tbuckley/cabot-search huggingface dataset:
Incidence and Trends in Hypoglycemia Hospitalization in Adults With Type 1 and Type 2 Diabetes in England, 1998–2013: A Retrospective Cohort Study
Authors: Victor W. Zhong, Juhaeri Juhaeri, Stephen R. Cole, Evangelos Kontopantelis, Christina M. Shay, Penny Gordon-Larsen, Elizabeth J. Mayer-Davis
Journal: Diabetes Care (2017)

To determine trends in hospitalization for hypoglycemia in adults with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in England.Adults with T1DM or T2DM were identified from 398 of the 684 practices within the Clinical Practice Research Datalink, for which linkage to the Hospital Episode Statistics was possible. Hypoglycemia as the primary reason for hospitalization between 1998 and 2013 was extracted. Trends were estimated using joinpoint regression models for adults with T1DM, young and middle-aged adults with T2DM (18-64 years), and elderly adults with T2DM (≥65 years), respectively.Among 23,246 adults with T1DM, 1,591 hypoglycemia hospitalizations occurred during 121,262 person-years. Among 241,441 adults with T2DM, 3,738 hypoglycemia hospitalizations occurred during 1,344,818 person-years. In adults with T1DM, the incidence increased 3.74% (95% CI 1.70-5.83) annually from 1998 to 2013. In young and middle-aged adults with T2DM, the annual incidence increase was 4.12% (0.61-7.75) from 1998 to 2013. In elderly adults with T2DM, the incidence increased 8.59% (5.76-11.50) annually from 1998 to 2009, and decreased 8.05% (-14.48 to -1.13) annually from 2009 to 2013, but the incidence was still higher in 2013 than 1998 (adjusted rate ratio 3.01 [1.76-5.14]). Trends in HbA1c level did not parallel trends of hypoglycemia hospitalization for both diabetes types. A possible reason for declined hypoglycemia trend in 2009-2013 in elderly adults with T2DM may be continuously decreased sulfonylurea use after 2009, which was not seen in young and middle-aged adults with T2DM.Hypoglycemia requiring hospitalization has been an increasing burden in adults with T1DM and T2DM in England in the previous two decades, with the exception of the decline in elderly adults with T2DM starting in 2009.
Prognostic Factors and Survival Prediction in 1,088 Patients with Mastocytosis Collected in the Registry of the European Competence Network on Mastocytosis (ECNM Registry)
Authors: Wolfgang R. Sperr, Michael Kundi, Hanneke Oude Elberink, Björn van Anrooij, Karoline V Gleixner, Emir Hadzijusufovic, Aleksandra Górska, Magdalena Lange, Anja Rabenhorst, Serena Merante, Chiara Elena, Anna Belloni Fortina, Elena Fontana, Juliana Schwaab, Mohamad Jawhar, Roberta Zanotti, Patrizia Bonadonna, Massimo Triggiani, Cecelia Perkins, Jason R. Gotlib, Michael Doubek, Khalid Shoumaryeh, David Fuchs, Vito Sabato, Knut Brockow, Agnes Bretterklieber, Nadja Jaekel, Andreas Reiter, Karin Hartmann, Marek Niedoszytko, Hanneke C. Kluin-Nelemans, Peter Valent
Journal: Blood (2016)
Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in Mesangial Expansion
Authors: Kojiro Nagai, Tatsuya Tominaga, Sayo Ueda, Eriko Shibata, Masanori Tamaki, Motokazu Matsuura, Seiji Kishi, Taichi Murakami, Tatsumi Moriya, Hideharu Abe, Toshio Doi
Journal: Journal of the American Society of Nephrology (2017)

Human glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)–S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]. Foxd1ER(+) TSC1 mice showed mesangial expansion with increased production of collagen IV, collagen I, and α –smooth muscle actin in glomeruli, but did not exhibit significant mesangial proliferation or albuminuria. Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion. Among biopsy specimens from patients with glomerular diseases, analysis of phosphorylated ribosomal protein S6 revealed mesangial cell mTORC1 activation in IgA nephropathy and in lupus mesangial proliferative nephritis but not in the early phase of diabetic nephropathy. In summary, mesangial cell mTORC1 activation can cause mesangial expansion and has clinical relevance for human glomerular diseases. This report also confirms that the tamoxifen-induced mesangium-specific Cre-loxP system is useful for studies designed to clarify the role of the mesangium in glomerular diseases in adults.
Important but incomplete data analysis?
Authors: Philipp Sewerin, Annika Hoyer, Matthias Schneider, Ben Ostendorf, Ralph Brinks
Journal: Annals of the Rheumatic Diseases (2017)

We are grateful to the article about incidence and prevalence of psoriatic arthritis (PsA) in Denmark by Egeberg et al .1 The comprehensive health registers from Denmark and other Nordic countries have proven to yield many insights into the epidemiology of chronic diseases. The authors of the article provide very detailed information about the age-specific incidence of PsA, including its time trend. However, we have a question about reporting the overall age-specific incidence rate, combined for both sexes. Could the authors comment …
An inverse association between H. pylori infection and esophageal cancer risk in Taiwan
Authors: Ming-Tsang Wu
Journal: Clinical Cancer Research (2008)

B22   PURPOSE: This study aims to clarify the role of  Helicobacter pylori ( Hp ) infection on the risk of digestive tract cancers, including oral squamous-cell carcinoma (SCC), esophageal SCC, gastric adenocarcinoma and colon adenocarcinoma.  METHODS: One observational study and  in vitro  studies were conducted. For the observational study, 199 oral SCC, 317 esophageal SCC, 196 gastric adenocarcinoma and 240 colon adenocarcinoma patients were recruited for serum tests of  Hp  infection. Two hospital- and one community-based controls were used for the comparisons.  Hp  seropositivity was determined by an ELISA method against  Hp  IgG. In  in vitro  studies, one esophageal SCC (CE 81T/VGH) cell line was co-cultured with  Hp , using one gastric adenocarcinoma (AGS) cell line as the control.  Hp -induced cell apoptosis was determined by flow cytometry, TUNEL assay and Western immunoblotting to detect caspase-3 protein expressions in cell lysates.  RESULTS: Presence of  Hp  infection was found to be inversely associated with esophageal SCC risk (adjusted odds ratio (AOR): 0.315-0.472; all  p -value  p -value  in vitro  studies, increased apoptosis was found in CE 81T/VGH, but not in AGS cells, after being co-cultured with  Hp  at a concentration ratio of 1  Hp  and 100 cancer cells for 36 hrs.  CONCLUSION: An inverse association between  Hp  seropositivity and esophageal SCC risk was observed; its possible mechanism may be due to  Hp -induced apoptosis in esophageal SCC cells.
THU0005 Erap polymorphisms and its association with HLA-B15 and HLA-B27 positive spondylarthritis patients
Authors: J Londono, AM Santos, JC Rueda, P Peña, I Briceño, E-L Saldarriaga, J-I Angarita, E Calvo, M Avila, N Martinez-Rodriguez, H Cubides, V Parra, JF Medina
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Since 1973, the association of HLA-B27 and spondyloarthritis (SpA) is well known, however in Colombian population it is present in only 40% of patients and HLA-B15 is present almost in 25%. A mechanism of polygenic mechanism has been proposed as an explanation for the development of SpA. Endoplasmic reticulum aminopeptidase (ERAP) genes 1 and 2 have been implicated. ERAP1 is strongly associated with HLA-B27 positive patients and ankylosing spondylitis, but not with ERAP2 <h3>Objectives</h3> To determine the association between ERAP polymorphisms and HLA-B27 or HLA-B15 positive SpA patients <h3>Methods</h3> 178 patients with SpA according to ASAS criteria were included in the study. HLA typing was performed by the PCR technique using the Biorad® HLA-SSP plates. The polymorphisms were determined by the RT-PCR technique using Roche® probes for ERAP1 rs27044, rs17482078, rs10050860, and rs30187. For ERAP2 the probes used were rs2910686, rs2248374 and rs2549782. The allele and genotype frequencies polymorphisms were obtained by direct counting. In each group the Hardy-Weinberg equilibrium was evaluated using the <sup>2</sup> test. Associations were assessed using odds ratio (OR). Stata v.12.0 program was used to analyse data. The construction and analysis of haplotypes was performed using Haploview v.4.2 <h3>Results</h3> In total 70 patients were HLA-B27 positive and 34 were HLA-B15 positive. 78 were women and 100 were men. Linkage disequilibrium map of the ERAP gene is depicted in figure 1. When analysed by ERAP2 haplotype it is observed that there is a statistically significant association with the combinations described in table 1. No associations were observed between ERAP1 haplotypes and HLA-B15 or B27 <h3>Conclusions</h3> In the group of patients analysed, a statistically significant association was found between patients with SpA HLA-B15 positive and the haplotype TGT of ERAP2. Also HLA-B27 positive SpA patients were associated with haplotype TGC and CAT of ERAP2 with statistical significance <h3>Disclosure of Interest</h3> None declared
Abstract 029: Autophagy is Essential For Myofibril Differentiation
Authors: Yoshimi Hiraumi, Chengqun Huang, Allen M Andres, Ying Xiong, Jennifer Ramil, Roberta A Gottlieb
Journal: Circulation Research (2013)

Introduction: Over the last decade, stem/progenitor cell therapy has emerged as an innovative approach to promote cardiac repair and regeneration. However, the therapeutic prospects of are currently limited by inadequate means to regulate cell proliferation, homing, engraftment, and differentiation. Autophagy, a lysosome-mediated degradation pathway for recycling organelles and protein aggregates, is recognized as important for facilitating cell differentiation. Studies have shown that induced pluripotent stem cells (iPCs), which exhibit a predominantly glycolytic metabolism, shift towards oxidative mitochondrial metabolism as a prerequisite for the formation of sarcomeres and differentiation into cardiomyocytes. C2C12 myoblasts are a mouse-derived myogenic progenitor cell line which can be induced to differentiate into myotubes. We hypothesize that autophagy is essential in coordinating transcription factor activity and metabolic reprogramming of mitochondria to support myocyte differentiation. Methods: C2C12 myoblasts were cultured in DMEM (10% FBS) and induced to differentiate into myotubes with DMEM (2% horse serum) for 6d. To disrupt autophagy, cells were: 1) transfected with 50nM Atg5 siRNA for 8h twice over a 48h period, or 2) treated with 10nM bafilomycin A1 or vehicle control for a 3h/day for the first 3d of differentiation. GFP-LC3 adenovirus was employed to visualize autophagy. Western blot and real-time qPCR were used to examine proteins and transcripts of interest. Results: We observed increased LC3-II levels and GFP-LC3 puncta during the differentiation of C2C12 cells, suggesting the involvement of autophagy in this process. Transient inhibition of autophagy during the early stages of differentiation with either Atg5 siRNA or bafilomycin A1 interfered with myotube formation and attenuated the upregulation of myogenic transcription factors MyoD and myogenin. Differentiation was accompanied by an increase in PGC1α mRNA, mitochondrial mass, and oxygen consumption, all of which were blocked by disruption of autophagy. Conclusions: Autophagy coordinates transcription factor expression and mitochondrial turnover essential for cell differentiation.
01.15 Type I IFN system activation in newborns exposed to anti-ro/ssa autoantibodies in utero
Authors: Malin Hedlund, Gudny Ella Thorlacius, Margarita Ivanchenko, Nikolaos Kyriakidis, Lars Rönnblom, Maija-Lena Eloranta, Alexander Espinosa, Sven-Erik Sonesson, Marie Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Overexpression of type I IFN-stimulated genes has been demonstrated in both SLE and SS, and induction of IFNα production in plasmacytoid dendritic cells by immune complexes containing RNA and autoantibodies, including Ro/SSA and La/SSB autoantibodies, has also been shown. During pregnancy, these autoantibodies pass over the placenta to the fetus, but it is not know if an IFN-activation takes place also in the fetus. In the present study, we therefore investigated if the type I IFN system is activated in newborns exposed to anti-Ro/SSA autoantibodies <i>in utero</i>. <h3>Materials and methods</h3> Anti-Ro/SSA positive mothers and their babies as well as healthy controls were included in the study. Maternal and cord blood drawn at birth was immediately separated into plasma and PBMC. mRNA expression was analysed by microarrays, cell surface markers were assessed by flow cytometry and circulating IFNα levels by DELFIA. <h3>Results</h3> We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/SSA positive women but also in their newborns, with maternal and fetal IFN scores showing a significant positive correlation (r=0.74, p=0.005). Increased expression of MHC class II was observed on CD14<sup>+</sup> monocytes of anti-Ro/SSA antibody-exposed babies, suggesting cellular activation. Notably, the IFN score of babies born to mothers receiving immunomodulatory treatment was similar to that of controls. <h3>Conclusions</h3> We demonstrate for the first time that anti-Ro/SSA antibody-exposed babies at risk for neonatal lupus have a pre-activated immune system with an IFN signature, elevated plasma IFNα, and increased MHC class II expression on circulating monocytes. Our data also suggest that maternal immunomodulatory treatment may modulate the IFN activity in the baby.
Marked leukemoid reaction in a patient with metastatic breast carcinoma
Authors: Yasmin Harvey, Shane Bleakley, Piers Blombery, Barbara J. Bain
Journal: American Journal of Hematology (2017)

Leukemoid reactions can be a paraneoplastic phenomenon associated with plasma cell neoplasms and, less often, carcinoma or sarcoma. Small numbers of cases have been associated with breast cancer with the leukemoid reaction sometimes acting as a tumor marker, preceding other evidence of recurrent disease. In this case, there was no leukemoid reaction at diagnosis or when metastases were initially identified. The leukemoid reaction progressed over a 4-month period, with worsening cytopenias, prior to the patient succumbing, supporting previous reports of a leukemoid reaction portending a poor prognosis. The marked granulocytic hyperplasia in this case resembles features observed in the marrow due to G-CSF therapy and is consistent with the hypothesis that the tumor cells secrete G-CSF. This mechanism has been reported in breast cancer.1 Nothing to report.
The frequency of a novel <i>KANK1</i> and <i>NTRK3</i> translocation and BRAF<sup>V600E</sup> mutation in patients diagnosed with metanephric adenoma utilizing molecular mechanisms.
Authors: Aida Catic, Ardis Sophian, Lech Mazur, Dinesh Rakheja, Amina Kurtovic Kozaric, Semir Beslija, Jillene Kogan, Michael Pins
Journal: Journal of Clinical Oncology (2017)

1537 Background: Renal metanephric adenoma (MA) is a very rare benign renal tumor, which is frequently misclassified when microscopic features alone are applied. Despite the classification of adenoma as a benign tumor, it is difficult to differentiate from other renal carcinomas such as malignant papillary renal cell carcinomas and in children it can be mistaken with Wilms tumor. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, there is limited data available regarding the genetic alterations critical to the metanephric adenoma development. Recent data suggest that 90% of MA have BRAF V600E mutations; the genetics of the remaining 10 % are unclear. Methods: This study was conducted on 13 FFPE specimens from patients who were diagnosed with renal metanephric adenoma. H&amp;E stained slides from all cases were reviewed by study pathologist, and representative tissue blocks were further selected for BRAF V600E sequencing and fluorescent in situ hybridization was adapted to detect chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3). Results: In this study, we identified a novel chromosomal translocation t(9;15)(p24;q24) between KANK1 and NTRK3, and provided new insights into molecular mechanisms which might identify a subset of metanephric adenomas. Such findings imply that recurrent cytogenetic aberrations may be of prognostic significance as well. Interestingly, our data suggested mutual exclusivity of BRAF V600E and t(9;15) aberrations. Conclusions: Molecular and cytogenetic analyses have allowed us to elucidate a genetic aberration, which may be specific to metanephric adenoma. Aberrant expression of the KANK1-NTRK3 gene fusion may be one mechanism by which functionally relevant genes are altered in the development of metanephric adenoma, and thus mark a subgroup of metanephric adenomas with particular clinicopathological features. Also, our study adds KANK1 and NTRK3 to the list of candidate genes that may play a role in the 10% of renal metanephric adenomas that lack a BRAF V600E mutation.
FDG-PET–driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study
Authors: R.-O. Casasnovas, L. Ysebaert, C. Thieblemont, E. Bachy, P. Feugier, A. Delmer, S. Tricot, J. Gabarre, M. Andre, C. Fruchart, N. Mounier, R. Delarue, M. Meignan, A. Berriolo-Riedinger, S. Bardet, J.-F. Emile, J.-P. Jais, C. Haioun, H. Tilly, F. Morschhauser
Journal: Blood (2017)
pH‐Responsive Nanoscale Coordination Polymer for Efficient Drug Delivery and Real‐Time Release Monitoring
Authors: Kai Han, Wei‐Yun Zhang, Jin Zhang, Zhao‐Yu Ma, He‐You Han
Journal: Advanced Healthcare Materials (2017)

Abstract Both excess dosages of drug and unwanted drug carrier can lead to severe side effects as well as the failure of tumor therapy. Here, an Fe 3+ –gallic acid based drug delivery system is designed for efficient monitoring of drug release in tumor. Fe 3+ and polyphenol gallic acid can form polygonal nanoscale coordination polymer in aqueous solution, which exhibits certain antitumor effect. Importantly, this coordination polymer possesses extremely high doxorubicin (DOX) loading efficacy (up to 48.3%). In vitro studies demonstrate that the fluorescence of DOX can be quenched efficiently when DOX is loaded on the coordination polymer. The acidity in lysosome also triggers the release of DOX and fluorescence recovery simultaneously, which realizes real‐time monitoring of drug release in tumor cells. In vivo studies further indicate that this polyphenol‐rich drug delivery system can significantly inhibit tumor growth with negligible heart toxicity of DOX. This system with minimal side effects should be a promising nanoplatform for tumor treatment.
Early MRD-Negativity May Predict for Favorable Outcome Irrespective of Allotransplantation in TKI-Treated Patients with Ph-Positive Acute Lymphoblastic Leukemia
Authors: Helena Hohtari, Marjatta Sinisalo, Tapio Nousiainen, Perttu Koskenvesa, Ulla Wartiovaara-Kautto, Satu Mustjoki, Pirjo Koistinen, Marjaana Säily, Maija Itälä-Remes, Erkki Elonen, Kari Remes, Kimmo Porkka
Journal: Blood (2016)
Over 100 US healthcare providers are charged in $1.3bn fraud case
Authors: Michael McCarthy
Journal: BMJ (2017)

US law enforcement officials have charged 412 individuals in more than 30 states—including 115 doctors, nurses, and other medical professionals—for allegedly participating in healthcare fraud schemes involving over $1.3bn (£1bn; €1.13bn) in false billings.

In a 13 July press conference announcing the indictments Jeff Sessions, US attorney general, said that many of the cases involved prescription and distribution of opioids and other narcotics, contributing to the country’s ongoing opioid addiction epidemic.

“Too many trusted medical professionals like doctors, nurses, and pharmacists have chosen to violate their oaths and put greed ahead of their patients,” said Sessions. …
Meningococcal B vaccination also cuts risk of gonorrhoea, study suggests
Authors: Susan Mayor
Journal: BMJ (2017)

People vaccinated with an outer membrane vesicle (OMV) group B meningococcal vaccine showed a 30% lower risk of gonorrhoea diagnosis in a large study, suggesting that vaccination provides a new approach for preventing gonorrhoea.1

Although very different diseases, an 80-90% genetic match exists between the bacterium that causes meningococcal disease ( Neisseria meningitidis ) and the gonorrhoea pathogen Neisseria gonorrhoeae . Observational surveillance data have previously suggested a decline in gonorrhoea after introducing …
FRI0196 Biosimilars in the uk: early real world data from the british society for rheumatology biologics registers for rheumatoid arthritis
Authors: D De Cock, K Watson, KL Hyrich
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Biosimilars, biopharmaceuticals assessed by regulatory agencies to have efficacy and safety similar to their reference products, were introduced to the UK market in February 2015 for rheumatoid arthritis (RA). Most research on RA biosimilars has been done in the context of clinical trials, but real world data are lacking. No national mandate exists in the UK to switch all patients from originator to biosimilars, but there are regional variations. <h3>Objectives</h3> This analysis aims to describe the characteristics of the first UK patients starting RA biosimilars registered with the British Society for Rheumatology Biologics Register for RA (BSRBR-RA). <h3>Methods</h3> Since 03/08/2015, the BSRBR-RA has captured data on patients starting biosimilars available in the UK: infliximab (Inflectra and Remsima) and etanercept (Benepali). At biosimilar start, information is captured from the hospital including demographic and clinical data, previous biologic exposure and if switching therapies, the reason for switch (as a tick box and free text). Follow-up data, including disease activity, occurrence of adverse events and changes to treatment is captured 6-monthly for 3 years and annually thereafter. Descriptive data are presented. <h3>Results</h3> To 15/12/2016, 417 RA patients were recruited to the BSRBR-RA at point of starting a biosimilar for whom data were available for analysis on 414 participants: 47 (11%) Inflectra, 78 (19%) Remsima and 289 (70%) Benepali. Of these, 138 started a biosimilar as first biologic, 242 switched directly from the originator product and 34 switched from an alternative biologic (Table). Patients switching from the originator did so after a median (IQR) of 6.7 (3.0–9.5) years and the majority had low disease activity (median DAS28 2.7 (IQR 2.0–3.9)). The switch reason was reported in 33% of patients, with cost listed as the main reason and “trust policy” included in 63% of 30 free text comments. Six-month follow-up data were available in 41 patients. Three patients on Remsima and 1 patient on Inflectra reported drug hypersensitivity reactions (rash, pruritus, hyperpigmentation), and 18% (6/34) of patients experienced a deterioration in their DAS28 of &gt;1.2 after 6 months. <h3>Conclusions</h3> This preliminary study gives an early review of biosimilar use in the UK, showing that these drugs are used in patients with active disease as both first-line and subsequent-line biologics. Many patients with low disease activity are also being switched from originators primarily for cost reasons. Outcome data are limited but data capture will continue and updated reports from the BSRBR-RA will continue to be presented. <h3>Disclosure of Interest</h3> None declared