tbuckley/cabot-search huggingface dataset:
ACCF/SCAI/STS/AATS/AHA/ASNC 2009 Appropriateness Criteria for Coronary Revascularization
Authors: Manesh R. Patel, Gregory J. Dehmer, John W. Hirshfeld, Peter K. Smith, John A. Spertus
Journal: Circulation (2009)

The American College of Cardiology Foundation (ACCF), Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and the American Association for Thoracic Surgery, along with key specialty and subspecialty societies, conducted an appropriateness review of common clinical scenarios in which coronary revascularization is frequently considered. The clinical scenarios were developed to mimic common situations encountered in everyday practice and included information on symptom status, extent of medical therapy, risk level as assessed by noninvasive testing, and coronary anatomy. Approximately 180 clinical scenarios were developed by a writing committee and scored by a separate technical panel on a scale of 1 to 9. Scores of 7 to 9 indicate that revascularization was considered appropriate and likely to improve health outcomes or survival. Scores of 1 to 3 indicate revascularization was considered inappropriate and unlikely to improve health outcomes or survival. The mid range (4 to 6) indicates a clinical scenario for which the likelihood that coronary revascularization would improve health outcomes or survival was considered uncertain. For the majority of the clinical scenarios, the panel only considered the appropriateness of revascularization irrespective of whether this was accomplished by percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). In a select subgroup of clinical scenarios in which revascularization is generally considered appropriate, the appropriateness of PCI and CABG individually as the primary mode of revascularization was considered. In general, the use of coronary revascularization for patients with acute coronary syndromes and combinations of significant symptoms and/or ischemia was viewed favorably. In contrast, revascularization of asymptomatic patients or patients with low-risk findings on noninvasive testing and minimal medical therapy were viewed less favorably. It is anticipated that these results will have an impact on physician decision making and patient education regarding expected benefits from revascularization and will help guide future research.
Characterization and biological significance of IL-23-induced neutrophil polarization
Authors: Yang Li, Linnan Zhu, Zhulang Chu, Tao Yang, Hai-Xi Sun, Fan Yang, Wei Wang, Yuzhu Hou, Peng Wang, Qingjie Zhao, Yaling Tao, Lianfeng Zhang, Xiaodong Zhang, Yong Zhao
Journal: Cellular and Molecular Immunology (2017)
Cationic microbubbles and antibiotic-free miniplasmid for sustained ultrasound–mediated transgene expression in liver
Authors: Simona Manta, Gilles Renault, Anthony Delalande, Olivier Couture, Isabelle Lagoutte, Johanne Seguin, Franck Lager, Pascal Houzé, Patrick Midoux, Michel Bessodes, Daniel Scherman, Michel-Francis Bureau, Corinne Marie, Chantal Pichon, Nathalie Mignet
Journal: Journal of Controlled Release (2017)
Returning ex-patriot Chinese to Guangdong, China, increase the risk for local transmission of Zika virus
Authors: Jiufeng Sun, De Wu, Haojie Zhong, Dawei Guan, Huan Zhang, Qiqi Tan, Huiqiong Zhou, Meng Zhang, Dan Ning, Baohuan Zhang, Changwen Ke, Tie Song, Jinyan Lin, Yonghui Zhang, Marion Koopmans, George F. Gao
Journal: Journal of Infection (2017)
Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies
Authors: Eleonora Molinaro, Cristina Romei, Agnese Biagini, Elena Sabini, Laura Agate, Salvatore Mazzeo, Gabriele Materazzi, Stefano Sellari-Franceschini, Alessandro Ribechini, Liborio Torregrossa, Fulvio Basolo, Paolo Vitti, Rossella Elisei
Journal: Nature Reviews Endocrinology (2017)
<i>t</i>BHQ Suppresses Osteoclastic Resorption in Xenogeneic‐Treated Dentin Matrix‐Based Scaffolds
Authors: Jingjing Sun, Jie Li, Hui Li, Hefeng Yang, Jinlong Chen, Bo Yang, Fangjun Huo, Weihua Guo, Weidong Tian
Journal: Advanced Healthcare Materials (2017)

Extracellularmatrix (ECM)‐based scaffolds are important for their potential therapeutic application. Treated dentin matrix (TDM), a kind of ECM, seeded with allogeneic dental follicle stem cells (TDM/aDFC) provides a suitable inductive microenvironment for tooth root regeneration. Considering the limited sources, xenogeneic TDM (xTDM) is a possible alternative to allogeneic TDM; however, xTDM‐based scaffold presents severe osteolysis and resorption lacunae causing regenerated tooth root failure. Immune response–induced excessive osteoclastogenesis plays a critical role in xenogeneic scaffold osteolysis and resorption. The impact of antioxidant, tert ‐butylhydroquinone ( t BHQ), on xTDM/aDFCs‐induced osteoclastogenesis and osteoclastic resorption in vivo and in vitro are investigated. t BHQ upregulates heme oxygenase‐1 release and downregulates high mobility group box 1 mRNA expression. mRNA expression of other osteoclast‐related genes including nuclear factor‐kappa Bp65, receptor activator of nuclear factor kappa‐B, nuclear factor of activated T‐cells cytoplasmic 1, cathepsin K, and integrin β3, also decreases significantly. Furthermore, t BHQ‐treated xTDM/aDFCs scaffolds implanted into rhesus macaques show reduced osteolysis and osteoclastic resorption by microcomputed tomography and tartrate‐resistant acid phosphatase staining. t BHQ‐induced suppression of xTDM/aDFC‐induced osteoclastogenesis and osteoclastic resorption presents a new strategy for the regeneration of biological tooth root and could be applied to the regeneration of other complex tissues and organs.
Efficacy and Safety of Spironolactone in Acute Heart Failure
Authors: Javed Butler, Kevin J. Anstrom, G. Michael Felker, Michael M. Givertz, Andreas P. Kalogeropoulos, Marvin A. Konstam, Douglas L. Mann, Kenneth B. Margulies, Steven E. McNulty, Robert J. Mentz, Margaret M. Redfield, W. H. Wilson Tang, David J. Whellan, Monica Shah, Patrice Desvigne-Nickens, Adrian F. Hernandez, Eugene Braunwald
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. <h3>Objective</h3> To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. <h3>Design, Setting, and Participants</h3> This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had NT-proBNP levels of 1000 pg/mL or more or B-type natriuretic peptide levels of 250 pg/mL or more, regardless of ejection fraction. <h3>Interventions</h3> High-dose spironolactone (100 mg) vs placebo or 25 mg spironolactone (usual care) daily for 96 hours <h3>Main Outcomes and Measures</h3> The primary end point was the change in NT-proBNP levels from baseline to 96 hours. Secondary end points included the clinical congestion score, dyspnea assessment, net urine output, and net weight change. Safety end points included hyperkalemia and changes in renal function. <h3>Results</h3> A total of 360 patients were randomized, of whom the median age was 65 years, 129 (36%) were women, 200 (55.5%) were white, 151 (42%) were black, 8 (2%) were Hispanic or Latino, 9 (2.5%) were of other race/ethnicity, and the median left ventricular ejection fraction was 34%. Baseline median (interquartile range) NT-proBNP levels were 4601 (2697-9596) pg/mL among the group treated with high-dose spironolactone and 3753 (1968-7633) pg/mL among the group who received usual care. There was no significant difference in the log NT-proBNP reduction between the 2 groups (−0.55 [95% CI, −0.92 to −0.18] with high-dose spironolactone and −0.49 [95% CI, −0.98 to −0.14] with usual care,<i>P</i> = .57). None of the secondary end point or day-30 all-cause mortality or heart failure hospitalization rate differed between the 2 groups. The changes in serum potassium and estimated glomerular filtration rate at 24, 48, 72, and 96 hours. were similar between the 2 groups. <h3>Conclusions and Relevance</h3> Adding treatment with high-dose spironolactone to usual care for patients with AHF for 96 hours was well tolerated but did not improve the primary or secondary efficacy end points. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02235077
Acute interstitial nephritis after sequential ipilumumab - nivolumab therapy of metastatic melanoma
Authors: Lea Bottlaender, Anne-Laure Breton, Louis de Laforcade, Frederique Dijoud, Luc Thomas, Stephane Dalle
Journal: Journal for ImmunoTherapy of Cancer (2017)

The anti-Programmed Death receptor 1 (anti-PD-1) antibodies nivolumab and pembrolizumab are new treatments in metastatic melanoma. Immunotherapies are best known to be responsible for thrombotic microangiopathy. However, immune interstitial nephritis has been described in a patient treated by nivolumab and ipilimumab concomitantly, and three cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. We report herein a case of acute interstitial immune nephritis in a patient treated with nivolumab after ipilimumab for pulmonary metastatic melanoma.Interstitial nephritis was diagnosed after acute kidney injury following three cycles and was confirmed by kidney biopsy. Kidney injury responded rapidly to prednisolone, which was then gradually reduced. As a follow-up computed tomography scan indicated mixed response, with minimal size progression of a pulmonary nodule, but a significant reduction in the size of the other nodules, nivolumab was reintroduced after renal function improvement. Low-dose corticosteroids were first maintained during nivolumab treatment and subsequently discontinued. Only one month after prednisolone discontinuation, creatinine levels increased. A second kidney biopsy confirmed relapse of acute interstitial nephritis.To our knowledge, this is the first case of nivolumab-induced acute interstitial immune nephritis. This case highlights that anti-PD-1 immunotherapy may be continued when renal function is adequate, and this requires close interaction between dermatologists and nephrologists. This adverse effect should be made known to prescribers as nivolumab is associated with significant improvement of survival in metastatic melanoma and may be used in many different types of cancer.
FRI0178 Rituximab is effective in the treatment of rheumatoid arthritis regardless of body mass index
Authors: DH Yoo, W Park, CH Suh, SC Shim, SJ Lee, YJ Bae, C Park, JH Koo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> High body mass index (BMI) is known to be associated with inadequate clinical response to anti-TNF agents in rheumatoid arthritis (RA) patients.<sup>1</sup> However, there are limited data on the effect of high BMI on the response to rituximab in RA patients, who showed an inadequate response or intolerance to anti-TNF agents. <h3>Objectives</h3> To investigate the impact of BMI on clinical response in the post-hoc analysis of randomized controlled trial that demonstrated clinical equivalence between a biosimilar of rituximab, CT-P10 and innovator rituximab, RTX<sup>2</sup> (NCT02149121). <h3>Methods</h3> A total of 332 patients who received two courses of either CT-P10 or RTX were included in this analysis. Patients were classified into 3 groups; normal weight (&lt;25kg/m<sup>2</sup>), overweight (≥25 kg/m<sup>2</sup>) and obesity (≥30 kg/m<sup>2</sup>) as per WHO BMI category. Improvement in disease activity by the Disease Activity Score using C-reactive protein (DAS28-CRP), remission (≤2.6), low disease activity rate (LDA, ≤3.2) and ACR response at Week 24 (Week 24 of 1st course) and Week 48 (Week 24 of 2nd course) and duration of sustained LDA (from the first LDA observed to the last LDA observed up to Week 48) were analysed by BMI categories in the each and combined group of CT-P10 and RTX. <h3>Results</h3> In the pooled group of CT-P10 and RTX, the mean weights were 59 kg in normal weight, 73kg in overweight and 91kg in obesity. All other baseline characteristics were comparable among BMI groups including baseline disease activity based on DAS28; Moderate disease activity, 22.3% vs. 22.8% vs. 25.7%, respectively; High disease activity, 77.7% vs. 77.2% vs. 74.3%, respectively. There was no statistical difference among BMI groups in terms of DAS28 change from baseline and ACR 20/50/70 response (Table). No particular trend was observed in remission and LDA rate by DAS28 at Week 24 and Week 48 among BMI groups (Figure). Mean duration of sustained LDA (months) were also comparable among the groups (4.5 vs. 4.7 vs. 5.0, respectively). Additionally, similar trends in all analyses were observed in each treatment group; CT-P10 and RTX. <h3>Conclusions</h3> The BMI does not affect the clinical response in RA patients with rituximab treatment. Therefore, this result supports that rituximab could be a reasonable therapeutic option for obese RA patients with inadequate response to anti-TNF agents. <h3>References</h3> Gremese E et al. Arthritis Care Res (Hoboken) 2013;65:94–100. Yoo DH, et al. American College of Rheumatology 2016; Abstract No. 1635. <h3>Disclosure of Interest</h3> D. H. Yoo Consultant for: Celltrion Inc., W. Park Consultant for: Celltrion Inc., C. H. Suh Consultant for: Celltrion Inc., S. C. Shim Consultant for: Celltrion Inc., S. J. Lee Employee of: Celltrion Inc., Y. J. Bae Employee of: Celltrion Inc., C. Park Employee of: Celltrion Inc., J. H. Koo Employee of: Celltrion Inc.
Role of prophylactic PEG and risk factors for PEG dependency in head and neck cancer patients undergoing radiotherapy.
Authors: Ruchika Gutt, Steven H. Krasnow, Hosai Hesham, Andrea Burmeister, JoAnn Manning
Journal: Journal of Clinical Oncology (2015)

e17017 Background: Percutaneous endoscopic gastrostomy (PEG) dependency is a major morbidity associated with radiotherapy for head and neck cancer. There is controversy surrounding prophylactic PEG use and whether it predisposes to worse long-term swallow function and PEG dependency. The purpose of this study is to assess the impact of prophylactic PEG on treatment time and weight loss, and to identify risk factors for long-term PEG dependency. Methods: This study included 52 head and neck squamous cell carcinoma patients treated with radiotherapy (RT) to the primary site and bilateral cervical lymph nodes. Data were collected on primary tumor site, stage, age, RT dose, chemotherapy, weight, body mass index (BMI), treatment time, visits with Nutrition, and visits with Swallowing/Speech Pathology. Associations of prophylactic PEG with treatment time (time from initiation to completion of RT) and with weight loss were evaluated. Long-term PEG dependency was defined as placement of a PEG with continued PEG use at last follow-up. Results: All patients coded as PEG dependent either died with the PEG in place or have been PEG dependent > 1 year. There was no significant effect of primary tumor site, age, RT dose, use of chemotherapy, smoking, living alone, Nutrition visits, or Swallowing/Speech Pathology visits on long-term PEG dependency. Factors significantly associated with long-term PEG dependency included prophylactic PEG placement vs no prophylactic PEG placement (64.7% vs 5.6%, p < 0.001), BMI < 22 vs > 22 (73.9% vs 20.7%, p < 0.001), and stage T3/4 vs T1/2 (56.3% vs 25.0%, p = 0.03). Prophylactic PEG use did not reduce treatment breaks or impact RT treatment times. Patients with prophylactic PEG lost less weight during RT (Median weight loss 19.9 lb no prophylactic PEG vs 9.7 lb prophylactic PEG, p = 0.01). Conclusions: Factors significantly associated with long-term PEG dependency include use of prophylactic PEG, low pretreatment BMI, and advanced T-stage. Prophylactic PEG use did not impact treatment times, but did reduce weight loss during radiotherapy. Prophylactic PEG should not be recommended routinely but considered in patients with poor nutritional status at baseline.
04.04 Suramin protects against osteoarthritis by increasing tissue inhibitor of matrix metalloproteinase-3 and glycosaminoglycans in the articular cartilage
Authors: Laura-An Guns, Maryna Kvasnytsia, Greet Kerckhofs, Jennifer Vandooren, Erik Martens, Ghislain Opdenakker, Rik J Lories, Frédéric Cailotto
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Purpose</h3> Drug repositioning is a recent pharmaceutical strategy to discover new uses for market-approved drugs, with known safety profiles that can provide quick transition from the laboratory bench to bedside. Here, we investigate the influence of suramin, a polysulfonated compound that has been used <i>in vitro</i> to isolate tissue inhibitor of metalloproteinase (TIMP)−3 from the rat uterus. We therefore hypothesised that suramin may protect articular cartilage against osteoarthritis, by decreasing the catabolic action of tissue destructive enzymes such as matrix metalloproteinases (MMPs) and ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs) through increasing TIMP3 levels in the cartilage matrix. <h3>Methods</h3> We cultured differentiating ATDC5 mouse chondroprogenitor cell line in micromasses, and freshly-isolated human articular chondrocytes (hAC) in pellets, each at 200.000 cells/10 µl, in the presence or absence of 10 µM suramin. ATDC5s were differentiated 14 days (proliferation) in DMEM/F12 with insulin-transferrin-sodium selenite (ITS), and then 7 days (hypertrophy) in α-MEM with ITS, β-glycerophosphate and ascorbic acid. Readouts included analyses of extracellular matrix components (dimethylmethylene blue assay for sulfated glycosaminoglycan (sGAG) content, and histology), MMPs- and ADAMTS-induced aggrecan neo-epitopes (VDIPEN and NITEGE, by immunostaining) and phenotypic markers (quantitative PCR). We assessed the effects of suramin <i>in vivo</i> using the papain-induced model of osteoarthritis in C57BL/6 with or without a single intra-articular injection of 1 mg suramin. Cartilage damage was analysed by histology (OARSI scoring), and by Hexabrix contrast-enhanced nanofocus computed tomography, thereby quantifying cartilage volume. <h3>Results</h3> In ATDC5 and hAC, TIMP-3 protein levels were increased. Presence of VDIPEN and NITEGE were decreased, thus sGAG content was increased. Noteworthy gene expression levels of phenotypic markers remained unaffected, suggesting a post-translational effect of suramin. Knees from Papain-triggered osteoarthritis in animals treated with suramin showed increased TIMP-3 and decreased VDIPEN and NITEGE levels. This potential protective mechanism effectively resulted in a decreased damage outcome and an increased cartilage volume. <h3>Conclusion</h3> Our data suggest that suramin has a protective effect by increasing the amount of TIMP3 in the articular cartilage, leading to higher sGAG levels. Therefore, suramin is a new potential osteoarthritic disease-modifying agent that appears to act specifically within the cartilage matrix.
ETO2-GLIS2 Controls Differentiation Arrest and Self-Renewal through Aberrant Enhancers Regulation in Pediatric Leukemia
Authors: Cecile Thirant, Cecile K Lopez, Cathy Ignacimouttou, M'Boyba Diop, Lou Le Mouël, Clarisse Thiollier, Aurelie Siret, Philippe Dessen, Zakia Aid, Julie Riviere, Philippe Rameau, Celine Lefebvre, Mehdi Khaled, Guy Leverger, Paola Fabiola Ballerini, Arnaud Petit, Hana Raslova, Catherine Carmichael, Benjamin T. Kile, Eric Soler, John Crispino, Christian Wichmann, Camille Lobry, Francoise Pfumio, Juerg Schwaller, Nathalie M. Droin, William Vainchenker, Olivier A. Bernard, Sebastien Malinge, Thomas Mercher
Journal: Blood (2016)
Farnesoid X Receptor Agonism Protects against Diabetic Tubulopathy: Potential Add-On Therapy for Diabetic Nephropathy
Authors: Andi Marquardt, Moh’d Mohanad Al-Dabet, Sanchita Ghosh, Shrey Kohli, Jayakumar Manoharan, Ahmed ElWakiel, Ihsan Gadi, Fabian Bock, Sumra Nazir, Hongjie Wang, Jonathan A. Lindquist, Peter Paul Nawroth, Thati Madhusudhan, Peter R. Mertens, Khurrum Shahzad, Berend Isermann
Journal: Journal of the American Society of Nephrology (2017)

Established therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established therapies may reflect the inability to target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR), which is highly expressed in tubular cells. We hypothesized that TUDCA ameliorates maladaptive ER signaling via FXR agonism specifically in tubular cells. Indeed, TUDCA induced expression of FXR-dependent genes ( SOCS3 and DDAH1 ) in tubular cells but not in other renal cells. In vivo , TUDCA reduced glomerular and tubular injury in db/db and diabetic endothelial nitric oxide synthase–deficient mice. FXR inhibition with Z-guggulsterone or vivo-morpholino targeting of FXR diminished the ER-stabilizing and renoprotective effects of TUDCA. Notably, these in vivo approaches abolished tubular but not glomerular protection by TUDCA. Combined intervention with TUDCA and the angiotensin-converting enzyme inhibitor enalapril in 16-week-old db/db mice reduced albuminuria more efficiently than did either treatment alone. Although both therapies reduced glomerular damage, only TUDCA ameliorated tubular damage. Thus, interventions that specifically protect the tubular compartment in dNP, such as FXR agonism, may provide renoprotective effects on top of those achieved by inhibiting angiotensin-converting enzyme.