tbuckley/cabot-search huggingface dataset:
Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection
Authors: Robert G. Sawyer, Jeffrey A. Claridge, Avery B. Nathens, Ori D. Rotstein, Therese M. Duane, Heather L. Evans, Charles H. Cook, Patrick J. O’Neill, John E. Mazuski, Reza Askari, Mark A. Wilson, Lena M. Napolitano, Nicholas Namias, Preston R. Miller, E. Patchen Dellinger, Christopher M. Watson, Raul Coimbra, Daniel L. Dent, Stephen F. Lowry, Christine S. Cocanour, Michaela A. West, Kaysie L. Banton, William G. Cheadle, Pamela A. Lipsett, Christopher A. Guidry, Kimberley Popovsky
Journal: New England Journal of Medicine (2015)

The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear.We randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections.Surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, -0.5 percentage point; 95% confidence interval [CI], -7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, -4.0 days; 95% CI, -4.7 to -3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes.In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials.gov number, NCT00657566.).
Prognostic Factors in High-Grade Osteosarcoma of the Extremities or Trunk: An Analysis of 1,702 Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols
Authors: S. S. Bielack
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease. PATIENTS AND METHODS: A total of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic, tumor-related, and treatment-related variables, response, and survival. The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions. RESULTS: Axial tumor site, male sex, and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis. Actuarial 10-year overall and event-free survival rates were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age (actuarial 10-year survival ≥ 40, 41.6%; < 40, 60.2%; P = .012), tumor site (axial, 29.2%; limb, 61.7%; P < .0001), and primary metastases (yes, 26.7%; no, 64.4%; P < .0001), and for extremity osteosarcomas, also size (≥ one third, 52.5%; < one third, 66.7%; P < .0001) and location within the limb (proximal, 49.3%; other, 63.9%; P < .0001), had significant influence on outcome. Two additional important prognostic factors were treatment related: response to chemotherapy (poor, 47.2%; good, 73.4%; P < .0001) and the extent of surgery (incomplete, 14.6%; macroscopically complete, 64.8%; P < .0001). All factors except age maintained their significance in multivariate testing, with surgical remission and histologic response emerging as the key prognostic factors. CONCLUSION: Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.
Tamoxifen and Chemotherapy for Lymph Node-Negative, Estrogen Receptor-Positive Breast Cancer
Authors: B. Fisher, J. Dignam, B. Emir, J. Bryant, A. DeCillis, N. Wolmark, D. L. Wickerham, N. V. Dimitrov, N. Abramson, J. N. Atkins, H. Shibata, L. Deschenes, R. G. Margolese
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor- positive breast cancer. Methods: Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with follow-up data received tamoxifen alone; 767 received methotrexate, fluorouracil, and tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and tamoxifen (CMFT). The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. Results: Through 5 years of follow-up, chemotherapy plus tamoxifen resulted in significantly better disease-free survival than tamoxifen alone (90% for MFT versus 85% for tamoxifen [ P = .01]; 89% for CMFT versus 85% for tamoxifen [ P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for tamoxifen [ P = .008]; 91% for CMFT versus 87% for tamoxifen [ P = .006]) and survival (97% for MFT versus 94% for tamoxifen [ P = .05]; 96% for CMFT versus 94% for tamoxifen [ P = .03]). Compared with tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. Conclusions: Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy.
European consensus on epidemiological studies of injuries in the thoroughbred horse racing industry
Authors: M Turner, C W Fuller, D Egan, B Le Masson, A McGoldrick, A Spence, P Wind, P-M Gadot
Journal: British Journal of Sports Medicine (2011)

Reported data for injuries sustained by jockeys in thoroughbred horse racing vary greatly. While the range of abilities and types of racing may account for some variation, the variations result mainly from differences in the definitions and methodologies employed in the studies.

The British Horseracing Authority (BHA) facilitated a meeting of experts from the four leading horse racing countries in Europe. Using an approach adopted by the previous consensus groups addressing sports injuries, issues related to definitions, methodology and implementation were discussed and voted on by the group during a structured one-day meeting. Following this meeting, two members of the consensus group produced a draft document, based on the group discussions, which was circulated for review; two revisions were prepared before the final consensus statement was produced.

The definition of injury and the criteria for recording the severity and nature of injuries are proposed for use in future epidemiological studies of injuries sustained by riders and associated support staff in the thoroughbred horse racing industry. Suggestions are made for recording participant baseline information together with recommendations on how injuries sustained during racing and associated activities should be reported.

The definitions and methodology proposed for recording injuries, sustained during thoroughbred horse racing activities will lead to more uniform data being collected. The surveillance procedures presented here may also be applicable to other equine sports such as trotting, polo, show jumping and eventing.

Based on injuries reported to racecourse medical officers in France, Ireland and the UK over the period 1992–2001, jockeys have an incidence of 1–2 injuries per 1000 rides in flat racing and 6–12 injuries per 1000 rides in jump racing.1 Insurance claims from injured jockeys indicate lower incidences of 1 injury per 1000 rides in flat racing and 3 injuries per 1000 rides in jump racing2 but …
Resveratrol, a Polyphenolic Phytoalexin Present in Red Wine, Enhances Expression and Activity of Endothelial Nitric Oxide Synthase
Authors: Thomas Wallerath, Göran Deckert, Thomas Ternes, Henrik Anderson, Huige Li, Klaus Witte, Ulrich Förstermann
Journal: Circulation (2002)

Background— Estrogens can upregulate endothelial nitric oxide synthase (eNOS) in human endothelial cells by increasing eNOS promoter activity and enhancing the binding activity of the transcription factor Sp1. Resveratrol, a polyphenolic phytoalexin found in grapes and wine, has been reported to act as an agonist at the estrogen receptor. Therefore, we tested the effect of this putative phytoestrogen on eNOS expression in human endothelial cells. Methods and Results— Incubation of human umbilical vein endothelial cells (HUVEC) and HUVEC-derived EA.hy 926 cells with resveratrol for 24 to 72 hours upregulated eNOS mRNA expression in a time- and concentration-dependent manner (up to 2.8-fold). eNOS protein expression and eNOS-derived NO production were also increased after long-term incubation with resveratrol. Resveratrol increased the activity of the eNOS promoter (3.5-kb fragment) in a concentration-dependent fashion, with the essential trans-stimulated sequence being located in the proximal 263 bp of the promoter sequence. In addition, eNOS mRNA was stabilized by resveratrol. The effect of resveratrol on eNOS expression was not modified by the estrogen receptor antagonists ICI 182780 and RU 58668. In electrophoretic mobility shift assays, nuclear extracts from resveratrol-incubated EA.hy 926 cells showed no enhanced binding activity of the eNOS promoter-relevant transcription factors Sp1, GATA, PEA3, YY1, or Elf-1. In addition to its long-term effects on eNOS expression, resveratrol also enhanced the production of bioactive NO in the short-term (after a 2-minute incubation). Conclusions— In concert with other effects, the stimulation of eNOS expression and activity may contribute to the cardiovascular protective effects attributed to resveratrol.
Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP)
Authors: K Forslind
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the role of anti-cyclic citrullinated peptide antibody (anti-CCP) for the prediction of radiological outcome in patients with early rheumatoid arthritis.Anti-CCP was assessed at baseline in 379 patients with early rheumatoid arthritis (disease duration <1 year). Radiological joint damage and progression were assessed by Larsen score after two years of follow up (end point) and used as outcome variables. The prognostic value of anti-CCP and other demographic and disease related baseline variables were assessed by univariate and multivariate analyses, including calculation of odds ratios (OR), predictive values, and multiple logistic regression models.The presence of anti-CCP was associated with significantly higher Larsen score both at baseline and at end point. Univariate predictor analysis showed that anti-CCP had the highest significant OR for radiological joint damage and progression after baseline Larsen score, followed by rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein, age, smoking status, and sex. In stepwise multiple regression analyses, baseline Larsen score, anti-CCP, and ESR were selected as significant independent predictors of the radiological outcomes.There is good evidence for an association of anti-CCP with radiological joint changes in rheumatoid arthritis. Anti-CCP is an independent predictor of radiological damage and progression. Though prediction in early rheumatoid arthritis is still far from perfect, the use of anti-CCP in clinical practice should make it easier for rheumatologists to reach judicious treatment decisions.
Size at Birth, Weight Gain in Infancy and Childhood, and Adult Diabetes Risk in Five Low- or Middle-Income Country Birth Cohorts
Authors: Shane A. Norris, Clive Osmond, Denise Gigante, Christopher W. Kuzawa, Lakshmy Ramakrishnan, Nanette R. Lee, Manual Ramirez-Zea, Linda M. Richter, Aryeh D. Stein, Nikhil Tandon, Caroline H.D. Fall
Journal: Diabetes Care (2011)

We examined associations of birth weight and weight gain in infancy and early childhood with type 2 diabetes (DM) risk in five cohorts from low- and middle-income countries.Participants were 6,511 young adults from Brazil, Guatemala, India, the Philippines, and South Africa. Exposures were weight at birth, at 24 and 48 months, and adult weight, and conditional weight gain (CWG, deviation from expected weight gain) between these ages. Outcomes were adult fasting glucose, impaired fasting glucose or DM (IFG/DM), and insulin resistance homeostasis model assessment (IR-HOMA, three cohorts).Birth weight was inversely associated with adult glucose and risk of IFG/DM (odds ratio 0.91[95% CI 0.84-0.99] per SD). Weight at 24 and 48 months and CWG 0-24 and 24-48 months were unrelated to glucose and IFG/DM; however, CWG 48 months-adulthood was positively related to IFG/DM (1.32 [1.22-1.43] per SD). After adjusting for adult waist circumference, birth weight, weight at 24 and 48 months and CWG 0-24 months were inversely associated with glucose and IFG/DM. Birth weight was unrelated to IR-HOMA, whereas greater CWG at 0-24 and 24-48 months and 48 months-adulthood predicted higher IR-HOMA (all P < 0.001). After adjusting for adult waist circumference, birth weight was inversely related to IR-HOMA.Lower birth weight and accelerated weight gain after 48 months are risk factors for adult glucose intolerance. Accelerated weight gain between 0 and 24 months did not predict glucose intolerance but did predict higher insulin resistance.
In vivo monitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography
Authors: M.O. Wielpütz, M. Eichinger, Z. Zhou, K. Leotta, S. Hirtz, S.H. Bartling, W. Semmler, H-U. Kauczor, M. Puderbach, M.A. Mall
Journal: European Respiratory Journal (2011)

The onset and spontaneous development of cystic fibrosis (CF) lung disease remain poorly understood. In the present study, we used volumetric computed tomography (VCT) as a new method for longitudinal in vivo monitoring of early lesions and disease progression in CF-like lung disease in β-epithelial Na + channel (ENaC)-transgenic (TG) mice. Using a VCT scanner prototype (80 kV, 50 mA·s, scan time 19 s and spatial resolution 200 μm), βENaC-TG mice and wild-type (WT) littermates were examined longitudinally at 10 time-points from neonatal to adult ages, and VCT images were assessed by qualitative and quantitative morphological parameters. We demonstrate that VCT detected early-onset airway mucus obstruction, diffuse infiltrates, atelectasis and air trapping as characteristic abnormalities in βENaC-TG mice. Furthermore, we show that early tracheal mucus obstruction predicted mortality in βENaC-TG mice and that the density of lung parenchyma was significantly reduced at all time-points in βENaC-TG compared with WT mice (median± sem -558±8 HU in WT versus -686±16 HU in βENaC-TG at 6 weeks of age; p&lt;0.005). Our study demonstrates that VCT is a sensitive, noninvasive technique for early detection and longitudinal monitoring of morphological abnormalities of CF-like lung disease in mice, and may thus provide a useful tool for pre-clinical in vivo evaluation of novel treatment strategies for CF.
Probability of continued low disease activity in patients with recent onset rheumatoid arthritis treated according to the disease activity score
Authors: S M van der Kooij, Y P M Goekoop-Ruiterman, J K de Vries-Bouwstra, A J Peeters, M V van Krugten, F C Breedveld, B A C Dijkmans, C F Allaart
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To assess the duration and the probability of maintaining low disease activity once a low disease activity score (DAS) is achieved in recent onset rheumatoid arthritis (RA) patients. <h3>Methods:</h3> The BeSt study is a randomised trial comparing four different treatment strategies in patients with recent onset, active RA. Treatment adjustments were mandatory as long as the DAS was &gt;2.4. If the DAS was ⩽2.4, treatment was continued and after 6 months, tapered to maintenance dose. We analysed thrice-monthly DAS calculations in order to assess the duration and the probability of maintaining a DAS ⩽2.4. <h3>Results:</h3> Patients treated with initial combination therapy achieved a DAS ⩽2.4 significantly earlier than patients treated with initial monotherapy. Independent of treatment strategy and without treatment adjustments, the probability of a next DAS ⩽2.4 3 months after a first DAS ⩽2.4 was 74%. The probability increased to 85% after two preceding DAS ⩽2.4 and to 88–97% after one to two preceding DAS&lt;1.6. The median duration of a DAS ⩽2.4 was 12 months. <h3>Conclusion:</h3> Once recent onset RA patients achieve a low DAS, the probability of maintaining a low DAS without treatment adjustments is high. This may have implications for the monitoring of patients in daily practice.
Melanoma inhibitory activity, a biomarker related to chondrocyte anabolism, is reversibly suppressed by proinflammatory cytokines in rheumatoid arthritis
Authors: B Vandooren, T Cantaert, M-J van Lierop, E Bos, L De Rycke, E M Veys, F De Keyser, B Bresnihan, F P Luyten, P C Verdonk, P P Tak, A H Boots, D Baeten
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> In mice, melanoma inhibitory activity (MIA) is a chondrocyte-specific molecule with similar regulation to collagen type II. As MIA is a small secreted protein, its value as cartilage biomarker in human inflammatory arthritis was assessed. <h3>Methods:</h3> MIA tissue distribution was studied by quantitative PCR and immunohistochemistry. The regulation of MIA production was studied in vivo in rheumatoid arthritis (RA) (n = 37) and spondyloarthritis (SpA) (n = 30) synovial fluid (SF), and in vitro in alginate embedded human chondrocytes. Therapeutic modulation of serum MIA was evaluated during tumour necrosis factor (TNF)α and interleukin (IL)1 blockade in RA. <h3>Results:</h3> MIA was primarily expressed by chondrocytes in the human joint. SF MIA levels were lower in RA than in SpA despite similar levels of overall synovial inflammation. Further analysis indicated that these levels were inversely correlated with the degree of joint inflammation in RA, but not in SpA, and that the levels of TNFα and IL1β were significantly increased in RA versus SpA. Accordingly, these proinflammatory cytokines suppressed MIA mRNA and protein in cultured chondrocytes. This suppression was paralleled by suppression of cartilage anabolism as assessed by collagen type 2 and aggrecan mRNA. Treatment of patients with RA with TNF blockade or IL1 blockade induced an increase of serum MIA levels. <h3>Conclusion:</h3> The decreased levels of MIA in the inflamed RA joint and the coregulation of MIA and cartilage matrix molecules by proinflammatory cytokines indicate that joint inflammation in RA not only drives accelerated cartilage degradation but also suppresses cartilage anabolism. This inflammation-driven suppression is reversible in vivo.
Prospective Randomized Multicenter Adjuvant Dermatologic Cooperative Oncology Group Trial of Low-Dose Interferon Alfa-2b With or Without a Modified High-Dose Interferon Alfa-2b Induction Phase in Patients With Lymph Node–Negative Melanoma
Authors: Axel Hauschild, Michael Weichenthal, Knuth Rass, Ruthild Linse, Jens Ulrich, Rudolf Stadler, Matthias Volkenandt, Stephan Grabbe, Ulrike Proske, Dirk Schadendorf, Norbert Brockmeyer, Thomas Vogt, Rainer Rompel, Roland Kaufmann, Martin Kaatz, Helmut Näher, Peter Mohr, Thomas Eigentler, Elisabeth Livingstone, Claus Garbe
Journal: Journal of Clinical Oncology (2009)

PURPOSE Interferon alfa (IFN-alpha) has shown clinical efficacy in the adjuvant treatment of patients with high-risk melanoma in several clinical trials, but optimal dosing and duration of treatment are still under discussion. It has been argued that in high-dose IFN-alpha (HDI), the intravenous (IV) induction phase might be critical for the clinical benefit of the regimen. PATIENTS AND METHODS In an attempt to investigate the potential role of a modified high-dose induction phase, lymph node-negative patients with resected primary malignant melanoma of more than 1.5-mm tumor thickness were included in this prospective randomized multicenter Dermatologic Cooperative Oncology Group trial. Six hundred seventy-four patients were randomly assigned to receive 4 weeks of a modified HDI scheme. This schedule consisted of 5 times weekly 10 MU/m(2) IFN-alpha-2b IV for 2 weeks and 5 times weekly 10 MU/m(2) IFN-alpha-2b administered subcutaneously (SC) for another 2 weeks followed by 23 months of low-dose IFN-alpha-2b (LDI) 3 MU SC three times a week (arm A). LDI 3 MU three times a week was given for 24 months in arm B. Results Of 650 assessable patients, there were 92 relapses among the 321 patients receiving high-dose induction as compared with 95 relapses among the 329 patients receiving LDI only. Five-year relapse-free survival rates were 68.0% (arm A) and 67.1% (arm B), respectively. Likewise, melanoma-related fatalities were similar between both groups, resulting in 5-year overall survival rates of 80.2% (arm A) and 82.9% (arm B). CONCLUSION The addition of a 4-week modified HDI induction phase to a 2-year low-dose adjuvant IFN-alpha-2b treatment schedule did not improve the clinical outcome.