tbuckley/cabot-search huggingface dataset:
The thymidylate synthase variable number of tandem repeats polymophism is predictive for response to 5-fluoracil in patients with colon cancer
Authors: Marleen Gosens, Elna Moerland, Valery Lemmens, Harm Rutten, Ivonne Tan-Go, Adriaan van den Brule
Journal: Clinical Cancer Research (2006)

B63   Introduction: Thymidylate synthase (TS) is an essential enzyme for cell proliferation and is the molecular target of 5 fluoracil (5-FU). Several TS gene polymorfisms have been described to affect cellular TS protein levels and can therefore modulate the efficiency of 5-FU based chemotherapy. In this study we investigated the contribution of two different polymorfisms of the TS gene on the response to 5-FU in patients with stage III colon cancer; the variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) of a G to C substitution in the 3R allele.Methods: 89 patients were genotyped for VNTR and SNP TS polymorfisms. Patients were categorized as low TS producers or high TS producers. In case SNP status was taken into account, low producers (TS-low + ) consisted of the 2R/2R, 2R/3RC and 3RC/3RC genotypes and high producers (TS-high + ) of 2R/3RG, 3RG/3RC and 3RG/3RG. Independently of the SNP status, the TS-low -  group consisted of the 2R/2R genotype only, all other genotypes were classified as TS-high - . Subsequently, these data were correlated with clinical outcome. Analysis of the effect of loss heterozygosity (LOH) and the correlation between TS genotype and immunohistochemical assessment, using the TS-106 monoclonal antibody, are currently under investigation.Results: In 61% of the 3R alleles a SNP was revealed. No significant differences in cancer-specific survival (CSS) or distant recurrence (DR) were found between the TS-low +  and TS-High +  groups. Classification based on the VNTR only resulted in a significant association with CSS (p=0.008) and DR (p=0.003) showing that the 2R homozygous genotype (n=27, 30%) had higher CSS rates and lower DR rates. In 9% of the patients homozygous for the 2R allel a distant recurrence occurred at 50 months compared to 44% of patients classified as TS-High - .Conclusions: The VNTR polymorphism of the TS gene significantly correlates with prognosis after 5-FU based chemotherapy in patients with colon cancer. Patients carrying two 2R alleles have favourable prognosis with respect to CSS and DR compared to patients having a 3R allele regardless the presence of a G to C substitution in this allele.
The lymphocyte transformation test for the diagnosis of Lyme borreliosis has currently not been shown to be clinically useful
Authors: R.B. Dessau, V. Fingerle, J. Gray, K.-P. Hunfeld, B. Jaulhac, O. Kahl, W. Kristoferitsch, G. Stanek, F. Strle
Journal: Clinical Microbiology and Infection (2014)
Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease
Authors: Jeffrey B. Schwimmer, Michael S. Middleton, Cynthia Behling, Kimberly P. Newton, Hannah I. Awai, Melissa N. Paiz, Jessica Lam, Jonathan C. Hooker, Gavin Hamilton, John Fontanesi, Claude B. Sirlin
Journal: Hepatology (2014)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI‐estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly ( P &lt; 0.01) correlated (0.725) with steatosis grade. The correlation of MRI‐estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly ( P &lt; 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly ( P &lt; 0.01) weaker in children with stage 2‐4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI‐estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. Conclusions : Advanced magnitude‐based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude‐based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child. (H epatology 2015;61:1887–1895)
Relation between Digoxin Arrhythmias and ABO Blood Groups
Journal: Circulation (1972)

In a series of 1,080 consecutively monitored patients who received digoxin, arrhythmias attributed to the drug were observed in 144 cases (13.3%). The proportion of arrhythmias among 510 patients with blood group O was 10%, while for the 570 patients of groups A, B, and AB (non-O), it was 16.3% ( P &lt; 0.002). The point estimate of relative risk for non-O patients relative to group O patients with 1.7, with 95% confidence limits of 1.2 and 2.5, and the increase in the risk was most prominent between the ages of 50 and 69 years.
Positional sleep apnoea syndrome: An underestimated pathology that needs to be explored
Authors: Jean Claude Meurice, Elise Antone, Jean Philippe Neau, Antoine Verbert, Joel Paquereau
Journal: European Respiratory Journal (2011)

Background:  Few epidemiological data have been published concerning the prevalence and significance of positional sleep apnoea syndrome (PSAS), and several different definitions have been used.   Aim of the study:  Our objective was to optimize the detection of PSAS and to evaluate its severity.   Methods:  We retrospectively analysed 1400 polysomnographic recordings performed during a 3 year-period. Recordings with less than 3 hours of total sleep time were excluded. PSAS was defined as pure when supine apnoea-hypopnoea index (AHI) >10/h with lateral AHI  10/h. We distinguished patients with normal global AHI  10/h.   Results:  1219 patients were included and were separated in 407 “Normal” (global and supine AHI  10 and lateral AHI 10, supine AHI 10, and 396 “mixed PSAS” with global AHI>10.  “Pure PSAS” patients were significantly younger and characterized by significant lower values for global AHI and body mass index (27.9±19.2/h; 28.3±5.4 kg/m 2 ) than “non PSAS” (36.6±23.3/h; 31.6±7.2 kg/m 2 ) and “mixed PSAS” (41.4±21.4; 30.5±7.0 kg/m 2 ). Minimal SpO 2  during sleep was significantly reduced in “Normal PSAS” when compared to “Normal”, and in “mixed PSAS” in comparison with “non PSAS” and “pure PSAS”.   Conclusion:  Our results point out the high prevalence of PSAS and its significant influence on nocturnal saturation, in normal patients as well as when associated with non positional SAS (“mixed PSAS”). PSAS could represent a transition before severe SAS occurrence that needs to be explored.
Detection of acute health status deterioration among COPD patients by monitoring COPD assessment test score
Authors: Chaicharn Pothirat, Waravut Chaiwong, Atkhun Limsukon, Attavuth Deesomchok, Chalerm Liewsrisakul, Chaiwat Bumroongkit
Journal: European Respiratory Journal (2011)

Background: The COPD Assessment Test (CAT) is a valid and simple questionaire to quantify health status of COPD in routine clinical practice;therefore, it should play a role for detecting acute health status deterioration during monitoring visit.

Objective: To evaluated the discriminative properties of the CAT scores for detecting worsening and exacerbation of COPD patients in Thailand

Methods: The CAT questionaire was administered to 123 stable COPD patients attended at our chest clinic. These patients were monitored every 1-3 month interval for detecting worsening and exacerbation by using CAT score, physician and patient global assessment.

Results: A total of 237 visits among 123 patients, age 70.9±8.5 years, FEV1=47.9±18.4% predicted were followed. The mean score change in stable COPD was 0.28 (95%CI=-0.06-0.97) and 0.45 (95%CI=-0.06-0.97) by patient and physician global assessment. CAT scores were significantly higher at the time of worsening and exacerbation;the mean score changes were 5.97 (95%CI=4.68-7.24) and 9.25 (95%CI=6.70-11.79), respectively. The area under the ROC curve of CAT score for detection of acute health status deterioration was 0.92 (95%CI=0.88-0.96) and the cut-off point score at ≥12 had sensitivity, specificity and accuracy=76.74%,64.43% and 66.67%, respectively.

Conclusions: The CAT score change during monitoring visits is useful for detecting acute health status deterioration
Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis: a single-centre prospective study
Authors: R.T. Woolf, S.L. West, M. Arenas-Hernandez, N. Hare, A.M. Peters van Ton, C.M. Lewis, A.M. Marinaki, J.N.W.N Barker, C.H. Smith
Journal: British Journal of Dermatology (2012)

Methotrexate is activated by the sequential addition of glutamic acid residues to form methotrexate polyglutamates (MTXPG(1-5)). MTXPG(1-5) inhibit enzymes of the folate-purine-pyrimidine pathways, and longer-chain MTXPG(3-5) species are more active.To determine the pattern of erythrocyte MTXPG(1-5) in patients initiated on oral methotrexate for psoriasis, and to investigate the potential utility of MTXPGs as markers of compliance and/or clinical response.This was a single-centre, prospective study of 55 adult patients with chronic plaque psoriasis initiated on weekly oral methotrexate. Erythrocyte MTXPG(1-5) concentrations were measured (at weeks 4, 8, 12, 24 and 52) using high-performance liquid chromatography. Methotrexate responders achieved ≥ 50% improvement in Psoriasis Area and Severity Index or physician's global score of 'clear'/'nearly clear' at 24 weeks.MTXPG levels were measured in 14-33 patients at each time point. All MTXPG(1-5) species were detected at week 4 of therapy. Steady state for long-chain MTXPG(3-5) and total MTXPG(1-5) was achieved by week 24. MTXPG(3) emerged as the predominant MTXPG species (from week 12 onwards) and reflected overall polyglutamate status (correlating strongly with MTXPG(2-5) , MTXPG(3-5) and MTXPG(4-5) ; R = 0·76-0·95, P < 1·55 × 10(-5)). Age, renal function and sex were not significant determinants of MTXPG(3) concentration. No significant association was identified between MTXPG and adverse events or responder status.This is the first study to demonstrate the prospective accumulation of MTXPG(1-5) in patients with psoriasis. The detection of MTXPGs early in therapy and the establishment of a steady state with continuous treatment may offer measuring of MTXPG as a test to monitor patient compliance with therapy. Larger studies are required to determine the role of MTXPG as a potential biomarker of clinical response.
Efficacy of behavioral versus triazolam treatment in persistent sleep- onset insomnia
Authors: H Y McClusky, J B Milby, P K Switzer, V Williams, V Wooten
Journal: American Journal of Psychiatry (1991)

This study compared differential effects of behavioral therapy and triazolam in a clinical population with sleep-onset insomnia. Triazolam was hypothesized to decrease sleep latency and frequency and duration of awakening, with some effects during the first night's administration. But at follow-up, sleep measures were predicted to return to baseline levels. Behavioral treatment was hypothesized to effect sleep after 2 or more weeks of training which persisted at follow-up.Thirty patients with average sleep latencies of 81.48 minutes, who reported chronic insomnia for an average of 2.6 years, were randomly assigned to one of two treatment groups: behavioral stimulus control/relaxation training and triazolam.Both treatments decreased sleep latency but differentially. Triazolam was effective immediately but maintained only some gains at follow-up. Behavioral treatment decreased sleep latency beginning the second week, when subjects expected no improvement, with gains maintained at follow-up. Comparisons showed that triazolam group latencies returned toward baseline, while behavioral group gains were maintained at follow-up.Triazolam treatment showed superior immediate treatment effects, while behavioral treatment showed superior treatment effects at follow-up, effects that accrued during the training period and differentially persisted at follow-up. One treatment strategy implied by these results would be to combine these two interventions concurrently. This would seem to use the immediate effects produced by the medication until the behavioral skills were learned, at which point medication would be terminated. This strategy could offer immediate relief and sustained effects at drug termination.
The Impact of Preoperative Thrombolysis on Long-Term Survival After Coronary Artery Bypass Grafting
Authors: Ioannis K. Toumpoulis, Constantine E. Anagnostopoulos, Demosthenes G. Katritsis, Joseph J. DeRose, Daniel G. Swistel
Journal: Circulation (2005)

Background— Coronary artery bypass grafting (CABG) is frequently used after thrombolytic therapy. However, there is little information regarding long-term survival in this setting. The purpose of the present study was to compare the long-term survival of patients subjected to CABG after thrombolysis to those without thrombolysis. Methods and Results— We studied 3760 consecutive patients with isolated CABG between 1992 and 2002. CABG patients without thrombolysis were compared with those who were treated with thrombolysis within 7 days before CABG. Groups were compared by Cox proportional hazard models and Kaplan-Meier survival plots. The propensity for thrombolysis was determined by logistic regression analysis, and each patient with thrombolysis was then matched to 5 patients without thrombolysis. One hundred ninety-six patients (5.2%) were treated with thrombolysis. Patients with thrombolysis were more likely to be male, younger, and with higher rates of unstable angina, emergency operation, recent or transmural myocardial infarction, preoperative intraaortic balloon pump, hemodynamic instability, shock, intravenous nitroglycerine, left-ventricular hypertrophy, sustained ventricular arrhythmia, and higher EuroSCORE. There were no differences in early outcome between matched groups, but the 5-year actuarial survival was higher in patients with thrombolysis (90.3±2.2% versus 78.5±1.6%; P =0.0007). After adjustment for all factors, the hazard ratio of long-term mortality for patients with thrombolysis was 0.54 (95% CI, 0.36 to 0.81; P =0.003) and, if deaths during the first 12 months were excluded, 0.46 (95% CI, 0.27 to 0.76; P =0.003). Conclusions— Patients subjected to CABG within 7 days after thrombolysis demonstrated increased long-term survival.
Derivation and Internal Validation of an Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis: A Consortium of Rheumatology Researchers of North America Registry Study
Authors: D. H. Solomon, J. Greenberg, J. R. Curtis, M. Liu, M. E. Farkouh, P. Tsao, J. M. Kremer, C. J. Etzel
Journal: Arthritis & Rheumatology (2015)

Objective Cardiovascular disease (CVD) is the leading cause of mortality in rheumatoid arthritis (RA), but CV risk prediction scores derived from the general population do not accurately predict CV risk in RA patients. The goal of these analyses was to develop and internally validate an expanded CV risk prediction score for RA. Methods Study participants were patients with RA and no known CVD from the Consortium of Rheumatology Researchers of North America registry. Two‐thirds of the cohort were used to derive the CV risk prediction score, and one‐third for internal validation. Traditional CV risk factors were included in the base Cox regression model, and RA‐related variables were assessed in an expanded model predicting confirmed CV events. Fit and utility of the expanded model were evaluated. Results The study cohort included 23,605 RA patients with 437 CV events over a median followup of 2.2 years. The RA variables found to be significant in the regression models and included in the expanded risk model were disease activity (Clinical Disease Activity Index &gt;10 versus ≤10), disability (modified Health Assessment Questionnaire disability index &gt;0.5 versus ≤0.5), daily prednisone use (any versus none), and disease duration (≥10 years versus &lt;10 years). The expanded model had good fit (Hosmer‐Lemeshow goodness of fit P = 0.94) and a lower Akaike's information criterion than the base model. In the internal validation cohort, the c‐statistic for model discrimination was significantly improved from the base model to the expanded model (from 0.7261 to 0.7609; P = 0.0104). The net reclassification index of CV risk in models using a 4‐category CV risk prediction tool was 40% (95% confidence interval 37–44%). Conclusion This newly developed, expanded risk score for CV outcomes in RA performs well and improves the classification of CV risk in comparison to a risk prediction score in which only traditional risk factors were included.
Abstract 16405: Prediction of Mortality in Congenital Heart Disease using Cardiopulmonary Exercise Testing: Development and External Validation of a Prognostic Score in 6,071 Patients
Authors: Robert M Radke, Gerhard-Paul Diller, Aleksander Kempny, Jan Muller, Helmut Baumgartner, Konstantinos Dimopoulos, Michael A Gatzoulis, Alfred Hager
Journal: Circulation (2013)

Background: Parameters of cardiopulmonary exercise testing (CPET) were identified as strong predictors of mortality in congenital heart disease (CHD). However, such prognostic CPET criteria have not been externally validated.

Methods and Results: 6,071 consecutive CHD patients (28±14 yrs) underwent CPET at one of two tertiary centers between 1999 and 2013. Peak oxygen consumption (peak VO2), anaerobic threshold, VE/VCO2 slope, and heart rate response were measured. During a median follow-up of 3.6 years, 206 patients died. All CPET parameters were strongly related to survival (p<0.0001) and showed good discriminative ability on ROC analysis (AUC 0.76 - 0.84, p<0.0001 for all). A logistic regression model predicting absolute probability of death within 3 years post CPET was constructed based on the 2,860 patients of one center serving as derivation sample. The model was started with age and sex, and additional variables were incrementally added until no further improvement in discriminative and reclassification ability was seen (judged by Akaike’s information criterion and Integrated Discrimination Improvement). The final model included peak VO2 and disease complexity in addition to demographics (c-index 0.85, p<0.0001). The model was well calibrated in the derivation sample, but substantially overestimated mortality in the external validation cohort (n=3,211, Figure - red line). Prediction was substantially improved by adjusting for annual mortality in the target population sample (green line).

Conclusions: Parameters of CPET are strong predictors of survival in CHD pts. The validity of CPET criteria developed at one CHD center may, however, be low when applied to external cohorts. This problem can be rectified by correcting for the annual mortality rate in the target population to adjust for different case mix and to avoid systematically misestimating mortality risks.

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Immunology indices in severe bronchial asthma with different levels of disease control in children
Authors: Marina Smolnikova, Svetlana Smirnova, Olga Tyutina, Sergey Tereshchenko
Journal: European Respiratory Journal (2013)

Aim: To study the main indices of immunity, peculiarities of cytokine regulation of cellular interactions in groups of children with severe/ moderate severe atopic bronchial asthma (BA) with different levels of disease control.  Methods: We have examined 2 groups of children – with controlled (n=50) and non-controlled (n=50) of severe/ moderate severe BA. Age was 10.9 ± 1.1 years. We have defined the indices of cellular link of immunity by fluorescent microscopy method using monoclonal antibodies to surface receptors. Humoral link indices and cytokines in blood had been defined by IFA.  Results: We have revealed peculiarities in BA controlled and non-controlled in the indices of common IgE (227.95±24.67 against 359.6±31.2, p=0.0057), IL-4 (8.090±1.03 against 9.23±2.6, p=0.0019), TNFα (21.52±2.60 against 37.39±7.09, p=0.001). True differences between the levels of IgA, IgM, IgG, IL-10, IL-2 had not been found. We have revealed distinctions between some indices of cellular link of immunity in controlled and non-controlled BA: CD3+-cells (1467±258.02 against 837.04±3.85, p=0.014), CD4+-cells (880±13.6 against 984±12.8, p=0.007).  Conclusion: There had been revealed laboratory markers of non-controlled atopic BA in children: higher level of IgE, IL-4, TNFα as well as higher number of CD3+-cells and the increase of sub-population of CD4+-cells as compared to the indices for controlled course of the disease.
HHV-8-related lymphoproliferative disorders during HIV infection: A monoinstitutional experience
Authors: C. Simonelli, R. Tedeschi, A. Gloghini, M. T. Bortolin, R. Talamini, R. Cinelli, E. Vaccher, P. de Paoli, A. Carbone, U. Tirelli
Journal: Journal of Clinical Oncology (2005)

6707 Background: HHV-8 has been established to be associated with: Multicentric Castleman Disease (MCD) and its related plasmoblastic lymphoma; Primary Effusion Lymphomas (PEL) and some cases of nodal lymphomas with anaplastic morphological characteristics (solid-HHV-8 L). Methods: The aim of our study was to describe the clinical features, outcome, immunological and virological characteristics and possible prognostic factors of HIV-infected patients (pts) affected by MCD, PEL and solid-HHV-8 L diagnosed and treated at the Aviano National Cancer Institute between April 1987 and June 2004. Results: Between April 1987 and June 2004 at the Aviano National Cancer Institute, 9 MCD, 13 PEL and only 3 solid-HHV-8 pts were diagnosed and treated out of a total number of 317 Non Hodgkin Lymphoma (NHL). The clinical outcome, the immunological and virological characteristics of the pts are described in the table. Conclusions: Our analysis demonstrated that MCD pts showed a significant shorter overall survival (OS) and a significant lower value of HHV-8 viraemia in comparison with solid-HHV-8 L pts (p=0.0002 and p=0.02). Solid-HHV-8 L pts had a significant shorter median OS and a lower HHV-8 viraemia in comparison with PEL pts (p=0.0003 and p=0.05); moreover they showed lower levels of HB, ALB and PTL in comparison with MCD and PEL pts. When the OS was stratified according to HHV-8 viraemia, we found that pts with HHV-8 viraemia >40000 cp/ml had a significant shorter OS in the overall lymphoproliferative disorders, but the multivariate analysis identified only the histology as a significant prognostic factor. HHV-8 viraemia seems to be associated with a shorter OS and solid-HHV-8 L, but further investigations are needed. Supported by ISS and AIRC grants. No significant financial relationships to disclose.