bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends inStaphylococcus aureusbacteraemia and impacts of infection control practices including universal MRSA admission screening in a hospital in Scotland, 2006–2010: retrospective cohort study and time-series intervention analysis
Authors: Lawes Timothy , Edwards Becky , López-Lozano José-Maria , Gould Ian 
Published: June 2012

ObjectivesTo describe secular trends inStaphylococcus aureusbacteraemia (SAB) and to assess the impacts of infection control practices, including universal methicillin-resistantStaphylococcus aureus(MRSA) admission screening on associated clinical burdens.DesignRetrospective cohort study and multivariate time-series analysis linking microbiology, patient management and health intelligence databases.SettingTeaching hospital in North East Scotland.ParticipantsAll patients admitted to Aberdeen Royal Infirmary between 1 January 2006 and 31 December 2010: n=420 452 admissions and 1 430 052 acute occupied bed days (AOBDs).InterventionUniversal admission screening programme for MRSA (August 2008) incorporating isolation and decolonisation.Primary and secondary measuresHospital-wide prevalence density, hospital-associated incidence density and death within 30 days of MRSA or methicillin-sensitiveStaphylococcus aureus(MSSA) bacteraemia.ResultsBetween 2006 and 2010, prevalence density of all SAB declined by 41%, from 0.73 to 0.50 cases/1000 AOBDs (p=0.002 for trend), and 30-day mortality from 26% to 14% (p=0.013). Significant reductions were observed in MRSA bacteraemia only. Overnight admissions screened for MRSA rose from 43% during selective screening to >90% within 4 months of universal screening. In multivariate time-series analysis (R20.45 to 0.68), universal screening was associated with a 19% reduction in prevalence density of MRSA bacteraemia (−0.035, 95% CI −0.049 to −0.021/1000 AOBDs; p<0.001), a 29% fall in hospital-associated incidence density (−0.029, 95% CI −0.035 to −0.023/1000 AOBDs; p<0.001) and a 46% reduction in 30-day mortality (−15.6, 95% CI −24.1% to −7.1%; p<0.001). Positive associations with fluoroquinolone and cephalosporin use suggested that antibiotic stewardship reduced prevalence density of MRSA bacteraemia by 0.027 (95% CI 0.015 to 0.039)/1000 AOBDs. Rates of MSSA bacteraemia were not significantly affected by screening or antibiotic use.ConclusionsDeclining clinical burdens from SAB were attributable to reductions in MRSA infections. Universal admission screening and antibiotic stewardship were associated with decreases in MRSA bacteraemia and associated early mortality. Control of MSSA bacteraemia remains a priority.
Postnatal corticosteroids and neurodevelopmental outcomes in extremely low birthweight or extremely preterm infants: 15-year experience in Victoria, Australia
Authors: Cheong Jeanie Ling , Anderson Peter , Roberts Gehan , Duff Julianne , Doyle Lex W ,   Victorian Infant Collaborative Study Group
Published: June 2012

ObjectivePostnatal corticosteroids (PCS) are used to prevent or treat bronchopulmonary dysplasia (BPD) in extremely low birthweight (ELBW; <1000 g) or extremely preterm (EPT; <28 weeks) infants. In the early 2000s, concerns were raised about increased risks of cerebral palsy (CP) in association with PCS, which may have affected prescribing of PCS, and influenced rates of BPD, mortality or long-term neurosensory morbidity. Our aim was to determine the changes over time in the rates of PCS use and 2-year outcomes in ELBW/EPT infants in Victoria, Australia.DesignAll ELBW or EPT infants born in Victoria, Australia in three distinct eras (1991–92, 1997 and 2005) who were alive at 7 days were included. Rates of PCS use, rates of BPD (oxygen dependency at 36 weeks' corrected age), death before 2 years of age, CP and major disability (any of moderate/severe CP, developmental quotient <−2 SD, blindness or deafness) were contrasted between cohorts.ResultsThe rate of PCS use and the dose prescribed diminished significantly in 2005 compared with earlier eras, but the rate of BPD rose. Non-significant changes in the rates of mortality over time were mirrored by non-significant changes in the rates of CP or major disability. Combined outcomes of mortality with either major disability or CP were similar over the three eras.ConclusionsPCS use decreased in 2005 compared with earlier eras, and was accompanied by a rise in BPD, with no significant changes in mortality or neurological morbidity.
Effect of thrombin receptor expression on microvessel endothelial cells, and survival by coagulation state in oesophageal squamous cell carcinoma
Authors: Shao Ying , Xu Qin-Qin , Li Chun , Wu Ming-Yao , Huang Xiao-Yan 
Published: June 2012

PurposeThe authors aimed to evaluate the prognostic value of thrombin receptor (TR) expression in microvessel endothelial cells (VECs) by coagulation state in oesophageal squamous cell carcinoma (ESCC).MethodsIn 138 ESCC normal and para-tumour samples, we investigated the association of the expression of TR and CD34 (microvessel marker) seen on immunohistochemical staining and clinicopathological parameters, coagulation state, microvessel density (MVD), and survival of patients.ResultIn total, 62 ESCC tissues were positive for TR in VECs, and in 48 cases, the activated partial thromboplastin time (APTT) was <28.5 s, with significant difference in tumour depth between TR-positive and -negative cases with APTT<28.5 s. Also with APTT<28.5 s, TR-positive MVD (TRMVD) was significantly greater with high than low CD34-positive MVD (CD34MVD; 7.96±4.27 vs 5.64±2.99; p=0.032). High CD34MVD was associated with increased TR expression in patients with APTT<28.5 than ≥28.5 s. In patients with high CD34MVD, the number of TR-positive microvessels was greater with APTT<28.5 than ≥28.5 s (n=17 vs n=6; p=0.002), and APTT and TR expressions were negatively correlated for patients with APTT<28.5 s (r2=−0.472, p=0.023). For patients with APTT<28.5 s, the cumulative survival rate was poorer with high than low TRMVD (p=0.027). On multivariate analysis, tumour size (p=0.006), tumour stage (p=0.004) and TRMVD (p=0.024) were independently associated with survival for patients with APTT<28.5 s. TRMVD had the second highest HR.ConclusionTR positivity in VECs may be an adverse prognostic factor for patients with ESCC and increased coagulation state. TR expression in VECs might be related to angiogenesis in ESCC.
Isolated cutaneous manifestation of IgG4-related disease
Authors: Hattori Tomoyasu , Miyanaga Tomomi , Tago Osamu , Udagawa Mai , Kamiyama Yuka , Nagai Yayoi , Ishikawa Osamu 
Published: June 2012

AimsThe cutaneous manifestation of IgG4-related disease has rarely been reported. The aim of this study is to identify and describe the cutaneous manifestations associated with IgG4-positive plasma cell infiltration in the skin.MethodsThe authors investigated two cases of IgG4-related disease with solitary skin lesions and compared the immunohistochemical characteristics of infiltrating cells among IgG4-related disease, Kimura's disease and cutaneous pseudolymphoma.ResultsIgG4-related disease manifested as an indurated plaque on the anterior chest in one case and a nodule on the toe in the other case. Histopathologically, skin lesions of IgG4-related disease showed a dense, mixed-cell infiltrate containing lymphocytes, plasma cells and eosinophils along with fibrosis. Plasma cells stained positively with anti-IgG and anti-IgG4antibodies, and the ratio of IgG4+/IgG+ cells was more than 50%. Serum levels of IgG and IgG4were not elevated and no lesions were found in other organs. Skin samples taken from Kimura's disease showed histopathological features similar to those of IgG4-related disease. The proportion of IgG4+/IgG+ was high in Kimura's disease, but not in cutaneous pseudolymphoma.ConclusionsThe solitary skin lesions of IgG4-related disease were similar histologically and immunohistochemically to the skin lesions of Kimura's disease. The concept of IgG4-related disease may help clarify the pathomechanism of diseases of unknown aetiology that possess features of IgG4-related disease.
The UK NEQAS for Molecular Genetics scheme for gastrointestinal stromal tumour: findings and recommendations following four rounds of circulation: Table 1
Authors: Wong Newton A C S , Deans Zandra C , Ramsden Simon C 
Published: June 2012

AimsTo describe the UK NEQAS for Molecular Genetics scheme for gastrointestinal stromal tumour (GIST) and to report and interpret the findings of four rounds of circulation of this quality assurance programme forKIT/PDGFRAmutation analyses.MethodsSamples of GISTs from formalin-fixed paraffin-embedded tissue blocks were circulated to registered participants of the UK NEQAS for Molecular Genetics scheme for GIST. Three samples were provided per annual circulation from 2008 to 2011 inclusive. The participants were required to analyse the samples forKITand/orPDGFRAmutations using their routine protocols, and the anonymised participants' reports were assessed and an annual scheme report issued.ResultsThe genotyping error rates for the 2008, 2009, 2010 and 2011 circulations were 13%, 33%, 19% and 4%, respectively. These errors were either missed or incorrectly described mutations. There was an overall false negative rate of 2% and false positive rate of 0%. The main recommendations that arose from these circulations were: (1) inclusion of reference accession numbers in reports; (2) avoidance of the term ‘heterozygous’ when analysing DNA from tumour tissue unless there was certainty that only neoplastic DNA was studied; and (3) the need to screenKITexons 9, 11, 13 and 17 andPDGFRAexons 12, 14 and 18 before classifying a GIST as ‘wild type’.ConclusionsThe UK NEQAS for Molecular Genetics scheme emphasises the potential complexities ofKIT/PDGFRAmutation analyses for GISTs and provides recommendations to help optimise such genotyping and reporting. The scheme has also demonstrated its educational value among participating laboratories.
Rsf-1/HBXAP overexpression is independent of gene amplification and is associated with poor outcome in patients with urinary bladder urothelial carcinoma
Authors: Liang Peir-In , Wu Li-Ching , Sheu Jim Jinn-Chyuan , Wu Ting-Feng , Shen Kun-Hung , Wang Yu-Hui , Wu Wen-Ren , Shiue Yow-Ling , Huang Hsuan-Ying , Hsu Han-Ping , Chen Yi-Hsien , Chen Li-Tzon , Li Chien-Feng , Liao Alex C 
Published: June 2012

BackgroundsUrothelial carcinoma of the urinary bladder (UCUB) is prevalent in developed countries. It often shows genetic instability and is associated with amplification (or gain) of various oncogenic genes or suppressive genes. Rsf-1, a subunit of ATP-dependent chromatin-remodelling complexes that mediates ATPase-dependent chromatin remodelling, confers tumour aggressiveness in certain carcinomas. The authors evaluate the Rsf-1 gene and expression status and its associations with clinicopathological features and survival in their UCUB collection.MethodsImmunohistochemistry was used to assess the Rsf-1 expression profile in 295 UCUB specimens, and was found to correlate with clinicopathological data. Real-time RT-PCR and fluorescence in situ hybridisation were used to detectRSF-1mRNA expression and gene dosage in 20 independent cases. Western blot analysis was used to evaluate Rsf-1 protein expression in human urothelial cell lines.ResultsRsf-1 overexpression was demonstrated in 101 cases (34.2%), and was significantly associated with advanced primary tumour (p<0.001), nodal metastasis (p=0.004), higher histological grades (p=0.001) and frequent mitoses (p<0.001). Moreover, it was predictive in disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (p<0.0001 for both). AlthoughRSF-1gene amplification can be barely detected, its mRNA expression is significantly enhanced in tumours with higher primary tumour (p=0.041) and positive nodal statuses (p=0.010), respectively. Rsf-1 protein was abundant in invasive urothelial carcinoma cells but was not benign.ConclusionsOverexpression of Rsf-1 is associated with higher tumour stage and poorer clinical outcome. The current study by the authors suggests gene amplification-independent mechanisms driving Rsf-1 overexpression during UCUB tumour progression.
Characteristics of HIV-positive patients infected by vertical transmission, Campo Grande, MS, Brazil, 1993–2009
Authors: Matos Vanessa Terezinha Gubert de , Oliveira Ana Lúcia Lyrio de , Souza Albert Schiaveto de , Dal Fabbro Márcia Maria Ferrairo Janini 
Published: June 2012

ObjectivesThe goal of the authors was to determine the epidemiological and clinical characteristics of all HIV-positive children and adolescents infected by vertical transmission.MethodsA descriptive, cross-sectional and retrospective study was conducted that included all HIV-positive patients infected by vertical transmission who attended the referral services of the municipality of Campo Grande from 1993 to 2009, and who used antiretrovirals (ARV). The data were collected from medical records after local institutional review board approval.Results78 patients were included, and almost half of the living patients (75) in 2009 were 11–15 years of age. The average age at diagnosis was 38.8 months, treatment was most often initiated from 12 to 35 months of age, and HAART was the most common treatment. Most patients (51.3%) were hospitalised between one and five times, and the first regimen was not associated with hospitalisation (p=0.2). The majority of patients did not exhibit virological suppression at the last examination, and genotyping revealed the presence of resistance mutations. Failure of therapy was often the result of non-adherence to therapy. Five patients died, and the causes of death were pneumonia, sepsis, cerebral cryptococcosis and myocarditis.ConclusionsDespite the availability of drugs and appropriate laboratory tests, a significant number of paediatric patients were failing ARV therapy due to non-adherence. Further interventions to enhance adherence in this population are needed.
Cancer Network Disruption by a Single Molecule Inhibitor Targeting Both Histone Deacetylase Activity and Phosphatidylinositol 3-Kinase Signaling
Authors: Qian Changgeng , Lai Cheng-Jung , Bao Rudi , Wang Da-Gong , Wang Jing , Xu Guang-Xin , Atoyan Ruzanna , Qu Hui , Yin Ling , Samson Maria , Zifcak Brian , Ma Anna Wai See , DellaRocca Steven , Borek Mylissa , Zhai Hai-Xiao , Cai Xiong , Voi Maurizio 
Published: June 2012

Abstract
Purpose: Given that histone deacetylase (HDAC) inhibitors are known to induce multiple epigenetic modifications affecting signaling networks and act synergistically with phosphatidylinositol 3-kinase (PI3K) inhibitors, we developed a strategy to simultaneously inhibit HDACs and PI3K in cancer cells.
Experimental Design: We constructed dual-acting inhibitors by incorporating HDAC inhibitory functionality into a PI3K inhibitor pharmacophore. CUDC-907, a development candidate selected from these dual inhibitors, was evaluated in vitro and in vivo to determine its pharmacologic properties, anticancer activity, and mechanism of action.
Results: CUDC-907 potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes. Through its integrated HDAC inhibitory activity, CUDC-907 durably inhibits the PI3K-AKT-mTOR pathway and compensatory signaling molecules such as RAF, MEK, MAPK, and STAT-3, as well as upstream receptor tyrosine kinases. CUDC-907 shows greater growth inhibition and proapoptotic activity than single-target PI3K or HDAC inhibitors in both cultured and implanted cancer cells.
Conclusions: CUDC-907 may offer improved therapeutic benefits through simultaneous, sustained disruption of multiple oncogenic signaling networks. Clin Cancer Res; 18(15); 4104–13. ©2012 AACR.
A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Authors: Hong David S. , Bowles Daniel W. , Falchook Gerald S. , Messersmith Wells A. , George Goldy C. , O'Bryant Cindy L. , Vo Alex C. H. , Klucher Kevin , Herbst Roy S. , Eckhardt S. Gail , Peterson Scott , Hausman Diana F. , Kurzrock Razelle , Jimeno Antonio 
Published: June 2012

Abstract
Purpose: The objectives of the study were to evaluate the maximum tolerated dose (MTD), safety, pharmacodynamics, pharmacokinetics, and antitumor activity of PX-866 in patients with incurable cancers.
Experimental Design: This was a phase I, open-label, dose-escalation study. Drug was administered orally once per day either on an intermittent (arm 1; days 1–5 and 8–12 of a 28-day cycle) or continuous (arm 2; days 1–28 of a 28-day cycle) schedule. Additional patients were treated at the arm 2 MTD in a food effects substudy.
Results: Eighty-four patients were treated in the arm 1 (n = 51), arm 2 (n = 20), and food effects (n = 13) cohorts. The most frequent study drug–related adverse events were gastrointestinal disorders (69.0%), with diarrhea being the most common (48.8%). The MTD was 12 and 8 mg for arm 1 and 2, respectively. The dose-limiting toxicities (DLT) consisted of grade III diarrhea (n = 3) and grade III elevated aspartate aminotransferase (AST; n = 1). The pharmacokinetics profile was dose proportional, with no evidence of drug accumulation. PX-866–associated inhibition of platelet pAKTSER473 was observed at the arm 2 MTD. The best response per Response Evaluation Criteria in Solid Tumors (RECIST) was stable disease in 22% of evaluable patients in arm 1, 53% in arm 2, and 11% in the food effects cohort. Eight patients were on study for 4 or more months.
Conclusions: This first-in-human study shows that PX-866, an irreversible small-molecule inhibitor of phosphatidylinositol 3-kinase (PI3K), was well tolerated and was associated with prolonged stable disease, particularly when using a continuous dosing schedule. Clin Cancer Res; 18(15); 4173–82. ©2012 AACR.
Glucose Variability and Mortality in Patients Hospitalized With Acute Myocardial Infarction
Authors: Lipska Kasia J. , Venkitachalam Lakshmi , Gosch Kensey , Kovatchev Boris , Van den Berghe Greet , Meyfroidt Geert , Jones Philip G. , Inzucchi Silvio E. , Spertus John A. , DeVries J. Hans , Kosiborod Mikhail 
Published: June 2012

Background—
Mean blood glucose (BG) during acute myocardial infarction (AMI) is an important predictor of inpatient mortality but does not capture glucose variability (GV), which has been shown to be independently associated with mortality in critically ill patients. Whether GV is associated with in-hospital mortality during AMI, after accounting for mean BG, is unknown.

Methods and Results—

We analyzed 18 563 consecutive patients with AMI with ≥3 BGs in the first 48 hours admitted to 61 US hospitals from 2000 to 2008. Five different GV metrics were compared for their ability to predict in-hospital mortality (range, standard deviation, mean amplitude of glycemic excursions, mean absolute glucose change, and average daily risk range) using hierarchical logistic regression models that sequentially adjusted for mean BG, hypoglycemia (<70 mg/dL), and multiple patient characteristics. In unadjusted analyses, range and average daily risk range had the highest C-indices (0.620 for range, 0.635 for average daily risk range; both
P
<0.0001). Greater GV was associated with higher mortality for all metrics (eg, mortality was 3.8%, 5.5%, 7.1%, and 11.3% for increasing quartiles of range,
P
<0.0001); however, the association between GV and mortality for each metric was no longer significant after multivariable adjustment. In contrast, mean BG remained an important predictor of survival (
P
<0.001, all models).

Conclusions—
Although greater GV is associated with increased risk of in-hospital mortality in patients with AMI in unadjusted analyses, GV is no longer independently predictive after controlling for multiple patient factors, including mean BG. These findings suggest that GV does not provide additional prognostic value above and beyond already recognized risk factors for mortality during AMI.
Coronary Computed Tomographic Angiography and Risk of All-Cause Mortality and Nonfatal Myocardial Infarction in Subjects Without Chest Pain Syndrome From the CONFIRM Registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry)
Authors: Cho Iksung , Chang Hyuk-Jae , Sung Ji Min , Pencina Michael J. , Lin Fay Y. , Dunning Allison M. , Achenbach Stephan , Al-Mallah Mouaz , Berman Daniel S. , Budoff Matthew J. , Callister Tracy Q. , Chow Benjamin J.W. , Delago Augustin , Hadamitzky Martin , Hausleiter Joerg , Maffei Erica , Cademartiri Filippo , Kaufmann Philipp , Shaw Leslee J. , Raff Gil L. , Chinnaiyan Kavitha M. , Villines Todd C. , Cheng Victor , Nasir Khurram , Gomez Millie , Min James K. 
Published: June 2012

Background—
The predictive value of coronary computed tomographic angiography (cCTA) in subjects without chest pain syndrome (CPS) has not been established. We investigated the prognostic value of coronary artery disease detection by cCTA and determined the incremental risk stratification benefit of cCTA findings compared with clinical risk factor scoring and coronary artery calcium scoring (CACS) for individuals without CPS.

Methods and Results—

An open-label, 12-center, 6-country observational registry of 27 125 consecutive patients undergoing cCTA and CACS was queried, and 7590 individuals without CPS or history of coronary artery disease met the inclusion criteria. All-cause mortality and the composite of all-cause mortality and nonfatal myocardial infarction were measured. During a median follow-up of 24 months (interquartile range, 18–35 months), all-cause mortality occurred in 136 individuals. After risk adjustment, compared with individuals without evidence of coronary artery disease by cCTA, individuals with obstructive 2- and 3-vessel disease or left main coronary artery disease experienced higher rates of death and composite outcome (
P
<0.05 for both). Both CACS and cCTA significantly improved the performance of standard risk factor prediction models for all-cause mortality and the composite outcome (likelihood ratio
P
<0.05 for all), but the incremental discriminatory value associated with their inclusion was more pronounced for the composite outcome and for CACS (C statistic for model with risk factors only was 0.71; for risk factors plus CACS, 0.75; for risk factors plus CACS plus cCTA, 0.77). The net reclassification improvement resulting from the addition of cCTA to a model based on standard risk factors and CACS was negligible.

Conclusions—
Although the prognosis for individuals without CPS is stratified by cCTA, the additional risk-predictive advantage by cCTA is not clinically meaningful compared with a risk model based on CACS. Therefore, at present, the application of cCTA for risk assessment of individuals without CPS should not be justified.