bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel method of delivery of continuous positive airway pressure for apnea testing during brain death evaluation
Authors: Hubbard Jennifer L , Dirks Rachel C , Veneman Wade L , Davis James W 
Published: December 2016

BackgroundThere are several methods for apnea testing for the evaluation of neurological death, including oxygen via T-piece, oxygen cannula inserted into the endotracheal tube, and continuous positive airway pressure (CPAP). Lung suitability for transplantation is determined in part by the partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2; P:F) ratio. We hypothesized that delivery of CPAP during apnea testing using a novel method would improve post-test P:F ratios.MethodsA retrospective review was performed at a level I trauma center for all patients undergoing apnea testing from 2010 to 2016. The CPAP system used a flow-inflating bag and was made available in 2012. It was used at the discretion of the clinician. Patients were classified as having an apnea test by CPAP or by non-CPAP method (T-piece, oxygen cannula in endotracheal tube, etc). The two groups were compared for baseline characteristics and the primary outcome of postapnea test P:F ratio.ResultsDuring the study period, 145 patients underwent apnea testing; 67 patients by the CPAP method and 78 by non-CPAP method. There were no significant differences in demographics, mechanism of brain injury, pneumonia rate, smoking status, or antibiotic usage between the two groups. The pretest P:F ratio was similar between groups, but the CPAP group had significantly higher post-test P:F ratio (304 vs 250, p=0.02). There were no reported complications arising from CPAP use.ConclusionsWe describe a novel method of delivering CPAP by a flow-inflating bag during examination for brain death. This method led to improved oxygenation, P:F ratios, and may decrease barotrauma. The flow-inflating bag was inexpensive, easily implemented, and without adverse effects. Multicentered, prospective trials are needed to elicit significant benefit in lung donation and transplantation.Level of evidenceLevel IV, diagnostic tests.
Association between Body Mass Index and Cancer Survival in a Pooled Analysis of 22 Clinical Trials
Authors: Greenlee Heather , Unger Joseph M. , LeBlanc Michael , Ramsey Scott , Hershman Dawn L. 
Published: December 2016

AbstractBackground: Data are inconsistent on the association between body mass index (BMI) at time of cancer diagnosis and prognosis. We used data from 22 clinical treatment trials to examine the association between BMI and survival across multiple cancer types and stages.Methods: Trials with ≥5 years of follow-up were selected. Patients with BMI &lt; 18.5 kg/m2 were excluded. Within a disease, analyses were limited to patients on similar treatment regimens. Variable cutpoint analysis identified a BMI cutpoint that maximized differences in survival. Multivariable Cox regression analyses compared survival between patients with BMI above versus below the cutpoint, adjusting for age, race, sex, and important disease-specific clinical prognostic factors.Results: A total of 11,724 patients from 22 trials were identified. Fourteen analyses were performed by disease site and treatment regimen. A cutpoint of BMI = 25 kg/m2 maximized survival differences. No statistically significant trend across all 14 analyses was observed (mean HR = 0.96; P = 0.06). In no cancer/treatment combination was elevated BMI associated with an increased risk of death; for some cancers there was a survival advantage for higher BMI. In sex-stratified analyses, BMI ≥ 25 kg/m2 was associated with better overall survival among men (HR = 0.82; P = 0.003), but not women (HR = 1.04; P = 0.86). The association persisted when sex-specific cancers were excluded, when treatment regimens were restricted to dose based on body surface area, and when early-stage cancers were excluded.Conclusion: The association between BMI and survival is not consistent across cancer types and stages.Impact: Our findings suggest that disease, stage, and gender-specific body size recommendations for cancer survivors may be warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 21–29. ©2016 AACR.See all the articles in this CEBP Focus section, “The Obesity Paradox in Cancer: Evidence and New Directions.”
Association of Weight Change after Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population
Authors: Meyerhardt Jeffrey A. , Kroenke Candyce H. , Prado Carla M. , Kwan Marilyn L. , Castillo Adrienne , Weltzien Erin , Cespedes Feliciano Elizabeth M. , Xiao Jingjie , Caan Bette J. 
Published: December 2016

Abstract
Background: Higher body mass index (BMI) is associated with incident colorectal cancer but not consistently with colorectal cancer survival. Whether weight gain or loss is associated with colorectal cancer survival is largely unknown.
Methods: We identified 2,781 patients from Kaiser Permanente Northern California diagnosed with stages I–III colorectal cancer between 2006 and 2011 with weight and height measurements within 3 months of diagnosis and approximately 18 months after diagnosis. We evaluated associations between weight change and colorectal cancer–specific and overall mortality, adjusted for sociodemographics, disease severity, and treatment.
Results: After completion of treatment and recovery from stage I–III colorectal cancer, loss of at least 10% of baseline weight was associated with significantly worse colorectal cancer–specific mortality (HR 3.20; 95% confidence interval [CI], 2.33–4.39; Ptrend &lt; 0.0001) and overall mortality (HR 3.27; 95% CI, 2.56–4.18; Ptrend &lt; 0.0001). For every 5% loss of baseline weight, there was a 41% increased risk of colorectal cancer–specific mortality (95% CI, 29%–56%). Weight gain was not significantly associated with colorectal cancer–specific mortality (Ptrend = 0.54) or overall mortality (Ptrend = 0.27). The associations were largely unchanged after restricting analyses to exclude patients who died within 6 months and 12 months of the second weight measurement. No significant interactions were demonstrated for weight loss or gain by gender, stage, primary tumor location, or baseline BMI.
Conclusions: Weight loss after diagnosis was associated with worse colorectal cancer–specific mortality and overall mortality. Reverse causation does not appear to explain our findings.
Impact: Understanding mechanistic underpinnings for the association of weight to worse mortality is important to improving patient outcomes. Cancer Epidemiol Biomarkers Prev; 26(1); 30–37. ©2016 AACR.
See all the articles in this CEBP Focus section, “The Obesity Paradox in Cancer: Evidence and New Directions.”
A Glycomics-Based Test Predicts the Development of Hepatocellular Carcinoma in Cirrhosis
Authors: Verhelst Xavier , Vanderschaeghe Dieter , Castéra Laurent , Raes Tom , Geerts Anja , Francoz Claire , Colman Roos , Durand François , Callewaert Nico , Van Vlierberghe Hans 
Published: December 2016

Abstract
Purpose: Cirrhosis is a major risk factor for the development of hepatocellular carcinoma but remains underdiagnosed in the compensated stage. Fibrosis progression and cirrhosis are associated with changes in blood serum glycomic profiles. Previously, the serum glycomics-based GlycoCirrhoTest was shown to identify 50% to 70% of compensated cirrhosis cases in chronic liver disease cohorts, at &gt;90% specificity. This study assessed GlycoCirrhoTest for the risk of hepatocellular carcinoma development in compensated cirrhosis.
Experimental Design: Serum glycomics were analyzed in sera of 133 patients, with compensated cirrhosis collected between 1995 and 2005 in a surveillance protocol for hepatocellular carcinoma using an optimized glycomic technology on a DNA sequencer.
Results: Baseline GlycoCirrhoTest values were significantly increased in patients who developed hepatocellular carcinoma after a median follow-up of 6.4 years as compared with patients who did not. For patients with a baseline GlycoCirrhoTest exceeding 0.2, the HR for hepatocellular carcinoma development over the entire study (Cox regression) was 5.1 [95% confidence interval (CI), 2.2–11.7; P &lt; 0.001], and the HR for hepatocellular carcinoma development within 7 years was 12.1 (95% CI, 2.8–51.6; P = 0.01) based on the cut-off value optimized in the same cohort. An absolute increase in GlycoCirrhoTest of 0.2 was associated with an HR of 10.29 (95% CI, 3.37–31.43; P &lt; 0.001) for developing hepatocellular carcinoma. In comparison, the HR for the development of hepatocellular carcinoma within 7 years for AFP levels above the optimal cutoff in this study (5.75 ng/mL) was 4.65 (95% CI, 1.59–13.61).
Conclusions: This prognostic study suggests that GlycoCirrhoTest is a serum biomarker that identifies compensated cirrhotic patients at risk for developing hepatocellular carcinoma. Screening strategies could be guided by a positive test on GlycoCirrhoTest. Clin Cancer Res; 23(11); 2750–8. ©2016 AACR.
Heterodimeric IL15 Treatment Enhances Tumor Infiltration, Persistence, and Effector Functions of Adoptively Transferred Tumor-specific T Cells in the Absence of Lymphodepletion
Authors: Ng Sinnie Sin Man , Nagy Bethany A. , Jensen Shawn M. , Hu Xintao , Alicea Candido , Fox Bernard A. , Felber Barbara K. , Bergamaschi Cristina , Pavlakis George N. 
Published: December 2016

AbstractPurpose: Adoptive cell transfer (ACT) is a promising immunotherapeutic approach for cancer. Host lymphodepletion is associated with favorable ACT therapy outcomes, but it may cause detrimental effects in humans. We tested the hypothesis that IL15 administration enhances ACT in the absence of lymphodepletion. We previously showed that bioactive IL15 in vivo comprises a stable complex of the IL15 chain with the IL15 receptor alpha chain (IL15Rα), termed heterodimeric IL15 (hetIL15).Experimental Design: We evaluated the effects of the combination regimen ACT + hetIL15 in the absence of lymphodepletion by transferring melanoma-specific Pmel-1 T cells into B16 melanoma-bearing mice.Results: hetIL15 treatment delayed tumor growth by promoting infiltration and persistence of both adoptively transferred Pmel-1 cells and endogenous CD8+ T cells into the tumor. In contrast, persistence of Pmel-1 cells was severely reduced following irradiation in comparison with mice treated with hetIL15. Importantly, we found that hetIL15 treatment led to the preferential enrichment of Pmel-1 cells in B16 tumor sites in an antigen-dependent manner. Upon hetIL15 administration, tumor-infiltrating Pmel-1 cells showed a “nonexhausted” effector phenotype, characterized by increased IFNγ secretion, proliferation, and cytotoxic potential and low level of PD-1. hetIL15 treatment also resulted in an improved ratio of Pmel-1 to Treg in the tumor.Conclusions: hetIL15 administration improves the outcome of ACT in lymphoreplete hosts, a finding with significant implications for improving cell-based cancer immunotherapy strategies. Clin Cancer Res; 23(11); 2817–30. ©2016 AACR.
Histone Deacetylase 3 Inhibition Overcomes BIM Deletion Polymorphism–Mediated Osimertinib Resistance in EGFR-Mutant Lung Cancer
Authors: Tanimoto Azusa , Takeuchi Shinji , Arai Sachiko , Fukuda Koji , Yamada Tadaaki , Roca Xavier , Ong S. Tiong , Yano Seiji 
Published: December 2016

Abstract
Purpose: The BIM deletion polymorphism is associated with apoptosis resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib and erlotinib, in non–small cell lung cancer (NSCLC) harboring EGFR mutations. Here, we investigated whether the BIM deletion polymorphism contributes to resistance against osimertinib, a third-generation EGFR-TKI. In addition, we determined the efficacy of a histone deacetylase (HDAC) inhibitor, vorinostat, against this form of resistance and elucidated the underlying mechanism.
Experimental Design: We used EGFR-mutated NSCLC cell lines, which were either heterozygous or homozygous for the BIM deletion polymorphism, to evaluate the effect of osimertinib in vitro and in vivo. Protein expression was examined by Western blotting. Alternative splicing of BIM mRNA was analyzed by RT-PCR.
Results: EGFR-mutated NSCLC cell lines with the BIM deletion polymorphism exhibited apoptosis resistance to osimertinib in a polymorphism dosage–dependent manner, and this resistance was overcome by combined use with vorinostat. Experiments with homozygous BIM deletion–positive cells revealed that vorinostat affected the alternative splicing of BIM mRNA in the deletion allele, increased the expression of active BIM protein, and thereby induced apoptosis in osimertinib-treated cells. These effects were mediated predominantly by HDAC3 inhibition. In xenograft models, combined use of vorinostat with osimertinib could regress tumors in EGFR-mutated NSCLC cells homozygous for the BIM deletion polymorphism. Moreover, this combination could induce apoptosis even when tumor cells acquired EGFR-T790M mutations.
Conclusions: These findings indicate the importance of developing HDAC3-selective inhibitors, and their combined use with osimertinib, for treating EGFR-mutated lung cancers carrying the BIM deletion polymorphism. Clin Cancer Res; 23(12); 3139–49. ©2016 AACR.
Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax
Authors: Montero Joan , Stephansky Jason , Cai Tianyu , Griffin Gabriel K. , Cabal-Hierro Lucia , Togami Katsuhiro , Hogdal Leah J. , Galinsky Ilene , Morgan Elizabeth A. , Aster Jon C. , Davids Matthew S. , LeBoeuf Nicole R. , Stone Richard M. , Konopleva Marina , Pemmaraju Naveen , Letai Anthony , Lane Andrew A. 
Published: December 2016

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with dismal outcomes for which no standard therapy exists. We found that primary BPDCN cells were dependent on the antiapoptotic protein BCL2 and were uniformly sensitive to the BCL2 inhibitor venetoclax, as measured by direct cytotoxicity, apoptosis assays, and dynamic BH3 profiling. Animals bearing BPDCN patient–derived xenografts had disease responses and improved survival after venetoclax treatment in vivo. Finally, we report on 2 patients with relapsed/refractory BPDCN who received venetoclax off-label and experienced significant disease responses. We propose that venetoclax or other BCL2 inhibitors undergo expedited clinical evaluation in BPDCN, alone or in combination with other therapies. In addition, these data illustrate an example of precision medicine to predict treatment response using ex vivo functional assessment of primary tumor tissue, without requiring a genetic biomarker.
Significance: Therapy for BPDCN is inadequate, and survival in patients with the disease is poor. We used primary tumor cell functional profiling to predict BCL2 antagonist sensitivity as a common feature of BPDCN, and demonstrated in vivo clinical activity of venetoclax in patient-derived xenografts and in 2 patients with relapsed chemotherapy-refractory disease. Cancer Discov; 7(2); 156–64. ©2016 AACR.
This article is highlighted in the In This Issue feature, p. 115
Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans
Authors: Reyes-Soffer Gissette , Pavlyha Marianna , Ngai Colleen , Thomas Tiffany , Holleran Stephen , Ramakrishnan Rajasekhar , Karmally Wahida , Nandakumar Renu , Fontanez Nelson , Obunike Joseph , Marcovina Santica M. , Lichtenstein Alice H. , Matthan Nirupa R. , Matta James , Maroccia Magali , Becue Frederic , Poitiers Franck , Swanson Brian , Cowan Lisa , Sasiela William J. , Surks Howard K. , Ginsberg Henry N. 
Published: December 2016

Background:
Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism. In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism. Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels. The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date.

Methods:
Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study. They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart. At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined. In 10 participants, postprandial triglycerides and apoB48 levels were measured.

Results:
Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%. The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR. The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL. The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR. Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations.

Conclusions:
Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition. The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a).

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01959971.
Impact of Incomplete Percutaneous Revascularization in Patients With Multivessel Coronary Artery Disease: A Systematic Review and Meta‐Analysis
Authors: Nagaraja Vinayak , Ooi Sze‐Yuan , Nolan James , Large Adrian , De Belder Mark , Ludman Peter , Bagur Rodrigo , Curzen Nick , Matsukage Takashi , Yoshimachi Fuminobu , Kwok Chun Shing , Berry Colin , Mamas Mamas A. 
Published: December 2016

Background

Up to half of patients undergoing percutaneous coronary intervention have multivessel coronary artery disease (
MVD
) with conflicting data regarding optimal revascularization strategy in such patients. This paper assesses the evidence for complete revascularization (
CR
) versus incomplete revascularization in patients undergoing percutaneous coronary intervention, and its prognostic impact using meta‐analysis.

Methods and Results

A search of PubMed,
EMBASE
,
MEDLINE
, Current Contents Connect, Google Scholar, Cochrane library, Science Direct, and Web of Science was conducted to identify the association of
CR
in patients with multivessel coronary artery disease undergoing percutaneous coronary intervention with major adverse cardiac events and mortality. Random‐effects meta‐analysis was used to estimate the odds of adverse outcomes. Meta‐regression analysis was conducted to assess the relationship with continuous variables and outcomes. Thirty‐eight publications that included 156 240 patients were identified. Odds of death (
OR
0.69, 95%
CI
0.61‐0.78), repeat revascularization (
OR
0.60, 95%
CI
0.45‐0.80), myocardial infarction (
OR
0.64, 95%
CI
0.50‐0.81), and major adverse cardiac events (
OR
0.63, 95%
CI
0.50‐0.79) were significantly lower in the patients who underwent
CR
. These outcomes were unchanged on subgroup analysis regardless of the definition of
CR
. Similar findings were recorded when
CR
was studied in the chronic total occlusion (
CTO
) subgroup (
OR
0.65, 95%
CI
0.53‐0.80). A meta‐regression analysis revealed a negative relationship between the
OR
for mortality and the percentage of
CR
.

Conclusion

CR
is associated with reduced risk of mortality and major adverse cardiac events, irrespective of whether an anatomical or a score‐based definition of incomplete revascularization is used, and this magnitude of risk relates to degree of
CR
. These results have important implications for the interventional management of patients with multivessel coronary artery disease.
Characterisation of some Scutellonema species (Tylenchida: Hoplolaimidae) occurring in Botswana, South Africa, Costa Rica and the USA, with description of S. clavicaudatum sp. n. and a molecular phylogeny of the genus
Authors: Van den Berg Esther , Tiedt Louwrens R. , Stanley Jason D. , Inserra Renato N. , Subbotin Sergei A. 
Published: December 2016

The genusScutellonemacontains more than 40 species of spiral nematodes with enlarged phasmids called scutella. In this study, we provide morphological and molecular characterisation ofS. clavicaudatumsp. n.,S. brachyurus,S. bradys,S. cavenessi,S. transvaalense,S. truncatumandScutellonemasp. A. from North and Central America, and Africa. The new species,S. clavicaudatumsp. n., was found on sugarcane in South Africa and is characterised by a lack of lip annuli as inS. africanum,S. siamenseandS. truncatum. The lip region, in both males and females, is conical and marked by six large rectangular blocks separated or fused with the submedian and lateral lip sectors, which surround a round and distinct labial disc. Females of this new species also have large vaginal glands, a functional spermatheca, the lateral field posterior to the scutellum ending in a bluntly pointed shape and a clavate tail. Morphological descriptions, measurements, light and scanning electron microscopic photos and drawings are also given forS. bradys,S. cavenessi,S. transvaalenseandS. truncatum. The study of spiral nematode samples from Florida, USA, confirmed the presence of a morphologically and genetically atypical populations ofS. bradys. The morphology of theS. bradyspopulation from Bermuda grass in pasture land from central Florida fits that of type specimens of this species, but differs in having a truncate tail terminus rather than round and also a prominent spermatheca filled with flagellate spermatozoa. Other FloridaScutellonemasamples analysed in this study belonged toS. cavenessi, a species native to West Africa. This is the first report ofS. cavenessiin Florida, where it parasitises the ornamental plantSansevieria trifasciata. Our study showed a high level of intraspecific variation forScutellonemarRNA and mtDNA genes, which can reach 5.6% for the D2-D3 of 28S rRNA, 12.9% for the ITS rRNA genes and 14.4% for theCOIgene. Phylogenetic relationships withinScutellonemaare given as inferred from the analyses of the D2-D3 of 28S rRNA, ITS rRNA and theCOImtDNA gene sequences.