tbuckley/cabot-search huggingface dataset:
Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians
Authors: Pauline Arends, Milan J Sonneveld, Roeland Zoutendijk, Ivana Carey, Ashley Brown, Massimo Fasano, David Mutimer, Katja Deterding, Jurriën G P Reijnders, Ye Oo, Jörg Petersen, Florian van Bömmel, Robert J de Knegt, Teresa Santantonio, Thomas Berg, Tania M Welzel, Heiner Wedemeyer, Maria Buti, Pierre Pradat, Fabien Zoulim, Bettina Hansen, Harry L A Janssen
Journal: Gut (2014)

Hepatocellular carcinoma (HCC) risk-scores may predict HCC in Asian entecavir (ETV)-treated patients. We aimed to study risk factors and performance of risk scores during ETV treatment in an ethnically diverse Western population.We studied all HBV monoinfected patients treated with ETV from 11 European referral centres within the VIRGIL Network.A total of 744 patients were included; 42% Caucasian, 29% Asian, 19% other, 10% unknown. At baseline, 164 patients (22%) had cirrhosis. During a median follow-up of 167 (IQR 82-212) weeks, 14 patients developed HCC of whom nine (64%) had cirrhosis at baseline. The 5-year cumulative incidence rate of HCC was 2.1% for non-cirrhotic and 10.9% for cirrhotic patients (p<0.001). HCC incidence was higher in older patients (p<0.001) and patients with lower baseline platelet counts (p=0.02). Twelve patients who developed HCC achieved virologic response (HBV DNA <80 IU/mL) before HCC. At baseline, higher CU-HCC and GAG-HCC, but not REACH-B scores were associated with development of HCC. Discriminatory performance of HCC risk scores was low, with sensitivity ranging from 18% to 73%, and c-statistics from 0.71 to 0.85. Performance was further reduced in Caucasians with c-statistics from 0.54 to 0.74. Predicted risk of HCC based on risk-scores declined during ETV therapy (all p<0.001), but predictive performances after 1 year were comparable to those at baseline.Cumulative incidence of HCC is low in patients treated with ETV, but ETV does not eliminate the risk of HCC. Discriminatory performance of HCC risk scores was limited, particularly in Caucasians, at baseline and during therapy.
The False-Negative Treponema pallidum Immobilization Test in Syphilis
Authors: J. Lawton Smith
Journal: JAMA (1967)

THE Treponema pallidum immobilization test has achieved worldwide recognition as a specific serological test for syphilis since its introduction by Nelson and Mayer in 1949. It has been particularly helpful to clinicians in two sets of circumstances: detecting late cases of seronegative syphilis and evaluating the biologic false-positive reactor. The latter (or the occurrence of a reactive serum reagin test in a patient not previously infected with T pallidum , but suffering from another entity, such as a collagen vascular disease) is a well-recognized phenomenon. The finding of a weakly reactive serum venereal disease research laboratory (VDRL) test in a patient on routine testing, but in whom on subsequent study a nonreactive TPI test is found, has come to be the serologic hallmark of the biologic false-positive reactor. However, false-negative TPI tests do occur. The development of a new specific blood test for syphilis, the fluorescent treponemal antibody absorbed (FTA-ABS) test,
A Review and Meta-Analysis of the Genetic Epidemiology of Anxiety Disorders
Authors: John M. Hettema, Michael C. Neale, Kenneth S. Kendler
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors conducted meta-analyses of data from family and twin studies of panic disorder, generalized anxiety disorder, phobias, and obsessive-compulsive disorder (OCD) to explore the roles of genetic and environmental factors in their etiology. METHOD: MEDLINE searches were performed to identify potential primary studies of these disorders. Data from studies that met inclusion criteria were incorporated into meta-analyses that estimated summary statistics of aggregate familial risk and heritability for each disorder. RESULTS: For family studies, odds ratios predicting association of illness in first-degree relatives with affection status of the proband (disorder present or absent) were homogeneous across studies for all disorders. The calculated summary odds ratios ranged from 4 to 6, depending on the disorder. Only for panic disorder and generalized anxiety disorder could the authors identify more than one large-scale twin study for meta-analysis. These yielded heritabilities of 0.43 for panic disorder and 0.32 for generalized anxiety disorder. For panic disorder, the remaining variance in liability could be attributed primarily to nonshared environment. For generalized anxiety disorder, this was true for men, but for women, a potentially significant role for common familial environment was also seen. CONCLUSIONS: Panic disorder, generalized anxiety disorder, phobias, and OCD all have significant familial aggregation. For panic disorder, generalized anxiety disorder, and probably phobias, genes largely explain this familial aggregation; the role of family environment in generalized anxiety disorder is uncertain. The role of nonshared environmental experience is significant, underscoring the importance of identifying putative environmental risk factors that predispose individuals to anxiety.
Evaluating the level of injury in English professional football using a risk based assessment process
Authors: S Drawer, C W Fuller
Journal: British Journal of Sports Medicine (2002)

To show how epidemiological data can be presented and analysed in frequency based and risk based formats and how risk based information can simplify management decisions on injury prevention strategies in professional football.The club physiotherapists at four English professional football clubs prospectively recorded players' injuries over the period November 1994 to May 1997. The nature, location, and mechanism of each injury and the specific numbers of days that players were unavailable to train or play as a result of injuries were recorded. The rates of injury were evaluated on a risk matrix using the number of days and the estimated costs of absence as measures of injury consequences.There was a significant difference in the time lost through injury as a function of injury severity (p<0.001). Slight and minor injuries accounted for 51% of all injuries but represented only 17% of the risk from injury, whereas major injuries accounted for only 12% of the number of injuries and 47% of the risk. Player to player contact injuries accounted for 39% of the risk of injury, and football specific activities accounted for 47% of the risk. The risks of acute injury in professional football were three orders of magnitude greater than those in the construction, manufacturing, and service sectors of industry.The risks associated with minor, moderate, and major acute injuries and osteoarthritis in lower limb joints of professional footballers were found to be unacceptable when evaluated against work based risk criteria used by the Health and Safety Executive. All stakeholders within professional football were shown to have an important contribution to make in reducing the overall level of risk to players through the provision of risk prevention strategies.
A Prescription for Drug Shortages
Authors: Barbara K Gehrett
Journal: JAMA (2012)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Hemostatic Disorders: Hemophilia and the Hemophilioid Diseases
Authors: K M Brinkhous, R D Langdell, R H Wagner
Journal: Annual Review of Medicine (1958)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting
Authors: L. J. Frigati, K. Kranzer, M. F. Cotton, H. S. Schaaf, C. J. Lombard, H. J. Zar
Journal: Thorax (2011)

Tuberculosis (TB) is a major cause of morbidity and mortality among children infected with HIV. Strategies to prevent TB in children include isoniazid preventive therapy (IPT) and antiretroviral therapy (ART). IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children.To investigate the combined effect of IPT and ART on TB risk in children infected with HIV.A cohort analysis was done within a prospective, double-blinded, placebo-controlled trial of isoniazid (INH) compared with placebo in children infected with HIV in Cape Town, South Africa, a high TB incidence setting. In May 2004 the placebo arm was terminated and all children were switched to INH. ART was not widely available at the start of the study, but children were started on ART following the establishment of the national ART program in 2004. Data were analysed using Cox proportional hazard regression.After adjusting for age, nutritional status and immunodeficiency at enrolment, INH alone, ART alone and INH combined with ART reduced the risk of TB disease by 0.22 (95% CI 0.09 to 0.53), 0.32 (95% CI 0.07 to 1.55) and 0.11 (95% CI 0.04 to 0.32) respectively. INH reduced the risk of TB disease in children on ART by 0.23 (95% CI 0.05 to 1.00).The finding that IPT may offer additional protection in children on ART has significant public health implications because this offers a possible strategy for reducing TB in children infected with HIV. Widespread use of this strategy will however require screening of children for active TB disease. Trial registration Trial registration-Clinical Trials NCT00330304.
Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial
Authors: Philippe Armand, Arnon Nagler, Edie A. Weller, Steven M. Devine, David E. Avigan, Yi-Bin Chen, Mark S. Kaminski, H. Kent Holland, Jane N. Winter, James R. Mason, Joseph W. Fay, David A. Rizzieri, Chitra M. Hosing, Edward D. Ball, Joseph P. Uberti, Hillard M. Lazarus, Markus Y. Mapara, Stephanie A. Gregory, John M. Timmerman, David Andorsky, Reuven Or, Edmund K. Waller, Rinat Rotem-Yehudar, Leo I. Gordon
Journal: Journal of Clinical Oncology (2013)

The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade.We conducted an international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT.Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab.This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease.
Sorafenib Is an Inhibitor of UGT1A1 but Is Metabolized by UGT1A9: Implications of Genetic Variants on Pharmacokinetics and Hyperbilirubinemia
Authors: Cody J. Peer, Tristan M. Sissung, AeRang Kim, Lokesh Jain, Sukyung Woo, Erin R. Gardner, C. Tyler Kirkland, Sarah M. Troutman, Bevin C. English, Emily D. Richardson, Joel Federspiel, David Venzon, William Dahut, Elise Kohn, Shivaani Kummar, Robert Yarchoan, Giuseppe Giaccone, Brigitte Widemann, William D. Figg
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Several case reports suggest sorafenib exposure and sorafenib-induced hyperbilirubinemia may be related to a (TA)5/6/7 repeat polymorphism in UGT1A1*28 (UGT, uridine glucuronosyl transferase). We hypothesized that sorafenib inhibits UGT1A1 and individuals carrying UGT1A1*28 and/or UGT1A9 variants experience greater sorafenib exposure and greater increase in sorafenib-induced plasma bilirubin concentration. Experimental Design: Inhibition of UGT1A1-mediated bilirubin glucuronidation by sorafenib was assessed in vitro. UGT1A1*28 and UGT1A9*3 genotypes were ascertained with fragment analysis or direct sequencing in 120 cancer patients receiving sorafenib on five different clinical trials. Total bilirubin measurements were collected in prostate cancer patients before receiving sorafenib (n = 41) and 19 to 30 days following treatment and were compared with UGT1A1*28 genotype. Results: Sorafenib exhibited mixed-mode inhibition of UGT1A1-mediated bilirubin glucuronidation (IC50 = 18 μmol/L; Ki = 11.7 μmol/L) in vitro. Five patients carrying UGT1A1*28/*28 (n = 4) or UGT1A9*3/*3 (n = 1) genotypes had first dose, dose-normalized areas under the sorafenib plasma concentration versus time curve (AUC) that were in the 93rd percentile, whereas three patients carrying UGT1A1*28/*28 had AUCs in the bottom quartile of all genotyped patients. The Drug Metabolizing Enzymes and Transporters genotyping platform was applied to DNA obtained from six patients, which revealed the ABCC2-24C&amp;gt;T genotype cosegregated with sorafenib AUC phenotype. Sorafenib exposure was related to plasma bilirubin increases in patients carrying 1 or 2 copies of UGT1A1*28 alleles (n = 12 and n = 5; R2 = 0.38 and R2 = 0.77; P = 0.032 and P = 0.051, respectively). UGT1A1*28 carriers showed two distinct phenotypes that could be explained by ABCC2-24C&amp;gt;T genotype and are more likely to experience plasma bilirubin increases following sorafenib if they had high sorafenib exposure. Conclusions: This pilot study indicates that genotype status of UGT1A1, UGT1A9, and ABCC2 and serum bilirubin concentration increases reflect abnormally high AUC in patients treated with sorafenib. Clin Cancer Res; 18(7); 2099–107. ©2012 AACR.
Paget's Disease of Bone (Osteitis Deformans): Symptomatic Lesions and Bone Scan
Authors: M. R. A. KHAIRI
Journal: Annals of Internal Medicine (1973)

The results of clinical, biochemical, radiological, and fluorine-18 bone scan observations on 22 symptomatic patients with Paget's disease are presented. "Sclerotic" lesions seen on radiographs were always asymptomatic. The involvement of ioints by Paget's disease was a major source of pain. A comparison of radiographic and bone scan findings showed that lesions seen by X ray and not by bone scan were always asymptomatic. In contrast, lesions seen by bone scan and not by X ray were symptomatic in most patients. We conclude that Na18F bone scan detects clinically active lesions more often and is an important adjunct to the assessment of skeletal involvement in patients with Paget's disease. These observations may have the bias inherent in selection of patients with "positive symptoms." The levels of serum alkaline phosphatase and urinary hydroxyproline showed highly significant correlation with percentage of skeletal involvement.
Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases
Authors: Rebecca S. Muraoka, Nancy Dumont, Christoph A. Ritter, Teresa C. Dugger, Dana M. Brantley, Jin Chen, Evangeline Easterly, L. Renee Roebuck, Sarah Ryan, Philip J. Gotwals, Victor Koteliansky, Carlos L. Arteaga
Journal: Journal of Clinical Investigation (2002)

TGF-betas are potent inhibitors of epithelial cell proliferation. However, in established carcinomas, autocrine/paracrine TGF-beta interactions can enhance tumor cell viability and progression. Thus, we studied the effect of a soluble Fc:TGF-beta type II receptor fusion protein (Fc:TbetaRII) on transgenic and transplantable models of breast cancer metastases. Systemic administration of Fc:TbetaRII did not alter primary mammary tumor latency in MMTV-Polyomavirus middle T antigen transgenic mice. However, Fc:TbetaRII increased apoptosis in primary tumors, while reducing tumor cell motility, intravasation, and lung metastases. These effects correlated with inhibition of Akt activity and FKHRL1 phosphorylation. Fc:TbetaRII also inhibited metastases from transplanted 4T1 and EMT-6 mammary tumors in syngeneic BALB/c mice. Tumor microvessel density in a mouse dorsal skin window chamber was unaffected by Fc:TbetaRII. Therefore, blockade of TGF-beta signaling may reduce tumor cell viability and migratory potential and represents a testable therapeutic approach against metastatic carcinomas.
Tailored cognitive-behavioural therapy and exercise training improves the physical fitness of patients with fibromyalgia
Authors: S. van Koulil, W. van Lankveld, F. W. Kraaimaat, T. van Helmond, A. Vedder, H. van Hoorn, A. R. T. Donders, L. Wirken, H. Cats, P. L. C. M. van Riel, A. W. M. Evers
Journal: Annals of the Rheumatic Diseases (2011)

Patients with fibromyalgia have diminished levels of physical fitness, which may lead to functional disability and exacerbating complaints. Multidisciplinary treatment comprising cognitive-behavioural therapy (CBT) and exercise training has been shown to be effective in improving physical fitness. However, due to the high drop-out rates and large variability in patients' functioning, it was proposed that a tailored treatment approach might yield more promising treatment outcomes.High-risk fibromyalgia patients were randomly assigned to a waiting list control group (WLC) or a treatment condition (TC), with the treatment consisting of 16 twice-weekly sessions of CBT and exercise training tailored to the patient's cognitive-behavioural pattern. Physical fitness was assessed with two physical tests before and 3 months after treatment and at corresponding intervals in the WLC. Treatment effects were evaluated using linear mixed models.The level of physical fitness had improved significantly in the TC compared with the WLC. Attrition rates were low, effect sizes large and reliable change indices indicated a clinically relevant improvement among the TC.A tailored multidisciplinary treatment approach for fibromyalgia consisting of CBT and exercise training is well tolerated, yields clinically relevant changes, and appears a promising approach to improve patients' physical fitness. ClinicalTrials.gov ID NCT00268606.
Does the Number of Lymph Nodes Removed in Extended D-2 Lymphadenectomy for Gastric Cancer Impact on Survival?
Authors: Chiappa Antonio, Bertani Emilio, Biffi Roberto, Venturino Marco, Fazio Nicola, Spada Francesca, Galdì Salvatore, Ferrari Carlo, Monfardini Lorenzo, Ravizza Davide, Maffini Fausto, Andreoni Bruno
Journal: Annals of Oncology (2014)
Prognostic Role of Lymphovascular Invasion in Patients with Urothelial Carcinoma of the Upper Urinary Tract: An International Validation Study
Authors: Giacomo Novara, Kazumasa Matsumoto, Wassim Kassouf, Thomas J. Walton, Hans-Martin Fritsche, Patrick J. Bastian, Juan I. Martínez-Salamanca, Christian Seitz, R. John Lemberger, Maximilian Burger, Assaad El-Hakim, Shiro Baba, Guido Martignoni, Amit Gupta, Pierre I. Karakiewicz, Vincenzo Ficarra, Shahrokh F. Shariat
Journal: European Urology (2010)
Imaging Biomarkers Predict Response to Anti-HER2 (ErbB2) Therapy in Preclinical Models of Breast Cancer
Authors: Chirayu Shah, Todd W. Miller, Shelby K. Wyatt, Eliot T. McKinley, Maria Graciela Olivares, Violeta Sanchez, Donald D. Nolting, Jason R. Buck, Ping Zhao, M. Sib Ansari, Ronald M. Baldwin, John C. Gore, Rachel Schiff, Carlos L. Arteaga, H. Charles Manning
Journal: Clinical Cancer Research (2009)

To evaluate noninvasive imaging methods as predictive biomarkers of response to trastuzumab in mouse models of HER2-overexpressing breast cancer. The correlation between tumor regression and molecular imaging of apoptosis, glucose metabolism, and cellular proliferation was evaluated longitudinally in responding and nonresponding tumor-bearing cohorts.Mammary tumors from MMTV/HER2 transgenic female mice were transplanted into syngeneic female mice. BT474 human breast carcinoma cell line xenografts were grown in athymic nude mice. Tumor cell apoptosis (NIR700-Annexin V accumulation), glucose metabolism [2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography ([18F]FDG-PET)], and proliferation [3'-[18F]fluoro-3'-deoxythymidine-PET ([18F]FLT-PET)] were evaluated throughout a biweekly trastuzumab regimen. Imaging metrics were validated by direct measurement of tumor size and immunohistochemical analysis of cleaved caspase-3, phosphorylated AKT, and Ki67.NIR700-Annexin V accumulated significantly in trastuzumab-treated MMTV/HER2 and BT474 tumors that ultimately regressed but not in nonresponding or vehicle-treated tumors. Uptake of [18F]FDG was not affected by trastuzumab treatment in MMTV/HER2 or BT474 tumors. [18F]FLT-PET imaging predicted trastuzumab response in BT474 tumors but not in MMTV/HER2 tumors, which exhibited modest uptake of [18F]FLT. Close agreement was observed between imaging metrics and immunohistochemical analysis.Molecular imaging of apoptosis accurately predicts trastuzumab-induced regression of HER2+ tumors and may warrant clinical exploration to predict early response to neoadjuvant trastuzumab. Trastuzumab does not seem to alter glucose metabolism substantially enough to afford [18F]FDG-PET significant predictive value in this setting. Although promising in one preclinical model, further studies are required to determine the overall value of [18F]FLT-PET as a biomarker of response to trastuzumab in HER2+ breast cancer.