tbuckley/cabot-search huggingface dataset:
Phase III Trial of Four Cisplatin-Containing Doublet Combinations in Stage IVB, Recurrent, or Persistent Cervical Carcinoma: A Gynecologic Oncology Group Study
Authors: Bradley J. Monk, Michael W. Sill, D. Scott McMeekin, David E. Cohn, Lois M. Ramondetta, Cecelia H. Boardman, Jo Benda, David Cella
Journal: Journal of Clinical Oncology (2009)

Assess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and recurrent cervical carcinoma.Patients were randomly assigned to paclitaxel 135 mg/m(2) over 24 hours plus Cis 50 mg/m(2) day 2 every 3 weeks (PC, reference arm); vinorelbine 30 mg/m(2) days 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (VC); gemcitabine 1,000 mg/m(2) day 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (GC); or topotecan 0.75 mg/m(2) days 1, 2, and 3 plus Cis 50 mg/m(2) day 1 every 3 weeks (TC). Survival was the primary end point with a 33% improvement relative to PC considered important (85% power, alpha = 5%). Quality-of-life data were prospectively collected.A total of 513 patients were enrolled when a planned interim analysis recommended early closure for futility. The experimental-to-PC hazard ratios of death were 1.15 (95% CI, 0.79 to 1.67) for VC, 1.32 (95% CI, 0.91 to 1.92) for GC, and 1.26 (95% CI, 0.86 to 1.82) for TC. The hazard ratios for progression-free survival (PFS) were 1.36 (95% CI, 0.97 to 1.90) for VC, 1.39 (95% CI, 0.99 to 1.96) for GC, and 1.27 (95% CI, 0.90 to 1.78) for TC. Response rates (RRs) for PC, VC, GC, and TC were 29.1%, 25.9%, 22.3%, and 23.4%, respectively. The arms were comparable with respect to toxicity except for leucopenia, neutropenia, infection, and alopecia.VC, GC, and TC are not superior to PC in terms of overall survival (OS). However, the trend in RR, PFS, and OS favors PC. Differences in chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing therapy.
Rhythm control for atrial fibrillation: Non-channel antiarrhythmic drugs are en vogue
Authors: I VANGELDER
Journal: Cardiovascular Research (2007)

See article by Shiroshita-Takeshita et al. (pages 75–84) in this issue. 

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Independent risk factors for AF are chronic heart failure and hypertension [1]. The incidence and prevalence of AF increase with the severity of chronic heart failure. Although recent trials showed that rate control can be adopted as first choice therapy [2], rhythm control still is the primary goal. Whether this also holds for patients with chronic heart failure is at present unsettled, but obviously, these patients would benefit most from sinus rhythm since with restoration and maintenance of sinus rhythm, left ventricular function, exercise capacity and maximal oxygen consumption may improve. At present, the cornerstone for rhythm-control therapy is serial ion-channel antiarrhythmic drug treatment with or without cardioversion. This strategy, however, often fails, especially in patients with heart failure. One reason is that antiarrhythmic drug treatment for prevention of AF always starts after the first development of AF, whereas the substrate for AF already has (in part) been developed during sinus rhythm, before the first episode of AF ever. Another reason is, notably, that the currently available ion-channel antiarrhythmic drugs only influence action potential duration and conduction velocity, but do not affect the substrate for AF.

New types of non-channel antiarrhythmic drugs may influence the development of the substrate. These drugs include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers, hydroxylmethylglutaryl CoA reductase inhibitors (statins), aldosterone antagonists and N-3 polyunsaturated fatty acids. Mechanisms by which this ‘upstream therapy’ or non-channel antiarrhythmic drugs may prevent or reduce … 

*Tel.: +31 (0)50 3611327; fax: +31 (0)50 3614391. Email address: I.C.van.Gelder{at}thorax.umcg.nl
The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics
Authors: Levi G Ledgerwood, Girdhari Lal, Nan Zhang, Alexandre Garin, Steven J Esses, Florent Ginhoux, Miriam Merad, Helene Peche, Sergio A Lira, Yaozhong Ding, Yu Yang, Xingxuan He, Edward H Schuchman, Maria L Allende, Jordi C Ochando, Jonathan S Bromberg
Journal: Nature Immunology (2007)
Quantitative assessment of postural stability using accelerometer and gyroscopic data during balance error scoring system
Authors: Jay L Alberts, Joshua R Hirsch, Richard Figler, Andrew N Russman, Robert Gray, Susan M Linder
Journal: British Journal of Sports Medicine (2013)

Objective The aim of this study was to validate a portable method of objectively quantifying postural stability using accelerometer and gyroscopic data from the iPad2 during BESS. Design Participants completed the six 20 s BESS conditions. BESS errors were recorded by trained evaluators. Linear and angular acceleration were simultaneously collected via the iPad2 accelerometer and gyroscope. Setting Academic medical center. Participants Fifty healthy participants aged 14–25 with no concussion in previous 6 months. Main Outcome Measurements The primary outcome measures were evaluator-reported errors and natural-logarithmic volume of a 3D ellipsoid (iVE) encompassing 95% of postural sway data. The iVE characterises movement along anterior–posterior, medial-lateral, and trunk-rotational movement axes. It was hypothesised that iVE would provide a more sensitive assessment of postural stability than traditional BESS error scoring. Results For the two double-leg stance conditions, BESS error scores were nearly identical, as few participants made errors. However, iVE data indicated a significant difference in stability between these conditions, as iVE for double-leg stance on firm surface was 0.3±0.16 s 3 while iVE on foam was 3.4±0.16 s 3 . Conclusions The objective data gathered using a consumer electronics device provides a reliable and valid assessment of postural stability and increases the sensitivity of the BESS. Accordingly, it is recommended that all six BESS conditions be completed in order to fulfill the current Zurich recommendation of a comprehensive balance assessment. We are currently using the ‘C3 App’ and BESS in the collection of baseline data in 12 000 high school and college athletes.
Experience of surgical treatment of massive purulent-destructive processes of the lungs and pleura
Authors: Stanislav Skryabin
Journal: European Respiratory Journal (2012)

Given the conditions of the Far North and the specificity of the social status of some patients, we have extensive experience in the surgical treatment of massive, widespread purulent-destructive processes. Despite the possibility of treating this disease patients conservatively, performing minimally invasive procedures, we concluded that it remains relevant surgical radical intervention - lung resection, removal of empyema cavity, to prevent chronicity and recurrence of the process. We have expirence treatment 679 patients: 310 conservatively, 369 surgical method of treatment.The main indications for radical surgery have been ineffective conservative therapy and the progression of the process, the recurrence of a chronic process, initially massive processes, life-saving operation: bleeding, a large pulmonary pleural fistula, the threat of sepsis(big abscess, gangrene  and empyema). We are get almost pations fit for the operation (conservative therapy). We performed 380 operations: 151-lobectomy, 15-bilobectomy, 64 atipical resections, 18- segmentectomy, 67- pneumonectomy, 40- decortications and elimination of empyema cavity without resections, 16- VATS decortications, 9- reamputations stump of bronchus. We have good results after operations: only 5 pations died (1,3%), 48 - complications (13%) (13 of them - inconsistence of stump of bronchus),360 pations (97.6%) - after radical intervations recovered.
Relation between laboratory test results and histological hepatitis activity in individuals positive for hepatitis B surface antigen and antibodies to hepatitis B e antigen
Authors: F ter Borg, FJW ten Kate, HTM Cuypers, A Leentvaar-Kuijpers, J Oosting, PME Wertheim-van Dillen, P Honkoop, MC Rasch, RA de Man, J van Hattum, RAFM Chamuleau, HW Reesink, EA Jones
Journal: The Lancet (1998)
Psoriasis and New-Onset Diabetes
Authors: Usman Khalid, Peter Riis Hansen, Gunnar Hilmar Gislason, Jesper Lindhardsen, Søren Lund Kristensen, Signe Abitz Winther, Lone Skov, Christian Torp-Pedersen, Ole Ahlehoff
Journal: Diabetes Care (2013)

Psoriasis is associated with increased risk of cardiovascular events and increased prevalence of cardiovascular risk factors. Diabetes mellitus (DM) is a major contributor to cardiovascular morbidity and mortality that may be associated with psoriasis, but conflicting results have been presented and nationwide data on the risk of new-onset DM in patients with psoriasis have not been reported.The study comprised a Danish population ≥ 10 years of age on 1 January 1997 who were followed until new-onset DM, death, or 31 December 2009. Information on comorbidity, concomitant medication, and socioeconomic status was linked on an individual level. The primary study end point was DM requiring pharmacotherapy. Incidence rates for the development of DM events per 1,000 observational years were calculated and adjusted. Incidence rate ratios (IRRs) were estimated by Poisson regression.A total of 4,614,807 subjects were eligible for analysis, with a maximum follow-up of 13 years. In the study period, 52,613 patients with psoriasis, including 6,784 patients with severe psoriasis, were identified. The overall incidence rates for new-onset DM were 3.67 (CI 3.65-3.69), 6.93 (6.63-7.25), and 9.65 (8.68-10.73) for the reference population, mild psoriasis, and severe psoriasis, respectively. Compared with the reference population, the IRR of new-onset DM was increased in all patients with psoriasis, i.e., IRR 1.49 (CI 1.43-1.56) and 2.13 (1.91-2.37) for those with mild and severe psoriasis.In this nationwide cohort, psoriasis was associated with increased incidence rates of new-onset DM. The association remained statistically significant after adjustment for confounding factors.
Positional oximetry to screen for pulmonary arteriovenous malformations in HHT: Table 1
Authors: Susan Carpenter, Janina Josepovici, Giuseppe Latino, Felix Ratjen
Journal: Thorax (2014)

Orthodeoxia has been described in patients with hereditary haemorrhagic telangiectasia (HHT) and pulmonary arteriovenous malformations (PAVM), but its usefulness in screening children for PAVMs is unknown. We show here that while oximetry is overall lower in children with significant PAVMs, supine and upright oximetry is of no additional diagnostic value indicating that positional oximetry is not a useful screening test for PAVMs.
Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome
Authors: C.M. Legendre, C. Licht, P. Muus, L.A. Greenbaum, S. Babu, C. Bedrosian, C. Bingham, D.J. Cohen, Y. Delmas, K. Douglas, F. Eitner, T. Feldkamp, D. Fouque, R.R. Furman, O. Gaber, M. Herthelius, M. Hourmant, D. Karpman, Y. Lebranchu, C. Mariat, J. Menne, B. Moulin, J. Nürnberger, M. Ogawa, G. Remuzzi, T. Richard, R. Sberro-Soussan, B. Severino, N.S. Sheerin, A. Trivelli, L.B. Zimmerhackl, T. Goodship, C. Loirat
Journal: New England Journal of Medicine (2013)

Atypical hemolytic–uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease.
Insights into the Abnormalities of Chronic Renal Disease Attributed to Malnutrition
Authors: William E. Mitch
Journal: Journal of the American Society of Nephrology (2002)

Low values of serum proteins and loss of lean body mass are commonly found in patients with chronic renal insufficiency (CRI) and especially in dialysis patients. These abnormalities have been attributed to malnutrition (i.e., an inadequate diet), but available evidence indicates that this is not the principal cause. In contrast, there is persuasive evidence that secondary factors associated with the CRI condition cause abnormalities in protein turnover and ultimately result in low serum protein levels and loss of lean body mass. Recent reports have identified some factors that could interfere with the control of protein turnover in CRI patients, including acidosis, inflammation, and/or resistance to anabolic hormones. Each of these stimulates protein breakdown in muscle and activates a common proteolytic pathway, the ubiquitin-proteasome pathway. Moreover, acidosis or inflammation suppress hepatic albumin synthesis. Understanding the biochemical mechanisms that regulate the ubiquitin-proteasome and other catabolic pathways are required to identify new strategies for preventing protein deficits that are associated with CRI.
Screening for Vitamin D Deficiency: A Systematic Review for the U.S. Preventive Services Task Force
Authors: Erin S. LeBlanc, Bernadette Zakher, Monica Daeges, Miranda Pappas, Roger Chou
Journal: Annals of Internal Medicine (2014)

Vitamin D deficiency has been associated with adverse health outcomes.To systematically review benefits and harms of vitamin D screening in asymptomatic adults.Ovid MEDLINE (through the third week of August 2014), Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews.Randomized trials of screening for and treatment of vitamin D deficiency and case-control studies nested within the Women's Health Initiative.One investigator abstracted data, a second reviewed data for accuracy, and 2 investigators independently assessed study quality using predefined criteria.No study examined the effects of vitamin D screening versus no screening on clinical outcomes. Vitamin D treatment was associated with decreased mortality versus placebo or no treatment (11 studies; risk ratio [RR], 0.83 [95% CI, 0.70 to 0.99]), although benefits were no longer seen after trials of institutionalized persons were excluded (8 studies; RR, 0.93 [CI, 0.73 to 1.18]). Vitamin D treatment was associated with possible decreased risk for having at least 1 fall (5 studies; RR, 0.84 [CI, 0.69 to 1.02]) and falls per person (5 studies; incidence rate ratio, 0.66 [CI, 0.50 to 0.88]) but not fractures (5 studies; RR, 0.98 [CI, 0.82 to 1.16]). Vitamin D treatment was not associated with a statistically significant increased risk for serious adverse events (RR, 1.17 [CI, 0.74 to 1.84]).Variability across studies in 25-hydroxyvitamin D assays and baseline levels, treatment doses, use of calcium, and duration of follow-up.Treatment of vitamin D deficiency in asymptomatic persons might reduce mortality risk in institutionalized elderly persons and risk for falls but not fractures.Agency for Healthcare Research and Quality.
Human Telomerase Reverse Transcriptase Gene Expression and the Surgical Management of Suspicious Thyroid Tumors
Authors: Christopher B. Umbricht, George T. Conrad, Douglas P. Clark, William H. Westra, Dañelle C. Smith, Marianna Zahurak, Motoyasu Saji, Robert C. Smallridge, Steven Goodman, Martha A. Zeiger
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Patients with a preoperative cytologic diagnosis of a suspicious thyroid nodule present a therapeutic dilemma because surgery differs for benign and malignant lesions. To address this issue, several molecular markers, including human telomerase reverse transcriptase (TERT), have been tested as markers of thyroid cancer. Because most studies select cases falling into well-defined categories to test new markers, they may overestimate their discriminatory power when applied to samples that are difficult to classify. Fine-needle aspirates (FNAs) of the thyroid with indeterminate cytology are an example of such cases. Experimental Design: We examined whether assessing TERT mRNA by reverse transcription-PCR could have improved the surgical management in a cohort of 100 patients undergoing thyroidectomy for indeterminate FNA results. Results: Ninety percent of 48 cancers were TERT positive, as were 35% of 52 benign lesions. When 10 cases with concomitant lymphocytic thyroiditis were excluded, the overall sensitivity of TERT was 91% (95% confidence interval, 80–98%) and specificity was 79% (64–90%). No clinical or tumor variable contributed to the predictive ability of TERT except for tumor size, which added only marginally. Basing the surgical approach on the TERT assay alone would have reduced lobectomies performed for malignant disease from 11 to 4 cases and reduced total thyroidectomies for benign lesions from to 15 to 9, an overall 50% reduction in suboptimal treatment. Conclusions: The overall performance of preoperative differential diagnosis for thyroid tumors with indeterminate FNA results can be substantially improved by the inclusion of molecular markers such as TERT.
Genome-based prediction of common diseases: methodological considerations for future research
Authors: A Cecile JW Janssens, Cornelia M van Duijn
Journal: Genome Medicine (2009)

The translation of emerging genomic knowledge into public health and clinical care is one of the major challenges for the coming decades. At the moment, genome-based prediction of common diseases, such as type 2 diabetes, coronary heart disease and cancer, is still not informative. Our understanding of the genetic basis of multifactorial diseases is improving, but the currently identified susceptibility variants contribute only marginally to the development of disease. At the same time, an increasing number of companies are offering personalized lifestyle and health recommendations on the basis of individual genetic profiles. This discrepancy between the limited predictive value and the commercial availability of genetic profiles highlights the need for a critical appraisal of the usefulness of genome-based applications in clinical and public health care. Anticipating the discovery of a large number of genetic variants in the near future, we need to prepare a framework for the design and analysis of studies aiming to evaluate the clinical validity and utility of genetic tests. In this article, we review recent studies on the predictive value of genetic profiling from a methodological perspective and address issues around the choice of the study population, the construction of genetic profiles, the measurement of the predictive value, calibration and validation of prediction models, and assessment of clinical utility. Careful consideration of these issues will contribute to the knowledge base that is needed to identify useful genome-based applications for implementation in clinical and public health practice.
Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function.
Authors: T Goodman, L Lefrancois
Journal: The Journal of Experimental Medicine (1989)

The function and structure of the TCR proteins of intraepithelial lymphocytes (IEL) were examined using a panel of mAbs specific for TCR-gamma/delta. Three subsets of TCR-gamma/delta+ IEL could be detected with five mAbs, termed GL1-GL5. The mAbs were able to trigger lysis via crosslinking of the IEL TCR and all of the subsets were constitutively cytolytic. Immunoprecipitation of IEL TCR proteins revealed that the GL2 mAb reacted only with gamma, delta heterodimers containing high Mr delta chains, while the other mAbs precipitated all of the observed gamma and delta proteins. Two-color fluorescence analysis showed that the GL2+ subset was contained within the larger GL1+ subset. The GL3 and GL4 mAbs appear to be specific for all TCR-gamma/delta while GL2 was V delta 4 specific. Analysis of IEL for TCR-alpha/beta expression demonstrated that approximately 20% of B6 IEL were TCR-alpha/beta+. Interestingly, this population of IEL contained Thy-1- and CT1+ cells, indicating that the unique phenotype of IEL was not restricted to TCR-gamma/delta+ cells. Moreover, the TCR-alpha/beta+ IEL were also constitutively cytolytic, suggesting that the intestinal milieu was controlling the functional programming of IEL regardless of TCR type. The mAbs reported here as well as the ability to exploit the distinct phenotype of IEL should prove useful in determining the function of IEL and the TCR-gamma/delta.
Reduced Cisplatin Sensitivity of Head and Neck Squamous Cell Carcinoma Cell Lines Correlates with Mutations Affecting the COOH-Terminal Nuclear Localization Signal of p53
Authors: Robert Mandic, Chantal J. Schamberger, Julia F. Müller, Matthias Geyer, Li Zhu, Thomas E. Carey, Reidar Grénman, Anja A. Dünne, Jochen A. Werner
Journal: Clinical Cancer Research (2005)

Head and neck squamous cell carcinomas (HNSCC) are the most frequent malignancies of the upper aerodigestive tract. Cisplatin resistance is a major problem in the treatment of a large number of HNSCC cancer patients. In this study, nine randomly selected HNSCC cell lines were investigated regarding expression, presence of mutations, nucleocytoplasmic distribution of p53, and sensitivity to cisplatin.Protein expression was evaluated by Western blot analysis. The whole open reading frame of p53 was determined by reverse transcription-PCR sequencing. Nucleocytoplasmic distribution was evaluated by confocal laser scanning microscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay was used to test for cisplatin sensitivity.p53 mutations were found in all nine investigated HNSCC cell lines. Nuclear p53 signal was detected in six cell lines, whereas three cell lines exhibited total loss of nuclear p53 signal. Nuclear signal depended on the presence or absence of the COOH-terminal nuclear localization signal in p53. Cisplatin sensitivity was highly reduced in the group with loss of nuclear p53 signal compared with those with detectable nuclear signal. Transfection of wild-type and mutant p53 into a rat embryonic cell system showed highly reduced activity of the nuclear localization signal mutant p53 protein.Taken together, these data suggest that "loss of nuclear p53 signal" correlates with cisplatin resistance in HNSCC. If these results can be validated on a larger number of tumor samples, including fresh tumor tissues, it potentially could help in sparing a subgroup of HNSCC patients the side effects associated with unnecessary chemotherapy by identifying cisplatin nonresponders before chemotherapy induction.