bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical impact of chromosomal rearrangements with breakpoints upstream of the SOX9gene: two novel de novo balanced translocations associated with acampomelic campomelic dysplasia
Authors: Fonseca Ana Carolina S , Bonaldi Adriano , Bertola Débora R , Kim Chong A , Otto Paulo A , Vianna-Morgante Angela M
Published: May 2013

Background

The association of balanced rearrangements with breakpoints near SOX9 [SRY (sex determining region Y)-box 9] with skeletal abnormalities has been ascribed to the presumptive altering of SOX9 expression by the direct disruption of regulatory elements, their separation from SOX9 or the effect of juxtaposed sequences.

Case presentation

We report on two sporadic apparently balanced translocations, t(7;17)(p13;q24) and t(17;20)(q24.3;q11.2), whose carriers have skeletal abnormalities that led to the diagnosis of acampomelic campomelic dysplasia (ACD; MIM 114290). No pathogenic chromosomal imbalances were detected by a-CGH. The chromosome 17 breakpoints were mapped, respectively, 917–855 kb and 601–585 kb upstream of the SOX9 gene. A distal cluster of balanced rearrangements breakpoints on chromosome 17 associated with SOX9-related skeletal disorders has been mapped to a segment 932–789 kb upstream of SOX9. In this cluster, the breakpoint of the herein described t(17;20) is the most telomeric to SOX9, thus allowing the redefining of the telomeric boundary of the distal breakpoint cluster region related to skeletal disorders to 601–585 kb upstream of SOX9. Although both patients have skeletal abnormalities, the t(7;17) carrier presents with relatively mild clinical features, whereas the t(17;20) was detected in a boy with severe broncheomalacia, depending on mechanical ventilation. Balanced and unbalanced rearrangements associated with disorders of sex determination led to the mapping of a regulatory region of SOX9 function on testicular differentiation to a 517–595 kb interval upstream of SOX9, in addition to TESCO (Testis-specific enhancer of SOX9 core). As the carrier of t(17;20) has an XY sex-chromosome constitution and normal male development for his age, the segment of chromosome 17 distal to the translocation breakpoint should contain the regulatory elements for normal testis development.

Conclusions

These two novel translocations illustrate the clinical variability in carriers of balanced translocations with breakpoints near SOX9. The translocation t(17;20) breakpoint provides further evidence for an additional testis-specific SOX9 enhancer 517 to 595 kb upstream of the SOX9 gene.
Determinants of lifestyle behavior in type 2 diabetes: results of the 2011 cross-sectional survey on living with chronic diseases in Canada
Authors: Agborsangaya Calypse B , Gee Marianne E , Johnson Steven T , Dunbar Peggy , Langlois Marie-France , Leiter Lawrence A , Pelletier Catherine , Johnson Jeffrey A
Published: May 2013

Background

Lifestyle behavior modification is an essential component of self-management of type 2 diabetes. We evaluated the prevalence of engagement in lifestyle behaviors for management of the disease, as well as the impact of healthcare professional support on these behaviors.

Methods

Self-reported data were available from 2682 adult respondents, age 20 years or older, to the 2011 Survey on Living with Chronic Diseases in Canada’s diabetes component. Associations with never engaging in and not sustaining self-management behaviors (of dietary change, weight control, exercise, and smoking cessation) were evaluated using binomial regression models.

Results

The prevalence of reported dietary change, weight control/loss, increased exercise and smoking cessation (among those who smoked since being diagnosed) were 89.7%, 72.1%, 69.5%, and 30.6%, respectively. Those who reported not receiving health professional advice in the previous 12 months were more likely to report never engaging in dietary change (RR = 2.7, 95% CI 1.8 – 4.2), exercise (RR = 1.7, 95% CI 1.3 – 2.1), or weight control/loss (RR = 2.2, 95% CI 1.3 – 3.6), but not smoking cessation (RR = 1.0; 95% CI: 0.7 – 1.5). Also, living with diabetes for more than six years was associated with not sustaining dietary change, weight loss and smoking cessation.

Conclusion

Health professional advice for lifestyle behaviors for type 2 diabetes self-management may support individual actions. Patients living with the disease for more than 6 years may require additional support in sustaining recommended behaviors.
Changes in plasma and erythrocyte omega-6 and omega-3 fatty acids in response to intravenous supply of omega-3 fatty acids in patients with hepatic colorectal metastases
Authors: Al-Taan Omer , Stephenson James A , Spencer Laura , Pollard Cristina , West Annette L , Calder Philip C , Metcalfe Matthew , Dennison Ashley R
Published: May 2013

Background

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are functionally the most important omega-3 polyunsaturated fatty acids (PUFAs). Oral supply of these fatty acids increases their levels in plasma and cell membranes, often at the expense of the omega-6 PUFAs arachidonic acid (ARA) and linoleic acid. This results in an altered pattern of lipid mediator production to one which is less pro-inflammatory. We investigated whether short term intravenous supply of omega-3 PUFAs could change the levels of EPA, DHA, ARA and linoleic acid in plasma and erythrocytes in patients with hepatic colorectal metastases.

Methods

Twenty patients were randomised to receive a 72 hour infusion of total parenteral nutrition with (treatment group) or without (control group) omega-3 PUFAs. EPA, DHA, ARA and linoleic acid were measured in plasma phosphatidylcholine (PC) and erythrocytes at several times points up to the end of infusion and 5 to 12 days (mean 9 days) after stopping the infusion.

Results

The treatment group showed increases in plasma PC EPA and DHA and erythrocyte EPA and decreases in plasma PC and erythrocyte linoleic acid, with effects most evident late in the infusion period. Plasma PC and erythrocyte EPA and linoleic acid all returned to baseline levels after the 5–12 day washout. Plasma PC DHA remained elevated above baseline after washout.

Conclusions

Intravenous supply of omega-3 PUFAs results in a rapid increase of EPA and DHA in plasma PC and of EPA in erythrocytes. These findings suggest that infusion of omega-3 PUFAs could be used to induce a rapid effect especially in targeting inflammation.

Trial registration

http://www.clinicaltrials.gov identifier NCT00942292
VPAC1 receptor expression in peripheral blood mononuclear cells in a human endotoxemia model
Authors: Storka Angela , Burian Bernhard , Führlinger Gerhard , Clive Breanna , Sun Terri , Crevenna Richard , Gsur Andrea , Mosgöller Wilhelm , Wolzt Michael
Published: May 2013

Background

Vasoactive intestinal peptide (VIP) exerts immune-modulatory actions mainly via VPAC1 receptor stimulation. VPAC1 may be a treatment target of inflammatory diseases, but little is known about the receptor expression profile in immune-competent cellsin vivo.

Material and methods

20 male healthy subjects received a single intravenous bolus of 2ng/kg body weight Escherichia coli endotoxin (LPS). Receptor status was evaluated in peripherial blood cells before and 3, 6 and 24 h after LPS by FACS analysis and q-PCR. VIP plasma concentrations were measured by ELISA.

Results

Granulocytes accounted for 51% of leukocytes at baseline and 58 ± 37% were positive for VPAC1. The granulocyte population increased 2.6 fold after LPS, and a transient down-regulation of VPAC1 to 28 ± 23% was noted at 3 h (p < 0.001), which returned to baseline at 24 hours. Baseline VPAC1 expression was low in lymphocytes (6.3 ± 3.2%) and monocytes (11 ± 9.6%). In these cells, LPS up-regulated VPAC1 at 6 h (13.2 ± 4.9%, p < 0.001) and 24 h (31.6 ± 20.5%, p = 0.001), respectively. Consistent changes were noted for the VIP-receptors VPAC2 and PAC1. VPAC1, VPAC2 and PAC1 mRNA levels were unchanged in peripheral blood mononuclear cells (PBMC). VIP plasma concentration increased from 0.5 ± 0.3 ng/ml to 0.7 ± 0.4 ng/ml at 6 h after LPS (p < 0.05) and returned to baseline within 24 h.

Conclusion

The time profile of VPAC receptor expression differs in granulocytes, monocytes and lymphocytes after LPS challenge in humans. Changes in circulating VIP concentrations may reflect innate immune responses.
The cytotoxicity evaluation of magnetic iron oxide nanoparticles on human aortic endothelial cells
Authors: Ge Gaoyuan , Wu Hengfang , Xiong Fei , Zhang Yu , Guo Zhirui , Bian Zhiping , Xu Jindan , Gu Chunrong , Gu Ning , Chen Xiangjian , Yang Di
Published: May 2013

One major obstacle for successful application of nanoparticles in medicine is its potential nanotoxicity on the environment and human health. In this study, we evaluated the cytotoxicity effect of dimercaptosuccinic acid-coated iron oxide (DMSA-Fe2O3) using cultured human aortic endothelial cells (HAECs). Our results showed that DMSA-Fe2O3 in the culture medium could be absorbed into HAECs, and dispersed in the cytoplasm. The cytotoxicity effect of DMSA-Fe2O3 on HAECs was dose-dependent, and the concentrations no more than 0.02 mg/ml had little toxic effect which were revealed by tetrazolium dye assay. Meanwhile, the cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without DMSA-Fe2O3). However, the endocrine function for endothelin-1 and prostacyclin I-2, as well as the urea transporter function, was altered even without obvious evidence of cell injury in this context. We also showed by real-time PCR analysis that DMSA-Fe2O3 exposure resulted in differential effects on the expressions of pro- and anti-apoptosis genes of HAECs. Meanwhile, it was noted that DMSA-Fe2O3 exposure could activate the expression of genes related to oxidative stress and adhesion molecules, which suggested that inflammatory response might be evoked. Moreover, we demonstrated by in vitro endothelial tube formation that even a small amount of DMSA-Fe2O3 (0.01 and 0.02 mg/ml) could inhibit angiogenesis by the HAECs. Altogether, these results indicate that DMSA-Fe2O3 have some cytotoxicity that may cause side effects on normal endothelial cells.
Mesonephric adenocarcinoma with a sarcomatous component, a notable subtype of cervical carcinosarcoma: a case report and review of the literature
Authors: Meguro Shiori , Yasuda Masanori , Shimizu Michio , Kurosaki Akira , Fujiwara Keiichi
Published: May 2013

Carcinosarcoma of the uterine cervix is less common than its counterpart in the uterine corpus. On the other hand, mesonephric adenocarcinoma is also a rare neoplasm in the uterine cervix, and it has been reported that mesonephric adenocarcinomas are often accompanied by sarcomatous components. We present a case of mesonephric adenocarcinoma with a sarcomatous component which arose in a 63-year-old postmenopausal woman. The hysterectomy specimen grossly showed an exophytic mass measuring 1.8 cm in the uterine cervix. Histologically, diffuse mesonephric hyperplasia and adenocarcinoma with malignant spindle cell proliferation was recognized, and therefore the tumor was diagnosed as “mesonephric adenocarcinoma with a sarcomatous component.” The review of the literature of cervical carcinosarcoma and cervical mesonephric adenocarcinoma revealed that 16% of cervical carcinosarcoma is of mesonephric duct origin, and that mesonephric adenocarcinoma seems to be more likely to have sarcomatous change. We think the presence of a sarcomatous component in the cervical biopsy specimen could be helpful in the diagnosis of mesonephric duct origin.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1243996503911062
Enhanced characteristics of genetically modified switchgrass (Panicum virgatum L.) for high biofuel production
Authors: Shen Hui , Poovaiah Charleson R , Ziebell Angela , Tschaplinski Timothy J , Pattathil Sivakumar , Gjersing Erica , Engle Nancy L , Katahira Rui , Pu Yunqiao , Sykes Robert , Chen Fang , Ragauskas Arthur J , Mielenz Jonathan R , Hahn Michael G , Davis Mark , Stewart C Neal , Dixon Richard A
Published: May 2013

Background

Lignocellulosic biomass is one of the most promising renewable and clean energy resources to reduce greenhouse gas emissions and dependence on fossil fuels. However, the resistance to accessibility of sugars embedded in plant cell walls (so-called recalcitrance) is a major barrier to economically viable cellulosic ethanol production. A recent report from the US National Academy of Sciences indicated that, “absent technological breakthroughs”, it was unlikely that the US would meet the congressionally mandated renewable fuel standard of 35 billion gallons of ethanol-equivalent biofuels plus 1 billion gallons of biodiesel by 2022. We here describe the properties of switchgrass (Panicum virgatum) biomass that has been genetically engineered to increase the cellulosic ethanol yield by more than 2-fold.

Results

We have increased the cellulosic ethanol yield from switchgrass by 2.6-fold through overexpression of the transcription factor PvMYB4. This strategy reduces carbon deposition into lignin and phenolic fermentation inhibitors while maintaining the availability of potentially fermentable soluble sugars and pectic polysaccharides. Detailed biomass characterization analyses revealed that the levels and nature of phenolic acids embedded in the cell-wall, the lignin content and polymer size, lignin internal linkage levels, linkages between lignin and xylans/pectins, and levels of wall-bound fucose are all altered in PvMYB4-OX lines. Genetically engineered PvMYB4-OX switchgrass therefore provides a novel system for further understanding cell wall recalcitrance.

Conclusions

Our results have demonstrated that overexpression of PvMYB4, a general transcriptional repressor of the phenylpropanoid/lignin biosynthesis pathway, can lead to very high yield ethanol production through dramatic reduction of recalcitrance. MYB4-OX switchgrass is an excellent model system for understanding recalcitrance, and provides new germplasm for developing switchgrass cultivars as biomass feedstocks for biofuel production.
Curation-free biomodules mechanisms in prostate cancer predict recurrent disease
Authors: Chen James L , Hsu Alexander , Yang Xinan , Li Jianrong , Lee Younghee , Parinandi Gurunadh , Li Haiquan , Lussier Yves A
Published: May 2013

Motivation

Gene expression-based prostate cancer gene signatures of poor prognosis are hampered by lack of gene feature reproducibility and a lack of understandability of their function. Molecular pathway-level mechanisms are intrinsically more stable and more robust than an individual gene. The Functional Analysis of Individual Microarray Expression (FAIME) we developed allows distinctive sample-level pathway measurements with utility for correlation with continuous phenotypes (e.g. survival). Further, we and others have previously demonstrated that pathway-level classifiers can be as accurate as gene-level classifiers using curated genesets that may implicitly comprise ascertainment biases (e.g. KEGG, GO). Here, we hypothesized that transformation of individual prostate cancer patient gene expression to pathway-level mechanisms derived from automated high throughput analyses of genomic datasets may also permit personalized pathway analysis and improve prognosis of recurrent disease.

Results

Via FAIME, three independent prostate gene expression arrays with both normal and tumor samples were transformed into two distinct types of molecular pathway mechanisms: (i) the curated Gene Ontology (GO) and (ii) dynamic expression activity networks of cancer (Cancer Modules). FAIME-derived mechanisms for tumorigenesis were then identified and compared. Curated GO and computationally generated "Cancer Module" mechanisms overlap significantly and are enriched for known oncogenic deregulations and highlight potential areas of investigation. We further show in two independent datasets that these pathway-level tumorigenesis mechanisms can identify men who are more likely to develop recurrent prostate cancer (log-rank_p = 0.019).

Conclusion

Curation-free biomodules classification derived from congruent gene expression activation breaks from the paradigm of recapitulating the known curated pathway mechanism universe.
Short term in-patient rehabilitation in axial spondyloarthritis - the results of a 2-week program performed in daily clinical practice
Authors: Eppeland Siv Grødal , Diamantopoulos Andreas P , Soldal Dag Magnar , Haugeberg Glenn
Published: May 2013

Background

From a health service perspective, society, with its limited resources, needs to be reassured that evidence-based medicine is also effective when carried out in the frame of ordinary clinical practice. The effectiveness of rehabilitation programs in ankylosing spondylitis (AS) has been proven to be effective in clinical trials. However, less is known when this is carried out in clinical practice. The aim of this study was to evaluate the effect of a 2-weeks rehabilitation program on self-reported outcome and physical function in patients with axial spondyloarthritis (ax-SpA) including AS patients carried out in ordinary clinical practice. The program contained of daily water exercises, exercises for flexibility, muscle strength, and cardio-respiratory fitness.

Results

A total of 87 ax-SpA patients (60 men, 27 women), aged ≥ 18 years were identified to have participated in the 2-weeks in-patient rehabilitation program. Mean age was 49 years and disease duration was 14 years. 92.5% were HLA-B27 positive, 62% were current users of non-steroidal anti-inflammatory drugs, and 17% were current users of tumour necrosis factor inhibitors. After 2-weeks, a statistical significant improvement (p < 0.001) was observed for patient-reported outcomes (Bath Ankylosing Spondylitis (BAS) Disease Activity Index 4.3 vs. 3.1, BAS Functional Index 3.1 vs. 2.4) and physical measured outcomes (BAS Metrology Index 3.23 vs. 2.29, Gait Velocity 2.2 vs. 2.6 m/s, timed-stands test 22.5 vs. 16.3 s, finger-floor distance 17.9 vs. 8.9 cm, chest expansion 3.9 vs. 4.6 cm).

Conclusion

Data, from our retrospective case series report, support that patient with ax-SpA benefit from short-term rehabilitation when it is carried out in ordinary clinical care. Data from ordinary clinical care may be important when discussing the effectiveness of a treatment and allocating resources in the health care system.
Improving quality of care for persons with diabetes: an overview of systematic reviews - what does the evidence tell us?
Authors: Worswick Julia , Wayne S Carolyn , Bennett Rachel , Fiander Michelle , Mayhew Alain , Weir Michelle C , Sullivan Katrina J , Grimshaw Jeremy M
Published: May 2013

Background

Ensuring high quality care for persons with diabetes remains a challenge for healthcare systems globally with consistent evidence of suboptimal care and outcomes. There is increasing interest in quality improvement strategies to improve diabetes management as reflected by a growing number of systematic reviews. These reviews are of varying quality and dispersed across many sources. In this paper, we present an overview of systematic reviews evaluating the impact of interventions to improve the quality of diabetes care.

Methods

We searched for systematic reviews evaluating the effectiveness of any intervention intended to improve intermediate patient outcomes and process of care measures for patients with any type of diabetes. Two reviewers independently screened search results, appraised each systematic review using AMSTAR and extracted data from high quality reviews (AMSTAR score ≥ 5). Within reviews, we used vote counting by direction of effect to report the number of studies favouring an intervention for each outcome. We produced summaries of results for each intervention category.

Results

We identified 125 reviews of varying methodological quality and summarised key findings from 50 high quality reviews. We categorised reviews by quality improvement intervention. Eight reviews were broad based (involving a variety of strategies). Other reviews considered: patient education and support (n = 21), telemedicine (n = 10), provider role changes (n = 7), and organisational changes (n = 4). Reviews reported intermediate patient outcomes (e.g. glycaemic control) (n = 49) and process of care outcomes (n = 9). There was evidence of considerable overlap of included studies between reviews.

Conclusions

There is consistent evidence from high quality systematic reviews that patient education and support, provider role changes, and telemedicine are associated with improvements in glycaemic and vascular risk factor control in patients. There is less evidence about the impact of quality improvement interventions on other key process measures such as screening patients for diabetic complications. This paper provides decision makers with a comprehensive overview of evidence from high quality systematic reviews about the effects of quality improvement interventions on improving diabetes care.
Vasculogenesis of decidua side population cells of first-trimester pregnancy
Authors: Wang Qiushi , Shen Licong , Huang Wei , Song Yong , Xiao Li , Xu Wenming , Liu Ying
Published: May 2013

Introduction

Sufficient uterine blood supply is essential for the fetus to develop normally in the uterus. Several mechanisms are involved in the process of vessel development in deciduas and villus. We focus on whether first-trimester decidua side population (SP) cells contain cells capable of differentiating into endothelial cells.

Methods

Eight decidua samples were collected from healthy women, 22- to 30-years old, undergoing elective terminations of early pregnancy (six to eight gestational weeks). The cell suspensions from human deciduas were stained by Hoechst 33342 and sorted by flow cytometry, further cultured under differentiation conditions and analyzed for specific markers. These cells were implanted into ischemic limbs of nude mice to test the capacity of angiogenesis in vivo by DiI tracers and immunohistochemistry.

Results

Decidua CD31-CD146- SP cells of first-trimester human pregnancy can differentiate into endothelial cells, express the corresponding specific markers of endothelial cells, such as CD31 and CD146, and form tube-like structures on Matrigel and part of newly formed vessels in the ischemic limbs of nude mice. Vascular endothelial growth factor was more effective in promoting proliferation of CD31-CD146-SP cells compared with other growth factors, and estrogen and progesterone at a final concentration of 10 μmol/L and 30 μmol/L, respectively, promoted the migration of CD31-CD146-SP cells in a dose-dependent manner.

Conclusions

CD31-CD146- SP cells may be involved in the formation of new vessels in the maternal aspect of the placenta in the first trimester.
Delayed wound healing due to increased interleukin-10 expression in mice with lymphatic dysfunction
Authors: Kimura Takayuki , Sugaya Makoto , Blauvelt Andrew , Okochi Hitoshi , Sato Shinichi
Published: May 2013

Skin wound healing is an interactive process involving soluble mediators, ECM, resident cells, and infiltrating cells. Little is known about wound healing in the presence of lymphedema. In this study, we investigated wound healing using kCYC+/− mice, which demonstrate severe lymphatic dysfunction. Wound healing was delayed significantly in kCYC+/− mice when compared with WT mice. In wounded skin of kCYC+/− mice, mast cell numbers were increased compared with WT mice, whereas macrophage numbers were decreased. Moreover, IL-10 expression by mast cells was increased, and expression of bFGF, mainly produced by macrophages, was decreased in wounded skin of kCYC+/− mice compared with WT mice. We next crossed kCYC+/− mice with IL-10−/− mice, which were reported to show accelerated wound closure. In kCYC+/−IL-10+/− mice, time course of wound healing, numbers of macrophages, and IL-10 mRNA expression levels in wounded skin were comparable with WT IL-10+/− mice. Similar results were obtained using a different lymphedema model, in which circumferential skin excision was performed on the tails of mice to remove the superficial lymphatics. In summary, these findings suggest that IL-10 plays an important role in delayed wound healing in the setting of lymphatic dysfunction.
Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors
Authors: Rørvig Sara , Østergaard Ole , Heegaard Niels H H , Borregaard Niels
Published: May 2013

Neutrophils are indispensable in the innate immune defense against invading microorganisms. Neutrophils contain SVs and several subsets of granules that are essential for their function. Proteins present in neutrophil SVs and granules are synthesized during terminal granulopoiesis in the bone marrow. The heterogeneity of granules, as determined by marker proteins characteristic of each granule subset, is thought to result from differences in the biosynthetic windows of major classes of granule proteins, a process referred to as targeting by timing. Qualitative proteomic analysis of neutrophil granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in-gel-digested with trypsin. The resulting peptides were analyzed using LTQ Orbitrap XL tandem MS. A total of 1292 unique proteins were identified and grouped, according to the neutrophil fraction, in which they displayed maximal expression. In addition to various known neutrophil proteins, several uncharacterized proteins were found, as well as proteins not described previously in neutrophils. To study the correlation between mRNA expression in neutrophil precursors and the localization of their cognate proteins, the distribution of 126 identified proteins was compared with their mRNA expression profiles. The neutrophil subcellular proteome profiles presented here may be used as a database in combination with the mRNA array database to predict and test the presence and localization of proteins in neutrophil granules and membranes.
Impact of PTEN Protein Expression on Benefit From Adjuvant Trastuzumab in Early-Stage Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer in the North Central Cancer Treatment Group N9831 Trial
Authors: Perez Edith A. , Dueck Amylou C. , McCullough Ann E. , Chen Beiyun , Geiger Xochiquetzal J. , Jenkins Robert B. , Lingle Wilma L. , Davidson Nancy E. , Martino Silvana , Kaufman Peter A. , Kutteh Leila A. , Sledge George W. , Harris Lyndsay N. , Gralow Julie R. , Reinholz Monica M.
Published: May 2013

Purpose

It has been suggested that PTEN, a negative regulator of PI3K/AKT signaling, is involved in tumor sensitivity to trastuzumab. We investigated the association between tumor PTEN protein expression and disease-free survival (DFS) of patients randomly assigned to receive chemotherapy alone (arm A) or chemotherapy with sequential (arm B) or concurrent trastuzumab (arm C) in the phase III early-stage human epidermal growth factor receptor 2 (HER2) –positive trial—North Central Cancer Treatment Group (NCCTG) N9831.

Patients and Methods

The intensity and percentage of invasive cells with cytoplasmic PTEN staining were determined in tissue microarray sections containing three cores per block (n = 1,286) or in whole tissue sections (WS; n = 516) by using standard immunohistochemistry (138G6 monoclonal antibody). Tumors were considered positive for PTEN (PTEN-positive) if any core or WS had any invasive cells with ≥ 1+ staining. Median follow-up was 6.0 years.

Results

Of 1,802 patients included in this analysis (of 3,505 patients registered to N9831), 1,342 (74%) had PTEN-positive tumors. PTEN positivity was associated with hormone receptor negativity (χ2 P < .001) and nodal positivity (χ2 P = .04). PTEN did not have an impact on DFS within the various arms. Comparing DFS of arm C to arm A, patients with PTEN-positive and PTEN-negative tumors had hazard ratios (HRs) of 0.65 (P = .003) and 0.47 (P = .005), respectively (interaction P = .16). For arm B versus arm A, patients with PTEN-positive and PTEN-negative tumors had HRs of 0.70 (P = .009) and 0.85 (P = .44), respectively (interaction P = .47).

Conclusion

In contrast to selected preclinical and limited clinical studies suggesting a decrease in trastuzumab sensitivity in patients with PTEN-negative tumors, our data show benefit of adjuvant trastuzumab for patients with HER2-positive breast cancer, independent of tumor PTEN status.
Health-Related Quality of Life of Adolescent and Young Adult Patients With Cancer in the United States: The Adolescent and Young Adult Health Outcomes and Patient Experience Study
Authors: Smith Ashley Wilder , Bellizzi Keith M. , Keegan Theresa H.M. , Zebrack Brad , Chen Vivien W. , Neale Anne Victoria , Hamilton Ann S. , Shnorhavorian Margarett , Lynch Charles F.
Published: May 2013

Purpose

Adolescents and young adults (AYAs) diagnosed with cancer face numerous physical, psychosocial, and practical challenges. This article describes the health-related quality of life (HRQOL) and associated demographic and health-related characteristics of this developmentally diverse population.

Patients and Methods

Data are from the Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) study, a population-based cohort of 523 AYA patients with cancer, ages 15 to 39 years at diagnosis from 2007 to 2009. Comparisons are made by age group and with general and healthy populations. Multiple linear regression models evaluated effects of demographic, disease, health care, and symptom variables on multiple domains of HRQOL using the Pediatric Quality of Life Inventory (PedsQL) and the Short-Form Health Survey 12 (SF-12).

Results

Overall, respondents reported significantly worse HRQOL across both physical and mental health scales than did general and healthy populations. The greatest deficits were in limitations to physical and emotional roles, physical and social functioning, and fatigue. Teenaged patients (ages 15 to 17 years) reported worse physical and work/school functioning than patients 18 to 25 years old. Regression models showed that HRQOL was worse for those in treatment, with current/recent symptoms, or lacking health insurance at any time since diagnosis. In addition, sarcoma patients, Hispanic patients, and those with high school or lower education reported worse physical health. Unmarried patients reported worse mental health.

Conclusion

Results suggest that AYAs with cancer have major decrements in several physical and mental HRQOL domains. Vulnerable subgroups included Hispanic patients, those with less education, and those without health insurance. AYAs also experienced higher levels of fatigue that were influenced by current symptoms and treatment. Future research should explore ways to address poor functioning in this understudied group.
Narratives of Catastrophe in the Early Modern Period: Awareness of Historicity and Emergence of Interpretative Viewpoints
Authors: Lavocat Françoise
Published: May 2013

When, why, and how do people write about a natural disaster? The article characterizes three ways of narrating catastrophe—allegorical, anecdotal, and historical—and shows that a shift toward the historical narrative takes place at the beginning of the seventeenth century, more precisely around 1630, and mainly in Italy. The most likely explanation is twofold. First, the interpretation of catastrophes no longer relies solely on religious explanations, but political and polemical ones are also starting to be considered. Second, the expression of a point of view contributes to this increased recourse to the narrative. This article argues that the flourishing of catastrophe narratives is related to interpretative conflicts. The second issue raised by this article is the difference between factual and fictional narratives. This question is examined in the context of the historical experience constructed by the narrative. The fictional accounts of catastrophe will be characterized as such: fiction allows the disaster to be experienced in a paradoxical relation to time, through the point of view of an “impossible witness.”
Diabetes is predictive of longer hospital stay and increased rate of Clavien complications in spinal surgery in the UK
Authors: Sharma A , Muir R , Johnston R , Carter E , Bowden G , Wilson-MacDonald J
Published: May 2013

Introduction

Diabetes is a common co-morbidity of patients undergoing spinal surgery in the UK but there are no published studies from the UK, particularly with respect to length of hospital stay and complications. The aims of this study were to identify complications and length of hospital stay in patients with diabetes undergoing spinal surgery.

Methods

Data were collected retrospectively for 111 consecutive patients with diabetes (and 97 age and sex matched control patients, identified using computer records) who underwent spinal surgery between 2004 and 2010 in a single centre. The data collected included operative time, blood loss, details of surgery, Clavien complications and length of hospital stay.

Results

No significant differences were found by group in operative time, blood loss, instrumentation, use of graft or revision surgery. Overall complication rates were higher in the patients with diabetes than in the controls (28.8% vs 15.5%). The mean hospital stay was significantly longer for patients with diabetes than for control patients (4.6 vs 3.2 days, p<0.001).

Conclusions

This study identified a significantly higher Clavien grade I complication rate and length of hospital stay in patients with diabetes undergoing spinal surgery than control patients (p=0.02). This has resulted in a predictive model being generated. Of note, no infections were seen in patients with diabetes, suggesting that infection rates in this particular group of patients undergoing spinal surgery might not be as high as considered previously.
The cost effectiveness of early management of acute appendicitis underlies the importance of curative surgical services to a primary healthcare programme
Authors: Kong V , Aldous C , Handley J , Clarke D
Published: May 2013

Introduction

Appendicitis in the developing world is a cause of significant preventable morbidity. This prospective study from a regional hospital in South Africa constructs a robust cost model that demonstrates the cost effectiveness of an efficient curative surgical service in a primary healthcare-orientated system.

Methods

A prospective audit of all patients with acute appendicitis admitted to Edendale Hospital was undertaken from September 2010 to September 2011. A microcosting approach was used to construct a cost model based on the estimated cost of operative and perioperative interventions together with the associated hospital stay. For cost analysis, patients were divided into the following cohorts: uncomplicated appendicitis, complicated appendicitis with localised intra-abdominal sepsis, complicated appendicitis with generalised intra-abdominal sepsis, with and without intensive care unit admission.

Results

Two hundred patients were operated on for acute appendicitis. Of these, 36% (71/200) had uncomplicated appendicitis and 57% (114/200) had perforation. Pathologies other than appendicitis were present in 8% (15/200) and these patients were excluded. Of the perforated appendices, 45% (51/114) had intra-abdominal contamination that was localised while 55% (63/114) generalised sepsis. The mean cost for each patient was: 6,578 ZAR (£566) for uncomplicated appendicitis; 14,791 ZAR (£1,272) for perforation with localised intra-abdominal sepsis and 34,773 ZAR (£2,990) for perforation with generalised intra-abdominal sepsis without intensive care admission. With intensive care admission it was 77,816 ZAR (£6,692). The total cost of managing acute appendicitis was 4,272,871 ZAR (£367,467). Almost 90% of this total cost was owing to advanced disease with abdominal sepsis and therefore potentially preventable.

Conclusions

Early uncomplicated appendicitis treated appropriately carries little morbidity and is relatively inexpensive to treat. As the pathology progresses, the cost rises exponentially. An efficient curative surgical service must be regarded as a cost effective component of a primary healthcare orientated system.
Bearing exchange in the management of pseudotumours
Authors: Kemp MA , Mitra A , Mendes da Costa T , Spencer RF
Published: May 2013

Introduction

Soft tissue reactions following metal-on-metal (MoM) arthroplasty of the hip have been under considerable discussion. These reactions are seen following both hip resurfacing and MoM total hip arthroplasty (THA). The phenomenon may arise owing to shedding of metal particles in high wear states, hypersensitivity with normal metal wear rates or a combination of the two.

Methods

Three patients were identified who had developed a soft tissue reaction (pseudotumour) following MoM hip resurfacing procedures. The prostheses were revised to ceramic-on-ceramic (CoC) THA with only minimal debridement of the pseudotumour. Pre and postoperative magnetic resonance imaging was performed to assess the size of the lesions.

Results

Progressive and satisfactory resolution of the associated pseudotumours was identified following revision of the prostheses to CoC THA.

Conclusions

In the early stages of pseudotumour formation following MoM hip resurfacing, this potentially devastating condition can be managed adequately with revision to a CoC bearing THA with minimal soft tissue excision.
A decade of experience of thyroglossal cyst excision
Authors: Ubayasiri KM , Brocklehurst J , Judd O , Beasley N
Published: May 2013

Introduction

We report our ten-year experience of thyroglossal cyst excision at Queen’s Medical Centre, Nottingham, comparing outcomes, practice and technique.

Methods

Retrospective case note analysis was conducted alongside surgical histopathology review for all thyroglossal cyst excisions performed between 2000 and 2010. This yielded 108 patients with histopathology results confirming a thyroglossal cyst.

Results

The mean patient age was 21 years (range: 1 week – 76 years). Over half the patients (n=59, 55%) were less than 18 years of age. Fifty-five patients (51%) were male and fifty-three (49%) were female. Seventy cases (63%) were operated on by ear, nose and throat (ENT) surgeons. The rest were performed by paediatric surgeons (n=35, 32%), maxillofacial surgeons (n=2, 2%) and general surgeons (n=1, 1%). Paediatric surgeons undertook 35 (69%) of the 59 paediatric cases, with ENT surgeons operating on the rest (n=24, 41%). The primary surgeon was a consultant in 59 operations (55%) while in 49 cases (45%) it was a registrar. Thyroglossal cysts were ruptured in 21 operations (19%) during removal. The central portion of the hyoid bone was not excised in seven cases (6%). Twelve patients (11%) suffered postoperative complications, six of which were recurrences.

Conclusions

There was a combined recurrence rate of 6% across all specialties for the Sistrunk procedure. This is in keeping with commonly reported recurrence rates. However, we found that central compartment neck dissection, as a modification of the original Sistrunk procedure, provides a highly effective method for permanently excising a thyroglossal cyst and, in our experience, it eliminates recurrence.
Pancreatic trauma
Authors: Lahiri R , Bhattacharya S
Published: May 2013

Introduction

Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised.

Methods

A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: ‘pancreatic trauma’, ‘pancreatic duct injury’, ‘radiology AND pancreas injury’, ‘diagnosis of pancreatic trauma’, and ‘management AND surgery’. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors.

Results

Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon.

Conclusions

The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases, experienced HPB surgeons should be involved. Complications following pancreatic trauma are common and the majority can be managed without further surgery.
Tofacitinib
Authors: Cada Dennis J. , Demaris Kendra , Levien Terri L. , Baker Danial E.
Published: May 2013

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The May 2013 monograph topics are ado-trastuzumab emtansine, pomalidomide, mipomersen, pasireotide diaspartate, and glycerol phenylbutyrate. The DUE/MUE is on atypical antipsychotics, extended release.
Issues Facing Pharmacy Leaders in 2013
Authors: O'Connor Michael , Weber Robert J.
Published: May 2013

The Director's Forum provides directors of pharmacy practical ways to develop patient-centered pharmacy services. Pharmacy directors must understand the key issues facing their departments and incorporate strategies for these issues as part of their strategic planning process. Health care reform and the Affordable Care Act require that departments operate efficiently and closely monitor their drug expense. The American Society of Health-System Pharmacists’ Pharmacy Practice Model Initiative will serve as a valuable resource during 2013 to enhance the pharmacy practice model. By using their health care workforce, particularly pharmacy technicians, in an innovative way, pharmacy directors will allow the pharmacists to increase their clinical activity. By promoting the role of the hospital pharmacist to patients, directors will help to improve patients’ understanding of their medications and increase their satisfaction with their care. Finally by changing the activities of pharmacy students in practice models, the patient care role of the pharmacist can be expanded. Through a greater understanding of the issues facing them and their effect on the operations of the pharmacy, pharmacy directors will learn effective ways to develop patient-centered pharmacy services.
Racial and Ethnic Differences in the Transition To a Teenage Birth in the United States
Authors: Manlove Jennifer , Steward‐Streng Nicole , Peterson Kristen , Scott Mindy , Wildsmith Elizabeth
Published: May 2013

Context

Rates of teenage childbearing are high in the United States, and they differ substantially by race and ethnicity and nativity status.

Methods

Data from the National Longitudinal Survey of Youth 1997 cohort were used to link characteristics of white, black, U.S.‐born Hispanic and foreign‐born Hispanic adolescents to teenage childbearing. Following a sample of 3,294 females aged 12–16 through age 19, discrete‐time logistic regression analyses were used to examine which domains of teenagers’ lives were associated with the transition to a teenage birth for each racial and ethnic group, and whether these associations help explain racial and ethnic and nativity differences in this transition.

Results

In a baseline multivariate analysis controlling for age, compared with whites, foreign‐born Hispanics had more than three times the odds of a teenage birth (odds ratio, 3.5), while blacks and native‐born Hispanics had about twice the odds (2.1 and 1.9, respectively). Additional controls (for family environments; individual, peer and dating characteristics; characteristics of first sexual relationships; and subsequent sexual experience) reduced the difference between blacks and whites, and between foreign‐born Hispanics and whites, and eliminated the difference between U.S.‐born Hispanics and whites. Further, if racial or ethnic minority adolescents had the same distribution as did white teenagers across all characteristics, the predicted probability of a teenage birth would be reduced by 40% for blacks and 35% for U.S.‐born Hispanics.

Conclusions

Differences in the context of adolescence may account for a substantial portion of racial, ethnic and nativity differences in teenage childbearing.
Complementation of ditransitive verbs in South Asian Englishes: a multifactorial analysis
Authors: Schilk Marco , Mukherjee Joybrato , Nam Christopher , Mukherjee Sach
Published: May 2013

This paper examines parallels and differences between South Asian Englishes and British English with regard to various factors driving the selection of verb-complementation patterns. Focusing on the prototypical ditransitive verb give and its complementation, we use large web-derived corpora and distinguish between two possible response cases, one based on the dative and prepositional construction (i.e. the dative alternation), the other including monotransitive complementation. Our data has been additionally coded for a number of potential driving factors, such as pronominality and discourse accessibility of the participants in the constructions. Applying a model-exploration technique we isolate the main driving factors for the varieties under scrutiny (Indian English, Pakistani English and British English) and analyze their influence on pattern selection based on a multinomial logistic regression formulation. Our findings show that, while there is a large area of overlap between the varieties, Pakistani English is closer to British English with regard to relevant driving factors than Indian English. Furthermore, we reveal interesting parallels between all three varieties in the use of monotransitive complementation.