tbuckley/cabot-search huggingface dataset:
Recurrent Scapular Metastasis From Hepatoblastoma Shown on FDG PET/CT and F-DOPA PET/CT
Authors: Bing Zhang, Qiao He, Xinchong Shi, Xiaoyan Wang, Xiangsong Zhang
Journal: Clinical Nuclear Medicine (2017)

We report the case of a 4-year-old girl with a biochemical relapse (plasma α-fetoprotein of 57,987.6 μg/L) after hepatoblastoma and extrahepatic metastases removal and adjuvant chemotherapy. Abdominal ultrasound, CT, and MRI failed to determine the site of recurrence. F-FDG PET/CT showed increased activity in the region of left scapula and adjacent soft tissue, which was incorrectly interpreted as the postoperative repair or inflammatory change. F-DOPA PET/CT showed increased activity and noticeable progressed lesion in the same place. Finally, the left scapula was identified as the site of recurrent metastasis from hepatoblastoma by pathological examination.
Waiting list for elective surgery tops four million for first time since 2007
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The number of patients on waiting lists for elective surgery at NHS hospitals in England has passed four million for the first time in 10 years, official figures show.1

Service leaders and experts said the figures showed that the NHS was at “full stretch” even in the summer months and urged the government to take act now to increase capacity.

The data, from NHS England, show that 3.83 million people were on the waiting list for non-urgent hospital treatment at the end of June 2017. But NHS England said the number was likely to be over four …
Nitroprusside and Isoproterenol Use after Major Price Increases
Authors: Umesh N Khot, Eric D Vogan, Michael A Militello
Journal: New England Journal of Medicine (2017)

Data from 47 hospitals show sharp decreases in the use of nitroprusside and isoproterenol after large increases in price. These findings refute public testimony that price increases would not reduce patients’ access to these medications.
05.08 Increased turnover of monocytes in patients with rheumatoid arthritis identified by transcriptome and cytometric profiling
Authors: Biljana Smiljanovic, Anna Radzikowska, Ewa Kuca-Warnawin, Weronika Kurowska, Joachim R Grün, Bruno Stuhlmüller, Marc Bonin, Till Sörensen, Anne Bruns, Sandra Hermann, Sarah Ohrndorf, Karlfried Aupperle, Marina Backhaus, Gerd R Burmester, Andreas Radbruch, Andreas Grützkau, Wlodzimierz Maslinski, Thomas Häupl
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Targeting molecules involved in monocyte activation is an important treatment strategy for RA. In this study we aimed to determine monocyte maturation and activation from bone marrow (BM) via blood into synovial fluid (SF) by investigating monocytes transcriptomes and by cytometric profiling of classical (CD14<sup>++</sup>CD16<sup>-</sup>), intermediated (CD14<sup>++</sup>CD16<sup>+</sup>) and non-classical (CD14<sup>+</sup>CD16<sup>+</sup>) monocytes. <h3>Materials and methods</h3> CD14<sup>+</sup> cells from BM and blood of RA and osteoarthritis (OA) patients were profiled with Affymetrix microarrays. A detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and egress from BM induced by G-CSF (granulocyte colony-stimulating factor). Cytometric profiling of CD14, CD16, HLA-DR and CD163 expression were used to determine monocyte subsets and to follow their activation and differentiation in BM, blood and SF. <h3>Results</h3> Transcriptomes of RA-BM monocytes exhibited i) pronounce gene pattern of early myeloid precursors from BM and ii) weak gene pattern of late myeloid precursors from BM. Transcriptomes of RA blood monocytes demonstrated i) pattern of late myeloid precursors from BM and ii) reduced pattern of terminally differentiated CD14<sup>+</sup>CD16<sup>+</sup> monocytes from blood. Cytometric profiling of BM, blood and SF monocytes in RA and OA showed that all three body compartments have their own distribution of monocyte subsets. BM was characterised with classical and intermediate subsets and both subsets showed decreased CD16 expression in RA when compared to OA. As expected, blood was characterised with three subsets, and RA blood showed decreased CD14 and HLA-DR expression on classical monocytes and reduced frequency of non-classical subset. In RA-SF, classical monocytes were absent, intermediate were most dominant and cell-phenotype with low CD16 expression but similar to non-classical monocytes was related to macrophages. Cell frequency of intermediate subset in SF positively correlated with inflammation (ESR; R&gt;0.85) and showed the highest expression of HLA-DR, CD14, CD163. <h3>Conclusions</h3> Monocyte turnover is increased in RA and characterised with accelerated monocytopoiesis, faster BM egress and migration into inflamed joints. Permanent monocyte activation in the joint and their role in linking innate and adaptive immunity, which is targeted by biologics, emphasises their high diagnostic value and relevance for therapeutic stratification.
Final results of OV16, a phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel (CP) versus CP in first-line chemotherapy for advanced epithelial ovarian cancer (EOC): A GCIG study of NCIC CTG, EORTC-GCG, and GEICO.
Authors: Andres Cervantes-Ruiperez, Paul Hoskins, Ignace Vergote, Elizabeth A. Eisenhauer, Prafull Ghatage, Mark Carey, Dionyssios Katsaros, Andres Poveda, Diane M. Provencher, Dongsheng Tu, Gavin Stuart
Journal: Journal of Clinical Oncology (2013)

5502 Background: Topotecan was evaluated in a novel combination regimen in comparison to standard therapy in front-line EOC. Methods: Women with newly diagnosed advanced EOC stages IIB-IV, ECOG performance status (PS) 0-1, age &lt; 75, were randomized to either Arm 1: cycles 1 - 4: cisplatin 50 mg/m 2 d1 plus topotecan 0.75 mg/m 2 d1-5 IV; cycles 5 - 8: paclitaxel 175 mg/m 2 over 3 hrs d1 followed by carboplatin AUC5 day 1 or Arm 2: paclitaxel plus carboplatin as in Arm 1 for 8 cycles. The primary endpoint was progression free survival (PFS) and secondary endpoints included objective response, overall survival (OS), adverse event (AE) and Quality of Life (QoL). The sample size required 800 pts and 631 events to detect an improvement in PFS from 16 to 20 months (power 80%, 2-sided alpha 0.05). Results with 3.6 years median follow-up (MFU) were reported previously: there was no significant difference in PFS (Hoskins P, JNCI 2010). Final results including OS after MFU of 8.2 years are reported. Results: From 2001 to 2005, 819 pts (409 Arm 1, 410 Arm 2) were randomized. 704 PFS events and 605 deaths have occurred. PFS results are similar to first report: Median (months [mo]): 14.6 (Arm 1) and 16.2 (Arm 2), hazard ratio (HR) 1.03 (95% CI:0.81-1.30; p = 0.83). Median OS is 44.2 mo (Arm 1) and 44.8 mo (Arm 2), HR: 0.92 (95% CI:0.71-1.19; p=0.54). Baseline factors found to be independent predictors of OS in multivariate analysis are: a) pre-randomization surgery (debulking with no macro residual disease (MRD) to no debulking HR: 0.47; 95%CI:0.37-0.58; p &lt; 0.0001; debulking with MRD (&lt;1 cm) to no debulking HR: 0.76; 95%CI:0.61-0.94; p = 0.01), b) Stage (stage II to III or IV HR:0.52; 95%CI:0.36-0.76; p = 0.0007) and c) PS (0 vs 1 HR:0.76; 95%CI:0.63-0.91; p = 0.004). Post-treatment AEs were not significantly different in the two arms. Conclusions: OV16 final results confirm that sequential doublets of topotecan and cisplatin followed by carboplatin and paclitaxel offer no improvement in outcomes compared to carboplatin and paclitaxel. Pretreatment debulking, stage II and PS 0 are predictive of longer OS. Clinical trial information: NCT00028743.
Effects of Withdrawal From Metformin on the Development of Diabetes in the Diabetes Prevention Program
Journal: Diabetes Care (2003)

OBJECTIVE—In the Diabetes Prevention Program (DPP), metformin significantly reduced the risk of diabetes in individuals with impaired glucose tolerance. Diabetes status was assessed by oral glucose tolerance tests (OGTTs) performed while participants were still taking metformin or placebo. To determine whether the observed benefit was a transient pharmacological effect or more sustained, we performed a repeat OGTT after a short “washout” period during which medications (metformin or placebo) were withheld. RESEARCH DESIGN AND METHODS—All participants assigned to medication who had not developed diabetes at the end of the DPP were asked to have a repeat OGTT after discontinuing the study medication for 1–2 weeks. The predesignated outcome was the odds of diabetes in metformin versus placebo comparisons during the trial and washout combined RESULTS—There were 1,274 participants who participated in the washout study and 529 who did not because they had already developed diabetes. Before the washout, the odds of diabetes in the metformin group was lower than that in the placebo group (odds ratio 0.66, 95% CI 0.54–0.82, P &amp;lt; 0.001). After the washout, diabetes was somewhat more frequently diagnosed in the metformin participants (1.49, 0.93–2.38, P = 0.098). Combining diabetes conversions during the DPP and during the washout, diabetes was diagnosed significantly less frequently in the metformin than the placebo group (0.75, 0.62–0.92, P = 0.005). CONCLUSIONS—The primary analysis of the DPP demonstrated that metformin decreased the risk of diabetes by 31%. The washout study shows that 26% of this effect can be accounted for by a pharmacological effect of metformin that did not persist when the drug was stopped. After the washout the incidence of diabetes was still reduced by 25%.
A HISTORY OF CONCUSSIONS IS ASSOCIATED WITH SYMPTOMS OF COMMON MENTAL DISORDERS IN FORMER MALE PROFESSIONAL ATHLETES ACROSS A RANGE OF SPORTS
Authors: Vincent Gouttebarge, Haruhito Aoki, Mike Lambert, William Stewart, Gino Kerkhoffs
Journal: British Journal of Sports Medicine (2017)

Background Recent reports suggest that exposure to repetitive concussions in sports is associated with an increased risk of symptoms of Common Mental Disorders (CMD) and of later development of neurodegenerative diseases, in particular chronic traumatic encephalopathy (CTE). Objective To explore the relationship between sports career-related concussions and the subsequent occurrence of symptoms of CMD among former male professional athletes. Design Cross-sectional analyses performed on baseline electronic questionnaires from three prospective cohort studies. Setting National unions or players' associations in professional football, ice hockey and rugby. Patients (or Participants) A total of 576 former male professional athletes were enrolled. Mean age at recruitment was 37 years; mean duration of sports career was 10 years. Interventions (or Assessment of Risk Factors) The total number of confirmed concussion incidents during an athlete's career and diagnosed by a medical professional was examined. Main Outcome Measurements Several Patient Reported Outcome Measures (PROMs) were included and assessed with validated scales, namely symptoms of distress, anxiety/depression, sleep disturbance, adverse alcohol use. Results The number of sports career-related concussions was a predictor for all outcome measures (β=0.072–0.100; P≤0.035). Specifically, former professional athletes who reported a history of four or five concussions were approximately 1.5 times more likely to report symptoms of CMD, rising to a two- to four-fold increase in those reporting a history of six or more sports career-related concussions. Conclusions These data demonstrate a direct relationship between exposure to sports concussion and subsequent risk of symptoms of CMD in former professional athletes across a range of contact sports. Further work to explore the association between sports concussion and symptoms of CMD is required; in meantime strategies for effective risk reduction and improved management appear indicated.
RUNX1 is required for oncogenic Myb and Myc enhancer activity in T-cell acute lymphoblastic leukemia
Authors: AHyun Choi, Anuradha Illendula, John A. Pulikkan, Justine E. Roderick, Jessica Tesell, Jun Yu, Nicole Hermance, Lihua Julie Zhu, Lucio H. Castilla, John H. Bushweller, Michelle A. Kelliher
Journal: Blood (2017)
酸化還元ナノ粒子はピオグリタゾンの化学療法効率を増加させ,その毒性副作用を抑制する【Powered by NICT】
Authors: Thangavel Sindhu, Yoshitomi Toru, Sakharkar Meena Kishore, Nagasaki Yukio
Journal: Biomaterials (2016)
DEATHS IN ORGANISED SPORTS IN AUSTRALIA: A CASE SERIES REVIEW OF THE NATIONAL CORONIAL INFORMATION SYSTEM
Authors: Andrew McIntosh, Lauren Fortington, Declan Patton, Caroline Finch
Journal: British Journal of Sports Medicine (2017)

Background Organised sports include individual water sports and athletic activities, team ball sports, team bat/stick sports and racquet sports. The causes of death, contributing factors and potential to prevent deaths in organised sports are poorly understood. Objective To understand the causes of death and contributing factors in organised sports in Australia. Design A case-series analysis was undertaken using the National Coronial Information System (NCIS) in Australia. Setting Organised sports, including recreational and professional participants. Patients Cases are ‘closed’ NCIS fatal cases aged 15 to 74 years who died in the period 2000 to 2016 as a result of participating in an organised sport. Interventions No interventions were assessed. Main Outcome Measurements These include the cause of death, mechanism of injury, contributing factors, demographic data, and sport participation. Results There were 913 deaths in organised sports, with 89% being male. The largest group was 45–54 year olds (23%) and the smallest was 65 to 74 year olds (15%). The three sports groups accounting for the highest proportion of deaths were team ball sports (23%), wheeled motor sports (12%) and individual water sports (11%). Within team ball sports there were 98 deaths in organised football (Australian Rules, Rugby Union and Rugby League). Overall, the cause of death was cardiac, e.g. congestive cardiac failure and acute coronary syndrome, in 56% of cases, blunt force trauma in 29% and drowning in 7%. Cardiac deaths increased with age while blunt force trauma deaths reduced with age. Conclusions There are age related differences in sport participation at time of death and cause of death that need consideration in planning for life long active participation in organised sport. Organised sports are governed by organisations with responsibility for setting player safety standards – informing these organisations of risks is critical for injury prevention, medical emergency policy and planning.
THE HEAD COACH INFLUENCE IN INJURIES FREQUENCY IN ELITE WOMEN VOLLEYBALL PLAYERS
Authors: Marcela Leite, Natália Bittencourt, Bruna Melato, Guilherme Bernardone, Tatiana Ribeiro, Leonardo Veloso
Journal: British Journal of Sports Medicine (2017)

Background Elite female volleyball players have a high risk for shoulder, knee and ankle injuries. The head coach approach is crucial to prevent injuries. Objective To compare the frequency of complaints and time loss injuries during two elite volleyball seasons with different head coaches, the second having more expertise in elite female volleyball players than the first. Design Prospective cohort study. Setting Minas Tênis Club elite female volleyball team. Patients (or Participants) One team, consisting of 15 players in the first season (age 25.4 yrs (SD±5.4); body mass 72.7 kg (±3.1); height 182.0 cm (±0.1) and 16 players in the second season (age 23.5 yrs (±4.7); body mass 74.4 kg (±9.7); height 182.0 cm (±6.6) were followed up. Interventions (or Assessment of Risk Factors) The same physiotherapist conducted the data collection during two seasons. The injury definition was time loss from full participation in sports, and a complaint was any symptoms that need physical therapy intervention and/or modifying training load. The complaints/injuries were categorized as acute or chronic. Main Outcome Measurements The frequency of complaints and time-loss injuries during two seasons of follow up. Results The total number of complaints/injuries was 33 in the first season and 41 in the second season, with an annual average of 2.5 complaints/injuries per athlete in the first season and 2.9 in the second. In the first season, 58% of complaints/ injuries resulted in time loss, while in the next season only 34% did. The number of complaints/injuries increased, but there was a 40% reduction in time-loss injuries. Another important factor was the reduction in 33% of chronic cases. Conclusions The physiotherapy interventions were the same during the two seasons, but the head coach expertise may have influenced the rate of time-loss injuries, resulting in more athletes being available for practices and games.
03.02 Evaluation of anti-inflammatory effects of steroids and arthritis-related biotherapies in an in vitro co-culture model with immune cells and synoviocytes
Authors: Mélissa Noack, Ndiémé Ndongo-Thiam, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> During rheumatoid arthritis (RA), steroids and biotherapies are two different ways to diminish inflammation, by reducing cytokine production and they are used alone and combined. Their efficacy has been established in clinical trials but their differential effects at the cellular level are less documented. The aim was to study these cellular effects using an <i>in vitro</i> model with synoviocytes interacting with peripheral blood mononuclear cells (PBMC) to reproduce the interactions in the RA synovium. <h3>Materials and Methods</h3> Activated-PBMC were co-cultured with RA synoviocytes during 48 hour. A dose-response of methylprednisolone (MP) was tested and different biotherapies (Infliximab, Etanercept, Adalimumab, Tocilizumab, Abatacept and Rituximab) were added alone or in combination with MP. Cytokine production (IL-17, IL-6, IL-1β, IFN-γ and IL-10) was measured by ELISA. <h3>Results</h3> Addition of MP to co-cultures inhibited the production of pro-inflammatory cytokines, IL17, IL-6, IL-1β and IFN-γ, but also the anti-inflammatory IL-10 secretion. The lower doses of MP were mostly as efficient as higher doses. The response to the biotherapies alone was treatment-dependent and the inhibitory effect was obtained with the lower dose. IL-17 production was inhibited only by Tocilizumab (p<i>=</i><i>0.004</i>) while IL-6 was decreased only by Infliximab (p<i>≤</i><i>0.002</i>). IL-1β level was affected in all conditions (p<i>≤</i><i>0.03</i>). IFN-γ production was mainly decreased by Infliximab (p<i>=</i><i>0.004</i>), and IL-10 by Infliximab and Tocilizumab (p<i>≤</i><i>0.004</i>). The combination MP and biotherapies, even at low doses did not induce an additional effect on the inhibition of pro-inflammatory cytokine production. Further, the addition of a biotherapy seemed to reduce the effect of MP alone. Nevertheless, the combination MP and biotherapies induced a higher IL-10 secretion than MP alone, mainly with Rituximab. <h3>Conclusion</h3> Steroids inhibited the secretion of all cytokines, and low doses were as potent. A global inhibitory effect of all biotherapies was observed but with differences between treatments depending on their mechanism of action. MP and biotherapy combination did not enhance the inhibitory effect on pro-inflammatory cytokines but could have a beneficial effect by increasing IL-10 production.
有意に改善された幹細胞骨形成分化と頭蓋骨形成を伴った3次元電気紡糸PCL/PLAブレンドナノ繊維足場【Powered by NICT】
Authors: Yao Qingqing, G L Cosme Jaqueline, Xu Tao, M Miszuk Jacob, H S Picciani Paulo, Fong Hao, Sun Hongli
Journal: Biomaterials (2017)
02.27 Myostatin-induced mechanisms of inflammatory bone destruction by invasive fibroblast-like synoviocytes
Authors: Michelle Fennen, Vanessa Kracke, Georg Varga, Thomas Pap, Berno Dankbar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Myostatin, a secreted member of the transforming growth factor-β (TGF-β) family, is predominantly expressed in skeletal muscle and negatively regulates muscle growth. We previously demonstrated that myostatin deficiency leads to reduced joint inflammation and joint destruction in arthritic human TNF transgenic mice (Mstn<sup>-/-</sup> hTNFtg). Additionally, myostatin was highly expressed in rheumatoid arthritis (RA) synovial tissues with most prominent staining of synovial fibroblasts (FLS). Moreover, further studies have shown that myostatin participates in the complex interplay of inflammatory cytokines, increasing tissue and systemic levels of IL1, IL6 and TNFα. Here we investigate the regulatory role of myostatin on joint inflammation and inflammatory cytokine expression in the development of RA. <h3>Material and methods</h3> Immunophenotyping of isolated spleen and bone marrow derived cells of wt, Mstn<sup>-/-</sup>, hTNFtg and Mstn<sup>-/-</sup>hTNFtg mice was performed by FACS analysis. Moreover, hTNFtg mice with a Col1α2-specific deletion of myostatin (Col1α2-Cre/Mstn<sup>fl/fl</sup> hTNFtg) were generated and clinical severity and histological changes were determined by μCT and histomorphometry. Effects of myostatin on the secretion of IL-6 by human and mouse FLS and the expression of Interleukin-17 receptor C (IL-17RC) were evaluated by ELISA and western blotting. The secretion of various cytokines/chemokines by FLS of Mstn<sup>-/-</sup>hTNFtg and hTNFtg mice was investigated using a specific antibody array. <h3>Results</h3> <i>In vivo</i>, the bone marrow of Mstn<sup>-/-</sup>hTNFtg mice showed a decreased number of B-cells compared to control mice, which might influence the development of the disease. Moreover, comparison of hTNFtg mice, which exhibit a Col1α2-specific deletion of myostatin, with hTNFtg control mice, lead to decreased bone destruction and inflammation examined by µCT and histomorphometric analysis. <i>In vitro</i>, stimulation of FLS with myostatin enhanced the IL-17-mediated secretion of IL-6 by FLS through upregulation of the IL-17RC. Furthermore, analyses of IL-17-mediated cytokine regulation revealed differences in the secretion profile of cytokines/chemokines between FLS of Mstn<sup>-/-</sup>hTNFtg and FLS of hTNFtg control mice, suggesting that myostatin is involved in the regulation of joint inflammation. <h3>Conclusion</h3> These data suggest that myostatin could be an indirect regulator of cytokine expression by FLS, associated with enhanced inflammation and thus promote joint destruction during chronic inflammatory arthritis.
Type 2 Diabetes in the Real World: The Elusive Nature of Glycemic Control
Authors: Steven V. Edelman, William H. Polonsky
Journal: Diabetes Care (2017)

Despite U.S. Food and Drug Administration (FDA) approval of over 40 new treatment options for type 2 diabetes since 2005, the latest data from the National Health and Nutrition Examination Survey show that the proportion of patients achieving glycated hemoglobin (HbA1c) <7.0% (<53 mmol/mol) remains around 50%, with a negligible decline between the periods 2003-2006 and 2011-2014. The Healthcare Effectiveness Data and Information Set reports even more alarming rates, with only about 40% and 30% of patients achieving HbA1c <7.0% (<53 mmol/mol) in the commercially insured (HMO) and Medicaid populations, respectively, again with virtually no change over the past decade. A recent retrospective cohort study using a large U.S. claims database explored why clinical outcomes are not keeping pace with the availability of new treatment options. The study found that HbA1c reductions fell far short of those reported in randomized clinical trials (RCTs), with poor medication adherence emerging as the key driver behind the disconnect. In this Perspective, we examine the implications of these findings in conjunction with other data to highlight the discrepancy between RCT findings and the real world, all pointing toward the underrealized promise of FDA-approved therapies and the critical importance of medication adherence. While poor medication adherence is not a new issue, it has yet to be effectively addressed in clinical practice-often, we suspect, because it goes unrecognized. To support the busy health care professional, innovative approaches are sorely needed.