bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant Chemotherapy Compared With Surgery Alone for Locally Advanced Cancer of the Stomach and Cardia: European Organisation for Research and Treatment of Cancer Randomized Trial 40954
Authors: Schuhmacher Christoph , Gretschel Stephan , Lordick Florian , Reichardt Peter , Hohenberger Werner , Eisenberger Claus F. , Haag Cornelie , Mauer Murielle E. , Hasan Baktiar , Welch John , Ott Katja , Hoelscher Arnulf , Schneider Paul M. , Bechstein Wolf , Wilke Hans , Lutz Manfred P. , Nordlinger Bernard , Cutsem Eric Van , Siewert Jörg R. , Schlag Peter M. 
Published: November 2010

Purpose Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines. Patients and Methods Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required. Results This trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466). Conclusion This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).
A Phase 1 Trial and Pharmacokinetic Study of Cediranib, an Orally Bioavailable Pan–Vascular Endothelial Growth Factor Receptor Inhibitor, in Children and Adolescents With Refractory Solid Tumors
Authors: Fox Elizabeth , Aplenc Richard , Bagatell Rochelle , Chuk Meredith K. , Dombi Eva , Goodspeed Wendy , Goodwin Anne , Kromplewski Marie , Jayaprakash Nalini , Marotti Marcelo , Brown Kathryn H. , Wenrich Barbara , Adamson Peter C. , Widemann Brigitte C. , Balis Frank M. 
Published: November 2010

Purpose To determine the toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of cediranib administered orally, once daily, continuously in children and adolescents with solid tumors. Patients and Methods Children and adolescents with refractory solid tumors, excluding primary brain tumors, were eligible. DLT at the starting dose of 12 mg/m2/d resulted in de-escalation to 8 mg/m2/d and subsequent re-escalation to 12 and 17 mg/m2/d. Pharmacokinetic and pharmacodynamic studies were performed during cycle 1. Response was evaluated using WHO criteria. Results Sixteen patients (median age, 15 years; range, 8 to 18 years) were evaluable for toxicity. DLTs (grade 3 nausea, vomiting, fatigue in one; hypertension and prolonged corrected QT interval in another) occurred in patients initially enrolled at 12 mg/m2/d. Subsequently, 8 mg/m2/d was well tolerated in three patients. An additional seven patients were enrolled at 12 mg/m2/d; one had DLT (grade 3 diarrhea). At 17 mg/m2/d, two of four patients had DLTs (grade 3 nausea; intolerable grade 2 fatigue). Non–dose-limiting toxicities included left ventricular dysfunction, elevated thyroid stimulating hormone, palmar-plantar erythrodysesthesia, weight loss, and headache. The MTD of cediranib was 12 mg/m2/d (adult fixed dose equivalent, 20 mg). At 12 mg/m2/d, the median area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) was 900 ng·h/mL, which is similar to adults receiving 20 mg. Objective responses were observed in patients with Ewing sarcoma, synovial sarcoma, and osteosarcoma. Conclusion The recommended monotherapy dose of cediranib for children with extracranial solid tumors is 12 mg/m2/d administered orally, once daily, continuously. A phase II study is in development.
Accrual Experience of National Cancer Institute Cooperative Group Phase III Trials Activated From 2000 to 2007
Authors: Korn Edward L. , Freidlin Boris , Mooney Margaret , Abrams Jeffrey S. 
Published: November 2010

Purpose Recent reports have suggested that 40% or more of National Cancer Institute (NCI) –sponsored Cooperative Group phase III trials failed to achieve their accrual goals. We examine in detail the accrual experience of the Cooperative Group phase III trials. Patients and Methods All Cooperative Group phase III trials activated from 2000 to 2007 were examined for their accrual experience. For trials that stopped accrual with < 90% of their accrual goal, the reasons for having < 90% accrual were documented. We focus on trials that ended with < 90% accrual because of inadequate accrual rates rather than for other reasons, such as an interim monitoring analysis by an independent data monitoring committee that stops the trial early because one treatment is clearly superior. Results There were 191 trials activated from 2000 to 2007. We project that 22.0% of these trials will have < 90% accrual because of inadequate accrual rates. We project that there will be 176,627 patients eventually accrued on the 191 trials (current accrual, 154,579) and that 2,991of these patients will be on trials that have < 90% accrual because of inadequate accrual rates (1.7%). For nonpediatric cancer trials, the corresponding percentages are 26.7% and 2.0%. Conclusion We find that insufficient accrual rates are not as high as previously reported and that only a small proportion of patients were enrolled on trials that ended with insufficient accrual because of an inadequate accrual rate. NCI has implemented new procedures to reduce the number of trials that fail to reach their accrual goals and to minimize the number of patients accrued on these trials.
Plasma Myeloperoxidase Predicts Incident Cardiovascular Risks in Stable Patients Undergoing Medical Management for Coronary Artery Disease
Authors: Tang WH Wilson , Wu Yuping , Nicholls Stephen J , Hazen Stanley L 
Published: November 2010

BACKGROUND
Myeloperoxidase (MPO) concentrations predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but the prognostic role of MPO in stable patients with known atherosclerotic burden is unclear.

METHODS
We examined plasma MPO concentrations and their relationship with prevalent significant coronary artery disease (defined as &gt;50% stenosis in any coronary vessel) and incident major adverse cardiovascular events (MACEs), including death, myocardial infarction, and stroke, in a 3-year prospective follow-up study of 1895 patients undergoing elective coronary angiography.

RESULTS
The median plasma MPO concentration was 101 pmol/L (interquartile range 68–187 pmol/L). Patients with plasma MPO concentrations &gt;322 pmol/L (14.6% of population) had increased risk of developing future MACEs [hazard ratio (HR) 1.78, 95% CI 1.33–2.37, P &lt; 0.001], and MPO as a single variable predictor of MACE showed an area under the ROC curve of 0.67. After adjusting for traditional cardiac risk factors, creatinine clearance, B-type natriuretic peptide, and high-sensitivity C-reactive protein (hsCRP), increased MPO concentrations remained significantly associated with incident MACEs over the ensuing 3-year period (HR 1.71; 95% CI 1.27–2.30, P &lt; 0.001). In patients with increased hsCRP, MPO ≤322 pmol/L was associated with lower event rates than observed with MPO &gt;322 pmol/L.

CONCLUSIONS
Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high.
Probleme der PSA-Bestimmung bei älteren Patienten: was ist sinnvoll? / PSA measurements in elderly patients: what makes sense?
Authors: Maruschke Matthias , Hakenberg Oliver W. 
Published: November 2010

Zusammenfassung
Das Prostatakarzinom ist der beim Mann heute am häufigsten diagnostizierte Tumor, dessen biologische Aggressivität primär wesentlich vom Tumorvolumen bestimmt wird. Aufgrund der verbreiteten PSA-basierten Frühdiagnostik sind heute bei Diagnosestellung zwei Drittel aller Prostatakarzinome organbegrenzt und damit kurativ therapierbar. Eine entscheidende Bedeutung hat daher die empfohlene PSA-Bestimmung bei Männern zwischen dem 40. und 75. Lebensjahr mit noch mindestens zehnjähriger Lebenserwartung und dem Willen zur Durchführung von notwendiger Diagnostik und Therapie bei auffälligen Befunden. Einen großen Stellenwert hat die regelmäßige PSA-Bestimmung bei bekannten Prostatakarzinomen ohne aktive Therapie unter Überwachungsmanagement, nach kurativer Lokaltherapie zur Verlaufskontrolle und zur Rezidivdiagnostik sowie bei systemischer Erkrankung zur Therapiekontrolle unter Hormonablation und/oder Chemotherapie.
Translation of next-generation sequencing (NGS) into molecular diagnostics / Umsetzung von Next Generation Sequencing in der molekularen Diagnostik
Authors: Kotschote Stefan , Wagner Carola , Marschall Christoph , Mayer Karin , Hirv Kaimo , Kerick Martin , Timmermann Bernd , Klein Hanns-Georg 
Published: November 2010

Abstract
In the past 5 years, next-generation sequencing (NGS) has been established as a valuable tool for several research applications. Commercially available platforms from Helicos, Illumina, Life Technologies, Pacific Biosciencies, and Roche allow for massively parallel sequencing and analysis in the fields of genomics, transcriptomics, and epigenomics. As in most projects, data throughput of the sequencers is not the limiting factor; genomic DNA samples are directly prepared for sequencing without prior conditioning. However, there are some applications such as targeted resequencing that do not require sequencing of whole genomes. Therefore, a technology called target enrichment was established more than 2 years ago. Different PCR- or hybridization-based approaches were further commercially developed and refined. The combination of this method with NGS can improve analysis of disease-related gene sets in molecular diagnostics by reducing time and costs. By taking advantage of the enormous data output, several genes and patients can be analyzed in parallel in one single instrument run.
Anti-AQP4-Antikörper als Biomarker zur Früherkennung von Neuromyelitis Optica-Spektrum-Erkrankungen / AQP4-IgG antibodies as biomarkers for early diagnosis of neuromyelitis optica spectrum disorders
Authors: Mader Simone , Deisenhammer Florian , Reindl Markus 
Published: November 2010

Zusammenfassung
Die Neuromyelitis Optica (NMO), eine entzündliche, demyelinisierende Erkrankung, welche insbesondere durch den selektiven Befall des Sehnervs und Rückenmarks charakterisiert ist, wird fälschlicherweise häufig als schwere Form der Multiplen Sklerose (MS) diagnostiziert. Die Entdeckung der AQP4-Antikörper im Serum von NMO und Hochrisiko (HR)-Patienten ermöglichte erstmals eine frühzeitige Dia-gnose und spezielle Behandlung. In diesem Artikel möchten wir einen Überblick über die diagnostische und therapeutische Bedeutung von AQP4-Antikörpern im Serum und Li-quor von NMO und HR-Patienten geben und deren Relevanz für den Krankheitsverlauf diskutieren.
Serum proteome changes in acromegalic patients following transsphenoidal surgery: novel biomarkers of disease activity
Authors: Cruz-Topete Diana , Christensen Britt , Sackmann-Sala Lucila , Okada Shigeru , Jorgensen Jens Otto L , Kopchick John J 
Published: November 2010

ContextTranssphenoidal adenomectomy is the primary treatment for acromegaly. However, assessment of the therapeutical outcome remains problematic since the existing biomarkers of disease activity frequently show discordant results.ObjectiveTo discover novel serum biomarkers of disease activity in acromegalic patients before and after surgery.DesignSerum samples of eight newly diagnosed acromegaly patients before and after transsphenoidal surgery were analyzed for proteomic changes by two-dimensional gel electrophoresis. Protein spots displaying statistically significant changes, pre- versus post-surgery, were identified by mass spectrometry (MS), tandem MS (MS/MS), and western blot analysis.ResultsSix protein spots displaying decreased intensities after surgery were identified as transthyretin (two isoforms), haptoglobin α2, β-hemoglobin, and apolipoprotein A-1 (two isoforms). One protein spot, identified as complement C4B precursor, was increased after the surgery.ConclusionsSeven serum protein spots were differentially expressed following surgery in acromegalic patients. The identified proteins represent potential novel biomarkers to assess the effectiveness of surgical treatment in acromegalic individuals. Future studies will validate the use of the identified proteins as biomarkers of disease activity after medical treatment of acromegaly.
Serum paraoxonase and arylesterase activities in metabolic syndrome in Zahedan, southeast Iran
Authors: Hashemi Mohammad , Kordi-Tamandani Dor Mohammad , Sharifi Nooshin , Moazeni-Roodi Abdolkarim , Kaykhaei Mahmoud-Ali , Narouie Behzad , Torkmanzehi Adam 
Published: November 2010

ObjectiveParaoxonase (PON) is associated with high-density lipoprotein and protects serum lipid from oxidation. The aim of this study was to determine serum PON, arylesterase (ARE) activities, and total antioxidant capacity (TAC) in metabolic syndrome (MES).MethodsThis case–control study was performed on 106 patients with MES and 231 healthy subjects. Serum PON and ARE activities were determined spectrophotometrically. TAC was determined using ferric reducing ability of plasma assay.ResultsThe results showed that serum PON activity was significantly lower in patients with MES (69.62±59.86 IU/l) than healthy subjects (91.64±77.45 IU/l) (P<0.05). The serum ARE activity in MES and normal subjects were 45.23±23.24 and 65.69±31.10 kU/l respectively. The ARE activity was significantly lower in patients with MES than normal subjects (P<0.0001). No significant differences were observed between MES and normal subjects regarding TAC.ConclusionThe lower PON and ARE activities in MES may be considered an independent risk factor for cardiovascular disease, which remains to be cleared.
Prediction of incident diabetes mellitus by baseline IGF1 levels
Authors: Schneider Harald Jörn , Friedrich Nele , Klotsche Jens , Schipf Sabine , Nauck Matthias , Völzke Henry , Sievers Caroline , Pieper Lars , März Winfried , Wittchen Hans-Ulrich , Stalla Günter Karl , Wallaschofski Henri 
Published: November 2010

ObjectiveIGF1 is associated with metabolic parameters and involved in glucose metabolism. Low-IGF1 has been implicated in the etiology of glucose intolerance and subjects with pathological causes of either low- or high-IGF1 are at risk of diabetes. We hypothesized that both low- and high-IGF1 levels increase the risk of diabetes and aimed to assess the role of IGF1 in the risk of developing diabetes in a large prospective study.DesignAn analysis of two prospective cohort studies, the DETECT study and SHIP.MethodsWe measured IGF1 levels in 7777 nondiabetic subjects and assessed incident diabetes mellitus during follow-up.ResultsThere were 464 cases of incident diabetes during 32 229 person-years (time of follow-up in the DETECT study and SHIP: 4.5 and 5 years respectively). There was no heterogeneity between both studies (P>0.4). The hazard ratios (HRs) of incident diabetes in subjects with IGF1 levels below the 10th or above the 90th age- and sex-specific percentile, compared to subjects with intermediate IGF1 levels, were 1.44 (95% confidence interval (CI) 1.07–1.94) and 1.55 (95% CI 1.06–2.06) respectively, after multiple adjustment. After further adjustment for metabolic parameters, the HR for low-IGF1 became insignificant. Analysis of IGF1 quintiles revealed a U-shaped association of IGF1 with risk of diabetes. Results remained similar after exclusion of patients with onset of new diabetes within 1 year or with borderline glucose or HbA1c levels at baseline.ConclusionsSubjects with low- or high-IGF1 level are at increased risk of developing diabetes.
Gestational Age and Basic School Achievements: A National Follow-up Study in Denmark
Authors: Mathiasen René , Hansen Bo M. , Andersen Anne-Marie N. Nybo , Forman Julie L. , Greisen Gorm 
Published: November 2010

OBJECTIVE:
Children born at &lt;32 weeks' gestation are at increased risk of intellectual impairment. Few studies have focused on the majority of preterm children born at 32 to 36 weeks' gestation. We aimed to investigate the association between the full range of gestational ages at birth and the risk of not completing basic school.

METHODS:
This longitudinal, register-based study included all live-born infants in Denmark from 1988 to 1989. Data were obtained from national registers. School achievements were evaluated by using the examination marks. The association between gestational age and not completing basic school was estimated, taking into account the effect of their parents' educational level, being small for gestational age, plurality, and cerebral palsy.

RESULTS:
The cohort constituted 120 585 infants, of whom 118 281 (98.6%) were alive in 2007. Of these infants, 5.01% (n = 5.928) were born before 37 weeks' gestation. Of the subjects born before 37 weeks' gestation, 11.5% (95% confidence interval: 10.7–12.4) did not complete basic school compared with 7.5% (95% confidence interval: 7.3–7.6) of those born at term. The percentage of subjects who did not complete basic school increased with decreasing gestational age. The increase was steeper at &lt;31 weeks (4.2% per week) than at 31 to 36 weeks' gestation (0.5% per week).

CONCLUSIONS:
The risk of not completing basic school increased with decreasing gestational age. The risk was moderate at ≥31 weeks' gestation and increased steeply at &lt;31 weeks' gestation. The increase at &lt;31 weeks' gestation was only partly explained by cerebral palsy.
Wartime Military Deployment and Increased Pediatric Mental and Behavioral Health Complaints
Authors: Gorman Gregory H. , Eide Matilda , Hisle-Gorman Elizabeth 
Published: November 2010

BACKGROUND:
Children of military personnel face stress when a parent deploys.

OBJECTIVE:
Our goal was to determine the effect of parental military deployment on the relative rate of outpatient visits for mental and behavioral health disorders in children aged 3 to 8 years.

METHODS:
This was a retrospective cohort study. Records of children of active-duty personnel during fiscal years 2006 and 2007 were linked with their parent's deployment records. Mental and behavioral health visits were identified by using International Classification of Diseases, Ninth Revision, codes. The incidence rate ratio (IRR) of visits per year according to parental deployment status was determined with random-effects negative binomial regression modeling with longitudinal data analysis.

RESULTS:
A total of 642 397 children aged 3 to 8 years and 442 722 military parents were included. Mean child age was 5.0 years (SD: 1.9 years); 50.6% were male, and 68.0% were white. Ninety percent of the parents were male, and 90.5% were married; 32.0% of the parents were deployed during the study. There were 1 049 081 person-years with 611 115 mental and behavioral health visits (0.6 visit per year). The IRR of mental and behavioral health visits for children with a deployed parent compared with when a parent was home was 1.11 (95% confidence interval [CI]: 1.07–1.14; P &lt; .001). IRRs of pediatric anxiety, behavioral, and stress disorders when a parent deployed were 1.14 (95% CI: 0.98–1.32; P = .095), 1.19 (95% CI: 1.07–1.32; P &lt; .001), and 1.18 (95% CI: 1.10–1.26; P &lt; .001), respectively. Older children and children with military fathers and married parents had larger increases in rates of mental and behavioral health visits during parental deployments. In contrast, the overall outpatient rate and rates of visits for other diagnoses decreased when a parent was deployed.

CONCLUSIONS:
Mental and behavioral health visits increased by 11% in these children when a military parent deployed; behavioral disorders increased 19% and stress disorders increased 18%. Rates especially increased in older children and children of married and male military parents.
Risk of Renal Scarring in Children With a First Urinary Tract Infection: A Systematic Review
Authors: Shaikh Nader , Ewing Amy L. , Bhatnagar Sonika , Hoberman Alejandro 
Published: November 2010

BACKGROUND:
To our knowledge, the risk of renal scarring in children with a urinary tract infection (UTI) has not been systematically studied.

OBJECTIVE:
To review the prevalence of acute and chronic renal imaging abnormalities in children after an initial UTI.

METHODS:
We searched Medline and Embase for English-, French-, and Spanish-language articles using the following terms: “Technetium 99mTc dimercaptosuccinic acid (DMSA),” “DMSA,” “dimercaptosuccinic,” “scintigra*,” “pyelonephritis,” and “urinary tract infection.” We included articles if they reported data on the prevalence of abnormalities on acute-phase (≤15 days) or follow-up (&gt;5 months) DMSA renal scans in children aged 0 to 18 years after an initial UTI. Two evaluators independently reviewed data from each article.

RESULTS:
Of 1533 articles found by the search strategy, 325 full-text articles were reviewed; 33 studies met all inclusion criteria. Among children with an initial episode of UTI, 57% (95% confidence interval [CI]: 50–64) had changes consistent with acute pyelonephritis on the acute-phase DMSA renal scan and 15% (95% CI: 11–18) had evidence of renal scarring on the follow-up DMSA scan. Children with vesicoureteral reflux (VUR) were significantly more likely to develop pyelonephritis (relative risk [RR]: 1.5 [95% CI: 1.1–1.9]) and renal scarring (RR: 2.6 [95% CI: 1.7–3.9]) compared with children with no VUR. Children with VUR grades III or higher were more likely to develop scarring than children with lower grades of VUR (RR: 2.1 [95% CI: 1.4–3.2]).

CONCLUSIONS:
The pooled prevalence values provided from this study provide a basis for an evidence-based approach to the management of children with this frequently occurring condition.