bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of the pro-apoptotic genes BID and FAS in septic shock patients
Authors: Turrel-Davin Fanny , Guignant Caroline , Lepape Alain , Mougin Bruno , Monneret Guillaume , Venet Fabienne 
Published: July 2010

Abstract
Introduction
Lymphocyte apoptosis has been suggested to play a central role in sepsis pathophysiology, and studies in animal models demonstrated that blocking this pathway improves outcome. However, no routine biomarkers of apoptosis are so far available in patients. Thus, the aim of our study was to assess the different biomarkers of apoptosis putatively usable on a routine basis in septic shock.

Methods
Thirteen septic shock patients (sampled twice between days 1 to 2 and days 3 to 5 after diagnosis of shock) and 15 sex-matched and age-matched healthy controls were prospectively enrolled. Apoptosis was measured in lymphocyte subpopulations using flow cytometry (Annexin-V binding, activated caspase-3 and Bcl-2 expressions). Representative pro-apoptotic and anti-apoptotic gene expressions were assessed by quantitative reverse-transcription PCR. Monocyte HLA-DR expression and lymphocyte subpopulation cell counts were measured as markers of sepsis-induced immune dysfunctions. To test for statistical significance, the Mann-Whitney U test was used with correction by the number of tests performed.

Results
Flow cytometric measurements of apoptosis in septic shock patients showed an increased Annexin-V binding on CD4+ T cells and an increased active caspase-3 expression on B cells only at days 3 to 5 (sixfold change and twofold change, respectively). Gene expression analysis showed an increased BCL-XL mRNA and an upregulation of the pro-apoptotic genes BID and FAS in septic shock patients (10-fold change and fivefold change, respectively) compared with healthy controls.

Conclusions
The present study highlights the difficulties encountered in monitoring apoptosis on a routine basis in septic patients, whereas in the same sampling conditions and on the same patients, HLA-DR expression and lymphocyte subpopulation cell counts showed characteristics described in the literature. However, pro-apoptotic genes BID and FAS appear to constitute promising apoptosis markers in our hands.
Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective
Authors: Moran John L , Graham Petra L , Rockliff Sue , Bersten Andrew D 
Published: July 2010

Abstract
Introduction
Current low (stress) dose corticosteroid regimens may have therapeutic advantage in severe sepsis and septic shock despite conflicting results from two landmark randomised controlled trials (RCT). We systematically reviewed the efficacy of corticosteroid therapy in severe sepsis and septic shock.

Methods
RCTs were identified (1950-September 2008) by multiple data-base electronic search (MEDLINE via OVID, OVID PreMedline, OVID Embase, Cochrane Central Register of Controlled trials, Cochrane database of systematic reviews, Health Technology Assessment Database and Database of Abstracts of Reviews of Effects) and hand search of references, reviews and scientific society proceedings. Three investigators independently assessed trial inclusion and data extraction into standardised forms; differences resolved by consensus.

Results
Corticosteroid efficacy, compared with control, for hospital-mortality, proportion of patients experiencing shock-resolution, and infective and non-infective complications was assessed using Bayesian random-effects models; expressed as odds ratio (OR, (95% credible-interval)). Bayesian outcome probabilities were calculated as the probability (P) that OR ≥1. Fourteen RCTs were identified. High-dose (>1000 mg hydrocortisone (equivalent) per day) corticosteroid trials were associated with a null (n = 5; OR 0.91(0.31-1.25)) or higher (n = 4, OR 1.46(0.73-2.16), outlier excluded) mortality probability (P = 42.0% and 89.3%, respectively). Low-dose trials (<1000 mg hydrocortisone per day) were associated with a lower (n = 9, OR 0.80(0.40-1.39); n = 8 OR 0.71(0.37-1.10), outlier excluded) mortality probability (20.4% and 5.8%, respectively). OR for shock-resolution was increased in the low dose trials (n = 7; OR 1.20(1.07-4.55); P = 98.2%). Patient responsiveness to corticotrophin stimulation was non-determinant. A high probability of risk-related treatment efficacy (decrease in log-odds mortality with increased control arm risk) was identified by metaregression in the low dose trials (n = 9, slope coefficient -0.49(-1.14, 0.27); P = 92.2%). Odds of complications were not increased with corticosteroids.

Conclusions
Although a null effect for mortality treatment efficacy of low dose corticosteroid therapy in severe sepsis and septic shock was not excluded, there remained a high probability of treatment efficacy, more so with outlier exclusion. Similarly, although a null effect was not excluded, advantageous effects of low dose steroids had a high probability of dependence upon patient underlying risk. Low dose steroid efficacy was not demonstrated in corticotrophin non-responders. Further large-scale trials appear mandated.
Nomogram for Predicting the Risk of Local Recurrence After Breast-Conserving Surgery for Ductal Carcinoma In Situ
Authors: Rudloff Udo , Jacks Lindsay M. , Goldberg Jessica I. , Wynveen Christine A. , Brogi Edi , Patil Sujata , Van Zee Kimberly J. 
Published: July 2010

Purpose While the mortality associated with ductal carcinoma in situ (DCIS) is minimal, the risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) is relatively high. Radiation therapy (RT) and antiestrogen agents reduce the risk of IBTR and are considered standard treatment options after BCS. However, they have never been proven to improve survival, and in themselves carry rare but serious risks. Individualized estimation of IBTR risk would assist in decision making regarding the various treatment options for women with DCIS. Patients and Methods From 1991 to 2006, 1,868 consecutive patients treated with BCS for DCIS were identified. A multivariate Cox proportional hazards model was constructed using the 1,681 in whom data were complete. Ten clinical, pathologic, and treatment variables were built into a nomogram estimating probability of IBTR at 5 and 10 years after BCS. The model was validated for discrimination and calibration using bootstrap resampling. Results The DCIS nomogram for prediction of 5- and 10-year IBTR probabilities demonstrated good calibration and discrimination, with a concordance index of 0.704 (bootstrap corrected, 0.688) and a concordance probability estimate of 0.686. Factors with the greatest influence on risk of IBTR in the model included adjuvant RT or endocrine therapy, age, margin status, number of excisions, and treatment time period. Conclusion The DCIS nomogram integrates 10 clinicopathologic variables to provide an individualized risk estimate of IBTR in a woman with DCIS treated with BCS. This tool may assist in individual decision making regarding various treatment options and help avoid over- and undertreatment of noninvasive breast cancer.
Biologic Correlation of 2-[18F]-Fluoro-2-Deoxy-D-Glucose Uptake on Positron Emission Tomography in Thymic Epithelial Tumors
Authors: Kaira Kyoichi , Endo Masahiro , Abe Masato , Nakagawa Kazuo , Ohde Yasuhisa , Okumura Takehiro , Takahashi Toshiaki , Murakami Haruyasu , Tsuya Asuka , Nakamura Yukiko , Naito Tateaki , Hayashi Isamu , Serizawa Masakuni , Koh Yasuhiro , Hanaoka Hirofumi , Tominaga Hideyuki , Oriuchi Noboru , Kondo Haruhiko , Nakajima Takashi , Yamamoto Nobuyuki 
Published: July 2010

Purpose The usefulness of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) can help predict the grade of malignancy and staging in thymic epithelial tumors. However, no satisfactory biologic explanation exists for this phenomenon. The aim of this study was to investigate the underlying biologic mechanisms of [18F]FDG uptake. Patients and Methods Forty-nine patients with thymic epithelial tumors who underwent [18F]FDG PET were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3), hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial growth factor (VEGF), microvessels (CD31 and CD34), cell cycle control marker (p53), and apoptosis marker (bcl-2). We also conducted an in vitro study of [18F]FDG uptake in a thymic tumor cell line. Results There was a positive correlation between [18F]FDG uptake and GLUT1 (P < .0001), HIF-1α (P = .0036), VEGF (P < .0001), microvessel density (MVD; P < .0001), and p53 (P = .0002). GLUT3 and bcl-2 showed no positive correlation with [18F]FDG uptake. The expression of Glut1, HIF-1α, VEGF, CD31, CD34, and p53 was also significantly associated with the grade of malignancy and poor outcome in thymic epithelial tumors, whereas this relationship was not observed in GLUT3 and bcl-2. Our in vitro study demonstrated that upregulation of GLUT1 and HIF-1α was closely associated with [18F]FDG uptake into thymic tumor cell. Conclusion [18F]FDG uptake in thymic epithelial tumors is determined by the presence of glucose metabolism (GLUT1), hypoxia (HIF-1α), angiogenesis (VEGF and MVD), and cell cycle regulator (p53).
Hematopoietic Stem-Cell Transplantation for Acute Leukemia in Relapse or Primary Induction Failure
Authors: Duval Michel , Klein John P. , He Wensheng , Cahn Jean-Yves , Cairo Mitchell , Camitta Bruce M. , Kamble Rammurti , Copelan Edward , de Lima Marcos , Gupta Vikas , Keating Armand , Lazarus Hillard M. , Litzow Mark R. , Marks David I. , Maziarz Richard T. , Rizzieri David A. , Schiller Gary , Schultz Kirk R. , Tallman Martin S. , Weisdorf Daniel 
Published: July 2010

Purpose Patients with acute leukemia refractory to induction or reinduction chemotherapy have poor prognoses if they do not undergo hematopoietic stem-cell transplantation (HSCT). However, HSCT when a patient is not in complete remission (CR) is of uncertain benefit. We hypothesized that pretransplantation variables may define subgroups that have a better prognosis. Patients and Methods Overall, 2,255 patients who underwent transplantation for acute leukemia in relapse or with primary induction failure after myeloablative conditioning regimen between 1995 and 2004 were reported to the Center for International Blood and Marrow Transplant Research. The median follow-up of survivors was 61 months. We performed multivariate analysis of pretransplantation variables and developed a predictive scoring system for survival. Results The 3-year overall survival (OS) rates were 19% for acute myeloid leukemia (AML) and 16% for acute lymphoblastic leukemia (ALL). For AML, five adverse pretransplantation variables significantly influenced survival: first CR duration less than 6 months, circulating blasts, donor other than HLA-identical sibling, Karnofsky or Lansky score less than 90, and poor-risk cytogenetics. For ALL, survival was worse with the following: first refractory or second or greater relapse, ≥ 25% marrow blasts, cytomegalovirus-seropositive donor, and age of 10 years or older. Patients with AML who had a predictive score of 0 had 42% OS at 3 years, whereas OS was 6% for a score ≥ 3. Patients with ALL who had a score of 0 or 1 had 46% 3-year OS but only 10% OS rate for a score ≥ 3. Conclusion Pretransplantation variables delineate subgroups with different outcomes. HSCT during relapse can achieve long-term survival in selected patients with acute leukemia.
Pyridoxine Is Not Effective to Prevent Hand-Foot Syndrome Associated With Capecitabine Therapy: Results of a Randomized, Double-Blind, Placebo-Controlled Study
Authors: Kang Yoon-Koo , Lee Sung Sook , Yoon Dok Hyun , Lee So Young , Chun Young Ju , Kim Min Sun , Ryu Min-Hee , Chang Heung-Moon , Lee Jae-Lyun , Kim Tae Won 
Published: July 2010

Purpose To determine whether concurrent pyridoxine therapy can prevent the development of hand-foot syndrome (HFS) in patients being treated with capecitabine. Methods Chemotherapy-naive patients with GI tract cancers scheduled for capecitabine-containing chemotherapy were randomly assigned to concurrent oral pyridoxine (200 mg/d) or placebo. Patients were stratified by chemotherapy regimen and monitored until development of National Cancer Institute Common Toxicity Criteria grade 2 or worse HFS or capecitabine-containing chemotherapy ended. Patients in the placebo group who developed grade 2 or worse HFS were randomly assigned again to receive pyridoxine or placebo in the next chemotherapy cycle to determine whether pyridoxine could improve HFS. Results The median number of chemotherapy cycles to grade 2 or worse HFS was three in both groups. Grade 2 or worse HFS developed in 55 (30.6%) of 180 placebo-treated patients and in 57 (31.7%) of 180 pyridoxine patients. The cumulative dose of capecitabine to grade 2 or worse HFS was not different between the two groups (median not reached in either group; hazard ratio [HR] = 0.95; P = .788). Randomization of the 44 patients in the placebo group with grade 2 or worse HFS to placebo or pyridoxine for the next cycle resulted in no significant difference in the proportion showing improvement of HFS (42.9% v 47.8%; HR = 1.12; P = .94). By multivariate analysis, age ≥ 56 years (HR = 1.768; 95% CI, 1.190 to 2.628; P = .005) was an independent risk factor for grade 2 or worse HFS, and combined use of docetaxel (HR = 2.046; 95% CI, 0.880 to 4.755; P = .096) was of borderline significance. Conclusion Pyridoxine is not effective in prevention of capecitabine-associated HFS.
Therapy-Related Myeloid Neoplasms in Patients With Acute Promyelocytic Leukemia Treated With All-Trans-Retinoic Acid and Anthracycline-Based Chemotherapy
Authors: Montesinos Pau , González José D. , González José , Rayón Chelo , de Lisa Elena , Amigo Maria L. , Ossenkoppele Gert J. , Peñarrubia María J. , Pérez-Encinas Manuel , Bergua Juan , Debén Guillermo , Sayas María J. , de la Serna Javier , Ribera Josep M. , Bueno Javier , Milone Gustavo , Rivas Concha , Brunet Salut , Löwenberg Bob , Sanz Miguel 
Published: July 2010

PurposeWe analyzed the incidence, risk factors, and outcome of therapy-related myeloid neoplasms (t-MNs) in patients with acute promyelocytic leukemia (APL) in first complete remission (CR).Patients and MethodsFrom 1996 to 2008, 1,025 patients with APL were enrolled onto three sequential trials (LPA96, LPA99, and LPA2005) of the Programa Español para el Tratamiento de Enfermedades Hematológicas and received induction and consolidation therapy with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy.ResultsSeventeen of 918 patients who achieved CR developed t-MN (10 with < 20% and seven with ≥ 20% of bone marrow blasts) after a median of 43 months from CR. Partial and complete deletions of chromosomes 5 and 7 (nine patients) and 11q23 rearrangements (three patients) were the most common cytogenetic abnormalities. Overall, the 6-year cumulative incidence of t-MN was 2.2%, whereas in low-, intermediate-, and high-risk patients, the 6-year incidence was 5.2%, 2.1%, and 0%, respectively. Multivariate analysis identified age more than 35 years and lower relapse risk score as independent prognostic factors for t-MN. The median overall survival time after t-MN was 10 months.Conclusiont-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted.
Neoadjuvant Paclitaxel, Ifosfamide, and Cisplatin Chemotherapy for Metastatic Penile Cancer: A Phase II Study
Authors: Pagliaro Lance C. , Williams Dallas L. , Daliani Danai , Williams Michael B. , Osai William , Kincaid Michael , Wen Sijin , Thall Peter F. , Pettaway Curtis A. 
Published: July 2010

Purpose Men with penile squamous cell carcinoma and regional lymph node involvement have a low probability of survival with lymphadenectomy alone. A multimodal approach to treatment is desirable for such patients. We performed a phase II study of neoadjuvant chemotherapy with the objective of determining the response rate, time to progression (TTP), and overall survival (OS) among patients with bulky adenopathy. Patients and Methods Eligible patients had stage N2 or N3 (stage III or stage IV) penile cancer without distant metastases. Neoadjuvant treatment (four courses every 3-4 weeks) consisted of paclitaxel 175 mg/m2 administered over 3 hours on day 1; ifosfamide 1,200 mg/m2 on days 1 to 3; and cisplatin 25 mg/m2 on days 1 to 3. Clinical and pathologic responses were assessed, and patient groups were compared for TTP and OS. Results Thirty men received chemotherapy of whom 15 (50.0%) had an objective response and 22 (73.3%) subsequently underwent surgery. Three patients had no remaining tumor on histopathology. Nine patients (30.0%) remained alive and free of recurrence (median follow-up, 34 months; range, 14-59 months), and two patients died of other causes without recurrence. Improved TTP and OS were significantly associated with a response to chemotherapy (P < .001 and P = .001, respectively), absence of bilateral residual tumor (P = .002 and P = .017, respectively), and absence of extranodal extension (P = .001 and P = .004, respectively) or skin involvement (P = .009 and P = .012, respectively). Conclusion The neoadjuvant regimen of paclitaxel, ifosfamide, and cisplatin induced clinically meaningful responses in patients with bulky regional lymph node metastases from penile cancer.
Analysis of the Physicochemical State of C-Reactive Protein in Different Preparations Including 2 Certified Reference Materials
Authors: Rzychon Malgorzata , Zegers Ingrid , Schimmel Heinz 
Published: July 2010

BACKGROUND
Standardization of clinical measurements of C-reactive protein (CRP) is based on the availability of reference materials. The serum protein reference material ERM-DA470 was used as a calibrant for various commercially available immunoassays but has now been exhausted. The recently released ERM-DA470k/IFCC was intended to fully replace ERM-DA470. However, the new material was not suited for the certification of CRP because of a bias introduced by the lyophilization process that caused loss of about 20% of CRP measurable by routine immunoassays, compared with the nonlyophilized material that was stored in a liquid frozen state.

METHODS
We investigated the physicochemical state of CRP in a set of 4 lyophilized and 2 nonlyophilized serum-based CRP-containing materials by semi-native gel electrophoresis, Western blotting, and gel filtration.

RESULTS
We detected a monomeric form of CRP (mCRP) in lyophilized materials at a concentration significantly higher than seen in the materials not subjected to lyophilization. Different reconstitution protocols led to variations of the monomeric CRP fraction found in reconstituted, previously lyophilized material.

CONCLUSIONS
Most of the 20% loss in measured CRP after lyophilization of the material can be accounted for by the dissociation of natively pentameric CRP into subunits. The observed dissociation results from lyophilization and subsequent reconstitution of the material at insufficient concentration levels of calcium ions. In the presence of various protein forms, differences in antibody specificity and reactivity between immunoassays and alterations of stoichiometry of antigen–antibody interactions can contribute to the divergence of the measured values.
A proposed accelerated field stake test for rapid assessment of wood preservative systems
Authors: Schultz Tor P. , Nicholas Darrel D. 
Published: July 2010

Abstract
A ground-contact field test which would yield faster deterioration data when testing new wood preservative systems would be useful. This paper reports on an accelerated field test concept where wood samples are treated with a proposed preservative and a reference system with known efficacy, with the treated samples installed next to ground-contact wood feeder stakes that are already infected with wood decay fungi. This method was employed to compare decay efficacies of wood treated with four copper systems commonly available in the US. Two preliminary short-term studies show that this test method can provide differentiation between preservatives systems after only a short exposure period.
Duration of Illness in Infants With Bronchiolitis Evaluated in the Emergency Department
Authors: Petruzella Frank D. , Gorelick Marc H. 
Published: July 2010

OBJECTIVES:
To describe the duration of illness in infants with first-time bronchiolitis who present to an emergency department (ED) and assess the burden of the illness on caregivers and families.

METHODS:
This was a prospective cohort study of infants younger than 12 months who presented to a tertiary care children's hospital ED with a first episode of bronchiolitis. Subjects were excluded if they had a history of bronchodilator use or immunocompromise. Demographic and clinical data were collected in the ED. Outcomes data were collected by weekly telephone interviews for 4 weeks or until the subject was free of cough for 24 hours.

RESULTS:
Ninety-five infants were enrolled from November 2007 to March 2008. Median duration of symptoms was 15 days; 25% of the infants remained symptomatic after 21 days. Subjects with a history of eczema trended toward a longer median duration of symptoms when compared with those who did not (18 days [interquartile range (IQR): 15.5–24] and 15 days [IQR: 11–19], respectively; P = .055). Duration of symptoms did not significantly vary with regards to respiratory syncytial virus status or secondhand smoke exposure. Subjects missed a median of 2.5 days (IQR: 0.5–5.5) of day care, and caregivers missed a median of 2 days (IQR: 1–4) of work. Of these infants, 37.1% (95% confidence interval: 24.3–44.1) had a subsequent unscheduled medical visit.

CONCLUSIONS:
Infants seen in the ED for bronchiolitis have a prolonged disease course, with substantial burden to the family. Symptom duration may be influenced by a propensity toward atopy. Clinicians may use this information for counseling families.
Universal Versus Targeted Blood Cholesterol Screening Among Youth: The CARDIAC Project
Authors: Ritchie Susan K. , Murphy Emily C.-S. , Ice Christa , Cottrell Lesley A. , Minor Valerie , Elliott Eloise , Neal William 
Published: July 2010

OBJECTIVES:The goal was to determine the sensitivity and specificity of family history in identifying children with severe or genetic hyperlipidemias in a rural, predominantly white population.METHODS:A total of 20266 fifth-grade children in West Virginia, from the Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project, who completed a family history and fasting lipid profile were used in analyses. The relationship between hyperlipidemia and family history was determined, and the use of family history to predict the need for pharmacologic treatment among children with dyslipidemia was evaluated.RESULTS:A total of 71.4% of children met the National Cholesterol Education Program (NCEP) guidelines for cholesterol screening on the basis of positive family history. Of those, 1204 (8.3%) were considered to have dyslipidemia (low-density lipoprotein ≥130 mg/dL), and 1.2% of these children with dyslipidemia warranted possible pharmacologic treatment (low-density lipoprotein ≥160 mg/dL). Of the 28.6% who did not have a positive family history (did not meet NCEP guidelines), 548 (9.5%) had dyslipidemia, 1.7% of whom warranted pharmacologic treatment. Sensitivity and specificity data demonstrated that family history does not provide a strong indication as to whether pharmacologic treatment may be warranted.CONCLUSIONS:Results indicate that the use of family history to determine the need for cholesterol screening in children would have (1) missed many with moderate dyslipidemia and (2) failed to detect a substantial number with likely genetic dyslipidemias that would require pharmacologic treatment. The use of universal cholesterol screening would identify all children with severe dyslipidemia, allowing for proper intervention and follow-up and leading to the prevention of future atherosclerotic disease.