tbuckley/cabot-search huggingface dataset:
Real-time optical diagnosis for diminutive colorectal polyps using narrow-band imaging: the VALID randomised clinical trial
Authors: Tonya Kaltenbach, Amit Rastogi, Robert V Rouse, Kenneth R McQuaid, Tohru Sato, Ajay Bansal, Jon C Kosek, Roy Soetikno
Journal: Gut (2014)

<h3>Background</h3> Diminutive (≤5 mm) colorectal polyps are common, and overwhelmingly benign. Routinely, after polypectomy, they are examined pathologically to determine the surveillance intervals. Advances in equipment and techniques, such as narrow-band imaging (NBI) colonoscopy, now permit reliable real-time optical diagnosis. <h3>Methods</h3> We conducted a randomised single-masked study involving three institutions to determine whether optical diagnosis of diminutive colorectal polyps meets clinical practice standards and reduces the need for histopathology. We randomly assigned eligible patients undergoing routine high-definition colonoscopy to optical diagnosis using near focus versus standard view, using computer-generated block sequence. By validated criteria, we rendered an optical diagnosis and a confidence level (high vs low) for all polyps, using NBI. Our primary endpoint was the number of accurate high-confidence optical diagnoses compared with central blinded pathology in the two groups. We analysed data using intention to treat. <h3>Findings</h3> We enrolled 558 subjects, and randomly assigned 281 to near focus and 277 to standard view optical diagnosis. We detected 1309 predominantly diminutive (74.5%) and neoplastic (60.0%) polyps. Endoscopists were significantly more likely, OR 2.2 (95% CI 1.6 to 3.0, p&lt;0.0001), to make a high-confidence optical diagnosis with near focus (85.1%) than standard (72.6%) view. High-confidence diagnoses had 96.4% and 92.0% negative predictive value, respectively. Of all polyps, 75.3% (95% CI71.3% to 78.9%) had a high-confidence accurate prediction using near focus, compared with 63.1% (95% CI 58.5% to 67.6%) using standard view. Optical versus histopathological diagnosis showed excellent agreement between the surveillance intervals, 93.5% in near focus and 92.2% in standard view. The median diagnosis time was 14 s. <h3>Conclusions</h3> Real-time optical diagnosis using NBI colonoscopy may replace the pathology diagnosis for the majority of diminutive colorectal polyps. Using colonoscopy with near focus view increases the confidence level of the optical diagnosis. Optical diagnosis would be a paradigm shift in clinical practice of colonoscopy for colorectal cancer screening. <h3>Trial registration number</h3> ClinicalTrials.gov Identifier: NCT01288833.
Etanercept normalises left ventricular mass in patients with rheumatoid arthritis
Authors: Claire Immediato Daïen, Pierre Fesler, Guilhem du Cailar, Vincent Daïen, Thibault Mura, Anne-Marie Dupuy, Jean-Paul Cristol, Jean Ribstein, Bernard Combe, Jacques Morel
Journal: Annals of the Rheumatic Diseases (2012)

Background Cardiovascular mortality is increased in patients with rheumatoid arthritis (RA). RA is associated with an increased left ventricular mass index (LVMI), a strong marker of cardiovascular mortality, and vessel abnormalities. Experimental studies have suggested that tumour necrosis factor α (TNFα) may induce LV hypertrophy. Objective To study the effect of medium-term (3- and 6-months) treatment with the TNFα inhibitor etanercept (ETN) and synthetic disease-modifying antirheumatic drugs (sDMARDs) on LV morphological features and arterial stiffness in patients with RA. Methods Consecutive female patients with active RA requiring treatment with ETN (n=28) or sDMARDs (n=20) were included. Clinical and biological monitoring, echocardiography and pulse wave velocity (PWV) assessment were performed at inclusion and at 3 and 6 months after the start of treatment. Paired t tests and multivariate linear regression analysis were used. Results Mean LVMI tended to be higher at baseline in the ETN group than in the sDMARD group (96.5±19.8 vs 84.3±26.8 g/m 2 ; p=0.11 for the ETN and sDMARD groups, respectively). In patients with ETN treatment, mean LVMI was significantly decreased at 3 and 6 months (−6.3±7.6 and −14.2±9.3 g/m 2 ; p&lt;0.001), with no change from baseline for patients with sDMARD treatment (−2.2±10.9 and −2.7±10.2 g/m 2 , respectively). Blood pressure (BP) and aortic PWV were not changed by either treatment. Conclusions ETN induced a significant decrease in LVMI with medium-term treatment with no change in BP or PWV. TNFα may be an important factor of LV hypertrophy, which may explain the benefit of TNF inhibitors on cardiovascular morbidity and mortality in RA. These results need to be confirmed by larger studies and with other TNF inhibitors.
Sensitisation of the IFN -Stat1-signalling-pathway in rheumatoid arthritis monocytes
Authors: T. Karonitsch, K. Dalwigk, C. W. Steiner, S. Bluml, G. Steiner, H. Kiener, J. S. Smolen, M. Aringer
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Both, type I interferons (IFNα, IFNβ) and the type II IFN IFNγ signal via phosphorylating Stat1. Immunohistochemistry and gene expression signatures of synovial tissues suggest an activated IFN-Stat1-signalling-pathway in rheumatoid arthritis (RA). This study was performed to determine the activity of the IFN-Stat1-signalling-pathway in RA peripheral blood monocytes. <h3>Methods</h3> Flourocytometry or qPCR was used to measure the expression of Stat1, phospho-Stat1 (pStat1) and IFN-inducible genes, such as IP-10 and OAS in RA and healthy (HC) peripheral blood monocytes. To examine the significance of Stat1 and of the IFNγ-inducible chemokine MIG (monokine induced by IFNγ) were measured using fluorocytometry. <h3>Results</h3> Levels of Stat1 and pStat1 protein expression were significantly increased in RA monocytes when compared to HC (mfi 14.7±8.1 vs 8.0±3.9, p=0.0002; mfi 5.1±1.3 vs 3.2±0.7, p&lt;0.0001, respectively). Stat1 mfi in RA monocytes correlated with RA disease activity such as DAS28 (Disease Activity Score; r=0.47, p&lt;0.008) or CDAI (Clinical Disease Activity Index; r=0.51, p&lt;0.003). Further, Stat1 mRNA expression in RA monocytes correlated with the expression of other IFN target genes, such as IP-10 or OAS. RA monocytes demonstrated a considerably higher increase in pStat1 and MIG levels upon IFNγ stimulation when compared to monocytes from HC (pStat1: +2.8±1.8 vs +1.5±1.1, p&lt;0.03; MIG: +565±351 vs +303±253, p&lt;0.05), indicating that RA monocytes are more sensitive to IFNγ stimulation. <h3>Conclusions</h3> Consistent with a systemic proinflammatory activity of RA monocytes, these studies suggest activation of the IFNγ-Stat1-signalling pathway in RA.
Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-01
Authors: Francesco d'Amore, Thomas Relander, Grete F. Lauritzsen, Esa Jantunen, Hans Hagberg, Harald Anderson, Harald Holte, Anders Österborg, Mats Merup, Peter Brown, Outi Kuittinen, Martin Erlanson, Bjørn Østenstad, Unn-Merete Fagerli, Ole V. Gadeberg, Christer Sundström, Jan Delabie, Elisabeth Ralfkiaer, Martine Vornanen, Helle E. Toldbod
Journal: Journal of Clinical Oncology (2012)

Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large prospective phase II study in untreated systemic PTCL. This is the final report, with a 5-year median follow-up, of the NLG-T-01 study.Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were included. Anaplastic lymphoma kinase (ALK) -positive anaplastic large-cell lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was administered (in patients age > 60 years, etoposide was omitted). If in complete or partial remission, patients proceeded to consolidation with HDT/ASCT.Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The majority presented with advanced-stage disease, B symptoms, and elevated serum lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete remission at 3 months post-transplantation. Early failures occurred in 26%. Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83 patients were alive. Consolidated 5-year overall and progression-free survival (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively. Best results were obtained in ALK-negative ALCL.Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL.
THE STORY OF MEDICINE
Authors: E. A. Underwood
Journal: BMJ (1955)

Ninety-four patients receiving immunosuppressive therapy with azathioprine and prednisone after human cadaver kidney transplantation developed urinary tract infections and were treated with co-trimoxazole or another antibiotic in a controlled randomized prospective trial. The incidence of leucopenia in the group treated with co-trimoxazole (10·6%) was not significantly different from that in the group treated with other antibiotics (23·6%). Leucopenia when it occurred did so soon after transplantation at a time when the function of the renal transplant was poor in relation to the dosage of azathioprine given. In all cases the temporary withdrawal of azathioprine relieved the leucopenia despite continuation of the co-trimoxazole treatment. This study did not provide any evidence that co-trimoxazole plus azathioprine was a more potent cause of leucopenia than azathioprine alone.
Increased expression of CD40 ligand (CD154) on CD4+ T cells as a marker of disease activity in rheumatoid arthritis
Authors: B. Berner
Journal: Annals of the Rheumatic Diseases (2000)

The interaction between the activation induced surface glycoprotein CD40L (ligand) (CD154) on CD4+ T cells and its receptor CD40, which is expressed on various cell types, plays a crucial part in numerous cell mediated and humoral immune reactions that may be of pathogenetic importance in rheumatoid arthritis (RA). To further evaluate the pathogenetic role of CD40L in RA, expression of CD40L and various other T cell activation antigens as well as costimulatory molecules was investigated on CD4+ T cells in RA by flow cytometry.Two colour flow cytometry was used to determine the percentage of CD4+ T cells expressing CD40L, CD69, CD25, HLA-DR, CD39, CD27 and CD28 in peripheral blood (PB) of 62 RA patients in comparison to 20 healthy controls (HC). Disease activity was assessed by clinical, laboratory and radiological examination. Status of clinical remission of RA was evaluated according to the ACR preliminary criteria for complete clinical remission of RA.CD40L was expressed on > 10% of CD4+ T cells in 29% of RA patients thus defining a CD40L(high+) patient group. Disease activity as estimated by C reactive protein, rheumatoid factor and status of clinical remission of disease (p = 0.049) was higher in this subgroup than in the RA CD40L(low+) group. Expression of CD69, CD25, and HLA-DR was significantly increased in both RA patient groups in comparison with HC. However, the percentage of CD39+ CD4+ T cells was increased only in the RA CD40L(high+) subgroup (versus HC p = 0.019, versus RA CD40L(low+) p = 0.044). Furthermore, expression of CD40L and CD39 on CD4+ T cells correlated positively as estimated by Spearman rank correlation (p<0.001). The percentage of CD4+ T cells lacking the costimulatory molecules CD27 (p = 0.002) and CD28 (p = 0.026) was increased in RA CD40L(low+) patients in comparison with HC.These data suggest that increased expression of CD40L on CD4+ T cells in RA indicates prolonged and increased activation of CD4+ T lymphocytes and is associated with active disease and possibly an unfavourable prognosis. Whether this phenotypically defined RA CD40L(high+) subgroup will preferentially respond to an anti-CD40L antibody treatment remains to be elucidated.
Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and improved retention in and therapy of articular joints
Authors: Frédéric Schmitt, Lucienne Lagopoulos, Peter Käuper, Nathanaël Rossi, Nathalie Busso, Jérôme Barge, Georges Wagnières, Carsten Laue, Christine Wandrey, Lucienne Juillerat-Jeanneret
Journal: Journal of Controlled Release (2010)
Actual Causes of Death in the United States
Authors: J. Michael McGinnis
Journal: JAMA (1993)

<h3>Objective.</h3> —To identify and quantify the major external (nongenetic) factors that contribute to death in the United States. <h3>Data Sources.</h3> —Articles published between 1977 and 1993 were identified through MEDLINE searches, reference citations, and expert consultation. Government reports and compilations of vital statistics and surveillance data were also obtained. <h3>Study Selection.</h3> —Sources selected were those that were often cited and those that indicated a quantitative assessment of the relative contributions of various factors to mortality and morbidity. <h3>Data Extraction.</h3> —Data used were those for which specific methodological assumptions were stated. A table quantifying the contributions of leading factors was constructed using actual counts, generally accepted estimates, and calculated estimates that were developed by summing various individual estimates and correcting to avoid double counting. For the factors of greatest complexity and uncertainty (diet and activity patterns and toxic agents), a conservative approach was taken by choosing the lower boundaries of the various estimates. <h3>Data Synthesis.</h3> —The most prominent contributors to mortality in the United States in 1990 were tobacco (an estimated 400000 deaths), diet and activity patterns (300 000), alcohol (100 000), microbial agents (90 000), toxic agents (60 000), firearms (35 000), sexual behavior (30 000), motor vehicles (25 000), and illicit use of drugs (20 000). Socioeconomic status and access to medical care are also important contributors, but difficult to quantify independent of the other factors cited. Because the studies reviewed used different approaches to derive estimates, the stated numbers should be viewed as first approximations. <h3>Conclusions.</h3> —Approximately half of all deaths that occurred in 1990 could be attributed to the factors identified. Although no attempt was made to further quantify the impact of these factors on morbidity and quality of life, the public health burden they impose is considerable and offers guidance for shaping health policy priorities. (<i>JAMA</i>. 1993;270:2207-2212)
Addition of Bevacizumab to Fluorouracil-Based First-Line Treatment of Metastatic Colorectal Cancer: Pooled Analysis of Cohorts of Older Patients From Two Randomized Clinical Trials
Authors: Fairooz F. Kabbinavar, Herbert I. Hurwitz, Jing Yi, Somnath Sarkar, Oliver Rosen
Journal: Journal of Clinical Oncology (2008)

Colorectal cancer (CRC) occurs predominantly in older persons. To provide more statistical power to assess risk/benefit in older patients, we examined the clinical benefit of bevacizumab (BV) plus fluorouracil-based chemotherapy in first-line metastatic CRC (mCRC) treatment in patients aged > or = 65 years, using data pooled from two placebo-controlled studies.Pooled efficacy data for 439 patients > or = 65 years old randomized to BV plus chemotherapy (n = 218) or placebo plus chemotherapy (n = 221) in study 1 and study 2 were retrospectively analyzed on an intent-to-treat basis for overall survival (OS), progression-free survival (PFS), and objective response. Safety analysis was based on reports of targeted adverse events in treated patients.Median OS with BV plus chemotherapy was 19.3 v 14.3 months with placebo plus chemotherapy (hazard ratio [HR] = 0.70; 95% CI, 0.55 to 0.90; P = .006). Patients treated with BV plus chemotherapy had a median PFS of 9.2 v 6.2 months for placebo plus chemotherapy patients (HR = 0.52; 95% CI, 0.40 to 0.67; P < .0001). The objective response rate was 34.4% with BV plus chemotherapy versus 29.0% with placebo plus chemotherapy (difference not statistically significant). Rates of BV-associated adverse events in the pooled BV plus chemotherapy group were consistent with those reported in the overall populations for the two studies.Analysis of pooled patient cohorts age >/= 65 years from two similar trials in mCRC indicates that adding bevacizumab to fluorouracil-based chemotherapy improved OS and PFS, similar to the benefits in younger patients. Also, the risks of treatment do not seem to exceed those in younger patients with mCRC.
Psoriatic arthritis treated with oral zinc sulphate
Authors: O. J. CLEMMENSEN, J. SIGGAARD-ANDERSEN, A. M. WORM, D. STAHL, F. FROST, I. BLOCH
Journal: British Journal of Dermatology (1980)

Twenty-four patients suffering from psoriatic arthritis participated in a double blind cross-over trial of peroral zinc sulphate versus placebo (Trial I). Eleven patients continued an open trial of peroral zinc sulphate for an additional 24 weeks (Trial II). Remission was assessed by the disappearance of symptoms (overall condition, morning stiffness, functional capacity of the joints and joint pains), and signs (mobility and swelling of the joints). Reduction of joint pains as well as increase of mobility and decrease of swelling of several joints were observed. The clinical signs of reduced inflammation were accompanied biochemically by reduction of serum immunoglobulins and an increase of serum albumin. The need for analgesics was diminished. Severe side-effects and changes in the psoriatic skin involvement were not seen. Oral zinc sulphate seems to be valuable in the treatment of psoriatic arthritis.
Functional Genetic Variations in <i>Cytotoxic T-Lymphocyte Antigen 4</i> and Susceptibility to Multiple Types of Cancer
Authors: Tong Sun, Yifeng Zhou, Ming Yang, Zhibin Hu, Wen Tan, Xiaohong Han, Yuankai Shi, Jiarui Yao, Yongli Guo, Dianke Yu, Tian Tian, Xiaoyi Zhou, Hongbing Shen, Dongxin Lin
Journal: Cancer Research (2008)

Abstract Antitumor T lymphocytes play a pivotal role in immunosurveillance of malignancy. The CTL antigen 4 (CTLA-4) is a vital negative regulator of T-cell activation and proliferation. This study examined whether genetic polymorphisms in CTLA-4 are associated with cancer susceptibility. A two-stage investigation using haplotype-tagging single nucleotide polymorphism approach and multiple independent case-control analyses was performed to assess the association between CTLA-4 genotypes and cancer risk. Functional relevance of the polymorphisms was examined by biochemical assays. We found that the 49G&amp;gt;A polymorphism in the CTLA-4 leading sequence causing 17Ala to 17Thr amino acid substitution is associated with increased susceptibility to multiple cancers, including lung, breast, esophagus, and gastric cardia cancers. Genotyping in 5,832 individuals with cancer and 5,831 control subjects in northern and southern Chinese populations showed that the CTLA-4 49AA genotype had an odds ratio of 1.72 (95% confidence interval, 1.50−2.10; P = 3.4 × 10−7) for developing cancer compared with the 49GG genotype. Biochemical analyses showed that CTLA-4−17Thr had higher capability to bind B7.1 and stronger inhibitory effect on T-cell activation compared with CTLA-4−17Ala. T cells carrying the 49AA genotype had significantly lower activation and proliferation rates compared with T cells carrying the 49GG genotype upon stimulation. These results are consistent with our hypothesis and indicate that genetic polymorphisms influencing T-cell activation modify cancer susceptibility. [Cancer Res 2008;68(17):7025–34]
Clostridium difficile toxin in acute diarrhoea complicating inflammatory bowel disease.
Authors: M R Keighley, D Youngs, M Johnson, R N Allan, D W Burdon
Journal: Gut (1982)

The incidence of Clostridium difficile cytotoxin has been studied in 69 consecutive patients with inflammatory bowel disease complicated by severe diarrhoea or ileostomy flux during 74 admissions to hospital. The cytotoxin was identified in only four patients, all of whom had received antimicrobials. Clostridium difficle, but not cytotoxin, was identified in 10 of 43 admissions. This followed antimicrobial prophylaxis to cover a recent operation in two patients, and five were on long-term sulphasalazine. Only three patients with Clostridium difficile had not received an antimicrobial within one month of the study. Isolation of Clostridium difficile alone is of doubtful pathological significance, as it spontaneously disappeared without treatment in all patients.
Ichthyosis vulgaris: the filaggrin mutation disease
Authors: J.P. Thyssen, E. Godoy-Gijon, P.M. Elias
Journal: British Journal of Dermatology (2013)

Ichthyosis vulgaris is caused by loss-of-function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker-skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin-deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.