tbuckley/cabot-search huggingface dataset:
Long-Term Outcomes and Prognostic Factors of Complications in Takayasu Arteritis
Authors: Cloé Comarmond, Lucie Biard, Marc Lambert, Arsène Mekinian, Yasmina Ferfar, Jean-Emmanuel Kahn, Ygal Benhamou, Laurent Chiche, Fabien Koskas, Philippe Cluzel, Eric Hachulla, Emmanuel Messas, Matthieu Resche-Rigon, Patrice Cacoub, Tristan Mirault, David Saadoun
Journal: Circulation (2017)

Because of the wide variation in the course of Takayasu arteritis (TA), predicting outcome is challenging. We assess long-term outcome and prognosis factors for vascular complications in patients with TA.A retrospective multicenter study of characteristics and outcomes of 318 patients with TA fulfilling American College of Rheumatology and Ishikawa criteria was analyzed. Factors associated with event-free survival, relapse-free survival, and incidences of vascular complications were assessed. Risk factors for vascular complications were identified in a multivariable model.The median age at TA diagnosis was 36 [25-47] years, and 276 patients (86.8%) were women. After a median follow-up of 6.1 years, relapses were observed in 43%, vascular complications in 38%, and death in 5%. Progressive clinical course was observed in 45%, carotidodynia in 10%, and retinopathy in 4%. The 5- and 10-year event-free survival, relapse-free survival, and complication-free survival were 48.2% (42.2; 54.9) and 36.4% (30.3; 43.9), 58.6% (52.7; 65.1) and 47.7% (41.2; 55.1), and 69.9% (64.3; 76.0) and 53.7% (46.8; 61.7), respectively. Progressive disease course (P=0.018) and carotidynia (P=0.036) were independently associated with event-free survival. Male sex (P=0.048), elevated C-reactive protein (P=0.013), and carotidynia (P=0.003) were associated with relapse-free survival. Progressive disease course (P=0.017), thoracic aorta involvement (P=0.009), and retinopathy (P=0.002) were associated with complication-free survival.This nationwide study shows that 50% of patients with TA will relapse and experience a vascular complication ≤10 years from diagnosis. We identified specific characteristics that identified those at highest risk for subsequent vascular complications.
L-mind: MOR208 combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large b-cell lymphoma (R-R DLBCL)—A single-arm phase II study.
Authors: Kami J. Maddocks, Eva González Barca, Wojciech Jurczak, Anna Marina Liberati, Johannes Duell, Zsolt Nagy, Tomáš Papajík, Marc Andre, Nagesh Kalakonda, Martin H. Dreyling, Pier Luigi Zinzani, Sumeet Vijay Ambarkhane, Johannes Weirather, Gilles A. Salles
Journal: Journal of Clinical Oncology (2017)

7514 Background: The Fc-enhanced CD19 antibody MOR208 and the immunomodulatory drug LEN have demonstrated single agent activity in patients (pts) with R-R DLBCL. MOR208 and LEN have shown synergy in vitro and in vivo in preclinical lymphoma models. This ongoing phase II study assesses the safety and efficacy of MOR208 + LEN in pts with R-R DLBCL. Methods: Pts &gt;18 years old with R-R DLBCL, ECOG 0–2, adequate organ function, having previously received ≥1 but not more than 3 prior therapies, including ≥1 CD20-targeting regimen and who are not candidates for autologous stem cell transplant (ASCT), are eligible. Treatment comprises up to 12, 28-day (d) cycles (C) of MOR208 12 mg/kg IV, weekly during C1–3 (loading dose d4 of C1); every second week C4–12 + LEN 25 mg po d1–21, C1–12. Pts progression-free after 12 cycles receive up to 12 additional cycles of MOR208 (every second week). The primary endpoint is the overall response rate (ORR) by central radiology assessment. Secondary endpoints include disease control, duration of response, progression-free and overall survival, safety, and response by cell of origin and other biomarkers. A preplanned safety evaluation was undertaken. Results: 31 of 80 planned pts were enrolled prior to data cutoff (3 January 2017). Median age was 74 years (range 47–82); 45% of pts received ≥2 prior lines of therapy; 23% had rituximab refractory disease; 74% had Ann Arbor stage ≥III disease; 65% had elevated lactate dehydrogenase level, and 52% had a poor revised International Prognostic Index (3-5). The most common treatment-emergent adverse events (any grade/grade ≥3 [% pts]) were neutropenia (39/26), anemia (23/0) thrombocytopenia (16/6), infections (26/10) diarrhea (13/0), pyrexia (13/0), and rashes (13/6). Of 26 response evaluable pts (median follow-up 3.3 months), ORR (investigator assessed) was 58% (15 pts), with 7 (27%) complete responses. Median time to response was 1.8 months. Conclusions: The combination of MOR208 + LEN is well tolerated and shows promising activity in pts with R-R DLBCL. Accrual and follow-up of pts is ongoing, as are cell of origin and other biomarker analyses. Clinical trial information: NCT02399085.
Crispr/Cas9-Induced DNMT3A Mutations in the K562 Human Leukemic Cell Line As a Model of DNMT3A-Mutated Leukemogenesis
Authors: Lauren G. Banaszak, Valentina Giudice, Xin Zhao, Zhijie Wu, Kohei Hosokawa, Keyvan Keyvanfar, Danielle Townsley, Sachiko Kajigaya, Neal S. Young
Journal: Blood (2016)
AB1079-HPR Adaptation and Validation of The Systemic Sclerosis Quality of Life Questionnaire into Polish: Item Analysis Using Rasch Models: Table 1.
Authors: M. Sierakowska, S. Sierakowski, J. Sierakowska, E. Krajewska-Kułak, A. Redmond, M. Ndosi
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic Sclerosis SSc is a multisystem autoimmune disease with serious effects on patients9 Quality of Life (QoL). SScQoL questionnaire was developed in the in the UK to measure needs-based patient-reported quality of life in SSc.<sup>1</sup> <h3>Objectives</h3> The aim of this study was to adapt and validate the SScQoL for use in Poland. <h3>Methods</h3> This cross-sectional study involved the (i) adaptation phase and (ii) validation phase. In the adaptation phase, the SScQoL was translated into Polish using a standard process for adaptation of self-report quality of life measures.<sup>2</sup> In the validation phase, patients with SSc were recruited from 8 rheumatology centres in Poland and they were asked to complete the Polish version of the SScQoL. The data was then analysed using Rasch models to determine fit to the model, local dependency, internal consistency, unidimensionality and psychometric equivalence with other European versions of the SScQoL. <h3>Results</h3> The SScQoL translated well into Polish. The sample included 231 patients, 198 (86%) of whom were women. Their median age was 58 (IQR: 48 to 64) years, median disease duration, 6 (IQR: 3 to 12) years and the majority left school at age 19. The analysis of the 29 items revealed lack of fit to the Rasch model and suggested some multidimensionality (Table 1). Items were grouped into 5 subscales derived from components of the International Classification of Functioning, Disability and Health. Re-analysis of the 5-subscale SScQoL resulted into a valid, reliable and unidimensional scale (only 4.3% of independent t-tests were significant).<sup>3</sup> The scale was found to have measurement equivalence with five other European countries as described elsewhere. <h3>Conclusions</h3> The Polish version of the SScQoL is a valid measure of needs-based quality of life in SSc. Transformed scores can be compared across five European countries. <h3>References</h3> Reay N. The quality of life in patients with diffuse and limited systemic sclerosis [PhD Thesis]. Leeds: University of Leeds; 2008. Beaton DE, Bombardier C, Guillemin F, Ferraz MB. Guidelines for the process of cross-cultural adaptation of self-report measures. Spine (Phila Pa 1976) 2000; 25(24): 3186–91. Smith Jr E. Detecting and evaluating the impact of multidimensionality using item fit statistics and principal component analysis of residuals. Journal of Applied Measurement 2002; 3(2): 205. <h3>Disclosure of Interest</h3> None declared
Brentuximab vedotin in CD30<sup>+</sup>cutaneous lymphoma: How do we treat, how shall we treat? A review of the literature
Authors: R. Stranzenbach, E. Dippel, M. Schlaak, R. Stadler
Journal: British Journal of Dermatology (2017)

Brentuximab vedotin is an antibody–drug conjugate that brings the antimicrotubule agent monomethyl auristatin E into CD30‐expressing cells. Some prior studies demonstrated good efficacy in cutaneous lymphomas. The standard therapeutic scheme is 1·8 mg kg−1 every 3 weeks. The background of this work is the fact that cutaneous lymphoma has a different pathophysiology and a dynamic other than systemic lymphomas. The objectives of this review were to get an overview of the currently used therapeutic regimen, and to check whether dose reduction or modified time intervals could be of benefit in a similar way with less toxicity. Therefore, we conducted a systematic review of the literature indexed in PubMed and the Cochrane Central Register of Controlled Trials up to April 2016. The procedure was based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) criteria. The review showed that the currently used therapeutic regimen is 1·8 mg kg−1 every 3 weeks. No publications of dose‐finding studies in CD30+ cutaneous T‐cell lymphoma (CTCL) were found. Two cases of patients, treated with a dose < 1·8 mg kg−1, have been published. Brentuximab vedotin seems to be a powerful treatment option in refractory CD30+ CTCL, and there is a trend that dose reductions, as well as prolonged treatment intervals, work without any loss of response and with fewer side‐effects.
Lipid-polymer hybrid nanoparticles: Development &amp; statistical optimization of norfloxacin for topical drug delivery system
Authors: Vivek Dave, Renu Bala Yadav, Kriti Kushwaha, Sachdev Yadav, Swapnil Sharma, Udita Agrawal
Journal: Bioactive Materials (2017)

Poly lactic acid is a biodegradable, biocompatible, and non-toxic polymer, widely used in many pharmaceutical preparations such as controlled release formulations, parenteral preparations, surgical treatment applications, and tissue engineering. In this study, we prepared lipid-polymer hybrid nanoparticles for topical and site targeting delivery of Norfloxacin by emulsification solvent evaporation method (ESE). The design of experiment (DOE) was done by using software to optimize the result, and then a surface plot was generated to compare with the practical results. The surface morphology, particle size, zeta potential and composition of the lipid-polymer hybrid nanoparticles were characterized by SEM, TEM, AFM, and FTIR. The thermal behavior of the lipid-polymer hybrid nanoparticles was characterized by DSC and TGA. The prepared lipid-polymer hybrid nanoparticles of Norfloxacin exhibited an average particle size from 178.6 ± 3.7 nm to 220.8 ± 2.3 nm, and showed very narrow distribution with polydispersity index ranging from 0.206 ± 0.36 to 0.383 ± 0.66. The surface charge on the lipid-polymer hybrid nanoparticles were confirmed by zeta potential, showed the value from +23.4 ± 1.5 mV to +41.5 ± 3.4 mV. An Antimicrobial study was done against Staphylococcus aureus and Pseudomonas aeruginosa, and the lipid-polymer hybrid nanoparticles showed potential activity against these two. Lipid-polymer hybrid nanoparticles of Norfloxacin showed the %cumulative drug release of 89.72% in 24 h. A stability study of the optimized formulation showed the suitable condition for the storage of lipid-polymer hybrid nanoparticles was at 4 ± 2 °C/60 ± 5% RH. These results illustrated high potential of lipid-polymer hybrid nanoparticles Norfloxacin for usage as a topical antibiotic drug carriers.
Response by Vaidya et al to Letter Regarding Article, “Burden of Arrhythmia in Pregnancy”
Authors: Vaibhav R. Vaidya, Shilpkumar Arora, Nileshkumar Patel, Apurva Badheka, Nilay Patel, Kanishk Agnihotri, Zeenia Billimoria, Mintu P. Turakhia, Paul A. Friedman, Malini Madhavan, Suraj Kapa, Peter A. Noseworthy, Yong-Mei Cha, Bernard Gersh, Samuel J. Asirvatham, Abhishek J. Deshmukh
Journal: Circulation (2017)

In Response:We appreciate the interest from Stergiopoulos et al in our results and are thankful for the comment on our research letter.They report 24.7% increase in pregnant women with heart disease, mostly because of structural heart disease.They also report an 18.8% increase in major adverse cardiac events, mainly because of arrhythmia.As alluded to in our research letter, we agree that structural heart diseases such as congenital heart disease could be a potential contributor to the increase in arrhythmia in pregnancy.Among all comorbidities assessed, any arrhythmia was present most frequently in women with congestive heart failure (4654 per 100 000).Congestive heart failure had an elevated odds ratio for death (odds ratio, 22.45; 95% confidence interval, 16.08-31.36;P<0.0001) and maternal/fetal adverse events (odds ratio, 5.16; 95% confidence interval, 4.89-5.45;P<0.0001).In addition to structural heart disease, we hypothesized that increase in maternal age and risk factors such as hypertension, diabetes mellitus, and obesity could account for the increase in arrhythmias, specifically atrial fibrillation.We look forward to reading the authors' publication with regard to these findings.We agree with the authors that childbirth poses heightened hemodynamic stress and may result in adverse cardiac events such as arrhythmias.
Impact of an electronic health record alert in primary care on increasing hepatitis c screening and curative treatment for baby boomers
Authors: Monica A. Konerman, Mary Thomson, Kristen Gray, Meghan Moore, Hetal Choxi, Elizabeth Seif, Anna S.F. Lok
Journal: Hepatology (2017)

Despite effective treatment for chronic hepatitis C, deficiencies in diagnosis and access to care preclude disease elimination. Screening of baby boomers remains low. The aims of this study were to assess the impact of an electronic health record–based prompt on hepatitis C virus (HCV) screening rates in baby boomers in primary care and access to specialty care and treatment among those newly diagnosed. We implemented an electronic health record–based “best practice advisory” (BPA) that prompted primary care providers to perform HCV screening for patients seen in primary care clinic (1) born between 1945 and 1965, (2) who lacked a prior diagnosis of HCV infection, and (3) who lacked prior documented anti‐HCV testing. The BPA had associated educational materials, order set, and streamlined access to specialty care for newly diagnosed patients. Pre‐BPA and post‐BPA screening rates were compared, and care of newly diagnosed patients was analyzed. In the 3 years prior to BPA implementation, 52,660 baby boomers were seen in primary care clinics and 28% were screened. HCV screening increased from 7.6% for patients with a primary care provider visit in the 6 months prior to BPA to 72% over the 1 year post‐BPA. Of 53 newly diagnosed patients, all were referred for specialty care, 11 had advanced fibrosis or cirrhosis, 20 started treatment, and 9 achieved sustained virologic response thus far. Conclusion : Implementation of an electronic health record–based prompt increased HCV screening rates among baby boomers in primary care by 5‐fold due to efficiency in determining needs for HCV screening and workflow design. Streamlined access to specialty care enabled patients with previously undiagnosed advanced disease to be cured. This intervention can be easily integrated into electronic health record systems to increase HCV diagnosis and linkage to care. (H epatology 2017;66:1805–1813)
Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles
Authors: Gi-Wook Kim, Changsun Kang, Young-Bin Oh, Myoung-Hwan Ko, Jeong-Hwan Seo, Dongwon Lee
Journal: Theranostics (2017)

Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H2O2) are known to be generated during tissue damages such as mechanical injury and therefore H2O2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H2O2 and exerts antioxidant and anti-inflammatory activity in H2O2-associated diseases. Based on the notion that PVAX nanoparticles generate CO2 bubbles through H2O2-triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H2O2. In the agarose gel phantom study, PVAX nanoparticles continuously generated CO2 bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H2O2 in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries.
Surface‐Modified Mesh Filter for Direct Nucleic Acid Extraction and its Application to Gene Expression Analysis
Authors: Jae Bem You, Yong Tae Kim, Kyoung G. Lee, Yunho Choi, Seongkyun Choi, Chi Hyun Kim, Kyung Hoon Kim, Sung Jin Chang, Tae Jae Lee, Seok Jae Lee, Sung Gap Im
Journal: Advanced Healthcare Materials (2017)

Rapid and convenient isolation of nucleic acids (NAs) from cell lysate plays a key role for onsite gene expression analysis. Here, this study achieves one-step and efficient capture of NA directly from cell lysate by developing a cationic surface-modified mesh filter (SMF). By depositing cationic polymer via vapor-phase deposition process, strong charge interaction is introduced on the surface of the SMF to capture the negatively charged NAs. The NA capturing capability of SMF is confirmed by X-ray photoelectron spectroscopy, fluorescent microscopy, and zeta potential measurement. In addition, the genomic DNAs of Escherichia Coli O157:H7 can be extracted by the SMF from artificially infected food, and fluorescent signal is observed on the surface of SMF after amplification of target gene. The proposed SMF is able to provide a more simplified, convenient, and fast extraction method and can be applied to the fields of food safety testing, clinical diagnosis, or environmental pollutant monitoring.
Radiomic biomarkers for the prediction of immunotherapy outcome in patients with metastatic non-small cell lung cancer.
Authors: Stefano Trebeschi, Ieva Kurilova, Adriana M. Călin, Doenja M. J. Lambregts, Egbert F. Smit, Hugo Aerts, Regina GH Beets-Tan
Journal: Journal of Clinical Oncology (2017)

e14520 Background: PD-1 checkpoint inhibitors have recently been approved for the treatment of patients with metastatic NSCLC. Predicting to what extent patients will benefit from these treatments is challenging. Research on predictive biomarkers focus on genetic and histological markers from biopsies, necessarily limited to parts of the tumor. Radiomics is a novel approach to quantify characteristics of the tumor on medical imaging, which may have potential value as non-invasive biomarkers. In this study, we explored the value of radiomic data from primary tumors to predict overall survival (OS) in patients with metastatic NSCLC treated with Nivolumab Methods: We retrospectively selected 64 metastatic NSCLC patients treated in 2 nd line setting with Nivolumab (240 mg q 2 weeks until progression). Inclusion criteria were: primary tumor in situ with contrast enhanced CT scan (thorax abdomen; slice thickness ≤3mm) within 6 weeks before the start of the treatment. Exclusion criteria were: presence of atelectasis or fusion with other structures and presence of multiple lung lesions at first scan. A certified radiologist delineated the tumors on CT from which we extracted 1696 Radiomic features. Unsupervised feature selection was performed. Multivariate Cox Regression was used to model the OS based on the selected features, as well as, histopathological type (adeno vs squamous), age at the start of the treatment, and extent of metastatic disease ( &lt; 5, 5–10, or &gt; 10 metastasis) Results: The selection resulted in three textural features derived from a Laplacian of Gaussian (LoG): regions dissimilarity (GLRLM_rlnun), entropy (GLSZM_ze), and uniformity. The resulting model was significant (p = 0.005). Both regions dissimilarity (HR = 0.11, 95% CI 0.03–0.46, p = 0.002) and entropy (HR = 0.20, 95% CI 0.06–0.67, p = 0.009) were significant predictors of OS. Subtype and disease extent were close to significance (p = 0.099) Conclusions: Results indicate that more heterogeneous tumors with irregular patterns of intensities showed better OS. The availability of CT scans makes Radiomics a potentially valuable adjunct to other clinical biomarkers. Further validation of our findings in larger cohorts are warranted
A Transcriptional- and Posttranscriptional-Based Prognostic Model in Pediatric Acute Myeloid Leukemia
Authors: Antony Ceraulo, Aminetou Mint-Mohamed, Delphine Maucort-Boulch, Helene Lapillone, Guy Leverger, Etienne Paubelle, Lea Herpe, Christine Ragu, Franck Mortreux, Yves Bertrand, Eric Wattel
Journal: Blood (2016)
Epigallocatechin gallate induces phosphorylation of epidermal growth factor receptor via activation of p38 MAPK in colon cancer cells.
Authors: Seiji Adachi, Satoshi To, Masahito Shimizu, Hisataka Moriwaki, I. Weinstein
Journal: Cancer Research (2008)

616   We previously reported that (-)-Epigallocatechin Gallate (EGCG) inhibits epidermal growth factor (EGF) binding to the EGF receptor (EGFR) and the subsequent dimerization of the EGFR by altering plasma membrane organization, and that this is associated with loss of ordered domains, so called “lipid rafts” in the plasma membrane (Adachi S et al.,  Cancer Res.  2007 67:6493-501). Since lipid rafts are thought to play a role in endocytosis, we next examined the effects of EGCG on cellular localization of the EGFR in SW480 colon cancer cells and found that EGCG caused internalization of EGFRs and that these internalized EGFRs can recycle back to the cell surface. To further examine the mechanism of this we focused on p38 MAPK, a stress-inducible kinase believed to negatively regulate tumorigenesis, because it was recently reported that Cisplatin and UV can induce internalization of EGFR via activation of p38 MAPK.  We first found that EGCG can strongly induce phosphorylation of p38 MAPK (Thr180/Tyr182) in a time- and dose-dependent manner. EGFR underwent a gel mobility shift upon treatment with EGCG and this was canceled by the p38 MAPK inhibitor SB202190, indicating that EGCG might cause phosphorylation of the EGFR at serine or threonine, residues, sites phosphorylated by p38 MAPK. We also found that longer exposure to 50 μM EGCG for 12 hours can lead to degradation of the EGFR and IGF-1R, while exposure to 50 μM EGCG caused degradation of HER-2 within 1 hour. The degradation of these RTKs by treatment with EGCG was not blocked by SB202190 even though the internalization of EGFR by Cisplatin was blocked by this inhibitor. Interestingly, phosphorylation of p38 MAPK was seen by EGCG as well as cisplatin in SW480 cells, but cisplatin had much less effect than EGCG in CCD841 normal colon epithelial cells. Taken together, these results indicate that relatively high concentrations of EGCG can induce degradation of EGFR, IGF-1R and HER-2 but this is unlikely to be due to activation of the p38 MAPK pathway, even though EGCG activated this pathway. The pathway of internalization of the EGFR induced by EGCG appears to be different from that of Cisplatin-induced internalization of the EGFR. However, it is still of interest to further examine the function of p38 MAPK in anti-cancer effects of EGCG.