tbuckley/cabot-search huggingface dataset:
Changes in Opioid-Involved Overdose Deaths by Opioid Type and Presence of Benzodiazepines, Cocaine, and Methamphetamine — 25 States, July–December 2017 to January–June 2018
Authors: R. Matt Gladden, Julie O’Donnell, Christine L. Mattson, Puja Seth
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

From 2013 to 2017, the number of opioid-involved overdose deaths (opioid deaths) in the United States increased 90%, from 25,052 to 47,600.* This increase was primarily driven by substantial increases in deaths involving illicitly manufactured fentanyl (IMF) or fentanyl analogs† mixed with heroin, sold as heroin, or pressed into counterfeit prescription pills (1-3). Methamphetamine-involved and cocaine-involved deaths that co-involved opioids also substantially increased from 2016 to 2017 (4). Provisional 2018§ estimates of the number of opioid deaths suggest a small decrease from 2017. Investigating the extent to which decreases occurred broadly or were limited to a subset of opioid types (e.g., prescription opioids versus IMF) and drug combinations (e.g., IMF co-involving cocaine) can assist in targeting of intervention efforts. This report describes opioid deaths during January-June 2018 and changes from July-December 2017 in 25¶ of 32 states and the District of Columbia participating in CDC's State Unintentional Drug Overdose Reporting System (SUDORS).** Opioid deaths were analyzed by involvement (opioid determined by medical examiner or coroner to contribute to overdose death) of prescription or illicit opioids,†† as well as by the presence (detection of the drug in decedent) of co-occurring nonopioid drugs (cocaine, methamphetamine, and benzodiazepines). Three key findings emerged regarding changes in opioid deaths from July-December 2017 to January-June 2018. First, overall opioid deaths decreased 4.6%. Second, decreases occurred in prescription opioid deaths without co-involved illicit opioids and deaths involving non-IMF illicit synthetic opioids (fentanyl analogs and U-series drugs) (5). Third, IMF deaths, especially those with multiple illicit opioids and common nonopioids, increased. Consequently, IMF was involved in approximately two-thirds of opioid deaths during January-June 2018. Notably, during January-June 2018, 62.6% of all opioid deaths co-occurred with at least one common nonopioid drug. To maintain and accelerate reductions in opioid deaths, efforts to prevent IMF-involved deaths and address polysubstance misuse with opioids must be enhanced. Key interventions include broadening outreach to groups at high risk for IMF or fentanyl analog exposure and overdose. Improving linkage to and engagement in risk-reduction services and evidence-based treatment for persons with opioid and other substance use disorders with attention to polysubstance use or misuse is also needed.
P123 Extracellular matrix attenuated matrix-degrading effects of visfatin during adipogenic MSC differentiation
Authors: L Tsiklauri, J Werner, K Frommer, S Rehart, S Wenisch, U Müller-Ladner, E Neumann
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Osteoporosis (OP) is the most common age-related disorder characterized by bone loss and correlates with increased bone marrow adiposity due to a shift of osteogenic towards adipogenic differentiation of bone marrow mesenchymal stem cells (MSC). Therefore, bone marrow adipocytes are in direct contact with the altered bone matrix in OP. Adipose tissue is metabolically active. Therefore, adipocyte-derived factors such as adipokines might influence MSC differentiation. <h3>Objectives</h3> We analyzed the presence of adipokines (visfatin, resistin and leptin) in bone tissue and their effects on MSC differentiation under standard culture vs. spongiosa. <h3>Methods</h3> RNA and MSC were isolated from spongiosa of femoral heads of osteoarthritis patients after hip replacement surgery, or after osteoporotic femoral neck fracture. Adipogenic MSC differentiation was performed with/without adipokines and visfatin inhibitor Apo866 as well as SB203580 p38-MAPK inhibitor. For the transfer and differentiation of MSC on cancellous bone, bone fragments were purified and sterilized. Gene expression was evaluated by Realtime PCR. Protein production was analyzed by ELISA. <h3>Results</h3> Visfatin and leptin levels were increased in OP bone vs. non-osteoporotic OA bone, however, resistin was reduced. Visfatin induced the secretion of proinflammatory factors during adipogenesis in standard cell culture as well as on cancellous bone. Visfatin-induced cytokine release was markedly reduced during differentiation on spongiosa (e.g. 14d IL6, x-fold: standard culture 151±110, spong. 40±30, n=7). Significantly elevated MMP13 mRNA as well as protein expression induced by visfatin could be observed during adipogenesis in standard cell culture as well as on spongiosa, however visfatin-mediated MMP13 expression was reduced on cancellous bone (e.g. 21d, x-fold,: standard culture 81±89, spong. 13±21, n=7). The visfatin inhibitor Apo866 inhibited the visfatin-induced cytokine release. However, the MMP13 expression was not influenced during adipogenesis in culture (n=4). In contrast to Apo866, the p38-MAPK inhibitor did not reduce cytokine release during adipogenesis. <h3>Conclusions</h3> Visfatin and leptin levels were elevated in osteoporotic bone. Therefore, visfatin-mediated increase of MMPs and proinflammatory cytokines during adipogenic differentiation might influence bone turnover at the adipose tissue/bone interface. Our results support the idea that the extracellular matrix attenuates visfatin-mediated detrimental effects during adipogenesis. The observed visfatin-mediated effects most likely depend on different signaling pathways. <h3>Disclosure of Interest</h3> None declared.
Allosteric Bcr-Abl Inhibitor ABL001 Overcomes Bcr-Abl Tyrosine Kinase Inhibitor Resistance and Enhances MDM2 Inhibitor CGM097 Activity in Blast Crisis CML Cells
Authors: Wenjing Tao, Po Yee Mak, Michael Andreeff, Bing Z Carter
Journal: Blood (2017)
Prediction of short‐ and long‐term mortality in takotsubo syndrome: the InterTAK Prognostic Score
Authors: Manfred B. Wischnewsky, Alessandro Candreva, Beatrice Bacchi, Victoria L. Cammann, Ken Kato, Konrad A. Szawan, Sebastiano Gili, Fabrizio D'Ascenzo, Wolfgang Dichtl, Rodolfo Citro, Eduardo Bossone, Michael Neuhaus, Jennifer Franke, Ioana Sorici‐Barb, Milosz Jaguszewski, Michel Noutsias, Maike Knorr, Susanne Heiner, Christof Burgdorf, Behrouz Kherad, Carsten Tschöpe, Annahita Sarcon, Jerold Shinbane, Lawrence Rajan, Guido Michels, Roman Pfister, Alessandro Cuneo, Claudius Jacobshagen, Mahir Karakas, Wolfgang Koenig, Alexander Pott, Philippe Meyer, Jose David Arroja, Adrian Banning, Florim Cuculi, Richard Kobza, Thomas A. Fischer, Tuija Vasankari, K.E. Juhani Airaksinen, L. Christian Napp, Monika Budnik, Rafal Dworakowski, Philip MacCarthy, Christoph Kaiser, Stefan Osswald, Leonarda Galiuto, Christina Chan, Paul Bridgman, Daniel Beug, Clément Delmas, Olivier Lairez, Ibrahim El‐Battrawy, Ibrahim Akin, Ekaterina Gilyarova, Alexandra Shilova, Mikhail Gilyarov, Martin Kozel, Petr Tousek, David E. Winchester, Jan Galuszka, Christian Ukena, Gregor Poglajen, Pedro Carrilho‐Ferreira, Christian Hauck, Carla Paolini, Claudio Bilato, Abhiram Prasad, Charanjit S. Rihal, Kan Liu, P. Christian Schulze, Matteo Bianco, Lucas Jörg, Hans Rickli, Thanh H. Nguyen, Yoshio Kobayashi, Michael Böhm, Lars S. Maier, Fausto J. Pinto, Petr Widimský, Martin Borggrefe, Stephan B. Felix, Grzegorz Opolski, Ruediger C. Braun‐Dullaeus, Wolfgang Rottbauer, Gerd Hasenfuß, Burkert M. Pieske, Heribert Schunkert, Holger Thiele, Johann Bauersachs, Hugo A. Katus, John Horowitz, Carlo Di Mario, Thomas Münzel, Filippo Crea, Jeroen J. Bax, Thomas F. Lüscher, Frank Ruschitzka, Jelena R. Ghadri, Christian Templin
Journal: European Journal of Heart Failure (2019)
Plasma Cell Dyscrasias in HIV, Epidemiology, Presentation and Treatment Characteristics and Its Strong Association with Hepatitis C- Report Form a Large HIV Cohort
Authors: Nishi Shah, Sakshi Jasra, Ana Acuna-Villaorduna, Urvi A Shah, Gurbakhash Kaur, Mohammad Kazemi, Ioannis Mantzaris, Aditi Shastri, Olga Derman, Noah Kornblum, Ira Braunschweig, Amit Verma, Murali Janakiram
Journal: Blood (2018)
Integrin and transcriptomic profiles identify a distinctive synovial CD8+ T cell subpopulation in spondyloarthritis
Authors: Zoya Qaiyum, Eric Gracey, YuChen Yao, Robert D Inman
Journal: Annals of the Rheumatic Diseases (2019)

Objectives Current evidence suggests that immune events in the gut may impact joint inflammation in ankylosing spondylitis (AS) but the expression of gut-related trafficking molecules in the inflammed joint is poorly characterised. We aimed to (1) assess differential expression patterns of trafficking molecules between patients and controls, (2) generate joint-specific cellular signatures and (3) obtain transcriptomic profiles of noteworthy cell subpopulations. Methods Male subjects under 40 years of age fulfilling the mNY criteria were recruited. The following cells were surface stained using a 36-marker mass cytometry antibody panel: (1) peripheral blood mononuclear cells from AS patients, and healthy controls; (2) synovial fluid mononuclear cells from AS and rheumatoid arthritis (RA) patients. Additionally, RNA-seq was performed on CD8+ T cell subpopulations from the synovial fluid (SF). Results Mature CD8+ T cells were enriched in AS SF, with a distinct pattern of integrin expression (β7, CD103, CD29 and CD49a). RNA-seq analysis of SF-derived CD103+CD49a+CD8+ T cells revealed elevated TNFAIP3 , GZMB , PRF1 and IL-10 . Conclusions We have identified a novel integrin-expressing mature CD8+ T cell population (CD49a+CD103+β7+CD29+) that appears to be more prevalent in AS SF than RA SF. These cells seem to possess dual cytotoxic and regulatory profiles which may play a role in AS pathogenesis.
Clinical significance of altered expression of the retinoid acid receptors alfa and beta (RAR a and b) and the cellular retinol binding protein (CRBP-1) in stage I non-small cell lung cancer
Authors: M. G. Pallotta, L. Mauro, G. Z. Beguelin, L. M. Dallurzo, D. Smith, J. M. Lastiri, B. Vasallo, E. Val De Kier Joffé, L. Puricelli
Journal: Journal of Clinical Oncology (2007)

18117 Background: Retinoids, a group of natural and synthetic Vitamin A analogues, are known to play a major role in regulating growth, differentiation and apoptosis of many cell types. Its role as prognostic factors in non-small cell lung cancer (NSCLC) is poorly known. Methods: Patients who underwent a successful surgical resection for stage I NSCLC were elegible. Antigen expression was analyzed by immuno histochemistry on histological samples of the tumor to investigate the expression pattern of RARa, RARb and CRBP-1. 51 NSCLC patients stage I (18 Stage Ia and 33 Stage Ib) were tested . A case was considered positive when more than 10% of cells presented specific staining for the antigen. Prognostic evaluation was performed with the Log-Rank test and the multivariate proportional hazard model. Results: About 40% of cases were positive for RARa. In the case of RARb 58.3% NSCLC showed cytoplasm staining, while only 18% showed nuclear immunopositivity. Taken together, the 81.5% of NSCLC tumors expressed at least one RA receptor (RARa or RARb or both). CRBP-1 staining was observed in 52% of the lung tumors. No relationship was found between the number of cells expressing the studied molecules and clinical pathological features, including sex, T stage, histopathology, adjuvant therapy, smoking habit or the presence of tumor cells in the pleural fluid. The only exception was that a higher percentage of adenocarcinomas were positive for RARa as compared with epidermoid tumors (50.0 vs 14.3%, p=0.05). On the other hand RARb was expressed preferentially in epidermoid tumors (81.3% vs 42.9 %, p&lt;0.05). Univariate analysis showed a significant association between positive expression of RARb with shorter overall survival (log-rank test 3.7, p&lt;0.05). However, the multivariate study indicated that RARb expression was influenced by other clinical pathological parameters, suggesting that this antigen would not be able to predict cancer-specific survival in an independent way. Conclusions: A high number of stage I NSCLC express RARs and CRBP. This suggests that retinoid expression could harbour relevant prognostic information at an early stage of the disease. No significant financial relationships to disclose.
Retrospective analysis of stage IIIc uterine carcinoma patients: A single center experience.
Authors: Selim Yalcin, Samed Rahatli, Nadire Kucukoztas, Ozlem Ozen, Nihan Haberal, Cagla Tarhan, Polat Dursun, Omer Dizdar, Ferah Yildiz, Ozden Altundag, Ali Ayhan
Journal: Journal of Clinical Oncology (2012)

e15572 Background: Stage IIIC comprises 8% of all endometrial cancers. Both local and systemic relapse risks are high. Current standard of care is adjuvant chemotherapy; however the addition of radiotherapy seems to improve outcomes in retrospective series but prospective data is lacking. We herein report outcomes of our patients with stage IIIC endometrial cancer operated and treated with adjuvant chemotherapy±radiotherapy. Methods: 29 patients with stage IIIC endometrial cancer diagnosed between 2006-2011 were included. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of DFS and OS were analyzed. Results: Median age was 64 (41-82). Surgical procedure was TAH+BSO+BPPLND and omentectomy in 26 patients. 4 patients who were operated (TAH+BSO) in another center were restaged and BPPLND and omentectomy were performed. 13 patients (45%) had endometrioid histology, 11 (38%) had papillary serous carcinoma, 2 (7%) had clear cell carcinoma, 2 (7%) had mixed carcinoma and 1 (3%) had undifferentiated carcinoma. 6 patients had ovarian, 9 had uterine serosal involvement, 1 had positive cytology of abdominal washing, 18 (62%) had lymph node-only disease. 14 patients (48%) had positive nodes both in pelvic and paraaortic region, 9 (31%) only in pelvic region and 6 (21%) only in paraaortic region. 24 patients (83%) received chemotherapy with paclitaxel and carboplatin, 13 (45%) received external RT, 4 (14%) received brachytherapy and 3 (10%) patients received chemoradiation with weekly cisplatin or carboplatin. Median follow-up was 19 months. 10 patients recurred during follow-up and 6 patients died. All of the recurrences except one were intraabdominal. 3-year PFS was 64% and OS was 71.6%. Conclusions: With the use contemporary chemotherapy regimens and radiotherapy, we achieved ~70% 3-year survival rate in stage IIIC endometrial carcinoma patients with 45% of the patients having high risk histologies (serous and clear cell). We propose that combined adjuvant chemotherapy and radiation might improve survival in patients with advanced stage disease compared to either modality alone. Results of GOG258 and PORTEC 3 trials should be awaited for definitive conclusions.
RON tyrosine kinase: a potential target for colorectal cancer therapy
Authors: Ashwani Rajput, Rebecca Rose, Charles Levea, Alexander Beko, Michael G. Brattain, Jing Wang
Journal: Cancer Research (2006)

2692  INTRODUCTION: Recepteur d’Origine Nantais (RON) is a receptor tyrosine kinase that plays a role in tumorigenesis and invasion. Recent data demonstrates that human colon cancers have a 60% rate of RON overexpression. The purpose of this study was to determine the impact of RON silencing on tumor growth, invasion, downstream signal transduction, apoptosis and metastasis in a well characterized human colon cancer cell line, HCT116. METHODS: siRNA techniques targeting RON were used to stably transfect green fluorescent protein labeled HCT116 (which has a high level of RON expression) with a pSuper.retro vector (HCT116 siRNA RON). An empty vector transfection was used to generate a control cell line (HCT116 pSR). In vitro assessment of the 2 cell lines in regards to RON level, cell growth and motility was conducted by Western blot, colony formation and wound healing assays, respectively. Apoptosis was measured by PARP cleavage assay. In vivo growth was assessed by xenograft growth curves in BALB/c nude mice. Metastatic ability was assessed by microsurgical orthotopic implantation of tumor xenograft and fluorescence imaging in BALB/c nude mice. Four weeks post implantation, animals were sacrificed and tissues were procured for histological evaluation. RESULTS: HCT116 siRNA RON demonstrated decreased RON levels as compared to HCT116 pSR on Western blot analysis. The siRNA transfectants also demonstrated decreased colony formation and wound healing abilities as compared to control cells. Downstream activation of AKT was decreased in the siRNA RON cells as well on Western analysis with phosphoantibody. Increased apoptosis in siRNA RON cells was demonstrated by PARP cleavage assays. In vivo xenograft growth curves demonstrated growth inhibition in siRNA RON cells. In vivo orthotopic implantation and fluorescence imaging at 4 weeks post implantation demonstrated decreased peritoneal and distant metastasis. At necropsy 8 of 8 (100%) of the pSR vector control animals had distant metastases to either the liver or the lungs compared to 2 of 9 (22%) animals implanted with the RON siRNA xenografts. The burden of metastases was also higher in the pSR control cell lines. On average, there were 2 lung metastases in the RON siRNA animals with lung metastases and a mean of 14 lung metastases in animals with the pSR control vector. CONCLUSIONS: Decreased expression of RON in HCT116 via siRNA transfection resulted in decreased colony formation, cell motility and increased apoptosis as demonstrated by in vitro assays. Furthermore, in vivo assays demonstrated decreased xenograft growth and metastatic ability in an orthotopic model using cells with siRNA RON. These data suggest that RON may be a novel target for molecularly based therapies in patients with advanced colorectal malignancy.
Ferric citrate reduces fibroblast growth factor 23 levels and improves renal and cardiac function in a mouse model of chronic kidney disease
Authors: Connor Francis, Guillaume Courbon, Claire Gerber, Samantha Neuburg, Xueyan Wang, Corey Dussold, Maralee Capella, Lixin Qi, Tamara Isakova, Rupal Mehta, Aline Martin, Myles Wolf, Valentin David
Journal: Kidney International (2019)
Surgical Pathology and Therapeutics.
Journal: JAMA (1895)

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Quantification of IGF-1 Receptor May be Useful in the Differential Diagnosis of Essential Thrombocytosis from Reactive Thrombocytosis- Suggested to Add IGF-1Receptor Quantification As the Minor Criteria for the Diagnosis of ET
Authors: Guanfang Shi, Hui Chen, Andrei Bandarchuk, Ching Wong, Vladimir K. Gotlieb, Madhumati Kalavar, Jen-Chin Wang
Journal: Blood (2017)
The Crucial Role of NR4A1 Dependent Apoptosis Induced By Fenretinide in Acute Myeloid Leukemia
Authors: Jie Xiong, Xingyi Kuang, Tingting Lu, Bingqing Cheng, Danna Wei, Xinyao Li, Weili Wang, Zhaoyuan Zhang, Jishi Wang
Journal: Blood (2018)
Systemic therapy in advanced dermatofibrosarcoma protuberans: Imatinib and beyond.
Authors: Anshul Gupta, Sameer Rastogi, Santosh Kumar C, Adarsh Barwad, Ekta Dhamija, Rambha Panday, S. V. S. Deo, Sorun Shishak, Aditi Aggarwal, Rimlee Dutta, Parisa Manasa, Pankaj Kumar
Journal: Journal of Clinical Oncology (2019)

e22523 Background: Imatinib is the standard treatment of advanced Dermatofibrosarcoma (DFSP). However ideal treatment of advanced DFSP patients, who have progressive disease (PD) on imatinib, remains an unanswered question. Methods: We retrospectively analysed consecutive advanced DFSP patients who presented to AIIMS Sarcoma Medical Oncology clinic between January 2016 and January 2019. Results: There were eleven patients, with median age of 35 years, seven (63.6%) of which were males. Fibrosarcomatous transformation was present in six (54.5%) patients. Four (36.4%) had locally advanced disease, while seven (63.6%) had metastatic disease. Primary site was trunk in eight (63.7%) patients. Three (75%) of the four patients who received neoadjuvant imatinib, underwent complete surgical resection. Initial dose of imatinib was 400mg OD in eight (72.7%) patients, 600 mg OD in two (18.2%) and 800 mg OD in one (9.1%) patient. The best response to imatinib was Partial response (PR) in nine (81.8%) patients, stable disease (SD) in one (9.1%) and primary PD in one (9.1%) patient. Median progression free survival (PFS) was 16 months, after a median follow up of 14 months. Five (45.4%) patients had PD on imatinib. As mentioned in table, strategies used in these patients were pazopanib (n = 3), doxorubicin (n = 2), other chemotherapy (n = 2), dose escalation of imatinib (n = 2) and reintroduction of imatinib (n = 1). One patient had prolonged stable disease on pazopanib, while remaining had PD. Conclusions: Imatinib remains prominent first line therapy in advancved DFSP. Though pazopanib has shown some promise, the treatment outcomes in second line therapy and beyond have largely been dismal and need to be studied prospectively.[Table: see text]