tbuckley/cabot-search huggingface dataset:
Predicting tuberculosis relapse in patients treated with the standard 6-month regimen: an individual patient data meta-analysis
Authors: Kamila Romanowski, Robert F Balshaw, Andrea Benedetti, Jonathon R Campbell, Dick Menzies, Faiz Ahmad Khan, James C Johnston
Journal: Thorax (2018)

Background Relapse continues to place significant burden on patients and tuberculosis (TB) programmes worldwide. We aimed to determine clinical and microbiological factors associated with relapse in patients treated with the WHO standard 6-month regimen and then evaluate the accuracy of each factor at predicting an outcome of relapse. Methods A systematic review was performed to identify randomised controlled trials reporting treatment outcomes on patients receiving the standard regimen. Authors were contacted and invited to share patient-level data (IPD). A one-step IPD meta-analysis, using random intercept logistic regression models and receiver operating characteristic curves, was performed to evaluate the predictive performance of variables of interest. Results Individual patient data were obtained from 3 of the 12 identified studies. Of the 1189 patients with confirmed pulmonary TB who completed therapy, 67 (5.6%) relapsed. In multipredictor analysis, the presence of baseline cavitary disease with positive smear at 2 months was associated with an increased odds of relapse (OR 2.3(95% CI 1.3 to 4.2)) and a relapse risk of 10%. When area under the curve for each multipredictor model was compared, discrimination between low-risk and higher-risk patients was modest and similar to that of the reference model which accounted for age, sex and HIV status. Conclusion Despite its poor predictive value, our results indicate that the combined presence of cavitary disease and 2-month positive smear status may be the best currently available marker for identifying individuals at an increased risk of relapse, particularly in resource-limited setting. Further investigation is required to assess whether this combined factor can be used to indicate different treatment requirements in clinical practice.
Atopic dermatitis at preschool age and contact allergy in adolescence: a population‐based cohort study
Authors: M. Lagrelius, C.‐F. Wahlgren, M. Matura, A. Bergström, I. Kull, C. Lidén
Journal: British Journal of Dermatology (2018)

Atopic dermatitis (AD) is characterized by an impaired skin barrier, which can allow enhanced penetration of allergens. It is not clear whether AD influences the risk of developing contact allergy.To examine the association between AD at preschool age and contact allergy at 16 years of age.At 16 years of age, 2215 adolescents from the population-based cohort BAMSE were included. These adolescents had been followed with repeated questionnaires regarding AD throughout childhood, and contact allergy was assessed by skin patch test at 16 years.AD at preschool age was associated with contact allergy to at least one of the tested substances at 16 years of age among boys [adjusted odds ratio (OR) 1·51, 95% confidence interval (CI) 1·03-2·20] but not among girls (adjusted OR 0·77, 95% CI 0·54-1·10). AD at preschool age was not associated with contact allergy to nickel in either boys or girls. In contrast, AD at preschool age was associated with contact allergy to fragrance mix I (adjusted OR 3·10, 95% CI 1·66-5·80). This association was observed especially for AD at preschool age in combination with IgE sensitization to airborne or food allergens (adjusted OR 3·80, 95% CI 1·67-8·61).The results suggest that AD in early childhood may be associated with contact allergy to fragrances, but not to nickel, in adolescence.
The effects of lapatinib and neratinib on HER2 protein levels in breast cancer cell lines.
Authors: Denis Collins, Norma O'Donovan, Naomi Walsh, Kathy Gately, Connla Edwards, Anthony Davies, Kenneth John O'Byrne, John Crown
Journal: Journal of Clinical Oncology (2012)

637 Background: HER2, a member of the c-erbB receptor tyrosine kinase family, is over-expressed (HER2 gene amplification/IHC 3+, &gt;30% cells) in approx. 25% of breast cancers. Pre-clinical studies have shown that the HER2-targeted small molecule tyrosine kinase inhibitor (TKI) lapatinib (LAP) can increase HER2 levels in cell line models and can potentiate trastuzumab-mediated antibody dependent cell-mediated cytotoxicity. To assess the potential effects of the next generation TKI neratinib (NER) on expression of HER2 in breast cancer, this study compares the effects of LAP and NER on HER2 protein levels in the HER2-amplified SKBR3 and HER2-non-amplified T47D cell lines in vitro. Methods: SKBR3 and T47D were treated with LAP or NER (0.2, 1 and 2 µM) for 12, 24 and 48 hours.HER2 protein levels were determined by ELISA, immunoblotting and high content analysis (HCA). HER2 protein was examined using two antibodies targeting the extracellular domain (ECD) and the intracellular domain (ICD) of HER2. pHER2, EGFR/pEGFR, MAPK/pMAPK and AKT/pAKT levels were determined by immunoblotting. Proliferation studies utilized an acid phosphatase-based assay. Results: ELISA analysis confirmedsignificantly lower HER2 expression in T47D (44 +/- 17 pg/µg) compared to SKBR3 (748 +/- 296 pg/µg), p = 0.015. NER proved a more potent inhibitor of pHER2 and pEGFR as analyzed by immunoblotting and in proliferation studies (NER IC 50 - SKBR3 0.03 +/- 0.01 nM, T47D 199 +/- 70 nM, LAP IC 50 - SKBR3 20 +/- 1 nM, T47D 1.2 +/- 0.2 µM). LAP induced an increase in both ECD and ICD-containing HER2 protein levels in SKBR3 and T47D cells. No increase in HER-2 levels was observed with NER treatment, as determined by HCA and immunoblotting. EGFR protein levels increased in response to lapatinib in both cell lines. Conclusions: Our results suggest that LAP and NER have differing effects on HER2 protein levels in the models examined. NER provides greater inhibition of HER2 signaling activity but does not increase HER2 protein levels as was observed with LAP. Further pre-clinical assessment of combinations of LAP and NER with HER2 and EGFR monoclonal antibody therapies is warranted in HER2-amplified, HER2-non-amplified and EGFR-expressing breast cancer models.
Anticoagulant-Related Nephropathy
Authors: Sergey Brodsky, John Eikelboom, Lee A. Hebert
Journal: Journal of the American Society of Nephrology (2018)

Anticoagulant-related nephropathy (ARN) is a newly recognized form of AKI in which overanticoagulation causes profuse glomerular hemorrhage, which manifests on renal biopsy as numerous renal tubules filled with red cells and red cell casts. The glomeruli show changes, but they are not sufficient to account for the glomerular hemorrhage. We were the first to study ARN, and since then, our work has been confirmed by numerous other investigators. Oral anticoagulants have been in widespread use since the 1950s; today, >2 million patients with atrial fibrillation take an oral anticoagulant. Despite this history of widespread and prolonged exposure to oral anticoagulants, ARN was discovered only recently, suggesting that the condition may be a rare occurrence. This review chronicles the discovery of ARN, its confirmation by others, and our animal model of ARN. We also provide new data on analysis of "renal events" described in the
Abstract 15256: Musclular Lipid is Associated With a Risk Factor of Arterial Stiffness
Authors: Natsuki Hasegawa, Toshiyuki Kurihara, Koji Sato, Satoshi Fujita, Kiyoshi Sanada, Mitsuo Otsuka, Takafumi Hamaoka, Motoyuki Iemitsu
Journal: Circulation (2014)

Introduction: Obese and overweight patients increase the risk of arterial stiffness. Visceral fat accumulation may relate to the development of arterial stiffness with enhancing inflammatory cytoki...
AB0305 Remaining foot synovitis may predict relapse in rheumatoid arthritis patients in das28 remission (DAS28-CRP&lt;2.3)
Authors: S. Hattori, N. Hagino, K. Yomono, S. Tsuzuki, S. Suzuki, S. Takenouchi, R. Yokochi, T. Matsui, S. Tohma
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> DAS28 (Disease Activity Score based on 28 joints) is widely used to determine remission in rheumatoid arthritis (RA). The problems with DAS28 due to omission of the lower extremity joints have long been discussed. There are reports demonstrating that some patients meeting DAS28 remission criteria still have synovitis in their feet.<sup>1</sup> It is suggested that patients with remaining foot synovitis can experience up to a 2-fold increase in relapse rates.<sup>2</sup> Evidence supporting this hypothesis is still scarce. <h3>Objectives</h3> We hypothesised that RA patients in remission according to the DAS28 remission criterion with remaining foot synovitis are less likely to stay in remission. We aimed to test this hypothesis among Japanese patients with RA. <h3>Methods</h3> In 2015, 15,071 RA patients were registered in a large nationwide database in Japan (NinJa). Among those patients, those who were in remission based on DAS28-CRP were included. We used DAS28-CRP&lt;2.3 as the remission criteria. The study population was then divided into groups with or without tender/swollen joints in the feet. These patients were followed for one year and the remission rate was then calculated for each group. Comparison was performed with Chi-square test. <h3>Results</h3> We included 706 RA patients in remission based on DAS28-CRP with foot synovitis in 2015 and 5182 without foot synovitis. Among patients with foot synovitis in 2015, 225 (31.9%) were not in remission in 2016 while among those without foot synovitis, 985 (19.0%) were not in remission. (X-squared=62.953, df=1, p=2.117 × 10–1<sup>5</sup>) <h3>Conclusions</h3> In our study, RA patients in remission according to the DAS28 remission criterion with remaining foot synovitis had more relapses than those without it. Remission defined by DAS28-CRP does not take remaining foot synovitis into account. But a thorough foot examination may still be useful in RA patients with DAS28-CRP remission as they may be more at risk for relapse. <h3>References</h3> [1] van der Leeden, et al. Arthritis Res Ther. 2010;12,1:R3. [2] Wechalekar MD, et al. Arthritis Care Res. 2016;68,11:1616–1623. <h3>Disclosure of Interest</h3> None declared
Automated Cervical Screening and Triage, Based on HPV Testing and Computer-Interpreted Cytology
Authors: Kai Yu, Noorie Hyun, Barbara Fetterman, Thomas Lorey, Tina R Raine-Bennett, Han Zhang, Robin E Stamps, Nancy E Poitras, William Wheeler, Brian Befano, Julia C Gage, Philip E Castle, Nicolas Wentzensen, Mark Schiffman
Journal: JNCI Journal of the National Cancer Institute (2018)

State-of-the-art cervical cancer prevention includes human papillomavirus (HPV) vaccination among adolescents and screening/treatment of cervical precancer (CIN3/AIS and, less strictly, CIN2) among adults. HPV testing provides sensitive detection of precancer but, to reduce overtreatment, secondary "triage" is needed to predict women at highest risk. Those with the highest-risk HPV types or abnormal cytology are commonly referred to colposcopy; however, expert cytology services are critically lacking in many regions.To permit completely automatable cervical screening/triage, we designed and validated a novel triage method, a cytologic risk score algorithm based on computer-scanned liquid-based slide features (FocalPoint, BD, Burlington, NC). We compared it with abnormal cytology in predicting precancer among 1839 women testing HPV positive (HC2, Qiagen, Germantown, MD) in 2010 at Kaiser Permanente Northern California (KPNC). Precancer outcomes were ascertained by record linkage. As additional validation, we compared the algorithm prospectively with cytology results among 243 807 women screened at KPNC (2016-2017). All statistical tests were two-sided.Among HPV-positive women, the algorithm matched the triage performance of abnormal cytology. Combined with HPV16/18/45 typing (Onclarity, BD, Sparks, MD), the automatable strategy referred 91.7% of HPV-positive CIN3/AIS cases to immediate colposcopy while deferring 38.4% of all HPV-positive women to one-year retesting (compared with 89.1% and 37.4%, respectively, for typing and cytology triage). In the 2016-2017 validation, the predicted risk scores strongly correlated with cytology (P < .001).High-quality cervical screening and triage performance is achievable using this completely automated approach. Automated technology could permit extension of high-quality cervical screening/triage coverage to currently underserved regions.
The Role of Image Surveillance in Patients with Diffuse Large B-Cell Lymphoma: A Single-Center Validation Study
Authors: Takanori Fukuta, Noriko Nishimura, Yuko Shirouchi, Anna Nishihara, Norihito Inoue, Hideki Uryu, Yoshiharu Kusano, Yuko Mishima, Naoko Tsuyama, Kengo Takeuchi, Masahiro Yokoyama, Yasuhito Terui
Journal: Blood (2018)
Predicting the early risk of chronic kidney disease in patients with diabetes using real-world data
Authors: Stefan Ravizza, Tony Huschto, Anja Adamov, Lars Böhm, Alexander Büsser, Frederik F. Flöther, Rolf Hinzmann, Helena König, Scott M. McAhren, Daniel H. Robertson, Titus Schleyer, Bernd Schneidinger, Wolfgang Petrich
Journal: Nature Medicine (2018)
Impaired Lung Function, Lung Disease, and Risk of Incident Dementia
Authors: Pamela L. Lutsey, Nemin Chen, Maria C. Mirabelli, Kamakshi Lakshminarayan, David S. Knopman, Keith A. Vossel, Rebecca F. Gottesman, Thomas H. Mosley, Alvaro Alonso
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Growing evidence suggests that compromised lung health may be linked to dementia and worsening cognitive ability.
Prednisone for the Prevention of Paradoxical Tuberculosis-Associated IRIS
Authors: Graeme Meintjes, Cari Stek, Lisette Blumenthal, Friedrich Thienemann, Charlotte Schutz, Jozefien Buyze, Raffaella Ravinetto, Harry van Loen, Amy Nair, Amanda Jackson, Robert Colebunders, Gary Maartens, Robert J. Wilkinson, Lutgarde Lynen
Journal: New England Journal of Medicine (2018)

Early initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients who have tuberculosis reduces mortality among patients with low CD4 counts, but it increases the risk of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS).We conducted this randomized, double-blind, placebo-controlled trial to assess whether prophylactic prednisone can safely reduce the incidence of paradoxical tuberculosis-associated IRIS in patients at high risk for the syndrome. We enrolled HIV-infected patients who were initiating ART (and had not previously received ART), had started tuberculosis treatment within 30 days before initiating ART, and had a CD4 count of 100 cells or fewer per microliter. Patients received either prednisone (at a dose of 40 mg per day for 14 days, then 20 mg per day for 14 days) or placebo. The primary end point was the development of tuberculosis-associated IRIS within 12 weeks after initiating ART, as adjudicated by an independent committee.Among the 240 patients who were enrolled, the median age was 36 (interquartile range, 30 to 42), 60% were men, and 73% had microbiologically confirmed tuberculosis; the median CD4 count was 49 cells per microliter (interquartile range, 24 to 86), and the median HIV type 1 RNA viral load was 5.5 log10 copies per milliliter (interquartile range, 5.2 to 5.9). A total of 120 patients were assigned to each group, and 18 patients were lost to follow-up or withdrew. Tuberculosis-associated IRIS was diagnosed in 39 patients (32.5%) in the prednisone group and in 56 (46.7%) in the placebo group (relative risk, 0.70; 95% confidence interval [CI], 0.51 to 0.96; P=0.03). Open-label glucocorticoids were prescribed to treat tuberculosis-associated IRIS in 16 patients (13.3%) in the prednisone group and in 34 (28.3%) in the placebo group (relative risk, 0.47; 95% CI, 0.27 to 0.81). There were five deaths in the prednisone group and four in the placebo group (P=1.00). Severe infections (acquired immunodeficiency syndrome-defining illnesses or invasive bacterial infections) occurred in 11 patients in the prednisone group and in 18 patients in the placebo group (P=0.23). One case of Kaposi's sarcoma occurred in the placebo group.Prednisone treatment during the first 4 weeks after the initiation of ART for HIV infection resulted in a lower incidence of tuberculosis-associated IRIS than placebo, without evidence of an increased risk of severe infections or cancers. (Funded by the European and Developing Countries Clinical Trials Partnership and others; PredART ClinicalTrials.gov number, NCT01924286 .).
Antimicrobial synergy of monolaurin lipid nanocapsules with adsorbed antimicrobial peptides against Staphylococcus aureus biofilms in vitro is absent in vivo
Authors: René T. Rozenbaum, Linzhu Su, Anita Umerska, Matthieu Eveillard, Joakim Håkansson, Margit Mahlapuu, Fan Huang, Jianfeng Liu, Zhenkun Zhang, Linqi Shi, Henny C. van der Mei, Henk J. Busscher, Prashant K. Sharma
Journal: Journal of Controlled Release (2018)
Comparison of regulatory B cells in asthma and allergic rhinitis
Authors: Oliver F. Wirz, Anna Głobińska, Urs Ochsner, Willem van de Veen, Esben Eller, Elisabeth S. Christiansen, Susanne Halken, Christian Nielsen, Carsten Bindslev‐Jensen, Josep M. Antó, Jean Bousquet, Cezmi A. Akdis, Mübeccel Akdis
Journal: Allergy (2018)

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Long-Term Endocrine and Metabolic Consequences of Cancer Treatment: A Systematic Review
Authors: Judith Gebauer, Claire Higham, Thorsten Langer, Christian Denzer, Georg Brabant
Journal: Endocrine Reviews (2018)

The number of patients surviving ≥5 years after initial cancer diagnosis has significantly increased during the last decades due to considerable improvements in the treatment of many cancer entities. A negative consequence of this is that the emergence of long-term sequelae and endocrine disorders account for a high proportion of these. These late effects can occur decades after cancer treatment and affect up to 50% of childhood cancer survivors. Multiple predisposing factors for endocrine late effects have been identified, including radiation, sex, and age at the time of diagnosis. A systematic literature search has been conducted using the PubMed database to offer a detailed overview of the spectrum of late endocrine disorders following oncological treatment. Most data are based on late effects of treatment in former childhood cancer patients for whom specific guidelines and recommendations already exist, whereas current knowledge concerning late effects in adult-onset cancer survivors is much less clear. Endocrine sequelae of cancer therapy include functional alterations in hypothalamic-pituitary, thyroid, parathyroid, adrenal, and gonadal regulation as well as bone and metabolic complications. Surgery, radiotherapy, chemotherapy, and immunotherapy all contribute to these sequelae. Following irradiation, endocrine organs such as the thyroid are also at risk for subsequent malignancies. Although diagnosis and management of functional and neoplastic long-term consequences of cancer therapy are comparable to other causes of endocrine disorders, cancer survivors need individually structured follow-up care in specialized surveillance centers to improve care for this rapidly growing group of patients.
Abstract 19311: Identification of Novel Primary Graft Dysfunction Biomarkers Using Exosome Proteomics
Authors: Nicholas Giangreco, Emily Chen, Emmanuel Zorn, Susan Restaino, Paolo C Colombo, Nicholas Tatonetti, Barry Fine
Journal: Circulation (2017)

Background: Primary graft dysfunction (PGD) is defined as severe ventricular dysfunction within 24 hours of heart transplant without discernible etiology. PGD is the leading cause of mortality with...
Combined Ibrutinib and Venetoclax in Patients with Treatment-Naïve High-Risk Chronic Lymphocytic Leukemia (CLL)
Authors: Nitin Jain, Michael J Keating, Philip A. Thompson, Alessandra Ferrajoli, Jan A. Burger, Gautam Borthakur, Koichi Takahashi, Zeev E. Estrov, Nathan H. Fowler, Tapan M. Kadia, Marina Y. Konopleva, Yesid Alvarado, Musa Yilmaz, Courtney D. DiNardo, Prithviraj Bose, Maro N. Ohanian, Naveen Pemmaraju, Elias J. Jabbour, Koji Sasaki, Rashmi Kanagal-Shamanna, Keyur Patel, Jeffrey L. Jorgensen, Naveen Garg, Xuemei Wang, Katrina Sondermann, Nichole Cruz, Chongjuan Wei, Ana Ayala, William Plunkett, Hagop M. Kantarjian, Varsha Gandhi, William G. Wierda
Journal: Blood (2018)
FUS-NFATc2 sarcoma of bone, a novel molecular entity with aggressive behavior: Clinical and molecular pathology findings of two cases
Authors: M.D. Lacambra, H. Loong, K.F. To, X. Feng, G. Taylor, E. Pleasance, J. Laskin, M. Marra, J. Griffith, H.Y.M. Yeung, K.-C. Wong, C. Chow, S. Kumta, W.H.A. Ng, T. Tse, C. Tong, T. Ng
Journal: Annals of Oncology (2018)
The quality of studies evaluating antimicrobial stewardship interventions: a systematic review
Authors: V.A. Schweitzer, I. van Heijl, C.H. van Werkhoven, J. Islam, K.D. Hendriks-Spoor, J. Bielicki, M.J.M. Bonten, A.S. Walker, M.J. Llewelyn, S. Harbarth, B. Huttner, P. Little, J. Rodriguez-Baño, A. Savoldi, M. van Smeden, E. Tacconelli, J.F. Timsit, M. Wolkewitz
Journal: Clinical Microbiology and Infection (2018)
Liposomal irinotecan (nal-IRI) plus 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) progressing on gemcitabine-based treatment: Further subgroup analyses of the pivotal NAPOLI-1 study
Authors: L.-T. Chen, T. Macarulla Mercadé, K.-H. Lee, G. Lakatos, A. Wang-Gillam, B. Mirakhur, F. de Jong
Journal: Annals of Oncology (2018)
A CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate
Authors: Simone Caielli, Diogo Troggian Veiga, Preetha Balasubramanian, Shruti Athale, Bojana Domic, Elise Murat, Romain Banchereau, Zhaohui Xu, Manjari Chandra, Cheng-Han Chung, Lynnette Walters, Jeanine Baisch, Tracey Wright, Marilynn Punaro, Lorien Nassi, Katie Stewart, Julie Fuller, Duygu Ucar, Hideki Ueno, Joseph Zhou, Jacques Banchereau, Virginia Pascual
Journal: Nature Medicine (2018)