tbuckley/cabot-search huggingface dataset:
Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with low-grade non-Hodgkins lymphoma treated with tositumomab and iodine-131 tositumomab therapeutic regimen
Authors: J. M. Bennett, M. S. Kaminski, S. J. Knox, A. D. Zelenetz, J. P. Leonard, J. M. Vose, S. Horning
Journal: Blood (2003)
Response to: ‘Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care’ by Parperis <i>et al</i>
Authors: Edward Roddy, Christian D Mallen
Journal: Annals of the Rheumatic Diseases (2019)

Naproxen or low-dose colchicine for gout flares in primary care?Response to: 'Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care' by Parperis et al We concluded that naproxen should be considered as first-line treatment for gout flares in primary care based on there being no difference between naproxen and colchicine in pain intensity (the primary outcome), more analgesic use and self-reported side-effects in the colchicine group, and evidence that naproxen was cost-effective. 1 We note the Bayesian meta-analysis by Bally et al in which all non-steroidal anti-inflammatory drugs (NSAIDs), including naproxen, were associated with increased risk of myocardial infarction. 2 However, this review was limited by including only studies undertaken in healthcare databases risking bias due to residual confounding and, as the review's authors acknowledge, measuring drug dispensing or prescribing and not actual drug intake.A meta-analysis of individual patient data from 280 randomised trials of NSAID versus placebo found that naproxen did not significantly increase major vascular events or vascular deaths, in contrast to other NSAIDs. 3e acknowledge that the colchicine dose in our pragmatic trial differed from that subsequently recommended in the European League Against Rheumatism (EULAR) recommendations. 4Pragmatic trials evaluate interventions as prescribed, managed and used in routine clinical practice. 5We used the UK recommended colchicine dose, 6 consistent with the British Society for Rheumatology gout management guideline. 7Furthermore, the EULAR recommendations advocate a loading dose of colchicine of 1 mg followed by 0.5 mg 1 hour later in patients presenting within 12 hours of flare onset, 4 as per the Acute Gout Flare Receiving Colchicine Evaluation (AGREE) trial, 8 without making a dose recommendation for patients with longer flare durations.Over two-thirds of our participants initiated medication over 24 hours after flare onset, hence the appropriateness of this dose regimen for our trial population is uncertain.Our findings support informed decision-making based on an assessment of the balance of benefits and harms.Our conclusion was not that naproxen should be considered as the only first treatment option for gout flares, as stated by Parperis, 9 but importantly contained the caveat that naproxen should be considered as first-line treatment in primary care in the absence of contraindications.While colchicine would be a reasonable first therapeutic option in patients with cardiovascular risk factors, this is consistent with our conclusion that the choice of treatment should be influenced by the presence or absence of comorbidities.
Clec10a regulates mite-induced dermatitis
Authors: Kazumasa Kanemaru, Emiko Noguchi, Satoko Tahara-Hanaoka, Seiya Mizuno, Hiroaki Tateno, Yasuhiro Fujisawa, Yoshiyuki Nakamura, Kaori Denda-Nagai, Tatsuro Irimura, Hiroshi Matsuda, Fumihiro Sugiyama, Satoru Takahashi, Kazuko Shibuya, Akira Shibuya
Journal: Science Immunology (2019)

Clec10a on skin macrophages recognizes a mucin-like molecule of house dust mite and suppresses mite-induced dermatitis.
Abstract 13050: Incidence, Source, Determinants, and Prognostic Impact of Major Bleeding in Outpatients With Chronic Heart Failure: Insights From the CARDIONOR Registry
Authors: Gilles Lemesle, Sandro Ninni, Pascal De Groote, Nicolas Lamblin, Christophe Bauters
Journal: Circulation (2019)

Introduction: Risk, correlates, and consequences of major bleeding as well as the frequency of antithrombotic use in heart failure (HF) patients are largely unknown. Hypothesis: We sought to invest...
Genetic landscape of adult Langerhans cell histiocytosis with lung involvement
Authors: Fanélie Jouenne, Sylvie Chevret, Emmanuelle Bugnet, Emmanuelle Clappier, Gwenaël Lorillon, Véronique Meignin, Aurélie Sadoux, Shannon Cohen, Alain Haziot, Alexandre How-Kit, Caroline Kannengiesser, Céleste Lebbé, Dominique Gossot, Samia Mourah, Abdellatif Tazi
Journal: European Respiratory Journal (2019)

The clinical significance of the BRAFV600E mutation in adult Langerhans cell histiocytosis (LCH), including pulmonary Langerhans cell histiocytosis (PLCH), is not well understood. Similarly, the spectrum of molecular alterations involved in adult LCH has not been fully delineated. To address these issues, we genotyped a large number of adult LCH biopsies and searched for an association of identified molecular alterations with clinical presentation and disease outcome.Biopsies from 117 adult LCH patients, 83 with PLCH (median age 36.4 years, 56 females, 38 multisystem disease, 79 single system disease, 65 current smokers) were genotyped for the BRAFV600E mutation. In 69 cases, LCH lesions were also genotyped by whole-exome sequencing (WES) or targeted gene panel next-generation sequencing (NGS). Cox models were used to estimate the association of baseline characteristics with the hazard of LCH progression.MAPK pathway alterations were detected in 59 out of 69 cases (86%) (BRAFV600E mutation: 36%, BRAFN486_P490 deletion: 28%, MAP2K1 mutations: 15%, isolated NRASQ61 mutations: 4%), while KRAS mutations were virtually absent in PLCH lesions. The BRAFV600E mutation was not associated with LCH presentation at diagnosis, including smoking status and lung function, in PLCH patients. BRAFV600E status did not influence the risk of LCH progression over time.Thus, MAPK alterations are present in most lesions from adult LCH patients, particularly in PLCH. Unlike reports in paediatric LCH, BRAFV600E genotyping did not provide additional information on disease outcome. The search for alterations involved in the MAPK pathway, including BRAF deletions, is useful for guiding targeted treatment in selected patients with refractory progressive LCH.
An analysis of preoperatively HE4 and CA125 in matched samples of patients (pts) with benign disease and borderline ovarian tumors (BOT) with and without invasive implants (InvImp).
Authors: Mani Nassir, Elena Ioana Braicu, Rolf Richter, Radoslav Chekerov, Toon van Gorp, Dirk Timmerman, Ignace Vergote, Jalid Sehouli
Journal: Journal of Clinical Oncology (2013)

e22102 Background: Presence of InvImp, quality of surgical staging and residual tumor mass were shown to be major prognostic factors for BOT. Currently, there are no biomarkers that can predict the various types of BOT. Aim of our study was to assess the value of individual CA125 and HE4 values, and the combination of CA125 and HE4 according to the ROMA algorithm for detecting BOT, and for predicting the presence of InvImp. Methods: BOT pts with InvImp (n=14) were matched by age and histology and compared to consecutive pts with benign disease and BOT without InvImp (1 to 4 to 1, respectively). Blood was collected prior surgery. HE4 and CA125 were determined using ELISA. The performance of HE4 and CA125 were analyzed using the receiver operator characteristic (ROC) and logistic regression. Results: HE4 and CA125 were increased in BOT with InvImp (median=73.85pM and 49.5IU/dl) compared with benign diseases and BOT without InvImp (median values: 48pM and 18.5IU/dl, and 61.45pM and 26.5IU/dl, respectively). HE4 and CA125 expression were significantly increased in BOT with InvImp compared to benign diseases (p=0.029 and 0.004, respectively) but not to BOT without InvImp. Furthermore we grouped BOT without InvImp together with benign diseases and compared them with BOT with InvImp. HE4 and CA125 cut off values of 65pM and 60IU/dl, respectively were independent predictive factors for the presence of InvImp (p=0.018, OR=5.32, 95%CI 1.33-21.20 and p=0.031, OR=4.83, 95%CI=1.16-20.13, respectively). ROMA performed better than HE4 or CA125 alone (p=0.002, RR=9.17, 95%CI=2.31-36.36). The OR of a high ROMA score were 0.082 (95%CI: 0.02-0.34; p=0.001) for benign diseases and 0.27 (95%CI: 0.05-1.42; p=0.123) for BOT without InvImp compared to BOT with InvImp. Conclusions: The ROMA score can not predict sufficiently InvImp in BOT. Further multicenter and larger prospective studies are needed.
MCP (Mitoxantrone/Chlorambucil/Prednisolone) Chemotherapy Impairs the Subsequent Collection of Stem Cells in Comparison to CHOP Induction in Patients with Indolent Lymphomas - Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG).
Authors: Christina Nickenig, Martin Dreyling, Eva Hoster, Michael Pfreundschuh, Lorenz Truemper, Marcel Reiser, Hannes Wandt, Michael Unterhalt, Wolfgang Hiddemann
Journal: Blood (2005)
IL-1β Secreted from Mutant Cells Carrying JAK2-V617Ffavors Early Clonal Expansion and Promotes MPN Disease Initiation and Progression
Authors: Shivam Rai, Nils Hansen, Hui Hao-Shen, Stefan Dirnhofer, Nageswara Rao Tata, Radek C. Skoda
Journal: Blood (2019)
Delayed Achievement of Molecular Responses Is Associated with Increased Risk of Progression among Patients (pts) with Chronic Myelogenous Leukemia (CML) In Chronic Phase (CP) Treated with Imatinib (IM).
Authors: Alfonso Quintas-Cardama, Hagop M. Kantarjian, Dan Jones, Guillermo Garcia-Manero, Susan O’Brien, Jenny Shan, Farhad Ravandi, William G. Wierda, Jorge Cortes
Journal: Blood (2006)
Improved Immune Reconstitution with Low Incidence of Severe Graft-Versus-Host Disease after Transplantation of CD34+ or CD133+ Enriched Stem Cells with Add-Back of Ten Million T-Cells Per Kg.
Authors: Johann Greil, Peter Lang, Peter Bader, Matthias Eyrich, Paul G. Schlegel, Michael Schumm, Tobias Feuchtinger, Dietrich Niethammer
Journal: Blood (2004)
The Vectorcardiogram in Pulmonary Emphysema : Studies on Autopsy Cases
Authors: Satoru Matsushita, Kazuhiko Murata, Hiroshi Kurihara, Fujio Terasawa, Masuji Seki
Journal: Circulation (1968)

Upon analysis of QRS and T loops in Frank lead vectorcardiograms of 44 patients with autopsy proved pulmonary emphysema, the fairly large terminal portion of QRS loop directed to the right and superiorly with shift of the half-area QRS vector posteriorly and superiorly was found to be characteristic. A small or abnormally directed T loop was also frequently observed. Although thirteen of the 44 patients also had mild right ventricular hypertrophy, there was no significant vectorcardiographic difference between the groups with and without right ventricular hypertrophy. The direction of the terminal appendage in the sagittal and horizontal plane, Sx/Rx, Sy/Ry, and the ratio of the magnitude of terminal appendage to the maximum vector of the body of QRS loop in the frontal and horizontal plane provided good indices of the emphysema type vectorcardiogram. A set of criteria was proposed with the discussion on positivity and false positivity in the diagnosis of such condition.
Cardiac Performance Measure Compliance in Outpatients
Authors: Paul S. Chan, William J. Oetgen, Donna Buchanan, Kristi Mitchell, Fran F. Fiocchi, Fengming Tang, Philip G. Jones, Tracie Breeding, Duane Thrutchley, John S. Rumsfeld, John A. Spertus
Journal: Journal of the American College of Cardiology (2010)
The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4‐Related Disease
Authors: Zachary S. Wallace, Ray P. Naden, Suresh Chari, Hyon Choi, Emanuel Della‐Torre, Jean‐Francois Dicaire, Phil A. Hart, Dai Inoue, Mitsuhiro Kawano, Arezou Khosroshahi, Kensuke Kubota, Marco Lanzillotta, Kazuichi Okazaki, Cory A. Perugino, Amita Sharma, Takako Saeki, Hiroshi Sekiguchi, Nicolas Schleinitz, James R. Stone, Naoki Takahashi, Hisanori Umehara, George Webster, Yoh Zen, John H. Stone
Journal: Arthritis & Rheumatology (2019)

IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD.An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises, existing literature, derivation and validation cohorts of 1,879 subjects (1,086 cases, 793 mimickers), and multicriterion decision analysis to identify, weight, and test potential classification criteria. Two independent validation cohorts were included.A 3-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serologic, radiologic, and pathologic items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% confidence interval [95% CI] 97.2-99.8%) and a sensitivity of 85.5% (95% CI 81.9-88.5%). In the second, the specificity was 97.8% (95% CI 93.7-99.2%) and the sensitivity was 82.0% (95% CI 77.0-86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds.ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiologic, and basic science investigations.
A Pharmacological Chaperone Therapy for Acute Intermittent Porphyria
Authors: Helene J. Bustad, Karen Toska, Caroline Schmitt, Marta Vorland, Lars Skjærven, Juha P. Kallio, Sylvie Simonin, Philippe Letteron, Jarl Underhaug, Sverre Sandberg, Aurora Martinez
Journal: Molecular Therapy (2019)

Mutations in hydroxymethylbilane synthase (HMBS) cause acute intermittent porphyria (AIP), an autosomal dominant disease where typically only one HMBS allele is mutated. In AIP, the accumulation of porphyrin precursors triggers life-threatening neurovisceral attacks and at long-term, entails an increased risk of hepatocellular carcinoma, kidney failure, and hypertension. Today, the only cure is liver transplantation, and a need for effective mechanism-based therapies, such as pharmacological chaperones, is prevailing. These are small molecules that specifically stabilize a target protein. They may be developed into an oral treatment, which could work curatively during acute attacks, but also prophylactically in asymptomatic HMBS mutant carriers. With the use of a 10,000 compound library, we identified four binders that further increased the initially very high thermal stability of wild-type HMBS and protected the enzyme from trypsin digestion. The best hit and a selected analog increased steady-state levels and total HMBS activity in human hepatoma cells overexpressing HMBS, and in an Hmbs-deficient mouse model with a low-expressed wild-type-like allele, compared to untreated controls. Moreover, the concentration of porphyrin precursors decreased in liver of mice treated with the best hit. Our findings demonstrate the great potential of these hits for the development of a pharmacological chaperone-based corrective treatment of AIP by enhancing wild-type HMBS function independently of the patients' specific mutation.
Testicular Cancer Survivorship
Authors: Chunkit Fung, Paul C. Dinh, Sophie D. Fossa, Lois B. Travis
Journal: Journal of the National Comprehensive Cancer Network (2019)

Testicular cancer (TC) is the most common cancer among men aged 18 to 39 years. It is highly curable, with a 10-year relative survival approaching 95% due to effective cisplatin-based chemotherapy. Given the increasing incidence of TC and improved survival, TC survivors (TCS) now account for approximately 4% of all US male cancer survivors. They have also become a valuable cohort for adult-onset cancer survivorship research, given their prolonged survival. Commensurately, long-term treatment-related complications have emerged as important survivorship issues. These late effects include life-threatening conditions, such as second malignant neoplasms and cardiovascular disease. Moreover, TCS can also experience hearing loss, tinnitus, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, infertility, anxiety, depression, cognitive impairment, and chronic cancer-related fatigue. Characterization of the number and severity of long-term adverse health outcomes among TCS remains critical to develop risk-stratified, evidence-based follow-up guidelines and to inform the development of preventive measures and interventions. In addition, an improved understanding of the long-term effects of TC treatment on mortality due to noncancer causes and second malignant neoplasms remains paramount. Future research should focus on the continued development of large, well-characterized clinical cohorts of TCS for lifelong follow-up. These systematic, comprehensive approaches can provide the needed infrastructure for further investigation of long-term latency patterns of various medical and psychosocial morbidities and for more in-depth studies investigating associated etiopathogenetic pathways. Studies examining premature physiologic aging may also serve as new frontiers in TC survivorship research.
Impact of a multigene prognostic assay on postoperative management of early-stage non-small cell lung cancer.
Authors: Shane Dormady, Thierry Jahan, Michael J. Mann, David Jablons, Michael S. Broder, Alison H. DeCristofaro, Ayanna Anene
Journal: Journal of Clinical Oncology (2013)

e22124 Background: Many stage II and most stage I non-small cell lung cancer (NSCLC) patients forgo adjuvant chemotherapy, despite the likely presence of occult metastasis in the 30-60% of these patients who die within 5 years of surgery, and despite demonstration that patients with undetected, i.e. very early, metastasis can achieve long-term survival with this intervention. A multi-gene assay using quantitative RT-PCR and run on formalin-fixed, paraffin-embedded samples (Pervenio Lung RS) has been independently validated in two large international studies to better differentiate high- and low-risk non-squamous NSCLC patients than either traditional risk assessment criteria or conventional staging. A survey of physicians who used this multi-gene assay probed whether better risk discrimination changed post-operative management. Methods: Physicians were queried via a web-based survey on practice patterns, patient characteristics and treatment recommendations. The survey was developed through cognitive interviews with oncologists and thoracic surgeons. Physicians were allowed to respond regarding up to 4 patients (stage I or II) for whom the multi-gene test was ordered. Results: Forty-one physicians (12 surgeons, 29 oncologists/internists) of 61 contacted (67%) provided responses on 77 patients. Community practices accounted for 83%, and the average years in practice was 15. Seventy-one percent provided responses on either 1 or 2 patients. Mean patient age was 66±10 years, with stage I and stage II comprising 73% and 27%, respectively. Prior to obtaining assay results, chemotherapy was recommended in 30% of patients, including 5 stage I patients. The assay characterized 5-year mortality risk as high, intermediate and low in 52%, 23% and 25% of patients, respectively. Treatment recommendations were changed post-assay in 36% of patients, including 73% of high-risk patients for whom observation was recommended initially. Change in treatment intensity correlated with the degree of assay-assessed risk. Conclusions: Refinement of risk assessment achieved via a multi-gene prognostic assay resulted in changes in treatment recommendations for a substantial number of early stage NSCLC patients.
Topical treatment of oral lichen planus
Authors: S.‐L. Sun, J.‐J. Liu, B. Zhong, J.‐K. Wang, X. Jin, H. Xu, F.‐Y. Yin, T.‐N. Liu, Q.‐M. Chen, X. Zeng
Journal: British Journal of Dermatology (2019)

Oral lichen planus (OLP) is a skin disease affecting the mouth, which can cause a burning or stinging discomfort in the mouth when eating or drinking. Ulcers may occur and these are especially painful. The cause of oral lichen planus is not known in most instances, but it is likely to be related to the body's immune system. In this study, the authors from China aimed to compare the efficacy and safety of drugs called topical calcineurin inhibitors (TCI) with medicines applied to the skin called topical corticosteroids (TCS), in the treatment of OLP. The authors looked at globally published randomized controlled trials (RCTs) reporting TCI (tacrolimus, pimecrolimus, and cyclosporine) compared with TCS for OLP from eight medical databases. Twenty‐one RCTs with a total of 965 patients published between 1995 and 2017 were included (tacrolimus‐TCS: 12 studies, 578 patients; pimecrolimus‐TCS: 3 studies, 98 patients; cyclosporine‐TCS: 6 studies, 289 patients). The authors found that TCI including tacrolimus, pimecrolimus and cyclosporine were similar to TCS in efficacy for the short‐term treatment of OLP (3‐8 weeks). In addition, tacrolimus 0.1% was similar to TCS in relapse rate. The blood levels of tacrolimus and cyclosporine were usually extremely low, while the few cases of patients with high levels may have been caused by swallowing the drug accidentally. Although a few adverse events (unwanted side effects) were observed in the tacrolimus and cyclosporine groups, no serious events were found. Therefore, TCI may be an alternative approach when OLP does not improve with use of TCS. Due to the limited trials of pimecrolimus and cyclosporine, as well as a few adverse events and high cost of cyclosporine, tacrolimus 0.1% should be the first drug of choice in TCI for the short‐term treatment of OLP that is not improving with TCS. More well‐designed RCTs are needed to evaluate the long‐term efficacy and safety of TCI compared with TCS.
Haplotype-Based Sequencing To Delineate the Associated HLA Class I Region for EBV Positive Hodgkin Lymphoma.
Authors: Marijke Niens, Anke van den Berg, Arjan Diepstra, Ilja M. Nolte, Gerrit van der Steege, Ruth F. Jarrett, Siebrand Poppema, Gerard J. te Meerman
Journal: Blood (2005)