bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of locally and systemically administered soluble glycoprotein 130 on pain and inflammation in experimental arthritis
Authors: Boettger Michael K , Leuchtweis Johannes , Kümmel Diana , Gajda Mieczyslaw , Bräuer Rolf , Schaible Hans-Georg 
Published: July 2010

Abstract
Introduction
Interleukin-6 (IL-6) is a key player in systemic arthritis, involved in inflammation and joint destruction. IL-6 signalling has also been revealed in nerve cells. Recently, IL-6 and in particular IL-6 together with its soluble IL-6 receptor (sIL-6R) were shown to induce a long-lasting robust sensitization of joint nociceptors for mechanical stimuli which was difficult to reverse, suggesting that IL-6 signalling plays a significant role in the generation and maintenance of arthritic pain. Here we tested in a preclinical model of arthritis, antigen-induced arthritis (AIA) in the rat, whether systemic or local neutralization of IL-6/sIL-6R complexes with soluble glycoprotein 130 (sgp130) alters arthritic pain and how sgp130 influences the inflammatory process in AIA.

Methods
Rats with AIA were either treated with sgp130 or saline intra-peritoneally or intra-articularly (each group n = 9). Then, pain-related and locomotor behaviour, as well as joint swelling, were measured during an observation period of 21 days, followed by histopathological end-point analysis for inflammatory and destructive changes.

Results
A single intra-articular application of sgp130 at the time of AIA induction barely reduced the development of AIA, but significantly attenuated pain-related behaviour, that is, primary mechanical hyperalgesia in the acute phase of AIA. By contrast, repeated systemic application of sgp130 after onset of AIA only slightly attenuated pain at a late stage of AIA. None of the treatments reduced secondary hyperalgesia. Furthermore, in the present study joint destruction at 21 days was significantly attenuated after intra-articular sgp130 treatment, but not after systemic sgp130.

Conclusions
In addition to its role in chronic inflammation, IL-6 in the joint plays a significant role in the generation and maintenance of arthritic joint pain at acute and chronic stages of AIA. The particular effectiveness of intra-articular injection of sgp130 indicates, first, that IL-6/sIL-6R in the inflamed joint, rather than circulating IL-6/sIL-6R, is responsible for the generation of hyperalgesia, and, second, that early neutralization of IL-6/sIL-6R is particularly successful in producing antinociception. Furthermore, neutralization of IL-6/sIL-6R (and possibly other cytokines which use the transmembrane signal-transducing subunit gp130) directly at the site of joint inflammation seems to be effective in the prevention of joint destruction.
Phase III Study Comparing Second- and Third-Generation Regimens With Concurrent Thoracic Radiotherapy in Patients With Unresectable Stage III Non–Small-Cell Lung Cancer: West Japan Thoracic Oncology Group WJTOG0105
Authors: Yamamoto Nobuyuki , Nakagawa Kazuhiko , Nishimura Yasumasa , Tsujino Kayoko , Satouchi Miyako , Kudo Shinzoh , Hida Toyoaki , Kawahara Masaaki , Takeda Koji , Katakami Nobuyuki , Sawa Toshiyuki , Yokota Soichiro , Seto Takashi , Imamura Fumio , Saka Hideo , Iwamoto Yasuo , Semba Hiroshi , Chiba Yasutaka , Uejima Hisao , Fukuoka Masahiro 
Published: July 2010

Purpose This phase III trial of concurrent thoracic radiotherapy (TRT) was conducted to compare third-generation chemotherapy with second-generation chemotherapy in patients with unresectable stage III non–small-cell lung cancer (NSCLC). Patients and Methods Eligible patients received the following treatments: A (control), four cycles of mitomycin (8 mg/m2 on day 1)/vindesine (3 mg/m2 on days 1, 8)/cisplatin (80 mg/m2 on day 1) plus TRT 60 Gy (treatment break for 1 week); B, weekly irinotecan (20 mg/m2)/carboplatin (area under the plasma concentration-time curve [AUC] 2) for 6 weeks plus TRT 60 Gy, followed by two courses of irinotecan (50 mg/m2 on days1, 8)/carboplatin (AUC 5 on day1); C, weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) for 6 weeks plus TRT 60 Gy, followed by two courses of paclitaxel (200 mg/m2 on day1)/carboplatin (AUC 5 on day 1). Results The median survival time and 5-year survival rates were 20.5, 19.8, and 22.0 months and 17.5%, 17.8%, and 19.8% in arms A, B, and C, respectively. Although no significant differences in overall survival were apparent among the treatment arms, noninferiority of the experimental arms was not achieved. The incidences of grade 3 to 4 neutropenia, febrile neutropenia, and gastrointestinal disorder were significantly higher in arm A than in arm B or C (P < .001). Chemotherapy interruptions were more common in arm B than in arm A or C. Conclusion Arm C was equally efficacious and exhibited a more favorable toxicity profile among three arms. Arm C should be considered a standard regimen in the management of locally advanced unresectable NSCLC.
American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer
Authors: Burstein Harold J. , Prestrud Ann Alexis , Seidenfeld Jerome , Anderson Holly , Buchholz Thomas A. , Davidson Nancy E. , Gelmon Karen E. , Giordano Sharon H. , Hudis Clifford A. , Malin Jennifer , Mamounas Eleftherios P. , Rowden Diana , Solky Alexander J. , Sowers MaryFran R. , Stearns Vered , Winer Eric P. , Somerfield Mark R. , Griggs Jennifer J. 
Published: July 2010

Purpose To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor–positive breast cancer. Methods A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations. Results An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences. Conclusion The Update Committee recommends that postmenopausal women with hormone receptor–positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy.
Deletion of thePER3Gene on Chromosome 1p36 in Recurrent ER-Positive Breast Cancer
Authors: Climent Joan , Perez-Losada Jesus , Quigley David A. , Kim Il-Jin , Delrosario Reyno , Jen Kuang-Yu , Bosch Ana , Lluch Ana , Mao Jian-Hua , Balmain Allan 
Published: July 2010

PurposeTo investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development.Patients and MethodsThe frequency of genetic alterations at 1p36 and PER3 gene copy number status were analyzed in 180 lymph node–negative breast cancers from patients who had received treatment with chemotherapy and/or tamoxifen. The expression levels of PER3 were also analyzed using published microarray profiles from > 400 breast cancer samples. Finally, the effect of loss of Per3 on tumor susceptibility was tested using two mouse models of breast cancer.ResultsDeletion of PER3 is directly related to tumor recurrence in patients with estrogen receptor (ER) – positive breast cancers treated with tamoxifen. Low expression of PER3 mRNA is associated with poor prognosis, particularly in a subset of tumors that are ER positive, and either luminal A or ERBB2-positive tumors. Mice deficient in Per3 showed increased susceptibility to breast cancer induced by carcinogen treatment or by overexpression of Erbb2.ConclusionDisruption of PER3 function may serve as an indicator of probability of tumor recurrence in patients with ER-positive tumors. Further investigations of this pathway may reveal links between deregulation of sleep homeostasis and breast tumorigenesis.
Siltuximab, a Novel Anti–Interleukin-6 Monoclonal Antibody, for Castleman's Disease
Authors: van Rhee Frits , Fayad Luis , Voorhees Peter , Furman Richard , Lonial Sagar , Borghaei Hossein , Sokol Lubomir , Crawford Julie , Cornfeld Mark , Qi Ming , Qin Xiang , Herring Jennifer , Casper Corey , Kurzrock Razelle 
Published: July 2010

Purpose Interleukin-6 (IL-6) has emerged as a key factor in the pathogenesis of the atypical lymphoproliferative disorder Castleman's disease (CD). Siltuximab is a new anti–IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD. Methods We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals. The main efficacy end point of clinical benefit response (CBR) was defined as a composite of clinical and laboratory measures relevant to the management of CD. In addition, radiologic response was independently assessed by using modified Cheson criteria. Results Eighteen (78%) of 23 patients (95% CI, 56% to 93%) achieved CBR, and 12 patients (52%) demonstrated objective tumor response. All 11 patients (95% CI, 72% to 100%) treated with the highest dose of 12 mg/kg achieved CBR, and eight patients (73%) achieved objective tumor response. Overall objective-response duration ranged from 44 to ≥ 889 days, and one patient had complete response for ≥ 318 days. Hemoglobin increased markedly in 19 patients (median increase, 2.1 g/dL; range, 0.2 to 4.7 g/dL) in the absence of transfusion or erythropoiesis-stimulating agents. No dose-limiting toxicity was reported, and only three patients had grade 3 or higher adverse events after a median exposure of 331 days (range, 1 to 1,148 days). Conclusion These interim results strongly suggest that siltuximab is an effective treatment with favorable safety for the management of CD. An additional study is planned to fully evaluate safety and efficacy at the recommended dose of 12 mg/kg every 3 weeks.
Is Mammographic Breast Density a Breast Cancer Risk Factor in Women With BRCA Mutations?
Authors: Passaperuma Kavitha , Warner Ellen , Hill Kimberley A. , Gunasekara Anoma , Yaffe Martin J. 
Published: July 2010

Purpose Increased mammographic breast density is well recognized as a breast cancer risk factor in the general population. However, it is unclear whether it is a risk factor in women with BRCA mutations. We present the results of a nested case-control screening study investigating the relationship between breast density and breast cancer incidence in this population. Patients and Methods Women ages 25 to 65 years with known BRCA mutations were enrolled onto a single-center, high-risk breast cancer screening program. Using a computer-aided technique (Cumulus), quantitative percentage density (PD) was measured for each participant on her baseline mammogram by a single, blinded observer. Results Between November 1997 and March 2008, 462 women (mean age, 44 years; 245 BRCA1 and 217 BRCA2) were screened and 50 breast cancers were diagnosed (38 invasive, 12 ductal carcinoma in situ [DCIS]). Density was not measured in 40 women of whom four developed cancer (three invasive, one DCIS). Mean PD (± standard deviation [SD]) for 376 women who did not develop breast cancer was 34% (23) compared with 31% (21) for 46 women with cancer (P = .51). Logistic regression model of breast cancer incidence and PD revealed an odds ratio of 0.99 (± 0.01 SD) for a one-unit increase in PD (P = .44). Results remained nonsignificant in multivariate analysis, as well as when women with pure DCIS were excluded. Conclusion Increased mammographic breast density is not associated with higher breast cancer incidence in women with BRCA mutations. On the basis of these findings, density should not be considered a factor for these women in decision making regarding prophylactic surgery or chemoprevention.
Prognostic Impact of Isocitrate Dehydrogenase Enzyme Isoforms 1 and 2 Mutations in Acute Myeloid Leukemia: A Study by the Acute Leukemia French Association Group
Authors: Boissel Nicolas , Nibourel Olivier , Renneville Aline , Gardin Claude , Reman Oumedaly , Contentin Nathalie , Bordessoule Dominique , Pautas Cécile , de Revel Thierry , Quesnel Bruno , Huchette Pascal , Philippe Nathalie , Geffroy Sandrine , Terre Christine , Thomas Xavier , Castaigne Sylvie , Dombret Hervé , Preudhomme Claude 
Published: July 2010

Purpose Recently, whole-genome sequencing in acute myeloid leukemia (AML) identified recurrent isocitrate dehydrogenase enzyme isoform (IDH1) mutations (IDH1m), previously reported to be involved in gliomas as well as IDH2 mutations (IDH2m). The prognosis of both IDH1m and IDH2m in AML remains unclear. Patients and Methods The prevalence and the prognostic impact of R132 IDH1 and R172 IDH2 mutations were evaluated in a cohort of 520 adults with AML homogeneously treated in the French Acute Leukemia French Association (ALFA) -9801 and -9802 trials. Results The prevalence of IDH1m and IDH2m was 9.6% and 3.0%, respectively, mostly associated with normal cytogenetics (CN). In patients with CN-AML, IDH1m were associated with NPM1m (P = .008), but exclusive of CEBPAm (P = .03). In contrary, no other mutations were detected in IDH2m patients. In CN-AML patients, IDH1m were found in 19% of favorable genotype ([NPM1m or CEBPAm] without fms-related tyrosine kinase 3 [FLT3] internal tandem duplication [ITD]) and were associated with a higher risk of relapse (RR) and a shorter overall survival (OS). Favorable genotype in CN-AML could thus be defined by the association of NPM1m or CEBPAm with neither FLT3-ITD nor IDH1m. In IDH2m CN-AML patients, we observed a higher risk of induction failure, a higher RR and a shorter OS. In multivariate analysis, age, WBC count, the four-gene favorable genotype and IDH2m were independently associated with a higher RR and a shorter OS. Conclusion Contrarily to what is reported in gliomas, IDH1m and IDH2m in AML are associated with a poor prognosis. Screening of IDH1m could help to identify high-risk patients within the subset of CN-AML with a favorable genotype.
Dry-Reagent Double-Monoclonal Assay for Cystatin C
Authors: Ristiniemi Noora , Qin Qiu-Ping , Postnikov Alexander , Grubb Anders , Pettersson Kim 
Published: July 2010

BACKGROUNDCystatin C is a low molecular weight cysteine proteinase inhibitor whose plasma or serum concentrations have been shown to be better correlated with glomerular filtration rate than serum creatinine concentrations. Routine assays for cystatin C are based on use of polyclonal antibodies and immunoturbidimetric and nephelometric designs. This study aimed to develop a double-monoclonal immunoassay for cystatin C.METHODSWe tested functionality of 42 2-site antibody combinations involving 7 monoclonal antibodies with recombinant and plasma cystatin C. We developed a heterogeneous assay using 2 antibodies selected to give the best analytical performance. The assay used a dilution step and was based on a dry-reagent, all-in-one immunoassay concept with time-resolved fluorometry. The assay was performed on an automated immunoanalyzer in single wells that contained all the required assay components. We used heparin-derived plasma samples for methodological evaluation of the assay.RESULTSFrom a relative epitope map involving 7 cystatin C–specific antibodies, we selected a pair of antibodies for a 2-site sandwich-type dry-reagent assay. Total assay time was 15 min, and 10 μL of a 100-fold diluted sample was used. The analytical detection limit (background + 3SD) and functional detection limit (CV 20%) were 0.01 mg/L and 0.02 mg/L, respectively. Within-run and total assay imprecision were &lt;4.7% and &lt;5.6% (at 0.84–3.2 mg/L), respectively, and plasma recoveries of added cystatin C were 94%–110%. Regression analysis with the Roche particle-enhanced immunoturbidimetric method yielded the following (SD): slope, 1.391 (0.029); y-intercept, −0.152 (0.045) mg/L; Sy⊻x=0.294 mg/L (n=131).CONCLUSIONSThe developed assay enables rapid and reliable measurement of cystatin C.
Assessment of Risk of Bias Among Pediatric Randomized Controlled Trials
Authors: Crocetti Michael T. , Amin Diane D. , Scherer Roberta 
Published: July 2010

OBJECTIVE:
The goal was to assess the risk of bias among pediatric, randomized, controlled trials (RCTs) reported in 8 high-impact journals.

METHODS:
We searched PubMed for all pediatric RCTs reported between July 1, 2007, and June 30, 2008, in 8 journals with high impact factors. Using Cochrane Collaboration methods for risk assessment, we evaluated all reports for risk of bias according to domain (ie, randomized sequence generation, allocation concealment, masking, incomplete outcome data, selective outcome reporting, and other). We used multiple logistic regression to test for associations between the presence of a high risk of bias according to domain and funding source, intervention type, trial registration, and multicenter status.

RESULTS:
Industry-funded RCTs were more likely to show a high risk of bias for sequence generation, compared with government-funded RCTs (adjusted odds ratio [aOR]: 6.1 [95% confidence interval [CI]: 1.70– 21.89]), and behavioral/educational trials were more likely to show a high risk of bias for sequence generation (aOR: 2.8 [95% CI: 1.06–7.36]) and allocation concealment (aOR: 4.09 [95% CI: 1.69–9.90]), compared with drug trials. Registered trials were less likely to have a high risk of bias for sequence generation, compared with nonregistered trials (aOR: 0.33 [95% CI: 0.15–0.71]).

CONCLUSIONS:
Overall, we found a large proportion of pediatric RCT reports with a high risk of bias for sequence generation and allocation concealment. Factors associated with a high risk of bias included industry funding and assessment of behavioral/educational interventions, whereas trial registration was associated with a lower risk of bias.
Henoch-Schönlein Purpura and Polysaccharide Meningococcal Vaccine
Authors: Goodman Michael J. , Nordin James D. , Belongia Edward A. , Mullooly John P. , Baggs James 
Published: July 2010

BACKGROUND:
We describe here a case of Henoch-Schönlein purpura (HSP) that occurred 10 days after administration of the meningococcal polysaccharide vaccine and came to the attention of a Vaccine Safety Datalink (VSD) investigator (but did not occur in the VSD cohort). Periodic case reports have linked vaccines to HSP.

OBJECTIVE:
To better understand the potential risk for HSP after immunization with the meningococcal polysaccharide vaccine.

PATIENTS AND METHODS:
We studied the VSD cohort to estimate the 42-day postvaccination incidence rate of HSP in the VSD population 16 to 20 years of age. Electronic data from all 8 VSD sites were gathered. All subjects aged 16 to 20 years who received a meningococcal polysaccharide vaccine were followed for 42 days after that vaccination for evidence of HSP. Background rates were determined by examining all the nonexposed time of the same cohort.

RESULTS:
No cases of HSP were seen in the 42 days after 49027 doses of meningococcal polysaccharide vaccine among the entire VSD adolescent and young adult population. The background incidence rate was 4.2 per 100000 person-years.

CONCLUSION:
These data provide the strongest evidence so far that HSP is not associated with receipt of meningococcal polysaccharide vaccine in the 16- to 20-year age group.
Congenital Heart Surgery Outcomes in Down Syndrome: Analysis of a National Clinical Database
Authors: Fudge James C. , Li Shuang , Jaggers James , O'Brien Sean M. , Peterson Eric D. , Jacobs Jeffrey P. , Welke Karl F. , Jacobs Marshall L. , Li Jennifer S. , Pasquali Sara K. 
Published: July 2010

OBJECTIVE:We describe patient characteristics and postoperative morbidity and mortality rates for patients with Down syndrome undergoing congenital heart disease surgery.METHODS:This retrospective cohort study used the Society of Thoracic Surgeons Congenital Heart Surgery Database to compare patient characteristics and postoperative outcomes for patients (0–18 years) with or without Down syndrome who underwent surgery in 2000–2008.RESULTS:A total of 45 579 patients (4350 patients with Down syndrome and 41 229 without Down syndrome) were included (median age: 7 months [interquartile range [IQR]: 47 days to 4 years]; 56% male). Patients with Down syndrome were younger at surgery, with the exception of those undergoing tetralogy of Fallot repair or atrioventricular septal defect repair. Mortality rates for patients with or without Down syndrome did not differ significantly. Lengths of stay were prolonged for patients with Down syndrome undergoing atrial septal defect closure (median: 4 days [IQR: 3–5 days] vs 3 days [IQR: 2–4 days]; P &lt; .0001), ventricular septal defect closure (median: 5 days [IQR: 4–8 days] vs 4 days [IQR: 3–6 days]; P &lt; .0001), or tetralogy of Fallot repair (7 days [IQR: 5–10 days] vs 6 days [IQR: 5–9 days]; P &lt; .001) and were associated with postoperative respiratory and infectious complications. Patients with Down syndrome undergoing ventricular septal defect closure had a higher rate of heart block requiring pacemaker placement (2.9% vs 0.8%; P &lt; .0001).CONCLUSION:In this large, contemporary cohort, Down syndrome did not confer a significant mortality risk for the most common operations; however, postoperative morbidity remained common.
Office-Based Intervention to Reduce Bottle Use Among Toddlers: TARGet Kids! Pragmatic, Randomized Trial
Authors: Maguire Jonathon L. , Birken Catherine S. , Jacobson Sheila , Peer Michael , Taylor Carolyn , Khambalia Amina , Mekky Magda , Thorpe Kevin E. , Parkin Patricia 
Published: July 2010

OBJECTIVE:
The goal was to determine whether an office-based, educational intervention for parents of 9-month-old children could reduce bottle use and iron depletion at 2 years of age.

METHODS:
Between January 2006 and 2007, 251 healthy, 9-month-old infants attending a routine health maintenance visit were assigned randomly to intervention or control groups. Parents in the intervention group were introduced to a 1-week protocol to wean their children from the bottle. Iron depletion (ferritin levels of &lt;10 μg/L) and bottle use at 2 years were assessed.

RESULTS:
A total of 201 children were monitored to 2 years of age (follow-up rate: 81%). Rates of iron depletion (10 [10%] of 102 children vs 13 [13%] of 99 children; P = .42) and milk consumption of &gt;16 oz (16 [16%] of 102 children vs 17 [17%] of 99 children; P = .7) were not significantly different between the 2 groups at 2 years of age. However, children in the intervention group started using a cup 3 months earlier (9 vs 12 months; P = .001), were weaned from the bottle 4 months earlier (12 vs 16 months; P = .004), and were more than one-half as likely to be using a bottle at 2 years of age (15 [15%] of 102 children vs 39 [40%] of 99 children; P = .0004).

CONCLUSIONS:
This simple intervention administered during a health maintenance visit did not result in a decrease in iron depletion at 2 years of age but did result in a 60% reduction in prolonged bottle use.