tbuckley/cabot-search huggingface dataset:
Musculoskeletal symptoms in chronic myeloid leukemia patients after stopping tyrosine kinase inhibitors.
Authors: Maria Diab, Ghayathri Jeyakumar, Charles Alan Schiffer
Journal: Journal of Clinical Oncology (2017)

e18547 Background: TKIs have revolutionized outcomes for CML patients (pts) but are not without cost or side effects. For pts with a prolonged response to treatment, discontinuing (d/c) treatment is appealing and has been investigated in a number of trials. In pts in whom treatment was stopped, musculoskeletal (MSK) symptoms were reported that were shown in some cases to resolve with resuming TKIs. Methods: Records of pts with chronic phase CML who stopped TKIs were reviewed. Results: We report 8 pts with chronic phase CML whose TKI was stopped following a prolonged molecular remission. 5 pts were receiving imatinib and 3 dasatinib. 5 pts were experiencing intolerable side effects of TKIs and agreed to a trial of d/c; 2 pts requested d/c; a third pt was planning for pregnancy. The median duration of therapy with TKI before d/c was 10 years. 6/8 pts developed MSK complaints with arthralgias and joint stiffness after cessation. Involved joints included the cervical spine, shoulders, elbows, small joints of the hand, hips and knees. Arthralgia was Grade 1 in 3 pts, and Grades 2 and 3 in 1 and 2 pts, respectively. Joints were not swollen, erythematous or tender to touch. The median time from cessation of TKIs to the onset of symptoms was 2.25 mos (range: &lt; 1-6 months). 3 pts with symptoms underwent rheumatologic work up that was nonrevealing. 5/8 pts remain in molecular remission. Of the 3 with molecular relapse, 2 had arthralgias that improved with resuming TKIs; the third remained asymptomatic. Of those who did not relapse, 1 remains symptom-free and 2 had resolution of their MSK symptoms. 1 had little benefit with corticosteroid therapy and imatinib was resumed. However, this retreatment was d/c due to side effects and she continues to experience mild arthralgias. 1 pt did not benefit from resuming TKIs, which was therefore d/c. Conclusions: The etiology of the so-called TKI “withdrawal syndrome” remains unclear. The incidence of this syndrome has not been fully elucidated, and it seems to be underappreciated and perhaps under-reported by patients. Although most symptoms are relatively mild and self-limited, this should be discussed with patients considering stopping TKIs.
P319Bay 60-2770 attenuates doxorubicin-induced cardiotoxicity by preventing mitochondrial membrane potential loss
Authors: K H Lee, X X Zhao, H Cho, S R Lee, J S Woo, W Kim
Journal: Cardiovascular Research (2018)

Background: Anthracyclines, like doxorubicin (DOX), are among the most potent antitumor drugs.However, their clinical use is hampered by severe cardiotoxicity.We previously demonstrated that inhibition of phosphoinositide 3-kinase c (PI3Kc) protects against anthracyclineinduced cardiomyopathy (manuscript under revision), but the underlying molecular mechanisms are still unexplored.Purpose: Here, we further test the hypothesis that anthracycline-damaged mitochondria activate Toll-like receptor 9 (TLR9)/PI3Kc signaling, which in turn inhibits protective autophagy, thus exacerbating anthracycline cardiotoxicity.Methods: Neonatal cardiomyocytes (NCMs) were isolated from mice expressing a kinase inactive PI3Kc (PI3Kc kinase-dead; KD) and wild-type (WT) controls, and treated with DOX (1 mM) or TLR9 agonist ODN1826 (1 mg/ml) 6 PI3Kc inhibitor AS605240 (500 nM) or TLR9 antagonist ODN2088 (1 mg/ml), for 1 hour before analyzing Akt/mTOR/Ulk-1 signaling.For in vivo studies, WT and KD mice were treated with 4 mg/kg DOX weekly for 3 weeks.Cardiac function was analyzed with echocardiography 6 weeks after the first injection.Electron microscopy (EM) study of morphology and signaling transduction were studied 3 days after the treatment.To investigate the role of protective autophagy in KD hearts, mice were treated with hydroxychloroquine (HCQ) or AAV9-shATG7, which silences the autophagy regulator ATG7 specifically in cardiomyocytes, together with DOX, as described above.Results: In NCMs, DOX significantly increased the phosphorylation of PI3K downstream targets and autophagy inhibitors, Akt, mTOR and Ulk-1.These effects were completely prevented by the TLR9 antagonist ODN2088, the PI3Kc selective inhibitor AS605240 and genetic PI3Kg inactivation (KD NCMs).Notably, the TLR9 agonist ODN1826, mimicking mitochondrial DNA (mitoDNA), similarly upregulated Akt/mTOR/Ulk-1 signaling in WT but not in KD NCMs.These results suggest that DOX activates PI3Kc through mitoDNA/TLR9.In vivo, EM studies showed more abundance of autolysosomes containing injured mitochondria in KD than WT hearts, highlighting the efficient autophagydependent disposal of DOX-damaged mitochondria in KD mice.Enhanced activation of PI3Kgdependent pathway correlated with a significant blunt of autophagy in DOX-treated hearts, whereas inhibition of PI3Kc promoted autophagy and decreased DOX-induced contractile dysfunction.Finally, inhibition of autophagy by HCQ or AAV9-shATG7 erased the protection in KD mice.Conclusion: Overall, this study demonstrates that PI3Kc prevents autophagic disposal of DOXdamaged mitochondria, resulting in cardiomyopathy.We propose PI3Kc inhibition as a novel strategy to reactivate targeted autophagy and limit cancer therapy-related heart disease.
Preemptive direct-acting antiviral therapy in naive or NS5A-relapser liver transplant recipients: a single centre experience
Authors: S. Martini, C. Chialà, F. Calvo, F. Tandoi, D. Patrono, D. Cocchis, A. Ottobrelli, M. Salizzoni, G. Maria Saracco, R. Romagnoli
Journal: Journal of Hepatology (2018)
In vitro studies to understand gender differences in calcific aortic valve disease: crosstalk between JAK-STAT and TLR pathways
Authors: Iván Parra Izquierdo, Irene Castaños-Mollor, Javier López, Cristina Gómez, José Alberto San Román, Mariano Sánchez Crespo, Carmen García-Rodríguez
Journal: Cardiovascular Research (2018)

Trabajo presentado en Frontiers in CardioVascular Biology (Fifth Congress of the ESC Council on Basic Cardiovascular Science), celebrado en Viena (Austria) del 20 al 22 de abril de 2018.
P522Correlation between contrast-induced nephropathy and SYNTAX score among patients undergoing primary percutaneous coronary intervention
Authors: AHMED Abdel-Galeel, DINA Alaa Abdel-Aal Mubasher, HOSSAM Hassan Ali, YEHIA Taha Kishk
Journal: Cardiovascular Research (2018)

the number (DADinc¼ 4.7260.6#/min) and amplitude of DAD (DADampl¼2.760.4 mV) as well as the number of spontaneous APs in myocytes from the MI adjacent region, without affecting the overall global Ca2þ transient kinetics in both regions.Conclusion: Both in vitro and in vivo studies showed the peri-infarct region having a higher arrhythmogenic potential compared to the non-infarcted remote region.Hyperactive non-coupled RyRs are at the origin of these spontaneous Ca2þ releases and are responsive to drug treatment without affecting the overall global Ca2þ transient.
Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic and lipid-lowering efficacy
Authors: Yanbo Tang, Xiaolin Zhang, Zheng Chen, Wenwen Yin, Guanglei Nan, Jinying Tian, Fei Ye, Zhiyan Xiao
Journal: Acta Pharmaceutica Sinica B (2018)

Based on a non-competitive and selective PTP1B inhibitor reported by us previously, thirty-nine benzamido derivatives were designed and synthesized as novel PTP1B inhibitors. Among them, twelve compounds exhibited IC50 values at micromolar level against human recombinant PTP1B, and most of them exhibited significant selectivity to PTP1B over TC-PTP and CD45. Further evaluation of the most potent compound 27 on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that 27 could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.
P250Atypical case of ulnar-mammary syndrome with ventricular tachycardia and lack of TBX3 mutation
Authors: A Zlotina, A Kiselev, A Kostareva
Journal: Cardiovascular Research (2018)

Introduction: MicroRNAs are important regulators of cellular and physiological functions, both in health and in disease.Furthermore, most microRNAs display tissue-specific expression patterns.This renders them promising therapeutic targets.However, with regards to cardiovascular disease, vascular microRNA expression profiles are still widely unknown.Even though certain microRNAs have been defined as 'endothelial-specific' or 'smooth muscle cell-specific', little is known about differences in microRNA expression between different types of blood vessels or between different vascular beds.This could have a major impact on future microRNA-based therapeutics.Purpose: Here we aimed to map expression patterns of the vasoactive microRNAs of the 14q32 locus throughout the human vasculature.Methods: We collected 109 different blood vessels as surplus tissue during general and thoracic surgery.Origin of vessels differed widely as well as age, gender and indication of surgery.Tissue samples were collected anonymously and we only recorded the vessel name, indication for surgery, gender and age of the patient.Using rt/qPCR, 17 of the total 54 14q32 microRNAs were measured in each sample.
Contemporary practice patterns and outcomes after transjugular intrahepatic portosystemic shunt placement: A multicenter U.S. experience of 1146 patients
Authors: J. Boike, J. Ge, M. German, N. Jest, G. Morelli, E. Spengler, A. Said, A. Lee, A. Hristov, K.P. Kolli, J. Lai, A. Desai, S. Junna, B. Pokhrel, T. Couri, S. Paul, C. Frenette, N. Christian-Miller, M. Laurito, E. Verna, U. Rahim, A. Goel, A. Das, S. Pine, D. Gregory, L. Vanwagner
Journal: Journal of Hepatology (2018)
TCTAP A-011 Myocardial Salvage Effect of Remote Concomitant Post-conditioning Using Blood Pressure Cuff in Primary Percutaneous Coronary Intervention for ST-elevation Myocardial Infarction
Authors: Chee Hae Kim, Young-seok Cho, Woo Young Chung, Jae-Bin Suh, Hack-Lyoung Kim
Journal: Journal of the American College of Cardiology (2018)
NICE recommends prostate artery embolisation as a treatment option for BPH symptoms
Authors: Susan Mayor
Journal: BMJ (2018)

The National Institute for Health and Care Excellence (NICE) has recommended prostate artery embolisation as a treatment option for lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH). Updated guidance,1 published on 25 April, follows new data from a unique collaborative study run by UK interventional radiologists and urological surgeons working with the regulator.2

“Results from the study show prostate artery embolisation can help large numbers of men with …
The FXR agonist GS-9674 reduces fibrosis and portal hypertension in a rat model of NASH
Authors: P. Schwabl, G. Budas, E. Hambruch, P. Supper, M. Burnet, J. Liles, T. Sullivan, E. Huntzicker, M. Birkel, D. French, D. Tumas, M. Peck-Radosavljevic, W. Watkins, M. Trauner, D. Breckenridge, C. Kremoser, T. Reiberger
Journal: Journal of Hepatology (2018)
Potential Benefit of Intra-operative Administration of Ketorolac on Breast Cancer Recurrence According to the Patient’s Body Mass Index
Authors: Christine Desmedt, Romano Demicheli, Marco Fornili, Imane Bachir, Mariana Duca, Giulia Viglietti, Martine Berlière, Martine Piccart, Christos Sotiriou, Maurice Sosnowski, Patrice Forget, Elia Biganzoli
Journal: JNCI Journal of the National Cancer Institute (2018)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in some countries as analgesics in primary cancer surgery. Retrospective studies suggest that NSAIDs could reduce breast cancer recurrences. Because NSAIDs also act on biological mechanisms present in patients with increased adiposity, we aimed at assessing whether the intra-operative administration of ketorolac or diclofenac would be associated with a reduction of recurrence in patients with elevated body mass index (BMI).We considered two institutional retrospective series of 827 and 1007 patients evaluating the administration of ketorolac (n = 529 with, n = 298 without) or diclofenac (n = 787 with, n = 220 without). The BMI subgroups were defined as less than 25 kg/m2 (lean) and 25 or more kg/m2 (overweight and obese). Cumulative incidence estimation of distant metastases as well as Fine-Gray and Dixon-Simon models was used. These analyses were adjusted for clinico-pathological variables. All statistical tests were two-sided.The administration of ketorolac was statistically significantly associated with decreased incidence of distant recurrences (adjusted hazard ratio [aHR]= 0.59, 95% confidence interval [CI] = 0.37 to 0.96, P = .03). In particular, the association was evident in the high-body mass index (BMI) group of patients (aHR = 0.55, 95% CI = 0.31 to 0.96, P = .04). The administration of diclofenac was not statistically significantly associated with decreased incidence of distant recurrences, either in the global population or in the BMI subgroups.These results show that the intra-operative administration of ketorolac, but not diclofenac, is statistically significantly associated with a reduction of distant recurrences in patients with increased BMI. Altogether, this study points to a potentially important repositioning of ketorolac in the intra-operative treatment of patients with elevated BMI that, if prospectively validated, might be as impactful as and cheaper than adjuvant systemic anticancer therapies.
Renal health after long-term exposure to tenofovir disoproxil fumarate (TDF) in HIV/HBV positive adults in Ghana
Authors: G. Villa, R.O. Phillips, C. Smith, A.J. Stockdale, A. Beloukas, L.T. Appiah, D. Chadwick, A. Ruggiero, F.S. Sarfo, F. Post, AM Geretti
Journal: Journal of Infection (2018)

The study assessed markers of renal health in HIV/HBV co-infected patients receiving TDF-containing antiretroviral therapy in Ghana.Urinary protein-to-creatinine ratio (uPCR) and albumin-to-protein ratio (uAPR) were measured cross-sectionally after a median of four years of TDF. At this time, alongside extensive laboratory testing, patients underwent evaluation of liver stiffness and blood pressure. The estimated glomerular filtration rate (eGFR) was measured longitudinally before and during TDF therapy.Among 101 participants (66% women, median age 44 years, median CD4 count 572 cells/mm3) 21% and 17% had detectable HIV-1 RNA and HBV DNA, respectively. Overall 35% showed hypertension, 6% diabetes, 7% liver stiffness indicative of cirrhosis, and 18% urinary excretion of Schistosoma antigen. Tubular proteinuria occurred in 16% of patients and was independently predicted by female gender and hypertension. The eGFR declined by median 1.8 ml/min/year during TDF exposure (IQR -4.4, -0.0); more pronounced declines (≥ 5 ml/min/year) occurred in 22% of patients and were associated with receiving ritonavir-boosted lopinavir rather than efavirenz. HBV DNA, HBeAg, transaminases, and liver stiffness were not predictive of renal function abnormalities.The findings mandate improved diagnosis and management of hypertension and suggest targeted laboratory monitoring of patients receiving TDF alongside a booster in sub-Saharan Africa.
Digestion-ligation-only Hi-C is an efficient and cost-effective method for chromosome conformation capture
Authors: Da Lin, Ping Hong, Siheng Zhang, Weize Xu, Muhammad Jamal, Keji Yan, Yingying Lei, Liang Li, Yijun Ruan, Zhen F. Fu, Guoliang Li, Gang Cao
Journal: Nature Genetics (2018)
Role of kinesiophobia on pain, disability and quality of life in people suffering from chronic musculoskeletal pain: a systematic review
Authors: Alejandro Luque-Suarez, Javier Martinez-Calderon, Deborah Falla
Journal: British Journal of Sports Medicine (2018)

(1) To explore the level of association between kinesiophobia and pain, disability and quality of life in people with chronic musculoskeletal pain (CMP) detected via cross-sectional analysis and (2) to analyse the prognostic value of kinesiophobia on pain, disability and quality of life in this population detected via longitudinal analyses.A systematic review of the literature including an appraisal of the risk of bias using the adapted Newcastle Ottawa Scale. A synthesis of the evidence was carried out.An electronic search of PubMed, AMED, CINAHL, PsycINFO, PubPsych and grey literature was undertaken from inception to July 2017.Observational studies exploring the role of kinesiophobia (measured with the Tampa Scale for Kinesiophobia) on pain, disability and quality of life in people with CMP.Sixty-three articles (mostly cross-sectional) (total sample=10 726) were included. We found strong evidence for an association between a greater degree of kinesiophobia and greater levels of pain intensity and disability and moderate evidence between a greater degree of kinesiophobia and higher levels of pain severity and low quality of life. A greater degree of kinesiophobia predicts the progression of disability overtime, with moderate evidence. A greater degree of kinesiophobia also predicts greater levels of pain severity and low levels of quality of life at 6 months, but with limited evidence. Kinesiophobia does not predict changes in pain intensity.The results of this review encourage clinicians to consider kinesiophobia in their preliminary assessment. More longitudinal studies are needed, as most of the included studies were cross-sectional in nature.CRD42016042641.
Validation of NIS4 algorithm for detection of NASH at risk of cirrhosis in 467 NAFLD patients prospectively screened for inclusion in the RESOLVE-IT trial
Authors: R. Hanf, C. Pierre, M. Zouher, G. Cordonnier, J. Brozek, E. Praca, F.B. Sudrick, P. Bedossa, Q. Anstee, S. Francque, S. Harrison, V. Ratziu, S. Megnien, A. Roudot, D. Hum, A. Sanyal
Journal: Journal of Hepatology (2018)
Defective DNAM-1 mediated cytotoxicity in NK cells infiltrating hepatocellular carcinoma
Authors: B. Oliviero, S. Mantovani, D. Mele, M. Donadon, C. Soldani, G. Torzilli, R. Santambrogio, E. Opocher, S. Chiellino, C. Porta, M.U. Mondelli
Journal: Journal of Hepatology (2018)
Clinical significance of time related fluctuations of AFP and PIVKA-II serum levels in single patients with cirrhosis undergoing surveillance for hepatocellular carcinoma
Authors: G. Ricco, C. Cosma, G. Bedogni, A. Biasiolo, M. Guarino, P. Pontisso, F. Morisco, F. Oliveri, D. Cavallone, F. Bonino, M. Plebani, M.R. Brunetto
Journal: Journal of Hepatology (2018)
TTP or PFS as a surrogate endpoint in advanced hepatocellular carcinoma treated with systemic therapy.
Authors: Dae-Won Lee, Myoung-Jin Jang, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim
Journal: Journal of Clinical Oncology (2016)

4075 Background: While overall survival (OS) is the most important survival endpoint in oncology clinical trials, it can be affected by sequential treatment after progression or by crossover from control to experimental arms and requires longer follow up duration compared to surrogate endpoints. Because death resulting from liver cirrhosis might confound the treatment outcome, time to progression (TTP) is suggested as a reliable surrogate endpoint compared to progression free survival (PFS) in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP/PFS and OS has never been studied. Methods: We searched Pubmed and Embase data to obtain data source. Eligible studies were randomized controlled phase III trials which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association between TTP/PFS and OS was assessed by Spearman rank correlation coefficient (rs) and linear regression analysis. The association of treatment effects as shown by the hazard ratio (HR) of TTP/PFS and OS in each trial was also investigated. Results: Ten studies with a total of 20 treatment arms and 6689 patients were included. Median TTP/PFS was significantly correlated with median OS. The rs value between TTP/PFS and OS was 0.74 (95% confidence index (CI) 0.45 – 0.89, p < 0.001) and the corresponding R2 was 0.47. There was no difference in rs value (0.72 vs. 0.69) and R2 value (0.38 vs. 0.35) between TTP and OS, and PFS and OS. Incremental benefit from the study treatment in TTP/PFS from each trial was correlated with incremental benefit in OS. The rs value and R2 value between log (HRTTP/PFS ) and log (HROS ) was 0.76 (95% CI 0.25 – 0.94, p = 0.009) and 0.61. Conclusions: Our study results suggest that either TTP or PFS could serve as a surrogate marker for OS in the clinical trials of advanced HCC. TTP was not a superior surrogate marker compared to PFS. In addition, this trial level analysis shows that the gain of TTP/PFS leads to the gain of OS.
Un brote decreciente de LGV en los Países Bajos en 2004 y 2005
Authors: M J W van de Laar, F. D.H. Koedijk, H Götz, H Jc de Vries
Journal: Eurosurveillance (2006)

En 2004, se detecto un brote de LGV en hombres homosexuales en los Paises Bajos. En enero de 2006, se habian declarado 179 casos confirmados de LGV : 65 retrospectivamente en 2002/2003, 76 en 2004 y 38 en 2005. La evolucion del brote de LGV parece ser descendente y solamente se ha identificado un pequeno numero de casos durante los primeros meses de 2006.
The surgical challenges of salvage living donor liver transplantation for Hepatocellular carcinoma; The cumulative experience of 100 cases - A retrospective cohort study and a propensity score analysis
Authors: Chee-Chien Yong, Ahmed M. Elsarawy, Shih-Ho Wang, Tsan-Shiun Lin, Chih-Chi Wang, Wei-Feng Li, Ting-Lung Lin, Fang-Ying Kuo, Yu-Fan Cheng, Chao-Long Chen, Chih-Che Lin
Journal: International Journal of Surgery (2018)
Women see no benefit from colorectal cancer screening, study finds
Authors: Jacqui Wise
Journal: BMJ (2018)

A single screening test using flexible sigmoidoscopy reduced colorectal cancer incidence and mortality in men but had little or no effect in women, a large randomised controlled trial in Norway has shown.1

The study authors say that the findings may have implications for screening programmes such as those in Italy, Norway, and the UK. In England, bowel scope screening using flexible sigmoidoscopy is currently being rolled out to everyone aged 55, as a one-off test.

Previous analyses of four randomised trials have indicated that sigmoidoscopy screening …
透析患者の重度石灰化冠状動脈病変を治療する場合,低速バープラットフォームはロータブレーターに対して常に適切であり,安全であるか?
Authors: Kanoh H, Misumi K, Iiduka D, Kubo T, Hirose M, Itoh M, Yoshiwara H, Nitta M, Kitagawa M
Journal: Circulation (2004)
Prolonged detection of dengue virus RNA in the semen of a man returning from Thailand to Italy, January 2018
Authors: Eleonora Lalle, Francesca Colavita, Marco Iannetta, Saba Gebremeskel Teklè, Fabrizio Carletti, Laura Scorzolini, Licia Bordi, Donatella Vincenti, Concetta Castilletti, Giuseppe Ippolito, Maria Rosaria Capobianchi, Emanuele Nicastri
Journal: Eurosurveillance (2018)

This study reports the presence of dengue virus RNA in longitudinally collected semen samples of a previously healthy Caucasian man, returning to Italy from Thailand with primary dengue fever, up to 37 days post-symptom onset, when viraemia and viruria were undetectable. This finding, coupled with the evidence of dengue virus negative-strand RNA, an indirect marker of ongoing viral replication, in the cellular fraction of semen, indicates a need to further investigate possible sexual transmission.