bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing an endoscopic mucosal resection service in a district general hospital
Authors: Lamb Chris A , Barbour Jamie A 
Published: August 2012

ObjectiveTo describe the implementation of a formal single-operator led endoscopic mucosal resection (EMR) service in a district general hospital, and the effect on patient outcome of this service development.DesignProspective audit during initiation and subsequent development of EMR service.SettingDistrict general hospital.PatientsAll patients referred to EMR service between 1 January 2008 and 31 December 2011.InterventionsNil in addition to clinical care.Main outcomes measuredThe number of EMRs per year including polyp size and histology, recurrence of polyp tissue at 3 months following EMR, and complications including early/delayed bleeding and perforation.ResultsFollowing service implementation, the number of EMRs rose from 11 in 2008 to 35 in 2011, with the number of large polyps (>30 mm) rising from four in 2008 to 24 in 2011. Recurrent or residual adenomatous tissue fell from 75% in 2008 to 4.76% in 2011. Only one perforation occurred over the 4 years (0.8% perforation rate: 1 in 120 polypectomies). A reduction in surgical intervention for adenomatous polyp removal was observed during the audit period.ConclusionsProfessional engagement and support by medical, surgical and nursing members of the endoscopy team promoted development of skill and confidence in EMR. Exposure to higher volumes of EMR procedures allowed successful removal of larger lesions, while maintained patient safety and reduced the need for surgical removal of benign polyps.
Electronic chemical pathology consultation service and dried blood spot metabolic screening in hospital patients
Authors: Mak Chloe Miu , Siu Wai-Kwan , Law Chun-Yiu , Wong Chi-Keung , Lee Hon-Kit , Yeung Sam , Sham Chak-On , Tse Kong , Lee Hencher Han-Chih , Chen Sammy Pak-Lam , Ching Chor-Kwan , Au Chui-Kwan , Poon Wing-Tat , Lam Ching-Wan , Kwong Ngai-Shan , Chan Albert Yan-Wo 
Published: August 2012

AimInborn errors of metabolism (IEM) are an unpopular and difficult subject and most clinicians are unfamiliar with them. Although chemical pathologists have a long-standing practice in advising test strategy and result interpretation especially from primary care, such consultations are usually informal, unstructured and those related to IEM are infrequently requested. This study aims to provide a formal electronic consultation service and to apply tandem mass spectrometry-based dried blood spot metabolic screening (DBSM) as a rapid first-line test for patients suspected of IEM.MethodsDBSM and a chemical pathology consultation were ordered through the hospital computer terminals. DBSM detected 29 metabolic disorders. The clinical data and metabolic results for the 12-month period were reviewed.ResultsThere were 279 consultations of which 209 were initiated by paediatricians and 70 by adult physicians. The main reasons for consultation were developmental delay, neurological abnormalities, unexplained biochemical abnormalities and monitoring of patients with IEM. There were 158 DBSM requests. One positive case of isovaleric acidaemia was detected.ConclusionsAll high-risk paediatric patients should have a DBSM and a timely electronic chemical pathology consultation as a rapid and cost-effective first-line screening. Provision of a visible, accessible and helpful consultation service enables professional reimbursement.
Variation in postmortem liver sampling: implications for postmortem toxicology interpretation
Authors: Morley Stephen R , Bolton Jennifer 
Published: August 2012

AimsTo investigate the sites for postmortem liver sampling when toxicological analysis is required and to compare these to published guidelines which recommend sampling from deep within the right lobe of the liver.MethodsA questionnaire was sent to all pathologists who had supplied liver samples to the Sheffield toxicology laboratory in 2011. Practices were audited against published standards.Results79 liver samples had been provided from 39 pathologists. 30 pathologists replied. 15/30 pathologists had sampled from deep within the liver, but only 7/30 pathologists sampled from the deep within the right lobe.ConclusionsThe published guidelines for liver sampling were either not known or not being followed by pathologists. Although this did not directly affect any of the cases audited, such a lack of knowledge of the recommended site of liver sampling may lead to incorrect interpretation if the site of liver sample is unknown by the receiving laboratory.
Molecular Pathways: VCAM-1 as a Potential Therapeutic Target in Metastasis
Authors: Chen Qing , Massagué Joan 
Published: August 2012

AbstractInteractions between disseminated tumor cells (DTC) and stromal cells in the microenvironment are critical for tumor colonization of distal organs. Recent studies have shown that vascular cell adhesion molecule-1 (VCAM-1) is aberrantly expressed in breast cancer cells and mediates prometastatic tumor-stromal interactions. Moreover, the usefulness of VCAM-1 to DTCs in 2 different organs—lung and bone—is based on distinct mechanisms. In the lungs, VCAM-1 on the surface of cancer cells binds to its counterreceptor, the α4β1 integrin (also known as very-late antigen, VLA-4), on metastasis-associated macrophages, triggering VCAM-1–mediated activation of the phosphoinositide 3-kinase growth and survival pathway in the cancer cells. In the bone marrow, cancer cell VCAM-1 attracts and tethers α4 integrin–expressing osteoclast progenitors to facilitate their maturation into multinucleated osteoclasts that mediate osteolytic metastasis. These findings highlight the importance of direct interactions between DTCs and stromal cells during tumor dissemination and draw attention to the possibility of targeting the α4 integrin–VCAM-1 interactions in metastatic breast cancer. Anti-α4 integrin inhibitors have been developed to treat various diseases driven by massive leukocyte infiltrates and have gained U.S. Food and Drug Administration approval or are undergoing clinical trials. Testing these drugs against tumor-stromal leukocyte interactions may provide a new strategy to suppress lung and bone relapse of breast cancer. Clin Cancer Res; 18(20); 5520–5. ©2012 AACR.
A Multicenter Phase II Study of Single-Agent Enzastaurin in Previously Treated Waldenström Macroglobulinemia
Authors: Ghobrial Irene M. , Moreau Philippe , Harris Brianna , Poon Tiffany , Jourdan Eric , Maisonneuve Hervé , Benhadji Karim A. , Hossain Anwar M. , Nguyen Tuan S. , Wooldridge James E. , Leblond Veronique 
Published: August 2012

Abstract
Purpose: Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. These findings provided the rationale for a multicenter phase II trial of oral enzastaurin in previously treated patients with WM.
Experimental design: Patients who were treated with 1 to 5 prior regimens and who had a baseline immunoglobulin M level 2 times or more the upper limit of normal received oral enzastaurin 250 mg twice daily (500 mg total) after a single loading dose (day 1, cycle 1) of 375 mg 3 times daily (1,125 mg total) for 8 cycles of 28 days each or until progressive disease. Six patients who progressed during treatment with enzastaurin had dexamethasone added per protocol.
Results: From July 2008 to December 2010, 42 patients were enrolled. The objective response rate (RR) was 38.1% (2 partial and 14 minor responses). One patient had grade 3 leukopenia and one patient died during the study from septic shock; both events were considered drug related. A statistically significant association between RR and interleukin 15 (IL-15) was observed, suggesting that higher concentration levels of IL-15 may be associated with better response.
Conclusion: Enzastaurin was active and well tolerated in previously treated patients with WM. Because of the small sample size of this uncontrolled study, further assessment of the relationship between IL-15 and response to enzastaurin in patients with WM is required. These results warrant further investigation of enzastaurin for the treatment of WM. Clin Cancer Res; 18(18); 5043–50. ©2012 AACR.
LAP+CD4+ T Cells Are Suppressors Accumulated in the Tumor Sites and Associated with the Progression of Colorectal Cancer
Authors: Mahalingam Jayashri , Lin Yung-Chang , Chiang Jy-Ming , Su Po-Jung , Fang Jian-He , Chu Yu-Yi , Huang Ching-Tai , Chiu Cheng-Tang , Lin Chun-Yen 
Published: August 2012

AbstractPurpose: Suppressor T cells are one of the determinants of colorectal cancer (CRC) clinical outcome. LAP+CD4+ T cell is a recently identified subset of suppressor T cells. This study was designed to investigate their clinical relevance in patients with CRC.Experimental Design: Sixty patients with CRC and 24 healthy donors (HD) were enrolled in this study. The percentages of LAP+CD4+ T cells in peripheral blood and tumor tissue were measured. The phenotype and functional relevance of LAP+CD4+ T cells were analyzed subsequently.Results: The percentages of LAP+CD4+ T cells in peripheral blood of patients with CRC were significantly higher than HD (HD vs. CRC: 3.1% ± 0.78% vs. 8.8% ± 5.8%, P &lt; 0.0001) and in tumor tissue when compared with nontumor tissue (nontumor vs. tumor: 3.2% ± 1.1% vs. 9.5% ± 5.5%, P = 0.0002). In addition, LAP+CD4+ T cells with effector memory (EM) phenotype were more likely to accumulate in the tumor sites than in peripheral blood. These LAP+CD4+ T cells produced significantly higher levels of IFN-γ, IL-17 and comparatively lower IL-2 and very few IL-10. LAP+CD4+ T cells could suppress the proliferation of LAP−CD4+ T cells that were partially mediated by TGF-β. Furthermore, these LAP+CD4+ T cells accumulated in tumor site and increased further in the peripheral blood in patients with metastasis.Conclusions: LAP+CD4+ T cells as a suppressor subset could accumulate in the tumor microenvironment and circulated more in the peripheral blood with tumor progression in patients with CRC. Clin Cancer Res; 18(19); 5224–33. ©2012 AACR.
Counteracting Autophagy Overcomes Resistance to Everolimus in Mantle Cell Lymphoma
Authors: Rosich Laia , Xargay-Torrent Sílvia , López-Guerra Mónica , Campo Elías , Colomer Dolors , Roué Gaël 
Published: August 2012

Abstract
Purpose: Mantle cell lymphoma (MCL) is an aggressive B-lymphoid neoplasm with poor response to conventional chemotherapy and short survival. The phosphatidylinositol 3-kinase/Akt/mTOR survival pathway is constitutively activated in MCL cells, thereby making the mTOR inhibition an attractive therapeutic strategy. The first clinical studies of everolimus (RAD001), an mTOR inhibitor, in relapsed MCL patients have reported a significant response. Our aim was to analyze the mechanism related to everolimus resistance/sensitivity in MCL cells.
Experimental Design: Sensitivity to everolimus was analyzed in MCL cell lines and primary MCL cells. Everolimus mechanism of action was determined by flow cytometry and Western blot. Particularly, autophagy was studied by LC3BI/II expression, autophagolysosomes detection by flow cytometry and fluorescence microscopy, and siRNA-mediated gene silencing.
Results: Everolimus exerted antitumoral effect on MCL cells while sparing normal cells. In MCL cell lines, this phenomenon was associated to G1 cell-cycle arrest, dephosphorylation of the mTOR downstream targets, 4E-BP1 and S6RP, and rephosphorylation of Akt. A synergistic cytotoxic effect was observed between everolimus and an Akt inhibitor, which overcame the compensatory reactivation within the mTOR signaling pathway. Interestingly, MCL cells with low response to this combination showed high levels of autophagy. Accordingly, selective triple knockdown of the autophagy genes ATG7, ATG5 and ATG3, and pretreatment with the autophagy inhibitor hydroxychloroquine, efficiently overcame the resistance to Akt/mTOR inhibitors, leading to the activation of the mitochondrial apoptotic pathway.
Conclusions: These results suggest that autophagy induction protects MCL cells from Akt/mTOR targeting and counteracting autophagy may represent an attractive strategy for sensitizing MCL cells to everolimus-based therapy. Clin Cancer Res; 18(19); 5278–89. ©2012 AACR.
EWS-FLI-1-Targeted Cytotoxic T-cell Killing of Multiple Tumor Types Belonging to the Ewing Sarcoma Family of Tumors
Authors: Evans Christopher H. , Liu Fangjun , Porter Ryan M. , O'Sullivan Regina P. , Merghoub Taha , Lunsford Elaine P. , Robichaud Kyle , Van Valen Frans , Lessnick Stephen L. , Gebhardt Mark C. , Wells James W. 
Published: August 2012

Abstract
Purpose: The Ewing sarcoma family of tumors (ESFT) comprises a group of aggressive, malignant bone, and soft tissue tumors that predominantly affect children and young adults. These tumors frequently share expression of the EWS-FLI-1 translocation, which is central to tumor survival but not present in healthy cells. In this study, we examined EWS-FLI-1 antigens for their capacity to induce immunity against a range of ESFT types.
Design: Computer prediction analysis of peptide binding, HLA-A2.1 stabilization assays, and induction of cytotoxic T-lymphocytes (CTL) in immunized HLA-A2.1 transgenic mice were used to assess the immunogenicity of native and modified peptides derived from the fusion region of EWS-FLI-1 type 1. CTL-killing of multiple ESFT family members in vitro, and control of established xenografts in vivo, was assessed. We also examined whether these peptides could induce human CTLs in vitro.
Results: EWS-FLI-1 type 1 peptides were unable to stabilize cell surface HLA-A2.1 and induced weak CTL activity against Ewing sarcoma cells. In contrast, peptides with modified anchor residues induced potent CTL killing of Ewing sarcoma cells presenting endogenous (native) peptides. The adoptive transfer of CTL specific for the modified peptide YLNPSVDSV resulted in enhanced survival of mice with established Ewing sarcoma xenografts. YLNPSVDSV-specific CTL displayed potent killing of multiple ESFT types in vitro: Ewing sarcoma, pPNET, Askin's Tumor, and Biphenotypic sarcoma. Stimulation of human peripheral blood mononuclear cells with YLNPSVDSV peptide resulted in potent CTL-killing.
Conclusions: These data show that YLNPSVDSV peptide is a promising antigen for ESFT immunotherapy and warrants further clinical development. Clin Cancer Res; 18(19); 5341–51. ©2012 AACR.
Sex Differences in Clinical Characteristics and Outcomes in Elderly Patients With Heart Failure and Preserved Ejection Fraction
Authors: Lam Carolyn S.P. , Carson Peter E. , Anand Inder S. , Rector Thomas S. , Kuskowski Michael , Komajda Michel , McKelvie Robert S. , McMurray John J. , Zile Michael R. , Massie Barry M. , Kitzman Dalane W. 
Published: August 2012

Background—
There are few sex-specific outcome data in heart failure with preserved ejection fraction.

Methods and Results—

We assessed sex differences in baseline characteristics and outcomes among 4128 patients with heart failure with preserved ejection fraction in the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Women (n=2491) with heart failure with preserved ejection fraction were ≈1 year older (72±7 years versus 71±7 years) and more likely to be obese (46% versus 35%) and have chronic kidney disease (34% versus 26%) and hypertension (91% versus 85%) than men but less likely to have an ischemic cause (19% versus 34%), atrial fibrillation (27% versus 33%), or chronic obstructive pulmonary disease (8% versus 13%) (all
P
<0.001). During a mean of 49.5 months, there were 881 deaths (447 in women, 434 in men; risk ratio, 0.64; 95% CI, 0.56–0.74) and 5776 hospitalizations (3239 in women, 2537 in men; risk ratio, 0.80; 95% CI, 0.76–0.84). Women had lower risk of all-cause events (deaths and hospitalizations), even after adjusting for baseline characteristics (adjusted hazards ratio, 0.81; 95% CI, 0.73–0.89). However, the sex-related difference in risk of all-cause events was modified in the presence or absence of atrial fibrillation, renal dysfunction, stable angina pectoris, or advanced New York Heart Association class symptoms.

Conclusions—
In patients with typical heart failure with preserved ejection fraction, there were prominent sex differences in baseline characteristics and outcomes. Women had better overall prognosis, although the presence of 4 common baseline characteristics seemed to moderate this finding.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT000095238.
Aligning Coronary Anatomy and Myocardial Perfusion Territories
Authors: Cerci Rodrigo J. , Arbab-Zadeh Armin , George Richard T. , Miller Julie M. , Vavere Andrea L. , Mehra Vishal , Yoneyama Kihei , Texter John , Foster Courtney , Guo Wei , Cox Christopher , Brinker Jeffrey , Di Carli Marcelo , Lima Joao A.C. 
Published: August 2012

Background—
Appropriate clinical decisions concerning diagnosis and treatment of coronary artery disease rely on correct integration of data on coronary anatomy and myocardial perfusion. The purpose of this article is to introduce a new left ventricular segmentation model for improved alignment of coronary arterial segments and myocardial perfusion territories, designed for the CORE320 study.

Methods and Results—
CORE320 is a prospective, multicenter study with a primary objective to evaluate the diagnostic accuracy of 320-row detector computed tomography (CT) to detect coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected coronary artery disease compared with the gold standard of conventional coronary angiography and single-photon emission CT myocardial perfusion imaging. We describe a 19-coronary segment and 13-myocardial territory alignment model, its application in both standard and CT image data sets, and the adjudication process of the initial cohort of patients recruited for the CORE320 study. Adjudication committees reviewed the images of the first 101 gold standard and 107 CT data sets. On the basis of the presented model and rules, all cases for adjudication were correctly identified. During image review, 6 (5.9%) gold standard and 9 (8.4%) CT data sets needed further realignment not triggered by the algorithm.

Conclusions—
We present a vascular territory distribution model developed for the CORE320 multicenter study, which accounts for variability in coronary anatomy and potential myocardial perfusion territory overlap.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00934037.
3.0T Whole-Heart Coronary Magnetic Resonance Angiography Performed With 32-Channel Cardiac Coils
Authors: Yang Qi , Li Kuncheng , Liu Xin , Du Xiangying , Bi Xiaoming , Huang Feng , Jerecic Renate , Liu Zhi , An Jing , Xu Dong , Zheng Hairong , Fan Zhaoyang , Li Debiao 
Published: August 2012

Background—
Whole-heart coronary magnetic resonance angiography (MRA) is a promising method for noninvasive, radiation-free detection and exclusion of obstructive coronary artery disease; however, the required imaging time and robustness of the technique are not yet satisfactory. We evaluated the value of whole-heart coronary MRA at 3.0T using a 32-channel cardiac coil, which reduces image-acquisition times and hence allows to increase the clinical throughput.

Methods and Results—
A total of 110 consecutive patients with suspected coronary artery disease referred for clinically indicated conventional coronary angiography were included in this prospective study. Acquisition of 3.0T coronary MRA data was done by using 32-channel receiver coils. An ECG-triggered, navigator-gated, inversion-recovery prepared, segmented gradient-echo sequence was used for image acquisition with an acceleration factor of 3 in the phase-encoding direction using generalized auto calibrating partially parallel acquisitions reconstruction. Acquisition of coronary MRA was successfully completed in 101 of 110 (92%) patients with average imaging time of 7.0±1.8 minutes. The sensitivity, specificity, positive and negative predictive value of coronary MRA on a patient-based analysis were 95.9% (47/49, 95% CI, 86.0%–99.4%), 86.5% (45/52, 95% CI, 74.2%–94.4%), 87.0% (47/54, 95% CI, 75.1%–94.6%) and 95.7% (45/47, 95% CI, 85.4%–99.4%), respectively.

Conclusions—
Whole-heart coronary MRA at 3.0T using a 32-channel cardiac coil allows high overall accuracy for detecting significant coronary artery disease with reduced imaging time. It has potential to be a robust and alternative technique for ruling out significant coronary artery disease.

Clinical Trial Registration—

URL:
http://www.chictr.org
. Unique identifier: ChiCTR-DDT-07000121.
A Pilot Study Examining the Severity and Outcome of the Post–Cardiac Arrest Syndrome
Authors: Donnino Michael W. , Miller Joseph C. , Bivens Matthew , Cocchi Michael N. , Salciccioli Justin D. , Farris Sarah , Gautam Shiva , Cutlip Donald , Howell Michael 
Published: August 2012

Background—
Cardiac arrest occurs in >400 000 patients in the United States per year, and mortality rates vary across the country. Whether variations in cardiac arrest outcome are the result of differences in hospital or patient characteristics remains understudied. We tested whether hospital-independent factors would account for the difference in outcome between 2 geographically distinct hospitals.

Methods and Results—
Consecutive adult (age >18 years) out-of-hospital cardiac arrests were considered for analysis. The primary outcome was in-hospital mortality. Predictor variables were classified according to whether they were hospital-independent or whether they could be related to the hospital's quality of care. Only hospital-independent variables were considered for the analysis. Sequential logistic modeling was used to assess outcome. A propensity score was derived and was used in subsequent multivariate logistic regression to predict hospital outcome. A total of 208 subjects were included. Overall mortality in the Detroit cohort was 87% in comparison with 61% in the Boston cohort (odds ratio: 4.4; 95% confidence interval: 2.2–8.8). After sequential adjustments for baseline covariates, out-of-hospital cardiac arrest score and propensity score, city was not significantly associated with mortality (odds ratio: 1.16; 95% confidence interval: 0.45–2.97). After propensity matching there was no significant difference in the odds ratio for death between the 2 cities (odds ratio: 1.15; 95% confidence interval: 0.51–2.61).

Conclusions—
In this pilot study, we found that pre- and intra-arrest conditions contribute substantially to the severity of the postarrest syndrome and on outcomes. Postarrest quality-of-care evaluations should include inherent differences in the presenting syndrome rather than a crude mortality rate.