tbuckley/cabot-search huggingface dataset:
Trends in Chronic Kidney Disease in China
Authors: Luxia Zhang, Jianyan Long, Wenshi Jiang, Ying Shi, Xiangxiang He, Zhiye Zhou, Yanwei Li, Roseanne O Yeung, Jinwei Wang, Kunihiro Matsushita, Josef Coresh, Ming-Hui Zhao, Haibo Wang
Journal: New England Journal of Medicine (2016)

In this letter, the authors report that chronic kidney disease related to diabetes has become increasingly common both in the general population and among hospitalized urban patients in China, a finding that is preceded by decades of increasing prevalence of type 2 diabetes.
Long-term survival in AIDS-related primary central nervous system lymphoma
Authors: Neel K. Gupta, Amber Nolan, Antonio Omuro, Erin G. Reid, Chia-Ching Wang, Gabriel Mannis, Michael Jaglal, Julio C. Chavez, Paul G. Rubinstein, Ann Griffin, Donald I. Abrams, Jimmy Hwang, Lawrence D. Kaplan, Judith A. Luce, Paul Volberding, Patrick A. Treseler, James L. Rubenstein
Journal: Neuro-Oncology (2016)

The optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention.To identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX).We provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4 <100. This was confirmed in a multicenter analysis which demonstrated that integration of cART regimens with HD-MTX was generally well tolerated and resulted in longer progression-free survival than other treatments. No profound differences in immunophenotype were identified in an analysis of AR-PCNSL tumors that arose in the pre- versus post-cART eras. However, we detected evidence for a demographic shift, as the proportion of minority patients with AR-PCNSL increased since advent of cART.Long-term disease-free survival can be achieved in AR-PCNSL, even among those with histories of opportunistic infections, limited access to health care, and medical non-adherence. Given this, as well as the long-term toxicities of WBRT, we recommend that integration of cART plus first-line HD-MTX be considered for all patients with AR-PCNSL.
Carbonic anhydrase enzymes regulate mast cell–mediated inflammation
Authors: Everett K. Henry, Chandler B. Sy, Juan M. Inclan-Rico, Vanessa Espinosa, Saleena S. Ghanny, Daniel F. Dwyer, Patricia Soteropoulos, Amariliz Rivera, Mark C. Siracusa
Journal: The Journal of Experimental Medicine (2016)

Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine–mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2–associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy–like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell–mediated inflammation.
Interleukin-15-Dependent T-Cell-like Innate Intraepithelial Lymphocytes Develop in the Intestine and Transform into Lymphomas in Celiac Disease
Authors: Julien Ettersperger, Nicolas Montcuquet, Georgia Malamut, Nicolas Guegan, Silvia Lopez-Lastra, Ségolène Gayraud, Christian Reimann, Elodie Vidal, Nicolas Cagnard, Patrick Villarese, Isabelle Andre-Schmutz, Rita Gomes Domingues, Cristina Godinho-Silva, Henrique Veiga-Fernandes, Ludovic Lhermitte, Vahid Asnafi, Elizabeth Macintyre, Christophe Cellier, Kheira Beldjord, James P. Di Santo, Nadine Cerf-Bensussan, Bertrand Meresse
Journal: Immunity (2016)
A novel, multi-barrier, drug eluting calcium sulfate/biphasic calcium phosphate biodegradable composite bone cement for treatment of experimental MRSA osteomyelitis in rabbit model
Authors: Surajit Mistry, Subhasis Roy, Nilendu Jyoti Maitra, Biswanath Kundu, Abhijit Chanda, Someswar Datta, Mathew Joy
Journal: Journal of Controlled Release (2016)
Dissecting Genomic Aberrations In CML and Bcr-Abl Negative Myeloproliferative Neoplasms By The Use Of Multiplex-PCR and Parallel Resequencing
Authors: Martin M. Kirschner, Mirle Schemionek, Claudia Schubert, Nicolas Chatain, Stephanie Sontag, Susanne Isfort, Nadina Ortiz-Brüchle, Karla Bennemann, Klaus Zerres, Martin Zenke, Tim H. Bruemmendorf, Steffen Koschmieder
Journal: Blood (2013)
Outcome of 136 Children with Advanced Lymphoblastic Lymphoma Receiving an BFM-Type Therapy with Intensified Maintenance: A Report from the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 Study
Authors: Shosuke Sunami, Masahiro Sekimizu, Tetsuya Takimoto, Tetsuya Mori, Tetsuo Mitsui, Reiji Fukano, Takeshi Mori, Atsushi Kikuta, Koh Katsuyoshi, Toshihiko Imamura, Akiko Moriya Saito, Tomoyuki Watanabe, Kouichi Ohshima, Junichiro Fujimoto, Atsuko Nakazawa, Ryoji Kobayashi, Keizo Horibe, Masahito Tsurusawa
Journal: Blood (2014)
PWE-207 Bile duct leaks from an aberrant duct of Luschka: Abstract PWE-207 Figure 1
Authors: S Thayalasekaran, M Gibson, J Kinchen, J Booth, M Booth, A Mee
Journal: Gut (2012)

<h3>Introduction</h3> The Duct of Luschka is an accessory biliary radicle first described by the German anatomist Hubert von Luschka in the 19th century. If this aberrant duct goes unnoticed at the time of cholecystectomy, the patient is likely to develop a biliary leak post-operatively. The majority of post-operative leaks are from the cystic duct remnant and standard management is ERCP and stent insertion across the cystic duct +/-sphincterotomy. The aim of our study was to identify the number of leaks from an aberrant "Duct of Luschka" in patients who underwent laparoscopic cholecystectomy over a 14-year period and to evaluate the efficacy of ERCP in their management. <h3>Methods</h3> This retrospective study included all patients undergoing cholecystectomy between 1994 and 2010. Those who had a subtotal cholecystectomy were excluded. ERCP reports were reviewed to identify the number of biliary leaks. The medical notes of each patient with an aberrant duct leak were reviewed to evaluate their management. <h3>Results</h3> For 5221 laparoscopic cholecystectomies there were 97 biliary leaks (1.9%), 86 from the cystic duct remnant and 11 from an aberrant duct. In two patients found to have leaks from a Duct of Luschka during surgery, the laparoscopic approach was converted to an open procedure and one patient had a drain inserted at initial laparoscopy. Eight patients had a repeat laparoscopy with a washout and drain insertion. Two patients had CT guided drain insertion. Time to ERCP after presentation varied from 1 to 10 days, with the majority being done between day two and day five. Of the eleven, four patients had a sphincterotomy and stent insertion, five had stent insertion alone and two patients had no therapeutic intervention as the leak was felt to be too small. Eight patients had a repeat ERCP with stent removal and no residual leak on cholangiogram. One person was lost to follow-up. No patients required surgery after ERCP to control the leak. Arrow below: leaking aberrant Duct of Luschka. <h3>Conclusion</h3> In this study the likelihood of a post cholecystectomy bile leak arising from an aberrant duct of Luschka was 13%, in keeping with previous smaller series where the rate ranged from 0% to 21%. The standard managment with stent insertion +/− sphincterotomy appears to be effective even though the leak is not covered by the stent, presumably by providing preferential drainage. <h3>Competing interests</h3> None declared. <h3>References</h3> 1.<b>Tantia O</b>, Jain M, Khanna S, <i>et al.</i> Iatrogenic biliary injury. <i>Surg Endosc</i> 2008;<b>22</b>:1077–86. 2. <b>Sharma H</b>, Bird G. Endoscopic management of postcholecystectomy biliary leaks. <i>Frontline Gastroenterol</i> 2011;<b>2</b>:230–3. 3. <b>Bartofi J</b>, Baranya F, Simon E, <i>et al.</i> [Laparoscopic treatment of bile leakage from the Luschka Duct after laparoscopic cholecystectomy]. <i>Orv Hetil</i> 2004;<b>145</b>:1061–4.
US drug industry group launches campaign to defend pricing
Authors: Michael McCarthy
Journal: BMJ (2016)

A major drug industry group in the United States has launched a media campaign to defend pricing policies in the face of growing demand for government action to control the soaring prices of generic and brand name prescription drugs.1 2

Over the past year reports of steep price rises of many commonly used drugs such as insulin, rises of as much as 5000% for some off-patent generic drugs, and the introduction of new specialty drugs that can cost more than $100 000 (£75 000; €90 000) for a course of treatment have led to Congressional investigations and calls for legislation to curtail drug costs.

US residents pay the most in the world …
A Transcriptome-driven Analysis of Epithelial Brushings and Bronchial Biopsies to Define Asthma Phenotypes in U-BIOPRED
Authors: Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Ioannis Pandis, Uruj Hoda, Christos Rossios, Ana Sousa, Susan J. Wilson, Peter Howarth, Barbro Dahlen, Sven-Erik Dahlen, Pascal Chanez, Dominick Shaw, Norbert Krug, Thomas Sandstrӧm, Bertrand De Meulder, Diane Lefaudeux, Stephen Fowler, Louise Fleming, Julie Corfield, Charles Auffray, Peter J. Sterk, Ratko Djukanovic, Yike Guo, Ian M. Adcock, Kian Fan Chung
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms.Using transcriptomic profiling of airway tissues, we sought to define the molecular phenotypes of severe asthma.The transcriptome derived from bronchial biopsies and epithelial brushings of 107 subjects with moderate to severe asthma were annotated by gene set variation analysis using 42 gene signatures relevant to asthma, inflammation, and immune function. Topological data analysis of clinical and histologic data was performed to derive clusters, and the nearest shrunken centroid algorithm was used for signature refinement.Nine gene set variation analysis signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper cell type 2 cytokines and lack of corticosteroid response (group 1 and group 3). Group 1 had the highest submucosal eosinophils, as well as high fractional exhaled nitric oxide levels, exacerbation rates, and oral corticosteroid use, whereas group 3 patients showed the highest levels of sputum eosinophils and had a high body mass index. In contrast, group 2 and group 4 patients had an 86% and 64% probability, respectively, of having noneosinophilic inflammation. Using machine learning tools, we describe an inference scheme using the currently available inflammatory biomarkers sputum eosinophilia and fractional exhaled nitric oxide levels, along with oral corticosteroid use, that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity.This analysis demonstrates the usefulness of a transcriptomics-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target T-helper cell type 2-mediated inflammation and/or corticosteroid insensitivity.
Brostallicin versus doxorubicin as first-line chemotherapy in patients with advanced or metastatic soft tissue sarcoma: An EORTC Soft Tissue and Bone Sarcoma Group randomized phase II study.
Authors: H. Gelderblom, J. Blay, B. M. Seddon, M. Leahy, I. L. Ray-Coquard, A. De brauwer, E. Veyt, S. D. Weitman, P. C. Hogendoorn, P. Hohenberger
Journal: Journal of Clinical Oncology (2010)

10037 Background: Brostallicin (B) is a DNA minor groove binder which showed activity in a recent phase II study in patients with soft tissue sarcoma (STS) failing first line therapy (Leahy et al, Eur J Cancer 2007;43:308-15). The present study assessed the safety and efficacy of first line B compared to doxorubicin (D) in patients with advanced or metastatic STS older than 60 or not fit enough to receive combination chemotherapy. Methods: Patients (pts) with progressive advanced (metastatic or locally advanced and inoperable) intermediate to high grade STS were randomized in a 2:1 ratio between IV B 10mg/m2 and D 75 mg/m2 once every 3 weeks for a maximum of 6 cycles. The primary endpoint was documented disease stabilization (RECIST) at 26 weeks, and 35+/72 successes were required to consider results as positive. Results: 118 pts were included (B 79 pts and D 39 pts). Median age was 66 years (range 27-88), male/female ratio 50/50, WHO 0/1 ratio 51/49. Primary tumour or recurrence was present in 39% of patients at baseline. Dose escalation of B to 12.5mg/m2, allowed in case of limited toxicity, occurred in 17% of patients. B in comparison to D was well tolerated with fewer grade 3-4 neutropenia (67% vs. 95%), grade 2-3 systolic dysfunction (0 vs. 11%), alopecia (17% vs. 61%) and grade 2-3 mucositis (0 vs. 18%). Conversely, grade 3-4 tumor pain was worse for B (14% vs. 3%) . Only 5/77 successes were observed with B vs 10/36 with D. The median follow-up is 20 months. PFS at 1 year was 6.5% for B vs. 15.6% for D. Best overall response of PR/CR was 3.9% for B vs. 21.1% for D and overall survival at 1 year is 50.5% for B vs 57.9% for D. Conclusions: Although B was better tolerated than D in this patient population, B cannot be recommended at this dose and schedule for first line therapy in intermediate to high grade advanced or metastatic STS because of inferior antitumor activity compared to D. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration SML SML
Natural Experiments: An Overview of Methods, Approaches, and Contributions to Public Health Intervention Research
Authors: Peter Craig, Srinivasa Vittal Katikireddi, Alastair Leyland, Frank Popham
Journal: Annual Review of Public Health (2017)

Population health interventions are essential to reduce health inequalities and tackle other public health priorities, but they are not always amenable to experimental manipulation. Natural experiment (NE) approaches are attracting growing interest as a way of providing evidence in such circumstances. One key challenge in evaluating NEs is selective exposure to the intervention. Studies should be based on a clear theoretical understanding of the processes that determine exposure. Even if the observed effects are large and rapidly follow implementation, confidence in attributing these effects to the intervention can be improved by carefully considering alternative explanations. Causal inference can be strengthened by including additional design features alongside the principal method of effect estimation. NE studies often rely on existing (including routinely collected) data. Investment in such data sources and the infrastructure for linking exposure and outcome data is essential if the potential for such studies to inform decision making is to be realized.
Independent Prognostic Significance of Cytogenetics, Immunophenotype, Tumor Burden, and Age in Acute Myeloid Leukemia. Analysis of Patients Treated within PALG 1999 Prospective, Randomized Study.
Authors: Sebastian Grosicki, Jerzy Holowiecki, Sebastian Giebel, Olga Haus, Beata Stella-Holowiecka, Krystyna Jagoda, Aleksandra Bartkowska-Chrobok
Journal: Blood (2004)
Forecasted trends in vaccination coverage and correlations with socioeconomic factors: a global time-series analysis over 30 years
Authors: Alexandre de Figueiredo, Iain G Johnston, David M D Smith, Sumeet Agarwal, Heidi J Larson, Nick S Jones
Journal: The Lancet Global Health (2016)

BackgroundIncomplete immunisation coverage causes preventable illness and death in both developing and developed countries. Identification of factors that might modulate coverage could inform effective immunisation programmes and policies. We constructed a performance indicator that could quantitatively approximate measures of the susceptibility of immunisation programmes to coverage losses, with an aim to identify correlations between trends in vaccine coverage and socioeconomic factors.MethodsWe undertook a data-driven time-series analysis to examine trends in coverage of diphtheria, tetanus, and pertussis (DTP) vaccination across 190 countries over the past 30 years. We grouped countries into six world regions according to WHO classifications. We used Gaussian process regression to forecast future coverage rates and provide a vaccine performance index: a summary measure of the strength of immunisation coverage in a country.FindingsOverall vaccine coverage increased in all six world regions between 1980 and 2010, with variation in volatility and trends. Our vaccine performance index identified that 53 countries had more than a 50% chance of missing the Global Vaccine Action Plan (GVAP) target of 90% worldwide coverage with three doses of DTP (DTP3) by 2015. These countries were mostly in sub-Saharan Africa and south Asia, but Austria and Ukraine also featured. Factors associated with DTP3 immunisation coverage varied by world region: personal income (Spearman's ρ=0·66, p=0·0011) and government health spending (0·66, p<0·0001) were informative of immunisation coverage in the Eastern Mediterranean between 1980 and 2010, whereas primary school completion was informative of coverage in Africa (0·56, p<0·0001) over the same period. The proportion of births attended by skilled health staff correlated significantly with immunisation coverage across many world regions.InterpretationOur vaccine performance index highlighted countries at risk of failing to achieve the GVAP target of 90% coverage by 2015, and could aid policy makers' assessments of the strength and resilience of immunisation programmes. Weakening correlations with socioeconomic factors show a need to tackle vaccine confidence, whereas strengthening correlations point to clear factors to address.FundingUK Engineering and Physical Sciences Research Council.
Indocyanine green (ICG) fluorescence imaging versus radioactive colloid for sentinel lymph node identification in patients with breast cancer.
Authors: N. Tagaya, M. Tsumuraya, A. Nakagawa, Y. Iwasaki, H. Kato, K. Kubota
Journal: Journal of Clinical Oncology (2010)

674 Background: The usefulness of ICG fluorescence imaging produced by near-infrared ray for sentinel lymph node (SLN) identification in patients with breast cancer has been revealed. We herein compared and evaluated the outcomes between ICG fluorescence imaging with dye (ICG) and radioactive colloid with dye (RAC) in SLN identification in patients with operable breast cancer. Methods: Between March 2004 and December 2009, 309 patients with a tumor less than 3 cm in diameter and node-negative consisted of 149 patients in ICG and 160 in RAC were enrolled in this study. The mean age was 55 years in ICG and 54 in RAC. In the former, ICG was injected subdermally in the areola. Subcutaneous lymphatic channels draining from the areola to the axilla were visible by fluorescence imagings (Photodynamic eye: PDE, Hamamatsu Photonics Co.) immediately. After incising the axillary skin 1 cm cranial side from the disappeared point of fluorescence image, SLN was then dissected under the guidance of fluorescence with adequate adjustment of sensitivity. In the latter, radioactive colloid was injected subdermally in the areola the day before. After incising the axillary skin on the strong point of gamma probe (Navigator GPS power probe), SLN was then dissected under the guidance of gamma probe. Results: There were no significant differences between age, cancer stage and surgical procedures. The identification rate was 98.7% in ICG and 96.9% in RAC, respectively. The mean number of SLN was 3.7 (range: 1-11) in ICG and 2.0 (range 1-5) in RAC. The lymph node metastasis was revealed in 13.4% of ICG group and 13.8% of RAC group. The false negative rate was 0.67% in ICG and 0.62% in RAC. There were no intra- or postoperative complications associated with SLN identification. The cost was $46,007 (PDE: $46,000, ICG: $6.7) in ICG and $60,030 (GPS: $60,000, RAC: $30) in RAC. There were no significant differences in surgical outcomes between both methods. Conclusions: The evaluation of ICG fluorescence imaging is equal to that of radioactive colloid. In particular, ICG fluorescence imaging for SLN identification will be a greatly helpful tool for institutions without radioactive equipment. No significant financial relationships to disclose.
Phase I study of LY2127399, a human anti-BAFF antibody, and bortezomib in patients with previously treated multiple myeloma.
Authors: N. S. Raje, R. J. Hohl, E. A. Faber, P. G. G. Richardson, A. Forero-Torres, G. J. Schiller, A. D. Cohen, S. P. Carpenter, D. Cronier, M. Pashkevich, J. Wooldridge, K. C. Anderson
Journal: Journal of Clinical Oncology (2011)

8012 Background: LY2127399 (LY) is a human mAb that neutralizes membrane-bound and soluble B cell activating factor (BAFF). LY has activity in xenograft models of multiple myeloma (MM) and is being studied in phase III trials for treatment of rheumatoid arthritis and lupus. A combination of LY and bortezomib (BTZ) was evaluated in this phase I dose escalation study. Methods: The primary objective was to identify an efficacious dose of LY with BTZ. BTZ was given at 1.3 mg/m2 IV on days 1, 4, 8, and 11 q21d and LY at 1, 10, 30, 100, or 300 mg IV (30 min) on day 1 in Cycles 1 - 3, and every other cycle thereafter. Corticosteroids were not allowed. Response was assessed per IMWG criteria and adverse events per CTCAE v3.0. Pharmacokinetics (PK) were assessed, and pharmacodynamic studies included B cell immunophenotyping and serum markers of bone turnover. Results: Twenty pts were enrolled in groups receiving 1 mg (3), 10 mg (4), 30 mg (5), 100 mg (3), and 300 mg (5) of LY. The median age was 65.7 years and 50% were women. The median (range) number of prior therapies was 3 (1–6); 65% had prior BTZ, 85% prior IMiD, and 100% prior BTZ or IMiD. The median (range) cycles completed was 5 (2–14). No DLTs were observed. PK revealed a plateau in the LY peak/ trough ratio at ~ 100 mg suggesting target saturation. Grade 3/4 toxicities included: thrombocytopenia (4), neutropenia (3), anemia (1), diarrhea (2), neuropathy (2), hypercalcemia (1), hyperuricemia (1)1, mucositis (1), GI hemorrhage (1), renal failure (1), sepsis (1), and pain (1). Pts discontinued the study for neuropathy (2) and thrombocytopenia (1). One pt discontinued due to progressive disease in Cycle 5 and died 3 months later. Confirmed responses included 1 CR, 4 VGPR, and 6 PR (11/20; 55%). Responses correlated with non-secretory status, but not prior BTZ history. The percent change in the k-l SFLC difference correlated strongly with confirmed response. Conclusions: The 100 mg dose of LY was selected for further study with BTZ based on PK. The safety profile was similar to BTZ alone. An ORR of 55% was noted despite prior BTZ (65%). The percent change in k-l SFLC difference correlated strongly with response. This data supports further evaluation of LY in combination with BTZ.