tbuckley/cabot-search huggingface dataset:
Microenvironment Influences Expression of TOSO – a Novel NF-Kappa B Target Gene In Chronic Lymphocytic Leukemia
Authors: Lukas P. Frenzel, Alexandra Schulz, Christian P. Pallasch, Rainer Claus, Sabine Ponader, Jan A. Burger, Michael Hallek, Christoph Plass, Clemens-Martin Wendtner
Journal: Blood (2010)
US must address addiction as an illness, not as a moral failing, Surgeon General says
Authors: Michael McCarthy
Journal: BMJ (2016)

The US Surgeon General, Vivek Murthy, has called for the country to address its epidemic of substance abuse and addiction as a public health problem and not as a moral issue.1

“It’s time to change how we view addiction,” Murthy said in a new report, “Not as a moral failing but as a chronic illness that must be treated with skill, urgency, and compassion. The way we address this crisis is a test for America.”

According to the report released on 17 November, …
PWE-117 ‘Lies, Damned Lies and The Caecal Intubation Rate’ A Study of The Inappropriate Conversion of Incomplete Colonoscopies to Flexible-Sigmoidoscopy
Authors: S Beg, S Sansone, K Ragunath
Journal: Gut (2016)

<h3>Introduction</h3> A caecal intubation rate of &gt;90% is a well accepted quality indicator of colonoscopy and is consequently monitored within endoscopy units. Endoscopists’ desire to meet this target may mean that incomplete colonoscopies are recorded as flexible-sigmoidoscopies. The aim of this study was to examine whether the conversion of requested colonoscopies is a clinically significant phenomenon. <h3>Methods</h3> A retrospective review of all flexible sigmoidoscopies performed between 1<sup>st</sup> January 2015 and 31<sup>st</sup> December 2015 at Nottingham University Hospitals was performed. Where a colonoscopy was requested but a flexible-sigmoidoscopy performed, the patient’s records and endoscopy reports were reviewed to determine whether this conversion was decided before the start of the procedure and documented. <h3>Results</h3> During the 12 month period, 3096 flexible-sigmoidoscopies were performed by 48 endoscopists. 149 requests could not be retrieved and were therefore excluded from this analysis. Of the 2947 sigmoidoscopy requests reviewed, 3.2% (n = 98) procedures were originally requested as a colonoscopy, with 15 converted at the point of vetting. 40 of converted procedures were planned polypectomies or post polypectomy assessments in patients who had previously undergone complete visualisation of the colon, and could therefore be considered appropriate to the intended purpose. 43 conversions occurred in patients who had a valid documented indication for colonoscopy and had undergone full bowel preparation. The most common reasons cited included poor bowel preparation (n = 18), technical failure (n = 12) or clinically inappropriate (n = 8). A clear reason for conversion was not apparent in 5 cases. During the study period 8632 colonoscopies were performed and so conversions represent 0.5% of the total requests. This practice was observed amongst 14 endoscopists, when inappropriate conversions were included in individuals’ performance data, 6 endoscopists fell to ≤90% target caecal intubation target. <h3>Conclusion</h3> A small, but significant number of colonoscopies are converted to flexible sigmoidoscopies at the time of the procedure. This study demonstrates the conversion of colonoscopy to sigmoidoscopy as being a potential limitation of relying on caecal intubation rate alone. Endoscopy units should consider monitoring the rate of inappropriate conversions to ensure quality is maintained. <h3>Disclosure of Interest</h3> None Declared
Developing a vaccine against Zika
Authors: Joachim Hombach, Martin Friede, Vasee Moorphy, Anthony Costello, Marie Paule Kieny
Journal: BMJ (2016)

The race to develop a vaccine against Zika began in February 2016, when the unusual clustering of cases of microcephaly and other neurological disorders associated with Zika virus infection led to the declaration of a public health emergency of international concern. When the World Health Organization held its first consultation in March, 14 active vaccine projects had already been announced.1 Today, WHO’s pipeline tracker counts about 30 active projects, pursued by developers from endemic and non-endemic countries, private and public sector.2
Acute Kidney Injury in Critically Ill Children — An Ominous Legacy
Authors: Julie R. Ingelfinger
Journal: New England Journal of Medicine (2016)

Children are generally healthy. As we age, however, the chance of having ailments that affect our overall health increases. Recent data from the Centers for Disease Control and Prevention indicate that only 1.3% of children younger than 6 years of age and 2.8% of those 6 to 18 years of age have perceived poor health, as compared with 7.0% of adults 25 to 44 years of age; the prevalence increases further with advancing age.1 As is well known, children recover more quickly from serious illness than adults.Acute kidney injury complicates the course of many critically ill patients2 and may . . .
Relationship Between Myelodysplastic Syndrome and Paroxysmal Nocturnal Hemoglobinuria: Spanish Erythropathology Group and Spanish Paroxysmal Nocturnal Hemoglobinuria Working Group Experience
Authors: Montserrat Lopez Rubio, Anna Gaya, Marta Morado, Vicente Carrasco, Ataulfo Gonzalez Fernandez, Ana Villegas
Journal: Blood (2015)
Gene Expression of Insulin-Like Growth Factor Binding Proteins (IGFBP-2 and IGFBP-3) in Childhood Acute Myeloblastic Leukemia. Intr. by Herbert Sayer.
Authors: Kristin Dawczynski, Bernd Gruhn, Nadine Pfaffendorf, Wittig Susan, Astrit Voigt, Daniel Steinbach, Felix Zintl
Journal: Blood (2004)
AB1054 The Burden of Systemic Lupus Erythematosus on Patient's Occupational Activities
Authors: V. Sadovici-Bobeica, V. Salaru, L. Mazur-Nicorici, M. Cebanu, M. Pasali, M. Mazur
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To determine the burden on systemic lupus erythematosus (SLE) on patient9s occupational activities <h3>Methods</h3> We conducted a cross-sectional study of SLE patients, fulfilling SLICC/ACR 2012 classification criteria. All patients were assessed for disease activity by SLEDAI, damage index by SLICC/ACR DI, general assessments by PGA and MGDA. We collected data on work activity using the Work Productivity Activity Impairment (WPAI) questionnaire for lupus patients. All patients completed the SF-8 questionnaire, estimating physical and mental component summaries (PCS and MCS) of the quality of life (QoL). <h3>Results</h3> The study included 102 SLE patients, 94,1% females, mean age ±SD 42,4±13,3 (range 20–73) years, mean disease duration±SD 93,9±77,1 (range 0,1–228) months. A proportion of 34,3% of the patients had high university education. The employment history in our cohort included: 23,5% of subjects were working full time and 3,9% part time. Meantime, 58,8% of patients had disability for SLE and 6,9% - disability for other disease than SLE; 3,9% of the subjects were studying and 2% were not employed at the moment of the questionning. The results of WPAI questionnaire confirmed a dicrease of all work domains, by absenteism (10%) and presenteism (63.4%). To be noticed that 20 from 28 working subjects were missing from their work during last 12 months during 15,3 days (range 5–40 days) for SLE problems. The analysis of the QoL showed a dicrease of both components, PCS and MCS were 43,2±9,6 and 46,9±13,4 points, respectively. According to the results, the level of the QoL and the disease activity were predictors for impaired work productivity (R<sup>2</sup>=0.21 and R<sup>2</sup>=0.5, p&lt;0.05). <h3>Conclusions</h3> Systemic lupus erythematosus had a substantial burden on patient9s occupational activities, high disease activity and low indices of the quality of life were predictors for impaired work productivity. <h3>Disclosure of Interest</h3> None declared
AB0455 Dyslipidemia and Atherogenic Risk in Patients with Systemic Lupus Erythematosus
Authors: H.A. Radillo, J.A. Batún, E. Hernández
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Dyslipidemia is a common comorbidity in patients with systemic lupus erythematosus, it is favored by central obesity, nephrotic syndrome, glucocorticoids and immunosuppressants. <h3>Methods</h3> 51 patients, who were determined the lipid profile were included. Variables associated with the disease and the drugs used were recorded. Atherogenic risk was calculated. Chi square was used for categorical variables. ANOVA was performed to determine the relationship between mean lipid profile and a logistic regression model to determine the association of the variables with the presence of dyslipidemia. <h3>Results</h3> 68.6% had dyslipidemia. Significant difference between the presence of dyslipidemia and Activity index measured by SLEDAI (p=0.021) was found, the presence of lupus nephritis (P=0.021), use of prednisone ≥20 mg/day (p=0.0009), evolution disease &lt;3 years (P=0.027). Significance between the absence of dyslipidemia and use of hydroxychloroquine (P=0.021) was found. Activity index ≥4 (RR 6.34; p=0.038) and the use of prednisone &gt;20 mg/day (RR 6.67; p=0.036) were independently associated with the presence of dyslipidemia. The average of Castelli rate was 5.02±1.8, the Kannel index was 2.97±1.4 and triglyceride/HDL-C ratio was 5.24 ±3.3. <h3>Conclusions</h3> Patients with systemic lupus erythematosus have a high prevalence of dyslipidemia and a high atherogenic rate, which increases cardiovascular risk significantly. <h3>References</h3> Olusi S, George S. Prevalence of LDL atherogenic phenotype in patients with systemic lupus erythematosus. Vasc Health Risk Manag. 2011; 7: 75–80. Aguilar C, Gόmez F, Lerman I, Vázquez C, Pérez O, Posadas C. Diagnόstico y tratamiento de las dislipidemias. Revista de Endocrinología y Nutriciόn. 2004; 12 (1); 7–41. Graham I, Cooney M, Bradley D, Dudina A, Reiner Z. Dyslipidemias in the prevention of cardiovascular disease: risks and causality. Curr Cardiol Rep. 2012; 14 (6): 709–20. Manzi S, Meilahn E, Rairie J, Conte C, Medsger T, Jansen L, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: Comparison with the Framingham study. Am J Epidemiol. 1997; 145: 408–15. Amaya J, Sarmiento J, Caro J, Molano N, Mantilla R, Rojas A et al. Caridiovascular disease in Latin American patients with systemic lupus erythematosus: A cross sectional study and a systematic review. Autoimmune Diseases. 2013; 1: 1–20. Galindo J, Natividad J, Orellano C, Calvo A, Berrocal A. Dislipidemia en pacientes con artritis reumatoide atendidos en un hospital general. Rev Med Hered. 2011; 22: 47–53. - Trevisan R, Dodesini A, Lepore G. Lipids and renal disease. J Am Soc Nephrol. 2006; 17 (4): 145–7 <h3>Disclosure of Interest</h3> None declared
Preliminary Report on a Phase I/II Study of Intratumoral Injection of PF-3512676 (CpG 7909), a TLR9 Agonist, Combined with Radiation in Recurrent Low-Grade Lymphomas.
Authors: Wei Yun Z. Ai, Youn Kim, Richard T. Hoppe, Sumit Shah, Sandra J. Horning, Robert Tibshirani, Ronald Levy
Journal: Blood (2006)
Роль здатності букальних епітеліоцитів до адгезії Candida albicans та впливу на неї регуляторних цитокінів у перебігу інфекційного процесу у хворих на кандидоз слизової оболонки верхнього відділу травного тракту
Authors: I.V. Kushnirenko
Journal: GASTROENTEROLOGY (2016)

Роль букальних епітеліоцитів у розвитку кандидозу та їх взаємозв’язок із особливостями цитокінового балансу у хворих на кандидоз верхнього відділу травного тракту продовжує вивчатися й сьогодні. Мета дослідження. Вивчити рівні цитокінів інтерлейкіну‑1β (IL‑1β), IL‑4, IL‑6, IL‑8 та фактору некрозу пухлини альфа (ФНП-α) у хворих гастроентерологічного профілю з кандидозом верхнього відділу травного тракту і порівняти отримані дані з показниками здатності букальних епітеліоцитів до адгезії референтного штаму Candida albicans залежно від глибини ураження слизової оболонки. Матеріали та методи. Дослідження проведено на букальних епітеліоцитах від 66 пацієнтів, які за результатами мікробіологічного дослідження зскрібка з язика та біоптатів стравоходу і шлунка розподілені на три групи. Перша група (1) — 31 пацієнт із орофарингеальним кандидозом і поверхневим ростом грибів у біоптатах, із них 1А підгрупа — 8 осіб із поверхневим ростом, друга група (2) — 25 хворих із інвазією грибів у слизову оболонку, третя група (3) — 10 осіб без орофарингеального кандидозу та без росту грибів. Результати. Показано, що середнє значення індексу адгезії букальних епітеліоцитів було у 1,3 і 1,6 раза вищим у 2 групі порівняно з 1 групою та 1А підгрупою (р &lt; 0,05 і р &lt; 0,05 відповідно). В обстежених пацієнтів значно знижений рівень IL‑4 (р &lt; 0,001), на фоні якого у 1 і 2 групах спостерігається істотне підвищення рівня IL‑8 (р &lt; 0,01 і р &lt; 0,001), та у 1 групі — IL‑1β (р &lt; 0,05). Пацієнтів 1А підгрупи відрізняє значно вищий рівень IL‑6 та ФНП-α порівняно із 2 групою (р &lt; 0,05 і р &lt; 0,05 відповідно). Підвищення здатності букальних епітеліоцитів до адгезії Candida albicans знаходиться у прямому кореляційному зв’язку з рівнем IL‑8 та у зворотному — з рівнем IL‑4, а залежно від глибини ураження слизової оболонки має різноспрямований зв’язок із IL‑6 та ФНП-α. Висновки. Характер перебігу інфекційного процесу залежить від здатності букальних епітеліоцитів хворих до адгезії Candida albicans, що пов’язана з особливостями у цитокіновому статусі пацієнтів.
Pegylated Interferon-Alpha 2a in Combination with Nilotinib As First-Line Therapy in Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (Nilopeg trial). Four-Year Follow-up Results
Authors: Franck E. Nicolini, Gabriel Etienne, Viviane Dubruille, Lydia Roy, Françoise Huguet, Laurence Legros, Stéphane Giraudier, Valérie Coiteux, Agnes Guerci-Bresler, Pascal Lenain, Delphine Rea, Shanti Amé, Pascale Cony-Makhoul, Martine Gardembas, Eric Hermet, Philippe Rousselot, Marie-Claude Gagnieu, Stéphane Morisset, Christine Pivot, Madeleine Etienne, Francois Guilhot, Stéphanie Dulucq, Francois-Xavier Mahon
Journal: Blood (2015)
Dorsal horn interneuron-derived Netrin-4 contributes to spinal sensitization in chronic pain via Unc5B
Authors: Yasufumi Hayano, Keiko Takasu, Yoshihisa Koyama, Moe Yamada, Koichi Ogawa, Kazuhisa Minami, Toshiyuki Asaki, Kazuhiro Kitada, Satoshi Kuwabara, Toshihide Yamashita
Journal: The Journal of Experimental Medicine (2016)

Because of the incomplete understanding of the molecular mechanisms that underlie chronic pain, the currently available treatments for this type of pain remain inefficient. In this study, we show that Netrin-4, a member of the axon guidance molecule family, was expressed in dorsal horn inner lamina II excitatory interneurons in the rat spinal cord. A similar expression pattern for Netrin-4 was also observed in human spinal cord. Behavioral analysis revealed that tactile and heat hyperalgesia after peripheral nerve injury or inflammation were abolished in Netrin-4–mutant rats. Transient suppression of Netrin-4 or its receptor Unc5B after injury could also prevent allodynia. Conversely, intrathecal administration of Netrin-4 protein to naive rats enhanced excitatory synaptic transmission in the dorsal horn and induced allodynia, suggesting that Netrin-4 is involved in spinal sensitization. Furthermore, the Unc5B receptor and subsequent activation of the tyrosine phosphatase SHP2 mediated Netrin-4–induced pain signaling in the spinal cord. These results identify Netrin-4 as a novel protein regulating spinal sensitization leading to chronic pain. Our findings provide evidence for the function of Netrin in the adult nervous system, as well as a previously unknown function in inducing pain signals from dorsal horn interneurons.
CBIO-39DOWN-REGULATION OF NFIA SENSITIZES GLIOMA TO CHEMOTHERAPY-INDUCED APOPTOSIS
Authors: Junsung Lee, Edlira Hoxha, Hae-Ri Song
Journal: Neuro-Oncology (2015)

The Nuclear Factor I-A (NFIA) transcription factor was recently identified as a glioma tumor promoter. We previously reported that NFIA inhibits chemotherapy-induced apoptosis glioblastoma (GBM) cells. However, the mechanism by which the NFIA regulates cell survival and drug resistance is not fully understood. We now report that NFIA enhances apoptosis evasion through activating the NFkB p65 and its downstream anti-apoptotic factors (TRAF1 and cIAPs). Induction of NFkB by NFIA is required to protect cells from apoptosis, and inhibition of NFkB (siRNA or inhibitors) effectively reversed NFIA anti-apoptotic effect. Conversely, NFIA knockdown decreased NFkB and anti-apoptotic gene expression and ultimately induced apoptosis. Mechanistic investigation demonstrated that NFIA positively regulates NFkB transcription and protein level. Interestingly we also found that NFkB activates the NFIA promoter and increases NFIA level and that knockdown of NFIA is sufficient to attenuate NFkB pro-survival effect, suggesting a reciprocal regulation between NFIA and NFkB. Consistent with our findings, NFIA and NFkB levels and expression are highly associated in human primary GBM and patient-derived GBM cells. Collectively, these data define previously unknown NFIA-NFkB feed-forward regulation that controls GBM cell survival and drug resistance.
Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease
Authors: Viviany R. Taqueti, Leslee J. Shaw, Nancy R. Cook, Venkatesh L. Murthy, Nishant R. Shah, Courtney R. Foster, Jon Hainer, Ron Blankstein, Sharmila Dorbala, Marcelo F. Di Carli
Journal: Circulation (2016)

Cardiovascular disease (CVD) fatality rates are higher for women than for men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR), an integrated measure of large- and small-vessel CAD and myocardial ischemia, identifies patients at risk for CVD death, but is not routinely measured in clinical practice. We sought to investigate the impact of sex, CFR, and angiographic CAD severity on adverse cardiovascular events.Consecutive patients (n=329, 43% women) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography and with left ventricular ejection fraction >40% were followed (median, 3.0 years) for a composite end point of major adverse cardiovascular events, including cardiovascular death and hospitalization for nonfatal myocardial infarction or heart failure. The extent and severity of angiographic CAD were estimated by using the CAD prognostic index, and CFR was quantified by using positron emission tomography.Although women in comparison with men had lower pretest clinical scores, rates of prior myocardial infarction, and burden of angiographic CAD (P<0.001), they demonstrated greater risk of CVD events, even after adjustment for traditional risk factors, imaging findings, and early revascularization (adjusted hazard ratio, 2.05; 95% confidence interval, 1.05-4.02; P=0.03). Impaired CFR was similarly present among women and men, but in patients with low CFR (<1.6, n=163), women showed a higher frequency of nonobstructive CAD, whereas men showed a higher frequency of severely obstructive CAD (P=0.002). After also adjusting for CFR, the effect of sex on outcomes was no longer significant. When stratified by sex and CFR, only women with severely impaired CFR demonstrated significantly increased adjusted risk of CVD events (P<0.0001, P for interaction=0.04).Women referred for coronary angiography had a significantly lower burden of obstructive CAD in comparison with men but were not protected from CVD events. Excess cardiovascular risk in women was independently associated with impaired CFR, representing a hidden biological risk, and a phenotype less amenable to revascularization. Impaired CFR, particularly absent severely obstructive CAD, may represent a novel target for CVD risk reduction.
A-Type Proanthocyanidins Prevent Engraftment Of Primary Acute Myelogenous Leukemia Cells In Mice and Exhibit Potentially Novel Anti-Leukemia Mechanisms
Authors: Laura M Bystrom, Hongliang Zong, Hsiao-Ting Hsu, Neng Yang, Noa Greenberg, Qinghao Wang, Catherine Neto, Maolin Guo, Stefano Rivella, Monica L. Guzman
Journal: Blood (2013)
Comparison of Response Over 6 Years Between Patients with Chronic Myeloid Leukemia Who Received Imatinib as Initial Therapy and Those Who Received Imatinib as Secondary Therapy.
Authors: Hao Jiang, Xiaojun Huang, Shanshan Chen, Bin Jiang, Qian Jiang, Yazhen Qin, Yueyun Lai
Journal: Blood (2009)
Women’s groups fear Republicans will reduce access to contraception and abortion
Authors: Michael McCarthy
Journal: BMJ (2016)

In the wake of Donald Trump’s electoral victory that gave the Republican party control of the presidency and both chambers of Congress1 women’s health advocacy groups in the US have vowed to fight to preserve women’s access to contraceptive and abortion services.

Ilyse Hogue, president of NARAL Pro-Choice America, said that her organization would oppose any attempts by the Trump administration to limit access to abortion. “Donald Trump’s vision for America and the policies that he has proposed are a clear and present danger to …
THU0545 Comparative Efficacy and Tolerability of Duloxetine, Pregabalin, and Milnacipran for The Treatment of fibromyalgia: A Bayesian Network Meta-Analysis of Randomized Controlled Trials
Authors: Y.H. Lee, Y.H. Seo, S.J. Choi, G.G. Song
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Duloxetine, milnacipran, and pregabalin are the only drugs approved by the Food and Drug Administration (FDA) for fibromyalgia. The recommended dosages are duloxetine 60 mg once a day, milnacipran 100 mg/day in two divided doses; may be increased to 200 mg/day, and pregabalin 150 to 300 mg/day in two divided doses. However, data on the relative efficacy and safety of the drugs approved by the FDA with different dosages are limited, because it is difficult to integrate information regarding the relative efficacy and safety of all tested drugs at different doses due to the lack of multiple comparisons in classical meta-analysis. <h3>Objectives</h3> The aim of this study was to assess the relative efficacy and tolerability of duloxetine, pregabalin, and milnacipran at the recommended doses in patients with fibromyalgia. <h3>Methods</h3> Randomized controlled trials (RCTs) examining the efficacy and safety of duloxetine 60 mg, pregabalin 300 mg, pregabalin 150 mg, milnacipran 200 mg, and milnacipran 100 mg compared to placebo in patients with fibromyalgia were included in this Bayesian network meta-analysis. <h3>Results</h3> Nine RCTs including 5,140 patients met the inclusion criteria. The proportion of patients with &gt;30% improvement from baseline in pain was significantly higher in the duloxetine 60 mg, pregabalin 300 mg, milnacipran 100 mg, and milnacipran 200 mg groups than in the placebo group (pairwise odds ratio (OR) 2.33, 95% credible interval (CrI) 1.50–3.67; OR 1.68, 95% CrI 1.25–2.28; OR 1.62, 95% CrI 1.16–2.25; and OR 1.61; 95% CrI 1.15–2.24, respectively). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that duloxetine 60 mg had the highest probability of being the best treatment for achieving the response level (SUCRA =0.9431), followed by pregabalin 300 mg (SUCRA =0.6300), milnacipran 100 mg (SUCRA =0.5680), milnacipran 200 mg (SUCRA =0.5617), pregabalin 150 mg (SUCRA =0.2392), and placebo (SUCRA =0.0580). The risk of withdrawal due to adverse events was lower in the placebo group than in the pregabalin 300 mg, duloxetine 60 mg, milnacipran 100 mg, and milnacipran 200 mg groups. However, there was no significant difference in the efficacy and tolerability between the medications at the recommended doses. <h3>Conclusions</h3> Duloxetine 60 mg, pregabalin 300 mg, milnacipran 100 mg, and milnacipran 200 mg were more efficacious than placebo. However, there was no significant difference in the efficacy and tolerability between the medications at the recommended doses. <h3>References</h3> None <h3>Disclosure of Interest</h3> None declared