bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma soluble vascular endothelial growth factor receptor-1 levels predict outcomes of pneumonia-related septic shock patients: a prospective observational study
Authors: Yang Kuang-Yao , Liu Kuan-Ting , Chen Yu-Chun , Chen Chun-Sheng , Lee Yu-Chin , Perng Reury-Perng , Feng Jia-Yih 
Published: February 2011

Abstract
Introduction
Despite recent advances in the management of septic shock, mortality rates are still unacceptably high. Early identification of the high-mortality risk group for early intervention remains an issue under exploration. Vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR1) and urokinase plasminogen activator (uPA) have diverse effects in the pathogenesis of sepsis, which involve pro-inflammation, anti-inflammation, endothelial cell repair, and vascular permeability change. Their roles in predicting mortality and organ dysfunction remain to be clarified.

Methods
Pneumonia-related septic shock patients from medical intensive care units were enrolled for this prospective observational study. We also included 20 patients with pneumonia without organ dysfunction for comparison. Plasma levels of VEGF and sVEGFR1 and uPA activity within 24 hours of shock onset were measured. We compared plasma levels of these biomarkers with APACHE II scores between subgroups of patients, and evaluated their predictive value for 28-day mortality and organ dysfunction.

Results
A total of 101 patients, including 81 with pneumonia-related septic shock and 20 with pneumonia without organ dysfunction, were enrolled. Non-survivors of septic shock had significantly higher plasma sVEGFR1 levels (659.3 ± 1022.8 vs. 221.1 ± 268.9 pg/mL, respectively, P < 0.001) and uPA activity (47.2 ± 40.6 vs. 27.6 ± 17.2 units, respectively, P = 0.001) when compared with those of the survivors. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients with higher levels of sVEGFR1 (P < 0.001) and uPA activity (P = 0.031). In Cox regression analysis, plasma sVEGFR1 level was independently associated with, and best predicted, the 28-day mortality of septic shock (HR: 1.55, 95% CI: 1.05-2.30). Plasma sVEGFR1 level and uPA activity had good correlation with renal dysfunction, metabolic acidosis, and hematologic dysfunction; their levels significantly increased when the number of organ dysfunctions increased. In multivariate analysis, plasma sVEGFR1 level (HR: 2.82, 95% CI: 1.17-6.81) and uPA activity (HR: 2.75, 95% CI: 1.06-7.13) were independent predictors of the presence of concomitant multi-organ dysfunction. The predictive value of VEGF for mortality and organ dysfunction was limited in pneumonia-related septic shock patients.

Conclusions
High plasma sVEGFR1 level in the early stage of pneumonia-related septic shock independently predicted 28-day mortality and multi-organ dysfunction.
The dynamic pattern of end-tidal carbon dioxide during cardiopulmonary resuscitation: difference between asphyxial cardiac arrest and ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest
Authors: Lah Katja , Križmarić Miljenko , Grmec Štefek 
Published: February 2011

Abstract
Introduction
Partial pressure of end-tidal carbon dioxide (PetCO2) during cardiopulmonary resuscitation (CPR) correlates with cardiac output and consequently has a prognostic value in CPR. In our previous study we confirmed that initial PetCO2 value was significantly higher in asphyxial arrest than in ventricular fibrillation/pulseless ventricular tachycardia (VF/VT) cardiac arrest. In this study we sought to evaluate the pattern of PetCO2 changes in cardiac arrest caused by VF/VT and asphyxial cardiac arrest in patients who were resuscitated according to new 2005 guidelines.

Methods
The study included two cohorts of patients: cardiac arrest due to asphyxia with initial rhythm asystole or pulseless electrical activity (PEA), and cardiac arrest due to arrhythmia with initial rhythm VF or pulseless VT. PetCO2 was measured for both groups immediately after intubation and repeatedly every minute, both for patients with or without return of spontaneous circulation (ROSC). We compared the dynamic pattern of PetCO2 between groups.

Results
Between June 2006 and June 2009 resuscitation was attempted in 325 patients and in this study we included 51 patients with asphyxial cardiac arrest and 63 patients with VF/VT cardiac arrest. The initial values of PetCO2 were significantly higher in the group with asphyxial cardiac arrest (6.74 ± 4.22 kilopascals (kPa) versus 4.51 ± 2.47 kPa; P = 0.004). In the group with asphyxial cardiac arrest, the initial values of PetCO2 did not show a significant difference when we compared patients with and without ROSC (6.96 ± 3.63 kPa versus 5.77 ± 4.64 kPa; P = 0.313). We confirmed significantly higher initial PetCO2 values for those with ROSC in the group with primary cardiac arrest (4.62 ± 2.46 kPa versus 3.29 ± 1.76 kPa; P = 0.041). A significant difference in PetCO2 values for those with and without ROSC was achieved after five minutes of CPR in both groups. In all patients with ROSC the initial PetCO2 was again higher than 1.33 kPa.

Conclusions
The dynamic pattern of PetCO2 values during out-of-hospital CPR showed higher values of PetCO2 in the first two minutes of CPR in asphyxia, and a prognostic value of initial PetCO2 only in primary VF/VT cardiac arrest. A prognostic value of PetCO2 for ROSC was achieved after the fifth minute of CPR in both groups and remained present until final values. This difference seems to be a useful criterion in pre-hospital diagnostic procedures and attendance of cardiac arrest.
Menstrual History and Quality-of-Life Outcomes in Women With Node-Positive Breast Cancer Treated With Adjuvant Therapy on the NSABP B-30 Trial
Authors: Ganz Patricia A. , Land Stephanie R. , Geyer Charles E. , Cecchini Reena S. , Costantino Joseph P. , Pajon Eduardo R. , Fehrenbacher Louis , Atkins James N. , Polikoff Jonathan A. , Vogel Victor G. , Erban John K. , Livingston Robert B. , Perez Edith A. , Mamounas Eleftherios P. , Wolmark Norman , Swain Sandra M. 
Published: February 2011

Purpose Premenopausal women with breast cancer receiving adjuvant chemotherapy are at risk for amenorrhea. The National Surgical Adjuvant Breast and Bowel Project B-30 trial included menstrual history (MH) and quality-of-life (QOL) studies to compare treatments on these outcomes. Patients and Methods Patients were randomly assigned to sequential doxorubicin (A) and cyclophosphamide (C) followed by docetaxel (T; AC→T), concurrent TAC, or AT, which varied in duration (24, 12, 12 weeks, respectively), and use of C. Endocrine therapy was prescribed for women with hormone receptor–positive tumors. MH and QOL were assessed with standardized questionnaires at baseline; cycle 4, day 1; and every 6 months through 24 months. Prespecified analyses examined rates of amenorrhea by treatment arm, the relationship between amenorrhea and QOL, and QOL by treatment arm. Results Amenorrhea 12 months after random assignment was significantly different between treatment groups: 69.8% for AC→T, 57.7% for TAC, and 37.9% for AT (P < .001). The AT group without tamoxifen had the lowest rate of amenorrhea. QOL was poorer for patients receiving AC→T at 6 months but similar to others by 12 months. Post-treatment symptoms were increased above baseline for all treatments. Multivariable repeated measures modeling demonstrated that treatment arm, time point, age, and tamoxifen use were significantly associated with symptom severity (all P values < .002). Conclusion Amenorrhea rates differed significantly by treatment arm, with the AT arm having the lowest rate. Patients treated with longer duration therapy (AC→T) had greater symptom severity and poorer QOL at 6 months, but did not differ from shorter duration treatments at 12 months.
Quality of Life of Older Patients With Early-Stage Breast Cancer Receiving Adjuvant Chemotherapy: A Companion Study to Cancer and Leukemia Group B 49907
Authors: Kornblith Alice B. , Lan Lan , Archer Laura , Partridge Ann , Kimmick Gretchen , Hudis Clifford , Winer Eric , Casey Rebecca , Bennett Samantha , Cohen Harvey Jay , Muss Hyman B. 
Published: February 2011

Purpose A phase III trial (Cancer and Leukemia Group B CALGB-49907) was conducted to test whether older patients with early-stage breast cancer would have equivalent relapse-free and overall survival with capecitabine compared with standard chemotherapy. The quality of life (QoL) substudy tested whether capecitabine treatment would be associated with a better QoL than standard chemotherapy. Patients and Methods QoL was assessed in 350 patients randomly assigned to either standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin and cyclophosphamide [AC]; n = 182) or capecitabine (n = 168). Patients were interviewed by telephone before treatment (baseline), midtreatment, within 1 month post-treatment, and at 12, 18, and 24 months postbaseline by using questionnaires from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), a breast systemic adverse effects scale (EORTC BR23), and the Hospital Anxiety and Depression Scale (HADS). Results Compared with patients who were treated with standard chemotherapy, patients who were treated with capecitabine had significantly better QoL, role function, and social function, fewer systemic adverse effects, less psychological distress, and less fatigue during and at the completion of treatment (P ≤ .005). Capecitabine treatment was associated with less nausea, vomiting, and constipation and with better appetite than standard treatment (P ≤ .004), but worse hand-foot syndrome and diarrhea (P < .005). These differences all resolved by 12 months. Conclusion Standard chemotherapy was superior to capecitabine in improving relapse-free and overall survival for older women with early-stage breast cancer. Although capecitabine was associated with better QoL during treatment, QoL was similar for both groups at 1 year. The brief period of poorer QoL with standard treatment is a modest price to pay for a chance at improved survival.
Trajectory of Performance Status and Symptom Scores for Patients With Cancer During the Last Six Months of Life
Authors: Seow Hsien , Barbera Lisa , Sutradhar Rinku , Howell Doris , Dudgeon Deborah , Atzema Clare , Liu Ying , Husain Amna , Sussman Jonathan , Earle Craig 
Published: February 2011

Purpose Ontario's cancer system is unique because it has implemented two standardized assessment tools population-wide to improve care: the Edmonton Symptom Assessment System (ESAS) measures severity of nine symptoms (scale 0 to 10; 10 indicates the worst) and the Palliative Performance Scale (PPS) measures performance status (scale 0 to 100; 0 indicates death). This article describes the trajectory of ESAS and PPS scores 6 months before death. Patients and Methods Observational cohort study of cancer decedents between 2007 and 2009. Decedents required ≥1 ESAS or PPS assessment in the 6 months before death for inclusion. Outcomes were the decedents' average ESAS and PPS scores per week before death. Results Ten thousand seven hundred fifty-two (ESAS) and 7,882 (PPS) decedents were included. The mean age was 65 years, half were female, and approximately 75% of assessments occurred in cancer clinics. Average PPS score declined slowly over the 6 months before death, starting at approximately 70 and ending at 40, declining more rapidly in the last month. For ESAS symptoms, average pain, nausea, anxiety, and depression scores remained relatively stable over the 6 months. Conversely, shortness of breath, drowsiness, well-being, lack of appetite, and tiredness increased in severity over time, particularly in the month before death. More than one third of the cohort reported moderate to severe scores (ie, 4 to 10) for most symptoms in the last month of life. Conclusion In this large outpatient cancer population, trajectories of mean ESAS scores followed two patterns: increasing versus generally flat. The latter was perhaps due to available treatment (eg, prescriptions) for those symptoms. Future research should prioritize addressing symptoms that worsen over time.
Cetuximab Plus Capecitabine and Irinotecan Compared With Cetuximab Plus Capecitabine and Oxaliplatin As First-Line Treatment for Patients With Metastatic Colorectal Cancer: AIO KRK-0104—A Randomized Trial of the German AIO CRC Study Group
Authors: Moosmann Nicolas , von Weikersthal Ludwig Fischer , Vehling-Kaiser Ursula , Stauch Martina , Hass Holger G. , Dietzfelbinger Herrmann , Oruzio Daniel , Klein Stefan , Zellmann Klaus , Decker Thomas , Schulze Mathias , Abenhardt Wolfgang , Puchtler Gerhard , Kappauf Herbert , Mittermüller Johann , Haberl Christopher , Schalhorn Andreas , Jung Andreas , Stintzing Sebastian , Heinemann Volker 
Published: February 2011

Purpose The AIO KRK-0104 randomized phase II trial investigated the efficacy and safety of cetuximab combined with capecitabine and irinotecan (CAPIRI) or capecitabine and oxaliplatin (CAPOX) in the first-line treatment of metastatic colorectal cancer (mCRC). Patients and Methods A total of 185 patients with mCRC were randomly assigned to cetuximab (400 mg/m2 day 1, followed by 250 mg/m2 weekly) plus CAPIRI (irinotecan 200 mg/m2, day 1; capecitabine 800 mg/m2 twice daily days 1 through 14, every 3 weeks; or cetuximab plus CAPOX (oxaliplatin 130 mg/m2 day 1; capecitabine 1,000 mg/m2 twice daily day 1 through 14, every 3 weeks). The primary study end point was objective response rate (ORR). Results In the intention-to-treat patient population (n = 177), ORR was 46% (95% CI, 35 to 57) for CAPIRI plus cetuximab versus 48% (95% CI, 37 to 59) for CAPOX plus cetuximab. Analysis of the KRAS gene mutation status was performed in 81.4% of the intention to treat population. Patients with KRAS wild-type in the CAPIRI plus cetuximab arm showed an ORR of 50.0%, a PFS of 6.2 months and an OS of 21.1 months. In the CAPOX plus cetuximab arm, an ORR of 44.9%, a PFS of 7.1 months and an OS of 23.5 months were observed. While ORR and PFS were comparable in KRAS wild-type and mutant subgroups, a trend toward longer survival was associated with KRAS wild-type. Both regimens had manageable toxicity profiles and were safe. Conclusion This randomized trial demonstrates that the addition of cetuximab to CAPIRI or CAPOX is effective and safe in first-line treatment of mCRC. In the analyzed regimens, ORR and PFS did not differ according to KRAS gene mutation status.
Adverse Prognostic Factors for Testicular Cancer–Specific Survival: A Population-Based Study of 27,948 Patients
Authors: Fosså Sophie D. , Cvancarova Milada , Chen Linlin , Allan Annie L. , Oldenburg Jan , Peterson Derick R. , Travis Lois B. 
Published: February 2011

Purpose The prognostic significance of age at testicular cancer (TC) diagnosis, socioeconomic status (SES), race, and marital status on TC-specific mortality is not well-characterized. In a cancer that is so curable, it is important to identify any influence that confers an increased risk of TC-specific mortality. Patients and Methods Using multivariate cause-specific Cox regression models that accounted for competing risks, hazard ratios (HRs) were calculated for 10-year TC-specific mortality among 27,948 patients with TC reported to the Surveillance, Epidemiology and End Results program (1978 to 2006). Independent predictors were age at diagnosis, SES, race, marital status, extent of disease (EOD), calendar year of diagnosis, radiotherapy, and retroperitoneal lymph node dissection (RPLND). Results Compared with younger patients, diagnostic age 40+ was associated with increased mortality (seminoma, HR, 2.00, P < .001; nonseminoma, HR, 2.09; P < .001; most evident in metastatic disease, HR, 8.62; P < .001; HR, 6.35; P < .001, respectively). Unmarried men had two-to three-fold excess mortality compared to married men (HR, 2.97; P < .001; HR, 1.54; P < .001, respectively). Among nonseminoma patients, decreasing SES (P trend < .001) and nonwhite race (HR, 2.11; P < .001) increased mortality. Diagnosis after 1987 resulted in reduced mortality compared to earlier calendar years (HR, 0.58; P = .001; HR, 0.74; P = .001, respectively). Lack of RPLND was associated with seven-fold increase in death (P < .001). Conclusion TC-specific mortality is doubled among US patients diagnosed with seminoma or nonseminoma after age 40, even when initial treatment and EOD are taken into account. Among men with nonseminoma, nonwhite race and lower SES also significantly increase TC-specific mortality. Additional research is needed, enabling the development of interventional strategies and preventive approaches, as applicable.
Circulating Interleukin (IL)-8, IL-2R, IL-12, and IL-15 Levels Are Independently Prognostic in Primary Myelofibrosis: A Comprehensive Cytokine Profiling Study
Authors: Tefferi Ayalew , Vaidya Rakhee , Caramazza Domenica , Finke Christy , Lasho Terra , Pardanani Animesh 
Published: February 2011

Purpose Abnormal cytokine expression accompanies myelofibrosis and might be a therapeutic target for Janus-associated kinase (JAK) inhibitor drugs. This study describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis (PMF) and examines their phenotypic correlates and prognostic significance. Patients and Methods Patients included in this study were required to have archived plasma, bone marrow biopsy, and cytogenetic information available at the time of first referral to the Mayo Clinic. Multiplex biometric sandwich immunoassay was used to measure plasma levels of 30 cytokines. Results In total, 127 PMF patients were studied; comparison with normal controls (n = 35) revealed significantly increased interleukin-1β (IL-1β), IL-1RA, IL-2R, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, tumor necrosis factor α (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon alfa (IFN-α), macrophage inflammatory protein 1α (MIP-1α), MIP-1β, hepatocyte growth factor (HGF), IFN-γ–inducible protein 10 (IP-10), monokine induced by IFN-γ (MIG), monocyte chemotactic protein 1 (MCP-1), and vascular endothelial growth factor (VEGF) levels and decreased IFN-γ levels. In treatment-naive patients (n = 90), increased levels of IL-8 (P < .001), IL-2R (P < .001), IL-12 (P < .001), IL-15 (P = .001), and IP-10 (P = .003) were independently predictive of inferior survival. A similar multivariable analysis that included all 127 study patients confirmed the prognostic value of these five cytokines, and IL-8, IL-2R, IL-12, and IL-15 remained significant when risk stratification, according to the recently revised Dynamic International Prognostic Scoring System (DIPSS plus), was added to the multivariable model. Leukemia-free survival was predicted by IL-8, which was also the only cytokine associated with ≥ 1% circulating blasts. Other cytokine-phenotype associations included increased IL-8 and constitutional symptoms; IL-2R, IL-12, and transfusion need; IL-2R, IL-8, and leukocytosis; IP-10 and thrombocytopenia; HGF, MIG, IL-1RA, and marked splenomegaly; and IL-1RA, IL-2R, IP-10, MIP-1β, and JAK2V617F. A two-cytokine (IL-8/IL-2R) –based risk categorization delineated prognostically different groups within specific DIPSS plus risk categories. Conclusion This study signifies the presence of specific cytokine-phenotype associations in PMF and a prognostically relevant plasma cytokine signature that might prove useful as a laboratory tool for predicting and monitoring treatment response.
The Journey to Regulation of Protein-Based Multiplex Quantitative Assays
Authors: Boja Emily S , Jortani Saeed A , Ritchie James , Hoofnagle Andrew N , Težak Živana , Mansfield Elizabeth , Keller Penny , Rivers Robert C , Rahbar Amir , Anderson N Leigh , Srinivas Pothur , Rodriguez Henry 
Published: February 2011

BACKGROUND
Clinical proteomics presents great promise in biology and medicine because of its potential for improving our understanding of diseases at the molecular level and for detecting disease-related biomarkers for diagnosis, prognosis, and prediction of therapeutic responses. To realize its full potential to improve clinical outcome for patients, proteomic studies have to be well designed, from biosample cohorts to data and statistical analyses. One key component in the biomarker development pipeline is the understanding of the regulatory science that evaluates diagnostic assay performance through rigorous analytical and clinical review criteria.

CONTENT
The National Cancer Institute's Clinical Proteomic Technologies for Cancer (CPTC) initiative has proposed an intermediate preclinical “verification” step to close the gap between protein-based biomarker discovery and clinical qualification. In collaboration with the US Food and Drug Administration (FDA), the CPTC network investigators recently published 2 mock submission review documents, first-of-their-kind educational materials that may help the scientific community interested in developing products for the clinic in understanding the likely analytical evaluation requirements for multiplex protein technology–based diagnostic tests.

CONCLUSIONS
Building on this momentum, the CPTC continues with this report its collaboration with the FDA, as well as its interactions with the AACC and the Centers for Medicare and Medicaid Services, to further the understanding of regulatory requirements for approving multiplex proteomic platform–based tests and analytically validating multiple analytes.
Application of Statistical Methods in Evaluating Asphalt Mixture Homogeneity
Authors: Peng Y. , Sun L. J. 
Published: February 2011

Abstract
Homogeneity is one of the most important factors affecting the performance-related properties of asphalt mixtures. Pavement condition surveys have shown various patterns of distress due to segregation and other types of non-uniformity. Using digital image processing, a statistical method was developed to evaluate asphalt mixture homogeneity quantitatively. Aggregate particle distribution in asphalt mixtures was described and analyzed by aggregate particle frequency statistic and distance statistic. The index of homogeneity was presented through aggregate particle distribution. The relevance of homogeneity to some mixture performance properties was also investigated. Results show that asphalt mixture homogeneity can be assessed quantitatively by the values of aggregate particle frequency statistic and distance statistic. Moreover, homogeneity dominates variations in mixture performance properties.