.3%) patients had normal endoscopies, with 34 (63%) colonoscopies being normal. Abnormalities included inflammation, ulcers, diverticulosis and polyps with low grade dysplasia. 51 patients had mucosal biopsies at recent endoscopy, with 12 showing inflammation. From these 12 patients; mean FC was 135.9, though 3 had FC &lt; 100, 4 were diagnosed with IBD (mean FC = 167.5), 2 followed up for possible IBD, 1 had collagenous colitis, 3 had non-specific colitis and 2 had infective colitis. All patients with IBD or possible IBD had FC ≥ 100, with mean FC of 158.3. Patients with no inflammation on biopsy had mean FC of 100.3. Clinic letters showed 37 (33.9%) patients had a diagnosis of irritable bowel syndrome (IBS), with mean FC of 97. 21 (19.3%) patients with normal investigations lacked a formal diagnosis, being mostly discharged or not followed up. Many patients avoided endoscopy as alternative diagnoses were made. Other diagnoses included chronic pancreatitis (5.5%), gastroenteritis (5.5%), coeliac disease (2.8%), diverticulosis (5.5%) or symptoms improved (3.7%). <h3>Conclusion</h3> FC levels of 50–200 have a low association with subsequent diagnosis of IBD (3.6%). Many patients were diagnosed with IBS or had normal investigations indicating a functional condition. In this range of FC, patients with inflammation on biopsy had a higher FC than those with negative biopsies (p &lt; 0.05). Inflammation caused by IBD had a higher FC than other causes of inflammation. Negative predictive values of FC 50–99 were higher than FC 100–200 with regards to excluding IBD (100% v 91.8%) and mucosal inflammation if undergoing endoscopy (95% v 81.6%). Many patients with FC 50–200 were not referred to secondary care. This study suggests a low rate of missed IBD is likely as a result. <h3>Disclosure of Interest</h3> None Declared
Preliminary Results Concerning the Prognosis Value of Vascular Endothelial Growth Factor (VEGF) in Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate.
Authors: Laurence Legros, Sebastien Huault, Francois-Xavier Mahon, Anne-Odile Hueber, Irit Touitou, Jill-Patrice Cassuto, Joelle Guilhot, Claude Peudhomme
Journal: Blood (2006)
What we know so far about the STPs
Authors: Nigel Edwards
Journal: BMJ (2016)

Most have set out a long shopping list of measures to achieve efficiency savings



We are starting to see what England’s 44 new sustainability and transformation plans (STPs)1 might entail. Much of the process has been conducted behind closed doors, but some full versions of STPs have been released, the first being Birmingham and Solihull.2 We can begin to see how the STPs intend to keep the health service on an even financial keel through the very stormy years ahead—and how likely they are to work.

Their task, as forecast by NHS England, is to lay out plans to achieve £15bn (€18bn; $19bn) of the £22bn in productivity savings needed across England by 2020-21.3

Around half the savings is to come from the sort of standard programme of annual efficiency targets that the NHS has been used to. Squeezing down trusts’ costs through reducing the tariff of …
SF3B1 Mutation Is an Independent Predictor of Parenchymal Iron Overload in Myelodysplastic Syndromes
Authors: Ilaria Ambaglio, Valeria Pinto, Domenico Girelli, Chiara Elena, Natascia Campostrini, Daniela Pietra, Anna Gallì, Erica Travaglino, Mario Cazzola, Gian Luca Forni, Luca Malcovati
Journal: Blood (2015)
Safety, Efficacy, and Determination of the Recommended Phase 2 Dose for the Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330)
Authors: Christine Chen, Ramiro Garzon, Martin Gutierrez, Meagan A. Jacoby, Peter Brown, Ian Flinn, Richard M. Stone, Mary Lynn Savoie, Rachid Baz, Nashat Y. Gabrail, Michael Wang, Peter Martin, David Siegel, Morten Mau-Sørensen, Michael Andreef, Tracey Marshall, Jean-Richard Saint-Martin, Robert Carlson, Sharon Shacham, Michael Kauffman, John Kuruvilla
Journal: Blood (2015)
Lenalidomide and Rituximab for the Initial Treatment of Patients with Chronic Lymphocytic Leukemia (CLL) A Multicenter Study of the CLL Research Consortium
Authors: Danelle F. James, Jennifer R. Brown, Lillian Werner, William G. Wierda, Jaqueline C. Barrientos, Januario Castro, Andrew Greaves, Laura Z. Rassenti, Kanti R. Rai, Donna Neuberg, Thomas J. Kipps
Journal: Blood (2011)
DNA Methylation Changes In Patients With Chronic Lymphocytic Leukemia Relapsing After Treatment Are Not Stochastic But Rather Selectively Affect Critical Pathways For B-Cell Physiology
Authors: Nikos Papakonstantinou, Andigoni Malousi, Maria Tsagiopoulou, Jana Gutwein, Ole Ammerpohl, Michael Kneba, Achilles Anagnostopoulos, Matthias Ritgen, Nikos Maglaveras, Reiner Siebert, Christiane Pott, Kostas Stamatopoulos
Journal: Blood (2013)
Bcl-2 and mTOR as Effective Targets for Molecular Therapy of Acute Lymphoblastic Leukemia
Authors: Stefano Iacovelli, Maria Rosaria Ricciardi, Andrea Miele, Paola Bergamo, Roberto Licchetta, Antonella Vitale, Anna Testi, Maria Teresa Petrucci, Michele Milella, Robin Foà, Agostino Tafuri
Journal: Blood (2010)
Comparison Of Epigenetic Versus Intensive Chemotherapy For Newly Diagnosed Acute Myeloid Leukemia Patients ≥60 Years Old: The Roswell Park Experience
Authors: Neha Gupta, Shipra Gandhi, Austin Miller, Laurie A Ford, Elizabeth A. Griffiths, James E. Thompson, Meir Wetzler, Eunice S. Wang
Journal: Blood (2013)
A Novel Pan-PI3K/Akt Inhibitor, SF1126, Inhibits In Vitro Growth of Multiple Myeloma Cells.
Authors: Jeannine Silberman, Kimberly Dalbey, Claire Torre, Ebenezer David, Leif Bergsagel, Donald Durden, Joseph Garlich, Ulrich Schwertschlag, Sagar Lonial
Journal: Blood (2007)
Train-the-trainer education and colonoscopy quality indicators: where to now?
Authors: Stuart K Roberts
Journal: Gut (2016)

To the Editor In their recent national randomised trial published in Gut , Kaminski et al 1 reported that a quality improvement intervention involving dedicated training of endoscopy centre leaders in colonoscopy provided superior improvement in adenoma detection rates (ADRs) in screening colonoscopy compared with those randomised to receive simple audit and feedback. While study results are subject to a possible Hawthorne effect given ADRs were higher during the period when study participants were aware of being monitored, the findings otherwise appeared robust with ADR improvement observed across all endoscopist specialties, colonoscopy experience and types of screening facilities. These are important findings given that ADR is a key quality indicator of colonoscopy because of its role as an independent predictor of the …
Phenotype Correction of Hemophilia A Mice with Adeno-Associated Virus (AAV) Vectors Carrying the B Domain Deleted Canine Factor VIII Gene.
Authors: Jun Mimuro, Akira Ishiwata, Yuji Kashiwakura, Katsuhiro Takano, Tsukasa Ohmori, Seiji Madoiwa, Hiroaki Mizukami, Keiya Ozawa, Yoichi Sakata
Journal: Blood (2004)
Gene Expression Profiling of Mantle Cell Lymphoma in the Leukemic Phase Reveals Aberrant Expression of Genes from the TGF-β Signaling Pathway.
Authors: Edgar G. Rizzatti, Rodrigo A. Panepucci, Rodrigo Proto-Siqueira, Wilma T. Anselmo-Lima, Oswaldo K. Okamoto, Roberto P. Falcao, Marco A. Zago
Journal: Blood (2004)
PWE-029 Colon capsule endoscopy: a useful diagnostic modality that informs patient management: Abstract PWE-029 Table 1
Authors: MF Hale, K Drew, E Ejenavi, R Sidhu, ME McAlindon
Journal: Gut (2015)

<h3>Introduction</h3> Colon capsule endoscopy (CCE) has been demonstrated to be a feasible alternative to colonoscopy for the detection of polyps and neoplasia<sup>1</sup>and avoids intubation and sedation. This study evaluates the utility of CCE in routine clinical practice and its impact on patient outcomes. <h3>Method</h3> Retrospective, single-centre, including symptomatic patients attending for CCE using PillCam Colon 2 (Given Imaging, Israel). All patients with known inflammatory bowel disease (IBD) successfully passed a PillCam Patency device prior. Patient demographics, procedural data, final diagnosis and management outcomes were collected. <h3>Results</h3> 101 patients were included, mean age 43 years (range 16–95), 73 female, median follow-up 29 months (range 1–52). 48% refused colonoscopy, 29% had an incomplete colonoscopy, 17% chose CCE over colonoscopy and 6% were unfit for colonoscopy. Indication for the procedure: anaemia (24%), IBD assessment (16%) and suspected IBD (60%). The latter had predominant symptoms of diarrhoea (77%), abdominal pain (18%) or weight loss (5%). Procedure completion rate 69%, bowel preparation was adequate in 75%. There were no complications. Results are summarised in Table 1. In the anaemia group, CCE altered management in 15%: 3 further procedures (1 double balloon enteroscopy (DBE) and argon plasma coagulation, 1 catheter embolisation and 1 small bowel capsule endoscopy) and 1 altered medication. The remaining 20 were managed conservatively. In the known IBD group, CCE altered further management in 69% (7 altered medication, 2 surgery, 2 further procedures (1 DBE, 1 colonoscopy), the remaining 5 patients were managed conservatively. In those suspected as having IBD, this was identified in 7%. Other clinically significant diagnoses were made in 36%. The remaining 57% patients were thought to have functional bowel disorders and were discharged. 3 patients were excluded due to a non-diagnostic examination. <h3>Conclusion</h3> CCE may be a useful alternative for detecting clinically relevant pathology in symptomatic patients and can help guide management. An incomplete examination (i.e. distal colon not visualised) was less relevant in the 29 patients who had already had an incomplete colonoscopy beforehand or the 24 patients whose incomplete CCE was sufficient to provide a diagnosis. Although marketed as a colonic imaging device, a third of pathology identified by CCE was in the SB, serving as a reminder that it may be difficult to distinguish symptoms arising from the small or large bowel, or both. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Spada C, Hassan C, Munoz-Navas M, <i>et al</i>. Second-generation colon capsule endoscopy compared with colonoscopy. <i>Gastrointest Endosc</i>2011;<b>74</b>(3):581-89.e1
Treatment of Patients with Chronic Lymphoproliferative Disorders (CLPD) with Fludarabine, Cyclophosphamide, and Rituximab (FCR) Combination.
Authors: Athanasios G. Galanopoulos, Anastasia Tsakiridou, Eurydiki Michalis, Theodoros Marinakis, George Gortzolidis, Athanasios Zomas, Ioannis Tsourveloudis, Maria Tsirogianni, Stephanos Papadhimitriou, Elpiniki Kritikou-Griva, Nikolaos I. Anagnostopoulos
Journal: Blood (2004)
SP0107 Cannabinoids and Inflammation: Focus on The Joint
Authors: T. Biro
Journal: Annals of the Rheumatic Diseases (2016)

The emerging endocannabinoid system (ECS; comprising the endogenous lipid mediators endocannabinoids [eCBs], produced in virtually all tissues; their metabotropic and ionotropic cannabinoid receptors; biosynthetic pathways and metabolizing enzymes) has been implicated in multiple regulatory functions of the human body. Namely, the ECS and its "tone", defined by the local levels of eCBs, were shown to control major functions of the central nervous system as well as of multiple peripheral organs (e.g. liver and other metabolic tissues, skin, cardiovascular and pulmonary systems, etc.). Recent studies have intriguingly suggested the existence of a functional ECS in the immune system. Indeed, most immune cells functionally express the bioactive eCBs and the ECS where their activities chiefly exert immune-suppressive and anti-inflammatory actions. The ECS is functionally active in the joints as well. Importantly, the "eCB tone" was shown to modulate various symptoms and pathogenetic steps of rheumatoid arthritis (RA) and osteoarthritis (OA) in several models of the diseases. Indeed, activation of type-2 cannabinoid receptors (CB2) suppresses cytokine release, inhibits functions of various cells of innate and adaptive immunity, and conveys anti-inflammatory actions. Moreover, stimulation of CB1/CB2 receptors results in analgesic, anti-proliferative, and osteogenetic effects. Interestingly, with respect to fibroblast functions, CB2-coupled signaling exerts anti-fibrotic action whereas, conversely, engagement of CB1 mostly leads to augmentation of fibroblast proliferation. This presentation reviews the current state-of-the-art of the role of the ECS in the biology of the joints. Moreover, it delineates novel, promising ECS-targeted therapeutic possibilities where synthetic, semi-synthetic or naturally occurring (e.g. from the Cannabis sativa plant) modulators of the "ECS-tone" could be successfully employed in the future clinical management of RA and OA. <h3>Disclosure of Interest</h3> None declared
Reply
Authors: Kheng Choon Lim, Pierce K.H. Chow
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. We thank Dr. Mattos for his comments. Dr Mattos has misunderstood some parts of our article. Current practice guidelines on the treatment of patients with early hepatocellular carcinoma (HCC) and good liver function are variable.1 In our systemic review, the operative mortality rate for this group of patients ranges from 0% to 5%.2 Many of the cohorts included in the review are heterogeneous, comprising both Child‐Pugh A and selected early Child‐Pugh B patients. Our study aims to simulate this heterogenous group of patients, where there is equipoise in the outcomes between liver resection (LR) and liver transplantation (LT). Hence, the mortality rate used in the base‐case analysis represents an aggregated operative mortality rate with both Child‐Pugh A and selected B patients and not limited to either Child‐Pugh A or B only. It cannot be extrapolated to mean a 2.2% operative mortality in Child‐Pugh B patients. Sensitivity analysis was also performed on the range of operative mortality that was encountered in our systematic review, and it was found that the range of operative mortality did not alter the final outcome. Although results greater than 80% have been achieve in specialized LT centers and are often cited, reports from large LT registries, such as the Organ Procurement and Transplantation Network and European Liver Transplant Registry, involving 4,482 and 8,273 patients, demonstrate 5‐year overall survival of 51% and 60% respectively.3 The projected 5‐year overall survival of 57% predicted by our model closely approximates these values. A recent study by Vitale et al. has also shown that LT achieves poorer survival outcomes, compared to LR, for patients with resectable HCC and preserved liver function.5 Nevertheless, we acknowledge that approach and outcomes for treatment of early HCC with good liver function varies across cultures and countries. The selected treatment is often a balance of limited resource against best achievable outcomes. The concept of cost‐effectiveness is also affected by a particular society's expectation and thresholds for cost‐effectiveness. Our study does not aim to prescribe a single best treatment method, but to provide an alternative tool that amalgates various parameters, including resources, treatment approaches (e.g., neoadjuvant locoregional therapy and recurrence management), and outcomes, to help decision makers meet expectations.
Fibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older Adults
Authors: Kristen L. Nowak, Traci M. Bartz, Lorien Dalrymple, Ian H. de Boer, Bryan Kestenbaum, Michael G. Shlipak, Pranav S. Garimella, Joachim H. Ix, Michel Chonchol
Journal: Journal of the American Society of Nephrology (2016)

Within monocytes, 1,25-dihydroxyvitamin D [1,25(OH)2D] is important for production of cathelicidins, which in turn, are critical for antibacterial action. Fibroblast growth factor 23 (FGF23) decreases 1,25(OH)2D production and thus, could increase infection risk. We examined this possibility in 3141 community-dwelling adults ages ≥65 years old at baseline in the Cardiovascular Health Study using Cox proportional hazards models to examine the association between FGF23 concentrations and first infection-related hospitalizations and determine whether associations differed by the presence of CKD (eGFR<60 ml/min per 1.73 m2 [n=832] or urine albumin-to-creatinine ratio >30 mg/g [n=577]). Mean±SD age of participants was 78±5 years old, 60% of participants were women, and the median plasma FGF23 concentration was 70 (interquartile range, 53-99) relative units per milliliter. In fully adjusted models, higher FGF23 concentrations associated with higher risk of first infection-related hospitalization (hazard ratio [HR], 1.11; 95% confidence interval [95% CI], 1.03 to 1.20 per doubling of FGF23) during a median follow-up of 8.6 years. In participants with or without CKD (defined by eGFR), FGF23 concentration associated with first infection-related hospitalization with HRs of 1.24 (95% CI, 1.08 to 1.42) and 1.06 (95% CI, 0.97 to 1.17) per doubling of FGF23, respectively (P=0.13 for interaction). Associations did not differ between groups when stratified by urine albumin-to-creatinine ratio. In sensitivity analyses, the addition of serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone, and 24,25-dihydroxyvitamin D did not meaningfully change the estimates. In conclusion, in community-dwelling older adults, higher plasma FGF23 concentrations independently associated with the risk of first infection-related hospitalization.
Feasability and Toxicity After Induction Treatment with Rituximab-HCVAD and Metotrexate/Citarabine, Followed by Consolidation with Y-90 Ibritumomab Tiuxetan (Phase II GELTAMO–LCM 04-02 study).
Authors: Reyes Arranz, Ana Garcia-Noblejas, Carlos Grande, José Terol, José Javier Sánchez, Javier Perez-Calvo, Miguel Canales, Jose Antonio García-Marco, Eva Marti, Eulogio Conde, Antonio Salar, Dolores Caballero
Journal: Blood (2009)
Successful endoscopic closure of multiple tracheoesophageal fistulas following implantation of two atrial septal defect occluders
Authors: Jose Subtil, Victor Valenti, Javier Cienfuegos, Jose Calabuig, Jose Hernández-Lizoain, Miguel Muñoz-Navas
Journal: Endoscopy (2016)

Chronic tracheoesophageal fistulas [TEFs] represent one of the greatest challenges for endoscopists [1]. A 63-year-old man diagnosed with adenocarcinoma of the esophagogastric junction was treated with neoadjuvant chemoradiotherapy and esophagectomy. He developed two TEFs, which required the implantation of two self-expandable stents and a feeding jejunostomy. The prostheses were withdrawn 3 months later, and a tracheal prosthesis was put in place.
Refractory / Relapsed Myeloid Leukemia of Down Syndrome Is Resistant to Second-Line Chemotherapy and Hardly Salvaged by Hematopoietic Stem Cell Transplantation: A Retrospective Study by the Japanese Pediatric Leukemia / Lymphoma Study Group (JPLSG)
Authors: Takashi Taga, Akiko Saito, Kazuko Kudo, Daisuke Tomizawa, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Shotaro Iwamoto, Hideki Nakayama, Hiroyuki Takahashi, Akio Tawa, Akira Shimada, Tomohiko Taki, Hisato Kigasawa, Katsuyoshi Koh, Souichi Adachi
Journal: Blood (2011)