bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefit of a single recruitment maneuver after an apnea test for the diagnosis of brain death
Authors: Paries Marie , Boccheciampe Nicolas , Raux Mathieu , Riou Bruno , Langeron Olivier , Nicolas-Robin Armelle 
Published: July 2012

Abstract
Introduction
Many potential lung transplants are lost because of hypoxemia during donor management. We hypothesized that the apnea test, necessary to confirm the diagnosis of brain death in potential lung donors, was involved in the decrease in the ratio of partial pressure of arterial O2 to fraction of inspired O2 (PaO2/FiO2) and that a single recruitment maneuver performed just after the apnea test can reverse this alteration.

Methods
In this case-control study, we examined the effectiveness of the recruitment maneuver with a comparison cohort of brain dead patients who did not receive the maneuver. Patients were matched one-to-one on the basis of initial PaO2/FiO2 and on the duration of mechanical ventilation before the apnea test. PaO2/FiO2 was measured before (T1), at the end (T2) and two hours after apnea test (T3).

Results
Twenty-seven patients were included in each group. The apnea test was associated with a significant decrease in PaO2/FiO2 from 284 ± 98 to 224 ± 104 mmHg (P < 0.001). The decrease in PaO2/FiO2 between T1 and T3 was significantly lower in the recruitment maneuver group than in the control group (-4 (-68-57) vs -61 (-110--18) mmHg, P = 0.02). The number of potential donors with PaO2/FiO2 > 300 mmHg decreased by 58% (95% CI: 28-85%) in the control group vs 0% (95% CI: 0-34%) in the recruitment maneuver group (P < 0.001).

Conclusions
The apnea test induced a decrease in PaO2/FiO2 in potential lung donors. A single recruitment maneuver performed immediately after the apnea test can reverse this alteration and may prevent the loss of potential lung donors.
A tool kit for quantifying eukaryotic rRNA gene sequences from human microbiome samples
Authors: Dollive Serena , Peterfreund Gregory L , Sherrill-Mix Scott , Bittinger Kyle , Sinha Rohini , Hoffmann Christian , Nabel Christopher S , Hill David A , Artis David , Bachman Michael A , Custers-Allen Rebecca , Grunberg Stephanie , Wu Gary D , Lewis James D , Bushman Frederic D 
Published: July 2012

AbstractEukaryotic microorganisms are important but understudied components of the human microbiome. Here we present a pipeline for analysis of deep sequencing data on single cell eukaryotes. We designed a new 18S rRNA gene-specific PCR primer set and compared a published rRNA gene internal transcribed spacer (ITS) gene primer set. Amplicons were tested against 24 specimens from defined eukaryotes and eight well-characterized human stool samples. A software pipeline https://sourceforge.net/projects/brocc/ was developed for taxonomic attribution, validated against simulated data, and tested on pyrosequence data. This study provides a well-characterized tool kit for sequence-based enumeration of eukaryotic organisms in human microbiome samples.
Systematic assessment in an animal model of the angiogenic potential of different human cell sources for therapeutic revascularization
Authors: Barclay G Robin , Tura Olga , Samuel Kay , Hadoke Patrick WF , Mills Nicholas L , Newby David E , Turner Marc L 
Published: July 2012

Abstract
Introduction
Endothelial progenitor cells (EPC) capable of initiating or augmenting vascular growth were recently identified within the small population of CD34-expressing cells that circulate in human peripheral blood and which are considered hematopoietic progenitor cells (HPC). Soon thereafter human HPC began to be used in clinical trials as putative sources of EPC for therapeutic vascular regeneration, especially in myocardial and critical limb ischemias. However, unlike HPC where hematopoietic efficacy is related quantitatively to CD34+ cell numbers implanted, there has been no consensus on how to measure EPC or how to assess cellular graft potency for vascular regeneration. We employed an animal model of spontaneous neovascularization to simultaneously determine whether human cells incorporate into new vessels and to quantify the effect of different putative angiogenic cells on vascularization in terms of number of vessels generated. We systematically compared competence for therapeutic angiogenesis in different sources of human cells with putative angiogenic potential, to begin to provide some rationale for optimising cell procurement for this therapy.

Methods
Human cells employed were mononuclear cells from normal peripheral blood and HPC-rich cell sources (umbilical cord blood, mobilized peripheral blood, bone marrow), CD34+ enriched or depleted subsets of these, and outgrowth cell populations from these. An established sponge implant angiogenesis model was adapted to determine the effects of different human cells on vascularization of implants in immunodeficient mice. Angiogenesis was quantified by vessel density and species of origin by immunohistochemistry.

Results
CD34+ cells from mobilized peripheral blood or umbilical cord blood HPC were the only cells to promote new vessel growth, but did not incorporate into vessels. Only endothelial outgrowth cells (EOC) incorporated into vessels, but these did not promote vessel growth.

Conclusions
These studies indicate that, since EPC are very rare, any benefit seen in clinical trials of HPC in therapeutic vascular regeneration is predominantly mediated by indirect proangiogenic effects rather than through direct incorporation of any rare EPC contained within these sources. It should be possible to produce autologous EOC for therapeutic use, and evaluate the effect of EPC distinct from, or in synergy with, the proangiogenic effects of HPC therapies.
Phase I Multidose-Escalation Study of the Anti-CD19 Maytansinoid Immunoconjugate SAR3419 Administered by Intravenous Infusion Every 3 Weeks to Patients With Relapsed/Refractory B-Cell Lymphoma
Authors: Younes Anas , Kim Stella , Romaguera Jorge , Copeland Amanda , Farial Silvana de Castro , Kwak Larry W. , Fayad Luis , Hagemeister Frederick , Fanale Michelle , Neelapu Sattva , Lambert John M. , Morariu-Zamfir Rodica , Payrard Sandrine , Gordon Leo I. 
Published: July 2012

Purpose We determine the maximum-tolerated dose (MTD), pharmacokinetics, safety, and preliminary efficacy of SAR3419, an antibody-drug conjugate targeting CD19, in a first-in-man phase I clinical trial in patients with relapsed lymphoma. Patients and Methods Patients with relapsed CD19+ B-cell lymphoma were treated with escalating doses of SAR3419 given by intravenous infusion once every 21 days. Results Thirty-nine patients were treated on seven dose levels ranging from 10 to 270 mg/m2. The median number of prior treatment regimens was four (range, 1 to 9), and 11 patients had prior autologous or allogeneic stem-cell transplantation. The dose-limiting toxicities were reversible severe blurred vision associated with microcystic epithelial corneal changes reported in six patients and neuropathy in one patient. The MTD was 160 mg/m2 once every 21 days. Hematologic and hepatic toxicities were predominantly grade 1 or 2 in severity. A total of 35 patients have completed at least two cycles of treatment and were evaluable for tumor response. Twenty-six patients (74%) demonstrated reduction in their tumor size; six of those patients achieved partial or complete remissions. Seven (47%) of 15 patients with rituximab-refractory disease demonstrated reduction in their tumor sizes. The pharmacokinetic profile of SAR3419 is characterized by linear kinetics, low clearance from 0.2 to 0.6 L/d/m2, and an elimination half-life in the range of 3 to 7 days. Conclusion Using an every 3-week-schedule of SAR3419 for six cycles, the MTD is 160 mg/m2. SAR3419 can be safely administered to patients with relapsed B-cell lymphoma and demonstrates promising clinical activity, including patients who were refractory to rituximab.
Tumor Response and Toxicity of Neoadjuvant Erlotinib in Patients With Early-Stage Non–Small-Cell Lung Cancer
Authors: Schaake Eva E. , Kappers Ingrid , Codrington Henk E. , Valdés Olmos Renato A. , Teertstra Hendrik J. , van Pel Renée , Burgers Jacobus A. , van Tinteren Harm , Klomp Houke M. 
Published: July 2012

Purpose The development of targeted therapy has introduced new options to improve treatment outcome in selected patients. The objective of this prospective study was to investigate the safety of preoperative erlotinib treatment and the (in vivo) response in patients with early-stage resectable non–small-cell lung cancer (NSCLC). Patients and Methods This study was designed as an open-label phase II trial, performed in four hospitals in the Netherlands, according to a Simon's minimax two-stage procedure. Initially, operable patients with early-stage NSCLC (n = 15) were entered from an enriched population (never-smoker, female sex, nonsquamous histology, or Asian ethnicity); thereafter, unselected patients were included to a total of N = 60. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. Response to treatment was evaluated using [18F] fluorodeoxyglucose positron emission tomography (PET) and computed tomography (CT) scans during treatment and histologic examination of the resection specimen. Primary end points were toxicity and pathologic response. Results Sixty patients were included. Seven patients stopped treatment prematurely (12%). Skin toxicity was present in 37 patients (62%), and diarrhea was present in 21 patients (35%). PET evaluation revealed metabolic response (> 25% standardized uptake value decrease) in 16 patients (27%); CT evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) showed response in three patients (5%). At surgery, no unexpected complications occurred. Pathologic examination showed more than 50% necrosis in 14 patients (23%), of whom three (5%) had more than 95% tumor necrosis. The response rate in the enriched population was 34% (10 of 29 patients). Conclusion According to predefined criteria, neoadjuvant erlotinib has low toxicity and sufficient activity to deserve further testing in future studies in an enriched population.
Stage Migration, Selection Bias, and Survival Associated With the Adoption of Positron Emission Tomography Among Medicare Beneficiaries With Non–Small-Cell Lung Cancer, 1998-2003
Authors: Dinan Michaela A. , Curtis Lesley H. , Carpenter William R. , Biddle Andrea K. , Abernethy Amy P. , Patz Edward F. , Schulman Kevin A. , Weinberger Morris 
Published: July 2012

Purpose Previous studies have linked the use of positron emission tomography (PET) with improved outcomes among patients with non–small-cell lung cancer (NSCLC). However, this association may be confounded by PET-induced stage migration and selection bias. We examined the association between PET use and overall survival among Medicare beneficiaries with NSCLC. Patients and Methods Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) –Medicare data was used to characterize changes in overall survival, stage-specific survival, and stage distribution among Medicare beneficiaries with NSCLC between 1998 and 2003. Results A total of 97,007 patients with NSCLC diagnosed between 1998 and 2003 met the study criteria. Two-year and 4-year survival remained unchanged, despite widespread adoption of PET. The proportion of patients staged with advanced disease increased from 44% to 50%. Upstaging of disease was accompanied by stage-specific improved survival, with 2-year survival of stage IV disease increasing from 8% to 11% between 1998 and 2003. PET was more likely to be administered to patients with less advanced disease (stages I through IIIA) and greater overall survival. Conclusion Overall survival among Medicare beneficiaries with NSCLC was unchanged between 1998 and 2003, despite widespread adoption of PET. The association between PET use and increased survival likely reflects an artifact of selection bias and consequent stage migration.
Intrapatient Cetuximab Dose Escalation in Metastatic Colorectal Cancer According to the Grade of Early Skin Reactions: The Randomized EVEREST Study
Authors: Van Cutsem Eric , Tejpar Sabine , Vanbeckevoort Dirk , Peeters Marc , Humblet Yves , Gelderblom Hans , Vermorken Jan B. , Viret Frederic , Glimelius Bengt , Gallerani Elisa , Hendlisz Alain , Cats Annemieke , Moehler Markus , Sagaert Xavier , Vlassak Soetkin , Schlichting Michael , Ciardiello Fortunato 
Published: July 2012

Purpose Skin toxicity in patients receiving cetuximab has been associated positively with clinical outcome in several tumor types. This study investigated the effect of cetuximab dose escalation in patients with irinotecan-refractory metastatic colorectal cancer who had developed no or mild skin reactions after 21 days of treatment at the standard dose. This article reports clinical and pharmacokinetic (PK) data. Patients and Methods After 21 days of standard-dose cetuximab (400 mg/m2 initial dose, then 250 mg/m2 per week) plus irinotecan, patients with ≤ grade 1 skin reactions were randomly assigned to standard-dose (group A) or dose-escalated (to 500 mg/m2 per week; group B) cetuximab. Patients with ≥ grade 2 skin reactions continued on standard-dose cetuximab plus irinotecan (group C). Results The intent-to-treat population comprised 157 patients. PK profiles reflected the dose increase and were predictable across the dose range investigated. Weekly cetuximab doses of up to 500 mg/m2 were well tolerated, and grade 3 and 4 adverse events were generally comparable between treatment groups. Dose escalation (n = 44) was associated with an increase in skin reactions ≥ grade 2 compared with standard (n = 45) dosing (59% v 38%, respectively). Dose escalation, compared with standard dosing, showed some evidence for improved response rate (30% v 16%, respectively) and disease control rate (70% v 58%, respectively) but no indication of benefit in relation to overall survival. In an exploratory analysis, dose escalation seemed to increase response rate compared with standard dosing in patients with KRAS wild-type but not KRAS mutant tumors. Conclusion Cetuximab serum concentrations increased predictably with dose. Higher dose levels were well tolerated. The possible indication for improved efficacy in the dose-escalation group warrants further investigation.
International, Randomized, Placebo-Controlled, Double-Blind Phase III Study of Motesanib Plus Carboplatin/Paclitaxel in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer: MONET1
Authors: Scagliotti Giorgio V. , Vynnychenko Ihor , Park Keunchil , Ichinose Yukito , Kubota Kaoru , Blackhall Fiona , Pirker Robert , Galiulin Rinat , Ciuleanu Tudor-Eliade , Sydorenko Oleksandr , Dediu Mircea , Papai-Szekely Zsolt , Banaclocha Natividad Martinez , McCoy Sheryl , Yao Bin , Hei Yong-jiang , Galimi Francesco , Spigel David R. 
Published: July 2012

Purpose We evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) combined with carboplatin/paclitaxel improved overall survival (OS) versus chemotherapy alone in patients with nonsquamous non–small-cell lung cancer (NSCLC) and in the subset of patients with adenocarcinoma. Patients and Methods Patients with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) were randomly assigned 1:1 to carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m2) intravenously for up to six 3-week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. OS was the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS. Results A total of 1,090 patients with nonsquamous NSCLC were randomly assigned (arms A/B, n = 541 of 549); of those, 890 had adenocarcinoma (n = 448 of 442). Median OS in arms A and B was 13.0 and 11.0 months, respectively (hazard ratio [HR], 0.90; 95% CI, 0.78 to 1.04; P = .14); median OS for the adenocarcinoma subset was 13.5 and 11.0 months, respectively (HR, 0.88; 95% CI, 0.75 to 1.03; P = .11). In descriptive analyses (arms A v B), median PFS was 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). There was no association between PLGF change and OS in arm A. The incidence of grade ≥ 3 AEs (arms A and B, 73% and 59%, respectively) and grade 5 AEs (14% and 9%, respectively) was higher with motesanib treatment. Conclusion Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset.
Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis
Authors: Mauguen Audrey , Le Péchoux Cécile , Saunders Michele I. , Schild Steven E. , Turrisi Andrew T. , Baumann Michael , Sause William T. , Ball David , Belani Chandra P. , Bonner James A. , Zajusz Aleksander , Dahlberg Suzanne E. , Nankivell Matthew , Mandrekar Sumithra J. , Paulus Rebecca , Behrendt Katarzyna , Koch Rainer , Bishop James F. , Dische Stanley , Arriagada Rodrigo , De Ruysscher Dirk , Pignon Jean-Pierre 
Published: July 2012

Purpose In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation. Material and Methods We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy. Results In non–small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio [HR] = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non–lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities. Conclusion Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity.
The Nation before Taste: The Challenges of American Culinary History
Authors: Haley Andrew P. 
Published: July 2012

Abstract
Food is material and familiar, and because it is, we are often overconfident about our ability to understand the culinary past. It is easy to believe that if we can discover the recipe for some forgotten dish, the history of the dish becomes intelligible. When it does not, it tempts those who consume culinary history to impose modern sensibilities on our predecessors. “The Nation before Taste” argues that historians and museum curators must be especially vigilant when presenting the history of food. Reviewing a series of historical challenges that stemmed from studying the United States in the late nineteenth and early twentieth centuries, the author suggests three strategies for grounding food history in the past: recognizing that taste is constructed and temporal; engaging with material and social contexts, especially physiology, class, and gender; and admitting to our audiences that not all culinary mysteries have immediate or simple answers.
Economic Evaluation of Strategies to Reduce Sudden Cardiac Death in Young Athletes
Authors: Schoenbaum Michael , Denchev Peter , Vitiello Benedetto , Kaltman Jonathan R. 
Published: July 2012

OBJECTIVE:There is controversy about appropriate methods to reduce sudden cardiac death (SCD) in young athletes, but there is limited evidence on costs or consequences of alternative strategies. The objective of this study was to evaluate the cost-effectiveness of adding electrocardiogram (ECG) screening to the currently standard practice of preparticipation history and physical examination (H&P) to reduce SCD.METHODS:Decision analysis modeling by using a societal perspective, with annual Markov cycles from age 14 until death. Three screening strategies were evaluated: (1) H&P, with cardiology referral if abnormal (current standard practice); (2) H&P, plus ECG after negative H&P, and cardiology referral if either is abnormal; and (3) ECG only, with cardiology referral if abnormal. Children identified with SCD-associated cardiac abnormalities were restricted from sports and received cardiac treatment. Main outcome measures were costs of screening and treatment, quality-adjusted life years (QALYs), and premature deaths averted.RESULTS:Relative to strategy 1, incremental cost-effectiveness is $68 800/QALY for strategy 2 and $37 700/QALY for strategy 3. Monte Carlo simulation revealed the chance of incremental cost-effectiveness compared with strategy 1 was 30% for strategy 2 and 66% for strategy 3 (assumed willingness to pay ≤$50 000/QALY). Compared with strategy 1, strategy 2 averted 131 additional SCDs at $900 000 per case, and strategy 3 averted 127 SCDs at $600 000 per case.CONCLUSIONS:Under a societal willingness to pay threshold of $50 000/QALY, adding ECGs to current preparticipation evaluations for athletes is not cost-effective, with costs driven largely by false-positive findings.
Two-Year Follow-up of an Adolescent Behavioral Weight Control Intervention
Authors: Lloyd-Richardson Elizabeth E. , Jelalian Elissa , Sato Amy F. , Hart Chantelle N. , Mehlenbeck Robyn , Wing Rena R. 
Published: July 2012

OBJECTIVE:
This study examined the 24-month outcomes of a randomized controlled trial of a group-based behavioral weight control (BWC) program combined with either activity-based peer intervention or aerobic exercise.

METHODS:
At baseline, 118 obese adolescents (68% female; BMI = 31.41 ± 3.33) ages 13 to 16 years (mean = 14.33; SD = 1.02) were randomized to receive 1 of 2 weight loss interventions. Both interventions received the same 16-week group-based cognitive-behavioral treatment, combined with either aerobic exercise or peer-based adventure therapy. Eighty-nine adolescents (75% of original sample) completed the 24-month follow-up. Anthropometric and psychosocial measures were obtained at baseline, at the end of the 16-week intervention, and at 12 and 24 months following randomization.

RESULTS:
An intent-to-treat mixed factor analysis of variance indicated a significant effect for time on both percent over 50th percentile BMI for age and gender and standardized BMI score, with no differences by intervention group. Post hoc comparisons showed a significant decrease in percent overweight at 4 months (end of treatment), which was maintained at both 12- and 24-month follow-up visits. Significant improvements on several dimensions of self-concept were noted, with significant effects on physical appearance self-concept that were maintained through 24 months.

CONCLUSIONS:
Both BWC conditions were effective at maintaining reductions in adolescent obesity and improvements in physical appearance self-concept through 24-month follow-up. This study is one of the first to document long-term outcomes of BWC intervention among adolescents.