tbuckley/cabot-search huggingface dataset:
Clinical benefit of peretinoin for the suppression of hepatocellular carcinoma (HCC) recurrence in patients with Child-Pugh grade A (CP-A) and small tumor: A subgroup analysis in a phase II/III randomized, placebo-controlled trial.
Authors: T. Okusaka, M. Makuuchi, O. Matsui, H. Kumada, K. Tanaka, S. Kaneko, H. Moriwaki, N. Izumi, Y. Ohashi, K. Okita
Journal: Journal of Clinical Oncology (2011)

165 Background: HCC has a high recurrence rate and poor prognosis; however, no effective treatment has been established for preventing recurrence after resection or ablation. Peretinoin, an acyclic retinoid, of 600 mg/day reduced HCC recurrence and a strong effect after two years suggested that it mainly suppressed de novo carcinogenesis (ASCO2010). Liver impairment causes non- HCC-related deaths or adverse events, and can potentially mask drug efficacy. The size of the main HCC nodule associates vascular invasion and intrametastasis. To evaluate peretinoin efficacy and assess its mechanism of action, we performed subgroup analysis in CP-A patients who had undergone curative therapy for a small tumor. Methods: Eligibility criteria included HCV positive, CP-A or B, and prior curative resection or ablation for conventional HCC. The patients were randomized into groups to receive peretinoin 600 mg/day (high dose, H), peretinoin 300 mg/day (low dose, L), or placebo (P). The patients were grouped according to the CP grade and the size of the major tumor &lt;20mm at the time of diagnosis. Cumulative recurrence-free survival rates were calculated. Hazard ratio (HR) was calculated using Cox regression analysis. Results: Of the 401 patients, 310 showed CP-A, and 144 showed CP-A and tumor size &lt;20 mm. In the CP-A subgroup, the HR of H group (100) vs. P group (106) was 0.603 (95% CI, 0.408-0.891); in the CP-A and tumor size &lt;20 mm subgroup, the HR of H group (49) vs. P group (49) was 0.376 (95% CI, 0.200-0.705). The common treatment-related adverse events in the CP-A subgroup were albuminuria, hypertension, and headache, which were tolerated. Conclusions: Subgroup analysis with CP-A reinforced the peretinoin efficacy in preventing HCC recurrence. In addition, the CP-A and tumor size &lt;20mm subgroup results strongly suggested that peretinoin inhibited de novo carcinogenesis. The subgroup analyses results of our phase II/II study supported the efficacy and safety of peretinoin and showed that it has early benefits for patients with well-preserved liver function and undergone curative therapy for a small tumor. [Table: see text]
Economic evaluation of the cost of treating advanced gastric cancer (AGC) with capecitabine/cisplatin (XP) vs. 5-FU/cisplatin (FP) regimens in an Italian setting
Authors: G. Giuliani, A. Falcone, L. Garrison
Journal: Journal of Clinical Oncology (2007)

15022 Background: A recent randomized phase III trial of XP vs. continuous infusion of FP as first-line therapy in patients with AGC met its primary endpoint of non-inferior progression-free survival (PFS) [Kang et al. ASCO 2006]. There was a trend toward superior efficacy with XP in terms of both PFS (median 5.6 months for XP vs. 5.0 months for FP) and response rates. An economic evaluation was conducted to compare the costs of the two therapies from an Italian perspective. Methods: Direct medical costs during the study period were estimated from the perspective of the Italian health system. The costs of the 2 regimens were estimated based on the trial results on actual dose and the number of administrations, and unit costs in an Italian setting. The adverse event (AE) profiles were used to estimate the costs of treating AEs. An expert panel estimated typical treatment patterns and costs of treating major AEs. Indirect costs for time and travel for study drug administration were estimated. Results: Patients in the XP arm received 5.2 cycles of therapy vs. 4.6 cycles of FP. The substitution of oral capecitabine for infusional 5-FU reduced the number of hospital clinic visits by 17.6 (22.8 for FP vs. 5.2 for XP). Chemotherapy drug costs were estimated to be €1200 greater in the XP arm, but drug administration costs were €2900 lower, yielding a net cost saving of €1700 per patient. The AE profiles were similar: associated costs to treat major (grade 3/4) AEs were less than €170 per patient and were lower in the XP arm. Due to the additional 17.6 visits for infusion of 5-FU, FP patients incurred substantially greater indirect costs in terms of lost time and travel expenses. Conclusion: Oral capecitabine benefits AGC patients by reducing the number of infusion visits and time spent receiving treatment, and would produce significant direct medical cost savings in an Italian setting. AE costs are similar with the 2 regimens. Given the trend to superior efficacy, the projected direct and indirect cost savings, and the convenience of oral treatment, XP would be considered a dominant (less costly and more effective) regimen for AGC from both a health system and societal perspective. No significant financial relationships to disclose.
Human Endogenous Retroviral Genetic Element With Immunosuppressive Activity in Both Human Autoimmune Diseases and Experimental Arthritis
Authors: Magdalena Janina Laska, Anne Troldborg, Ellen‐Margrethe Hauge, Shervin Bahrami, Kristian Stengaard‐Pedersen
Journal: Arthritis & Rheumatology (2016)

Human endogenous retroviruses (HERVs) are remnants of past retroviral infections in the human genome and have been implicated in different aspects of human biology. The aim of this study was to identify HERVs that are associated with the pathogenesis of rheumatic diseases such as systemic lupus erythematosus (SLE).The study subjects included 45 female patients with SLE and 50 healthy controls matched for geographic area, age, and sex. Real-time reverse transcription-polymerase chain reaction analysis was used to examine the transcription levels of 11 genes with coding capacity for complete envelope (Env) protein in these individuals. In this way, 1 HERV locus was identified as a potential modulator of autoimmunity. The env gene encoded by this HERV locus was cloned and examined for the ability to express a functional protein with immunosuppressive potential.Expression of the env59 gene was negatively correlated with pathogenetic factors of human autoimmune rheumatic diseases, including such factors as the levels of interleukin-6 (IL-6) and Toll-like receptor 7. This gene was capable of encoding a fully functional Env glycoprotein that was found to contain a domain, the immunosuppressive (ISU) domain, that, when evaluated ex vivo in patients with SLE and those with rheumatoid arthritis as well as in animal models, showed strong antiinflammatory activity, including the ability to lower IL-6 levels.The env59 gene has been adapted by the immune system as a control mechanism in autoimmunity. The peptides derived from the ISU domain contained in the Env59 protein may be useful as potentially new biologic treatments in rheumatic diseases such as SLE.
Letter by Antignac et al Regarding Article “Access to Medications for Cardiovascular Diseases in Low- and Middle-Income Countries”
Authors: Marie Antignac, Eloi Marijon, Xavier Jouven
Journal: Circulation (2016)

We read with great interest the article by Wirtz et al, 1 which presents an overview on access to cardiovascular medications in low-and middle-income countries.It is noteworthy that, among the 5 health system dimensions of access described, the first 4 have been well researched through large multination studies.Low availability of cardiovascular disease medicines has been well reported; a fairly recent meta-analysis of surveys from 36 countries assessed access to different classes of cardiovascular medicines. 1Several peer-reviewed publications have also reported on the affordability of cardiovascular disease drugs. 1 Last, systematic reviews have been presented on the accessibility and acceptability of cardiovascular disease drugs, and the influence of the healthcare system in this regard in low-income countries, as well. 2 Thus, important steps toward progress in the first 4 dimensions have been made, and several potential novel solutions may be forthcoming. 3his is in stark contrast with the last dimension regarding the quality of cardiovascular disease drugs, for which data are quite lacking in the developing world.To date, studies on drug quality have almost exclusively focused on antimicrobial agents, such as antiretroviral and antimalarial drugs. 4Out of >200 original articles and 100 editorials and reviews 4 published on counterfeit drugs, only 1 addresses cardiovascular drugs.That study on cardiovascular drugs assessed the quality of 5 drugs in only 1 country. 5No large-scale studies on cardiovascular drug quality are available so far.In this particular area, cardiovascular research is clearly lagging behind in comparison with research in other disciplines.This is important because cardiovascular drug quality remains a major issue.Poorquality drugs lack efficacy, resulting in the patient's perceived failure of the healthcare system.This perception can be frustrating and demoralizing for healthcare practitioners.Administration of substandard drugs in cardiology results in treatment failure, leading to increased morbidity and mortality in the short (drugs such as β-blockers and anticoagulants) and long (drugs such as statins) term.Indeed, unknown variability in the quality of drugs such as anticoagulants can lead to incorrect dosage adjustments, resulting in serious adverse events such as thrombosis, stroke, bleeding, or death.Use of counterfeit drugs causes avoidable morbidity and mortality.According to the World Health Organization, nearly 100 000 deaths a year are caused by the use of counterfeit drugs in Africa.Thus, there is an important and urgent need to conduct systematic studies of cardiovascular drug quality in third-world countries and identify steps for improvement.Increasing public awareness, heightening international scrutiny, and improving access to drug quality testing using well-standardized methods are some key requirements in this regard.
Subclinical Hypothyroidism in Elderly Individuals—Overdiagnosis and Overtreatment?
Authors: Paola Portillo-Sanchez, Rene Rodriguez-Gutierrez, Juan P. Brito
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
PTH-065 To define and refine: host iron parameters in a mouse model of<i>Helicobacter</i>infection
Authors: M J Thomson, S A Boxall, J E Crabtree
Journal: Gut (2010)

<h3>Introduction</h3> Iron deficiency (ID) is the most common nutritional disorder globally. There is increasing evidence from clinical and population studies for a role of <i>H pylori</i> infection in the aetiology of ID. Rodent models of <i>Helicobacter</i> infection need to be refined to investigate any causal links to ID. The aim of this study is to examine haematological parameters during the acute phase of <i>Helicobacter</i> infection in mice fed on iron-replete and iron deficient diets. <h3>Methods</h3> Five-week-old female SPF C57Bl/6 mice were fed on iron deficient (2–6 ppm) or iron-replete (48 ppm) diets 3 weeks before oral gavage with <i>H felis</i>. Infected mice and uninfected controls were sacrificed at 4 and 8 weeks post-inoculation. <i>H felis</i> infection was confirmed by urease test and histology. Blood was collected and haematological data were assessed by automated counting machine. <h3>Results</h3> Red blood cell count (RBC) and mean corpuscular haemoglobin concentration were similar in groups on both diets regardless of <i>H felis</i> status at 4 and 8 weeks. In uninfected mice total haemoglobin levels were significantly decreased in iron deficient mice at 4 (p&lt;0.01) and 8 weeks (p=0.05). This decrease was abrogated by <i>H felis</i> infection in dietary replete groups due to a slight increase (NS) in haemoglobin. A dichotomy emerges between iron deficient and replete groups for parameters which reflect size and haemoglobin content of erythrocytes. The haematocrit test, mean corpuscular volume (MCV) and mean haemoglobin concentration (MHC) were significantly decreased (p&lt;0.001) in <i>H felis</i> infected and control mice on iron deficient diet compared to matched groups fed on iron-replete diet. A significant increase (p&lt;0.01) in red cell distribution width (RDW) in iron deficiency suggests erythrocytes have an increased variation in cell volume. <i>H felis</i> infection made no difference to the levels observed. White blood cell (WBC) counts were significantly increased at 4 weeks (p&lt;0.03) and 8 weeks (p&lt;0.001) in mice fed on iron defiecient diet, regardless of <i>H felis</i> status. <h3>Conclusion</h3> Iron deficiency in this mouse model results in reduced MCH indicating an increased percentage of hypochromic red cells and reduced MCV indicating microcytosis. Increased WBC counts as a result of ID, suggests a higher susceptibility to the effects of inflammation and infection. All other parameters measured showed no difference due to <i>H felis</i> status in either diet cohort. This suggests that <i>H felis</i> has no impact on haematological parameters of iron status in the acute stage of the infection. Other markers of iron status such as serum iron, TIBC and serum ferritin are needed to explore further the impact of <i>Helicobacter</i> infection.
Differential Expression of CD180 and sIgM by B Chronic Lymphocytic Leukaemia Cells (B-CLL) Using Mutated and Unmutated IgVh Genes.
Authors: Nino Porakishvili, Nino Kulikova, Maria Manoussaka, Andrew P. Jewell, Pierre Y. Youinou, S. Nedelec, Kwee Yong, Amit Nathwani, B. Heelan, Terry Hamblin, P. Wallace, P. Ely, Ed Clarke, Peter M. Lydyard
Journal: Blood (2004)
Therapeutic Efficacy of Semisynthetic Supra Perfusion Resuscitation Fluids, EAF Peg Alb and EAF Peg Hb, Are Differentiated By Their Cerebral Effects in Animal Models of Sickle Cell Disease
Authors: Craig A Branch, Min-Hui Cui, Sangeetha Thangaswamy, Nicholas Branch, Seetharama Acharya
Journal: Blood (2015)
Abstract 4015: miR-221 ans miR-222 expression in salivary gland tumors
Authors: Renata Carolina Fraga Ianez, Cláudia Coutinho-Camillo, Clóvis Pinto, Fernando Soares, Silvia Lourenço
Journal: Cancer Research (2015)

Abstract Background: MicroRNAs (miRNAs) are a class of short noncoding RNAs, that regulate the gene expression by binding to the 3′ - untranslated region of target mRNAS and by blocking the translation or degradation of the mRNAs that mediate various pathophysiological process including the pathogenesis of diverse human cancers and important cellular functions such as proliferation, apoptosis, differentiation, and cell signaling. Salivary gland tumors are complex, due to their broad histological spectrum resulting from multiple tumor cell differentiation. We previously detected that the protein c-kit is involved in the process of salivary gland morphogenesis and tumorigenesis; other recent studies reported alterations in KIT gene in adenoid cystic carcinoma. The aim of the present study is to determine the expression of microRNAs targeting KIT in pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC), the most common benign and malignant salivary gland neoplasms, respectively, and that originate from the intercalated duct region. Material and Methods: Twenty-five pleomorphic adenoma, 14 adenoid cystic carcinoma and 10 non-neoplastic salivary gland samples were used and miRNA expression was evaluated by Real Time RT-PCR using TaqMan miRNA Assays (miR- 221 and 222). Results: Expression of miR-221 was detected in 13 CAC samples and 19 PA samples. In CAC, expression of miR-221 was downregulated in 4 out of 13 (30,77%) samples, upregulated in 4 out of 13 (30,77%) samples, and normal in 5 out of 13 (38,46%) samples. In PA, miR-221 expression was downregulated in 7 out of 19 (36,84%) samples, upregulated in 2 out of 19 (10,53%) samples, and normal in 10 out of 19 (52,63%) samples. Expression of miR-222 was detected in 14 CAC samples and 22 PA samples. In the majority of CAC samples, the expression of miR-222 was similar to that observed in non-neoplastic samples. In PA samples, expression of miR-222 was downregulated in 7 out of 22 (31,8%) samples, upregulated in 8 out of 22 (36,4%) samples, and normal in 7 out of 22 (31,8%) samples. Conclusion: The expression of miRNAs 221 and 222 do not present a definite pattern to discriminate PA from ACC. This might be due to different mechanisms involved in their tumor biology or due to their common site of origin (the intercalated duct) which could add some similar biological features to both neoplasms. Citation Format: Renata Carolina Fraga Ianez, Cláudia Coutinho-Camillo, Clóvis Pinto, Fernando Soares, Silvia Lourenço. miR-221 ans miR-222 expression in salivary gland tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4015. doi:10.1158/1538-7445.AM2015-4015
Data Linkage Strategies to Advance Youth Suicide Prevention: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop
Authors: Holly C. Wilcox, Hadi Kharrazi, Renee F. Wilson, Rashelle J. Musci, Ryoko Susukida, Fardad Gharghabi, Allen Zhang, Lawrence Wissow, Karen A. Robinson
Journal: Annals of Internal Medicine (2016)

Background: Linking national, state, and community data systems to data from prevention programs could allow for longer-term assessment of outcomes and evaluation of interventions to prevent suicide. Purpose: To identify and describe data systems that can be linked to data from prevention studies to advance youth suicide prevention research. Data Sources: A systematic review, an environmental scan, and a targeted search were conducted to identify prevention studies and potentially linkable external data systems with suicide outcomes from January 1990 through December 2015. Study Selection: Studies and data systems had to be U.S.-based and include persons aged 25 years or younger. Data systems also had to include data on suicide, suicide attempt, or suicidal ideation. Data Extraction: Information about participants, intervention type, suicide outcomes, primary analytic method used for linkage, statistical approach, analyses performed, and characteristics of data systems was abstracted by 2 reviewers. Data Synthesis: Of 47 studies (described in 59 articles) identified in the systematic review, only 6 were already linked to data systems. A total of 153 unique and potentially linkable data systems were identified, but only 66 were classified as "fairly accessible" and had data dictionaries available. Of the data systems identified, 19% were established primarily for research, 11% for clinical care or operations, 29% for administrative services (such as billing), and 52% for surveillance. About one third (37%) provided national data, 12% provided regional data, 63% provided state data, and 41% provided data below the state level (some provided coverage for >1 geographic unit). Limitation: Only U.S.-based studies published in English were included. Conclusion: There is untapped potential to evaluate and enhance suicide prevention efforts by linking suicide prevention data with existing data systems. However, sparse availability of data dictionaries and lack of adherence to standard data elements limit this potential. Primary Funding Source: Agency for Healthcare Research and Quality.
Homoharringtonine (omacetaxine mepesuccinate) as an adjunct for <i>FLT3</i> <i>-</i> ITD acute myeloid leukemia
Authors: Stephen S. Y. Lam, Eric S. K. Ho, Bai-Liang He, Wui-Wing Wong, Chae-Yin Cher, Nelson K. L. Ng, Cheuk-Him Man, Harinder Gill, Alice M. S. Cheung, Ho-Wan Ip, Chi-Chiu So, Jerome Tamburini, Chi Wai Eric So, Dona N. Ho, Chun-Hang Au, Tsun-Leung Chan, Edmond S. K. Ma, Raymond Liang, Yok-Lam Kwong, Anskar Y. H. Leung
Journal: Science Translational Medicine (2016)

An in vitro drug screening using primary AML samples identified homoharringtonine (omacetaxine mepesuccinate) as an effective adjunct for treatment of FLT3-ITD AML.
Analysis of Hemorrhagic Phenotype and Cardiovascular Risk of Severe Hemophilia a Carriers and Difference with Female Working Population Control Group
Authors: María Eva Mingot-Castellano, María Jose Ariza-Corbo, Álvaro Amo Vázquez de la Torre, María Inmaculada Alonso-Calderón, Pedro Valdivielso, Ana Isabel Heiniger-Mazo, Miguel Angel Sánchez-Chaparro
Journal: Blood (2014)
Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial
Authors: Silvie Timmers, Marlies de Ligt, Esther Phielix, Tineke van de Weijer, Jan Hansen, Esther Moonen-Kornips, Gert Schaart, Iris Kunz, Matthijs K.C. Hesselink, Vera B. Schrauwen-Hinderling, Patrick Schrauwen
Journal: Diabetes Care (2016)

OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of standard diabetes care. RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes (T2D) were treated with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique. RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment. Intrahepatic lipid content also remained unaffected by resveratrol; however, the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels (R = −0.68, P = 0.03). Intramyocellular lipid content increased in type 2 muscle fibers (P = 0.03), and systolic blood pressure tended to decrease (P = 0.09) upon resveratrol treatment. In addition, resveratrol significantly improved ex vivo mitochondrial function (state 3 and state U respiration upon malate with octanoyl-carnitine, P &amp;lt; 0.005). Intriguingly, a correlation was found between plasma levels of a metabolite of resveratrol (dihydroresveratrol) and the metformin dose used by the patients (R = 0.66, P = 0.005), suggesting an interaction between metformin and resveratrol. It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction. CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity. Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes.
Re-Treatment with Rituximab Plus Chemotherapy in Patients with Diffuse Large-B Cell Lymphoma (DLBCL): A Spanish Multicenter Study.
Authors: Miguel A. Canales, A. Palacios, C. Martinez-Chamorro, M. A. Cruz, J. M. Moraleda, M. J. Terol, M. Almagro, J. A. Garcia-Vela, D. Aguiar, D. Caballero, J. M. Sancho, S. Ferrer, A. Rueda, J. M. Calvo, J. A. Fernandez, J. Diaz-Mediavilla, J. Gonzalez, J. Mayans, C. Montesinos, E. Rios, A. Ruedas, P. Sabin, A. Fernandez-Jurado
Journal: Blood (2005)