tbuckley/cabot-search huggingface dataset:
Assessment of gastric pH changes and food intake on ribociclib bioavailability: In silico and clinical evaluations
Authors: T. Samant, M. Elmeliegy, S. Dhuria, Y. Lu, M. Laisney, S. Yang, A. Grandeury, M. Mueller-Zsigmondy, K-I. Umehara, F. Huth, M. Miller, C. Germa
Journal: Annals of Oncology (2017)
Interruzione della trasmissione del morbillo a Gipuzkoa, Paesi baschi spagnoli
Authors: G Cilla, M Basterretxea, J Artieda, D Vicente, E Pérez-Trallero
Journal: Eurosurveillance (2004)

La vaccinazione contro il morbillo e stata introdotta in Gipuzkoa (Paesi Baschi spagnoli) nel 1978 e poi sostituita nel 1981 con la vaccinazione trivalente morbillo, parotite rosolia (MPR) per i bambini da 12 a 15 mesi. Una seconda dose di vaccino MPR e stata introdotta nel 1992. La popolazione ha reagito favorevolmente alla nuova vaccinazione in due dosi ed e stata raggiunta una elevata copertura vaccinale (nel periodo 1993-2003 rispettavamente 95% e 91% per la prima e la seconda dose). La circolazione del virus del morbillo e stata interrotta nella seconda meta degli anni 1990: tra il 1998 e il 2003 non e stato registrato nessun caso di morbillo autoctono, solo dei casi importati sono stati confermati in questo periodo. Questi dati suggeriscono che il programma di vaccinazione contro il morbillo e efficace. Tuttavia, bisogna mantenere dei tassi di copertura vaccinale elevati (g95%) per le due dosi al fine di evitare delle epidemie di morbillo dovute alla reintroduzione del virus.
PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC)
Authors: S. Loibl, O. Metzger, S.J. Mandrekar, C. Mundhenke, S. Seiler, P. Valagussa, A. DeMichele, E. Lim, D. Tripathy, E.P. Winer, C. Huang, L. Carey, P. Francis, K.D. Miller, M.P. Goetz, A. Prat, S. Loi, I. Krop, L. Gianni, E.M. Ciruelos
Journal: Annals of Oncology (2018)
miR93 regulates epithelial-to-mesenchymal transition process in metastatic colorectal cancer by targeting EphA4
Authors: S. Gao, B. Jiang, H. Liu, S. Hou, L. Wu, Z. Yang, J. Shen, L. Zhou, S-S Zheng, W. Bai
Journal: Annals of Oncology (2017)
Quality of life in patients with recurrent ovarian cancer (OC) treated with niraparib: Results from the ENGOT-OV16/NOVA Trial
Authors: A.M. Oza, U.A. Matulonis, S. Malander, J. Sehouli, J.M. del Campo, D. Berthon-Rigaud, S. Banerjee, G. Scambia, J.S. Berek, B. Lund, A.V. Tinker, F. Hilpert, I. Palacio Vázquez, V. D’Hondt, B. Benigno, D.M. Provencher, J. Buscema, S. Hudgens, S. Agarwal, M.R. Mirza
Journal: Annals of Oncology (2017)
Preclinical evaluation of genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer.
Authors: Andrew Wang, Natalie Dawn Cummings, Manish Sethi, Edina Wang, Rohit Sukumar, Dominic T. Moore, Michael Edward Werner
Journal: Journal of Clinical Oncology (2013)

e13546 Background: A key research objective in radiation oncology is to identify agents that can improve chemoradiotherapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiotherapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiotherapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer as a model disease. Methods: The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM’s efficacy as a radiosensitizer was evaluated in vitro using NSCLC cell lines and in vivousing mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared to that of after Taxol administration. Results: Genexol-PM have a size of 23.91 ± 0.41 nm and surface charge of -8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an excellent radiosensitizer and is more effective than Taxol, its small molecule counterpart at the half maximal inhibitory concentration (IC50). In vivostudy of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung and liver tissue than Taxol at 6 hours post administration. Conclusions: We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiotherapy for NSCLC.
Low-dose naltrexone: a novel treatment for Hailey-Hailey disease
Authors: V. Campbell, C. McGrath, A. Corry
Journal: British Journal of Dermatology (2017)

Hailey–Hailey disease (chronic benign familial pemphigus) is a rare inherited dermatosis typically characterized by erosions at intertriginous sites preceded by minor trauma or stress. We report a case of treatment‐resistant Hailey–Hailey disease having failed topical and oral steroids, prophylactic aciclovir and doxycycline, and systemic therapies including dapsone, acitretin and ciclosporin. Low‐dose naltrexone 4·5 mg once daily was commenced following an incidental benefit in this patient's similarly affected sister. The clinical and psychological response to date has been considerable.
Review: Genetics and the Classification of Arthritis in Adults and Children
Authors: Peter A. Nigrovic, Soumya Raychaudhuri, Susan D. Thompson
Journal: Arthritis & Rheumatology (2017)

Current classification of primary inflammatory arthritis begins from the assumption that adults and children are different. No form of juvenile idiopathic arthritis bears the same name as an adult arthritis, a nomenclature gap with implications for both clinical care and research. Recent genetic data have raised questions regarding this adult/pediatric divide, revealing instead broad patterns that span the age spectrum. Combining these genetic patterns with demographic and clinical data, we propose that inflammatory arthritis can be segregated into 4 main clusters, largely irrespective of pediatric or adult onset: seropositive, seronegative (likely including a distinct group that usually begins in early childhood), spondyloarthritis, and systemic. Each of these broad clusters is internally heterogeneous, highlighting the need for further study to resolve etiologically discrete entities. Eliminating divisions based on arbitrary age cutoffs will enhance opportunities for collaboration between adult and pediatric rheumatologists, thereby helping to promote the understanding and treatment of arthritis.
PYTHIA: A phase II study of palbociclib plus fulvestrant for pretreated patients with ER+/HER2- metastatic breast cancer
Authors: D. Zardavas, M. Regan, R. Maibach, B. Ruepp, A. Hiltbrunner, L. Blacher, R. Gelber, G. Gebhart, A. Di Leo, F. Hilbers, M. Colleoni, G. Zoppoli, G. Bertelli, J. Bliss, F. Duhoux, M. Piccart, L. Malorni
Journal: Annals of Oncology (2017)
Second interim analysis of HerSCin, a German non-interventional study of subcutaneous trastuzumab for HER2-positive early breast cancer in routine clinical practice
Authors: K. Lüdtke-Heckenkamp, S. Kümmel, A. Ruf-Dördelmann, A. Distelrath, J. Wacker, S. Schmatloch, S. Busch-Liles, M. Schmidt
Journal: Annals of Oncology (2017)
Concordance of genomic alterations by next generation sequencing (NGS) in tumor tissue vs. cell-free DNA in advanced breast cancer.
Authors: Andrew Davis, Young Kwang Chae, Sarika Jain, Cesar Augusto Santa-Maria, Lisa E. Flaum, Nike Beaubier, Leonidas C. Platanias, William John Gradishar, Francis J. Giles, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2016)

11528 Background: Cell-free DNA (cfDNA) is a non-invasive method of assessing mutations in the blood. This study compared the concordance between cfDNA and tissue biopsies across DNA genomic alterations in patients with advanced breast cancer (ABC). Methods: Forty-five patients with ABC who had both NGS testing with cfDNA (Guardant) and tissue DNA (Foundation One) for clinical management were included. 45-67 genes were common to both assays depending on when the assays were performed. Concordance was defined as the presence or absence of the identical genomic sequencing alteration(s) in a single gene. Results: Median time between assays was 3.3 months [range, 0-67 months]. Including all alterations and variants of unknown significance, the average number per patient for tissue and cfDNA was 4.50 (SD 2.96) and 1.98 (SD 2.13), respectively. Concordance between the two assays was 91.2%. Among only genes with reported genomic alterations in either assay (N=232), concordance was 10.3%. 15.0% of alterations found in tissue were detected in cfDNA. 34.1% of cfDNA mutations were detected in tumor biopsies. Across 5 clinically important genes, sensitivity and specificity were 26.8% and 95.3%, respectively, with a diagnostic accuracy of 71.6% (Table). Conclusions: This study demonstrated a high concordance between tissue and cfDNA NGS. Moreover, a larger number of mutations were detected by tissue NGS. Potential reasons include different sequencing techniques, spatial and temporal factors, tumor heterogeneity, subclones, and potential germline DNA contamination. The study suggests that both tissue and blood-based NGS can be used to describe the complex biology of ABC. Diagnostic accuracy of 5 genes associated with breast cancer. cfDNA mutations Tissue Mutations Sensitivity (%) Specificity (%) PPV (%) NPV (%) Diagnostic Accuracy (%) (+) (-) TP53 (+) 7 2 (-) 17 16 29.2 88.9 77.8 48.5 54.8 PIK3CA (+) 3 2 (-) 9 31 25.0 93.9 60.0 77.5 75.6 ERBB2 (+) 4 0 (-) 10 31 28.6 100.0 100.0 75.6 77.8 BRCA1 (+) 1 0 (-) 2 12 33.3 100.0 100.0 85.7 86.7 BRCA2 (+) 0 1 (-) 3 11 0.0 91.7 0.0 78.6 73.3 Total positive 15 5 Total negative 41 101 Total (positive + negative) 56 106 26.8 95.3 75.0 71.1 71.6 * Chae & Davis: equal contribution
Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the Kidney
Authors: Takashi Hato, Amy Zollman, Zoya Plotkin, Tarek M. El-Achkar, Bernhard F. Maier, S. Louise Pay, Shataakshi Dube, Pablo Cabral, Momoko Yoshimoto, Jeanette McClintick, Pierre C. Dagher
Journal: Journal of the American Society of Nephrology (2017)

Preconditioning with a low dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response generated by preconditioning remains unknown. Here, using the kidney as a model organ, we investigated cell type–specific responses to preconditioning. Compared with preadministration of vehicle, endotoxin preconditioning in the cecal ligation and puncture mouse model of sepsis led to significantly enhanced survival and reduced bacterial load in several organs. Furthermore, endotoxin preconditioning reduced serum levels of proinflammatory cytokines, upregulated molecular pathways involved in phagocytosis, and prevented the renal function decline and injury induced in mice by a toxic dose of endotoxin. The protective phenotype involved the clustering of macrophages around S1 segments of proximal tubules, and full renal protection required both macrophages and renal tubular cells. Using unbiased S1 transcriptomic and tissue metabolomic approaches, we identified multiple protective molecules that were operative in preconditioned animals, including molecules involved in antibacterial defense, redox balance, and tissue healing. We conclude that preconditioning reprograms macrophages and tubules to generate a protective environment, in which tissue health is preserved and immunity is controlled yet effective. Endotoxin preconditioning can thus be used as a discovery platform, and understanding the role and participation of both tissue and macrophages will help refine targeted therapies for sepsis.
A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis
Authors: Kris V. Kowdley, Velimir Luketic, Roger Chapman, Gideon M. Hirschfield, Raoul Poupon, Christoph Schramm, Catherine Vincent, Christian Rust, Albert Parés, Andrew Mason, Hanns‐Ulrich Marschall, David Shapiro, Luciano Adorini, Cathi Sciacca, Tessa Beecher‐Jones, Olaf Böhm, Richard Pencek, David Jones
Journal: Hepatology (2017)

Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double‐blind, placebo‐controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double‐blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6‐year open‐label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg −53.9% [−62.5, −29.3], OCA 50 mg −37.2% [−54.8, −24.6]) compared to placebo (−0.8% [−6.4, 8.7]; P &lt; 0.0001) at the end of the study, with similar reductions observed through 6 years of open‐label extension treatment. OCA improved many secondary and exploratory endpoints (including γ‐glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus. Conclusion: OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long‐term clinical outcomes. Pruritus increased dose‐dependently with OCA treatment. Biochemical improvements were observed through 6 years of open‐label extension treatment. (H epatology 2018;67:1890‐1902).
GW28-e1162 Clinical safety and Efficacy and long-term outcome of transcatheter occlusion for the patients with Valsalva aneurysm ruptured into right atrium
Authors: Jiawang Xiao, Zhu Xianyang, Wang Qiguang, Zhang Duanzhen, Cui Chunsheng, Zhang Po, Meng Lili, Chen Huoyuan, Zhao Ming, Wang Shuang
Journal: Journal of the American College of Cardiology (2017)
(Neo-)adjuvant ipilimumab + nivolumab (IPI+NIVO) in palpable stage 3 melanoma – updated relapse free survival (RFS) data from the OpACIN trial and first biomarker analyses
Authors: E.A. Rozeman, L. Fanchi, A.C.J. van Akkooi, P. Kvistborg, J.V. Thienen, B. Stegenga, B. Lamon, J.B. Haanen, T.N.M. Schumacher, C.U. Blank
Journal: Annals of Oncology (2017)
Abstract 13894: Prediction of Mode of Death by Model of End-Stage Liver Disease Excluding INR (MELD-XI) Scoring System in Patients Admitted for Acute Decompensated Heart Failure With Preserved and Reduced Ejection Fraction; a Comparison With Nonalcoholic Fatty Liver Disease Fibrosis Score
Authors: Takahisa Yamada, Takashi Morita, Yoshihiro Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Tatsuhisa Ozaki, Masahiro Seo, Yoshihiro Sato, Iyo Ikeda, Eiji Fukuhara, Makoto Abe, Jun Nakamura, Masatake Fukunami
Journal: Circulation (2016)

Backgrounds: Cardiohepatic interactions have been a focus of attention among heart failure. A model of end-stage liver disease excluding INR (MELD-XI), a robust scoring system of liver dysfunction, has been shown to provide prognostic information in heart failure patients (pts). Furthermore, it was reported that nonalcoholic fatty liver disease (NAFLD) is a risk factor for cardiovascular disease. There is a difference in mode of death (cardiac vs non-cardiac death) between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). We sought to investigate the prognostic significance of MELD-XI and NAFLD in the prediction of mode of death in pts admitted for acute decompensated heart failure (ADHF), relating to HFpEF and HFrEF. Methods and Results: We studied 303 consecutive ADHF pts (HFrEF[LVEF&lt;50%]; n=163, HFpEF[LVEF≥50%];n=140). MELD-XI score was calculated by the formula: 5.11х ln(bilirubin)+11.79х ln(creatinine)+9.44. NAFLD fibrosis score (NFS) was obtained by the formula: -1.675 + 0.037 х age + 0.094 х BMI + 1.13 х hyperglycemia or diabetes (yes = 1, no = 0) + 0.99 х AST/ALT - 0.013 х platelet ( х 10 9 /L) - 0.66 х albumin. During a follow-up period of 5.1±4.3 yrs, 65 pts had cardiac death and 56 pts had non-cardiac death. At multivariate Cox analysis, MELD-XI score, but not NFS, was significantly associated with cardiac death independently of prior heart failure hospitalization, BMI, systolic blood pressure and serum sodium level, while neither MELD-XI score nor NFS showed the association with non-cardiac death. MELD-XI of 13 was a fair discriminator for cardiac death (AUC 0.737[0.670-0.805]). In both groups with HFrEF and HFpEF, pts with higher MELD-XI score had a significantly higher risk of cardiac death than those with lower MELD-XI score. Conclusion: A MELD-XI scoring system might predict cardiac death but not non-cardiac death in ADHF pts, regardless of HFrEF or HFpEF, although NAFLD fibrosis score did not.
Abstract 15413: Utility of an Innovative Echocardiographic Parameter for Mitral Regurgitation Severity
Authors: Aika Matsumoto, Akiko Goda, Masataka Sugahara, Kumiko Masai, Yuko Soyama, Tohru Masuyama, Toshiaki Mano
Journal: Circulation (2016)

Background:  Generally, the severity of mitral regurgitation (MR) is evaluated with proximal isovelocity surface area (PISA) or volumetric methods. However, there are some difficulties for the quantification of mitral regurgitation severity. Recently, left ventricular early inflow-outflow index (LVEIO index), which is calculated by dividing the mitral E-wave velocity by the LV outflow velocity time integral has been proposed as a simple method. The aim of this study is to determine the ideal threshold of LVEIO index to diagnose severe MR in the different etiologies.   Methods and Results:  We reviewed 76721 transthoracic echocardiography reports at the hospital of Hyogo College of Medicine from 2008 to 2015. MR severities were evaluated according to the guideline of the American society of echocardiography. We excluded the cases with moderate or severe aortic valve regurgitation, any mitral stenosis, prior mitral valve surgery, congenital heart diseases, LV assist device, or any arrhythmias. Also cases with inadequate or missing LV inflow or outflow Doppler recordings were excluded. Finally we evaluated 18692 cases and classified them as 17961 of no, trivial, or mild MR(Grade 0/1), 600 of moderate MR(Grade 2), 82 of moderate to severe MR(Grade 3) and 49 of severe MR (Grade 4) . The average LVEIO index of Grade 0/1, Grade 2, Grade 3 and Grade 4 were 3.4 ± 2.7, 5.5 ± 5.0, 6.7 ± 6.2 and 9.1 ± 5.6, respectively. The optimal threshold of LVEIO was 5.4 to distinguish moderate to severe or severe MR from non-severe MR (sensitivity 84%, specificity 91%). There were no differences in the significance of LVEIO index between the cases with reduced LV ejection fraction (   Conclusion:  LVEIO is a simple useful method to diagnose severe MR by using adequate thresholds according to the etiology of MR regardless of LVEF.
Sistema Europeo de Vigilancia de Resistencias Antimicrobianas (European Antimicrobial Resistance Surveillance System, EARSS): susceptibilidad de los Staphylococcus aureus invasivos
Authors: I Veldhuijzen, S L A M Bronzwaer, J Degener, J. L. Kool, Earss participants
Journal: Eurosurveillance (2000)

Mas de 400 laboratorios participan en el EARSS y envian datos al Instituto Nacional de Sanidad y Medio Ambiente (Rijksinstituut voor Volksgezondheid en Milieu; –RIVM–) de los Paises Bajos. Cada ano, se reciben datos pertenecientes a unos 14.000 aislamientos de Staphylococcus aureus en sangre y unos 6.000 aislamientos de Streptococcus pneumoniae. Los resultados obtenidos, tras la fase de viabilidad del Sistema de 18 meses de duracion, sugieren que la resistencia a la meticilina en los aislamientos en sangre de S. aureus se da con mayor frecuencia en los paises del sur de Europa que en los del norte.
Plastic surgeons report surge in reoperations for patients treated abroad
Authors: Anne Gulland
Journal: BMJ (2017)

Plastic surgeons are warning about a rise in the number of patients needing treatment for complications after travelling abroad for cosmetic procedures.

A review of patients at the Royal Free Hospital in London found that between 2015 and 2017 plastic surgeons saw 21 patients who had been abroad for treatment. The complications resulted in 18 episodes of inpatient admission and 46 operations. The total cost for the 21 patients was £282 000 (€314 610; $368 610), with an average of £13 500 per patient.

Patients went to a range of countries, with Eastern European countries being the most common. Infection (42% of cases) was the …
AB0188 Bone mineral density(bmd), serum calcidiol and knee osteoarthritis
Authors: M Bonilla Hernán, P Aguado, L Vacchiano, E Martinez, F Gamero, B Berriatua, E Martín Mola
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Relationship between knee osteoarthritis (OA) and bone mass has brought a great interest. Serum calcidiol (CS) low level has been associated with a higher incidence and faster progression of OA in elderly women, but this relation has not been defined in young postmenopausal women. <h3>Objectives</h3> The aim of the study was to determine the prevalence of knee OA in postmenopausal women and its relationship with bone density and CS levels. <h3>Methods</h3> Prospective study realised in 89 women (mean age ± 5 years: range:47–66), all of them being diagnosed of natural menopause for at least 2 years before they were included in this study.(mean value of 7.9 ± 2). They were recruited at a rheumatology consultory. CS levels were determined by RIA, along the winter time because of the lest sunny hours during that period. Two critical values were established (&lt;10, to calculate deficit prevalence. BMD was measured in lumbar spine and hip with DEXA (Hologic QDR 1000). Patients had to fulfil the WHO criteria to be diagnosed of osteoporosis. Knee OA was defined by a grade &gt;2 in Kellgren-Lawrence radiologic scale. Prevalence difference was analysed by contingency tables. <h3>Results</h3> A total of 58 women had OP while 31 had normal BMD. SC mean value was 13 ± 7.1 ng/ml and there were no significant differences comparing osteoporotic (OP) women with non-OP women. Knee OA prevalence was 65 (73%). In the OP. group and 80.6 in the non-OP. group. &lt; 10 and 20 ng/ml CS deficit prevalence was 38.7% and 61.3% respectively women with knee OA and 39% and 78.3% respectively in women without knee OA. <h3>Conclusion</h3> No inverse relationship was found between OP and knee OA in our group. CS deficit was not associated with a higher prevalence of knee OA in young postmenopausal women.