bluuebunny/crossref_metadata_2025_split huggingface dataset:
ICD Lead Parameters, Performance, and Adverse Events following Continuous‐Flow LVAD Implantation
Authors: THOMAS ISAC C. , CORK DAVID P. , LEVY ANDREW , NAYAK HEMAL , BESHAI JOHN F. , BURKE MARTIN C. , MOSS JOSHUA D. 
Published: November 2013

BackgroundVentricular arrhythmias (VAs) in the months following continuous‐flow left ventricular assist devices (LVADs) implantation are common and associated with increased morbidity and mortality. We sought to evaluate for changes in implantable cardioverter defibrillator (ICD) performance following LVAD implantation.MethodsWe retrospectively reviewed the ICD interrogation reports and medical records of patients who received a continuous‐flow LVAD at the University of Chicago Medical Center between January 2008 and December 2010. Patients who did not have an ICD prior to LVAD implantation were excluded.ResultsForty‐four patients were included. Median right ventricular lead sensing amplitude decreased from 10.0 (interquartile range 7.6–13.6) mV prior to LVAD to 7.9 (5.9–9.3) mV after LVAD implantation (P < 0.01). Significant reductions in sensing threshold were associated with smaller lead diameters, smaller pace/sense electrode surface areas, and Medtronic ICD leads (Medtronic Inc., Minneapolis, MN, USA). Lead impedance and capture threshold did not change significantly. ICD‐related adverse events occurred in 30% of patients and led to ICD modification in 18% of patients.ConclusionsImplantation of a continuous‐flow LVAD is associated with changes in the performance of preexisting ICDs. ICD‐related adverse events were encountered following LVAD implantation in this cohort, and at times resulted in invasive and noninvasive ICD system modification. Reductions in ICD sensing threshold after LVAD implantation may adversely affect ICD function. Formal ICD interrogation in addition to the regular follow‐up testing is warranted post‐LVAD.
Anesthetic considerations for neonates undergoing modified Blalock‐Taussig shunt and variations
Authors: Holtby Helen M. 
Published: November 2013

SummaryThe first Blalock‐Taussig (BT) shunt was reported in 1944, and during the last 70 years, the procedure has evolved with the development of new materials and devices, and surgical approaches. It has, however, remained central to the palliation of neonates with complex congenital heart disease. The indications have expanded from the original aim of alleviating cyanosis and the pathophysiological results of chronic hypoxemia. They now include lesions with single ventricles, and rehabilitation of small pulmonary arteries. The physiology and hemodynamics of BT shunt circulations are very complex, and adverse hemodynamic events can be difficult to recognize. The consequences of shunt failure can be fatal, and the mortality (3–15%) and morbidity remain distressingly high even in the current era. Neonates undergoing BT shunt procedures or undergoing noncardiac surgery with this anatomy are challenging for the anesthesiologists to manage. There is a significant incidence of periprocedural cardiac arrest, often related to myocardial ischemia. A clear understanding of the anatomy and physiology is important. Any discussion of BT shunt in the current era has to include consideration of hypoplastic left heart syndrome and ‘single ventricle’ physiology.
Coagulation and the surgical neonate
Authors: Arnold Philip D. 
Published: November 2013

SummaryBoth coagulopathy and abnormal thrombosis can complicate the anesthetic and surgical management of neonatal patients; however, the patterns of bleeding and thrombosis in neonates differ from those in adults or older children. Severe coagulopathic bleeding most commonly occurs during heart surgery and almost certainly contributes to morbidity and mortality in this population. Such severe bleeding is rare during other surgery; the exception is babies presenting to the operating room with established coagulopathy secondary to severe sepsis. Alternatively, pathological thrombosis will mainly occur in association with indwelling vascular access devices or surgically created vascular shunts. There are important differences between the coagulation system in neonates and older patients. The implication of this is that therapies established in other patient groups will not be optimal for neonates without adaptation. While evidence from high‐quality clinical trials is rarely available, an understanding of how coagulation in neonates differs can help to guide practice. This review will discuss important differences between the coagulation system of neonates and older patients and how these relate to newer models of coagulation. The emphasis will be on issues likely to impact on perioperative care. In particular, the management of severe bleeding, the manipulation of coagulation during heart surgery, and the management of coagulopathy in septic neonates will be discussed in detail.
Pathways to adulthood and their precursors and outcomes
Authors: Skogbrott Birkeland Marianne , Leversen Ingrid , Torsheim Torbjørn , Wold Bente 
Published: November 2013

Norway has an extensive welfare system which may provide adolescents with many options and high levels of flexibility in terms of pathways to adulthood. This study aimed to describe Norwegian developmental pathways to adulthood, including changes in role statuses (such as living situations, education, work, marriage/cohabitation and parenthood) from 16 to 30 years of age, and their precursors and outcomes. Repeated measures latent class analysis of longitudinal data from 998 Norwegian individuals indicated three main pathways to adulthood among women and men. In both sexes, most individuals undertook a long period of education and postponed family formation. However, some individuals started working early, a group of women established families with partners and children early, and a group of men remained primarily single between 16 and 30 years of age. Furthermore, the results show that pathways to adulthood in Norway are surprisingly similar to pathways in other countries such as the US, UK and Finland. The results indicate that pathways to adulthood are influenced by social reproduction factors in a country with high levels of welfare benefits as well. In addition, the results suggest that pathways involving living with a partner and either higher education or work are associated with high life satisfaction at age 30.
Pest or patient?
Authors: Fawcett Anne , Woon Sy 
Published: November 2013

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved. In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Pest or patient?’, was submitted by a reader and is presented and discussed by Anne Fawcett and Sy Woon. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘The cow that got up’, which was published in the October issue of In Practice, appears on page 615.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
Monitoring antimicrobial resistance inNeisseria gonorrhoeaein selected countries of the WHO South-East Asia Region between 2009 and 2012: a retrospective analysis
Authors: Bala Manju , Kakran Monika , Singh Vikram , Sood Seema , Ramesh V ,   Members of the WHO GASP SEAR Network
Published: November 2013

ObjectiveThe aim of the present study was to retrospectively analyse the data reported on antimicrobial resistance (AMR) inNeisseria gonorrhoeaein six South-East Asia Region countries from 2009 to 2012 following the revitalisation of the WHO global Gonococcal Antimicrobial Surveillance Program (GASP).MethodsAMR data were generated for 7 antibiotics of 4675 isolates in 18 focal point laboratories using the calibrated dichotomous sensitivity (CDS) or Clinical and Laboratory Standards Institute (CLSI) methods and minimal inhibitory concentration testing by Etest in some of the centres. The results were interpreted using the breakpoints recommended.ResultsHigh-level resistance to traditional antibiotics, penicillin (25% to 100%) and tetracycline (10% to 100%) and the previously recommended ciprofloxacin (38% to 100%) was observed in all the countries. Overall, >90% of less susceptible and resistant isolates to penicillin and ciprofloxacin were identified from 15 laboratories. Decreased susceptibility to ceftriaxone and cefpodoxime was reported by nine and eight centres, respectively. Resistance to spectinomycin (0.6% to 10.5%) and azithromycin (<5%) was reported only by three centres. The increasing trends of resistance towards penicillin, tetracycline and ciprofloxacin were demonstrated in Bhutan, India, Sri Lanka and Thailand, and no large intercountry variations were evident. Insignificant trends in decreased susceptibility towards ceftriaxone were reported.ConclusionsExpansion of the WHO GASP facilitated enhanced AMR surveillance to meet the ongoing challenges of control of gonococcal AMR. The results highlight that the emergence of decreased susceptibility to ceftriaxone and resistance to spectinomycin and azithromycin will unavoidably lead to loss of therapeutic options, and a search for new effective agents needs to be initiated to respond to the emergence of resistant isolates.
Trends in antimicrobial resistance inNeisseria gonorrhoeaein the USA: the Gonococcal Isolate Surveillance Project (GISP), January 2006–June 2012
Authors: Kirkcaldy Robert D , Kidd Sarah , Weinstock Hillard S , Papp John R , Bolan Gail A 
Published: November 2013

BackgroundNeisseria gonorrhoeaehas progressively developed resistance to sulfonamides, penicillin, tetracycline and fluoroquinolones, and gonococcal susceptibility to cephalosporins has been declining worldwide.MethodsWe described trends in gonococcal antimicrobial susceptibility in the USA from January 2006 through June 2012. Susceptibility data for cefixime, ceftriaxone, azithromycin, penicillin, tetracycline and ciprofloxacin were obtained from the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance system that monitors antimicrobial susceptibility in urethral gonococcal isolates collected from symptomatic men at 25–30 sexually transmitted disease clinics throughout the USA.ResultsThe percentage of isolates with elevated cefixime minimum inhibitory concentrations (MICs) (≥0.25 µg/mL) increased from 0.1% in 2006 to 1.4% in 2010–2011 and was 1.1% in the first 6 months of 2012. The percentage with elevated ceftriaxone MICs (≥0.125 µg/mL) increased from 0.1% in 2006 to 0.3%–0.4% during 2009 through the first 6 months of 2012. There were no temporal trends in the prevalence of elevated azithromycin MICs (≥2 µg/mL) (0.2%–0.5%). The prevalence of resistance remained high for penicillin (11.2%–13.2%), tetracycline (16.7%–22.8%) and ciprofloxacin (9.6%–14.8%).ConclusionsThe proportion of gonococcal isolates with elevated cephalosporin MICs increased from 2006 to 2010, but plateaued during 2011 and the first 6 months of 2012. Resistance to previously recommended antimicrobials has persisted. As the number of antimicrobials available for gonorrhoea treatment dwindles, surveillance systems such as GISP will be critical to detect emerging resistance trends and guide treatment decisions.
Requirements for Aurora-A in Tissue Regeneration and Tumor Development in Adult Mammals
Authors: Pérez de Castro Ignacio , Aguirre-Portolés Cristina , Fernández-Miranda Gonzalo , Cañamero Marta , Cowley Dale O. , Van Dyke Terry , Malumbres Marcos 
Published: November 2013

Abstract
Aurora-A is a kinase involved in the formation and maturation of the mitotic spindle and chromosome segregation. This kinase is frequently overexpressed in human cancer, and its activity may confer resistance to antitumoral drugs such as Taxol. Inhibition of Aurora-A results in mitotic defects, and this kinase is considered as an attractive therapeutic target for cancer. Nevertheless, the specific requirements for this kinase in adult mammalian tissues remain unclear. Conditional genetic ablation of Aurora-A in adult tissues results in polyploid cells that display a DNA-damage–like response characterized by the upregulation of p53 and the cell-cycle inhibitor p21Cip1. This is accompanied by apoptotic, differentiation, or senescence markers in a tissue-specific manner. Therapeutic elimination of Aurora-A prevents the progression of skin and mammary gland tumors. However, this is not due to significant levels of apoptosis or senescence, but because Aurora-A–deficient tumors accumulate polyploid cells with limited proliferative potential. Thus, Aurora-A is required for tumor formation in vivo, and the differential response observed in various tissues might have relevant implications in current therapeutic strategies aimed at inhibiting this kinase in the treatment of human cancer. Cancer Res; 73(22); 6804–15. ©2013 AACR.
The Transcription Factor IRF8 Counteracts BCR-ABL to Rescue Dendritic Cell Development in Chronic Myelogenous Leukemia
Authors: Watanabe Tomoya , Hotta Chie , Koizumi Shin-ichi , Miyashita Kazuho , Nakabayashi Jun , Kurotaki Daisuke , Sato Go R. , Yamamoto Michio , Nakazawa Masatoshi , Fujita Hiroyuki , Sakai Rika , Fujisawa Shin , Nishiyama Akira , Ikezawa Zenro , Aihara Michiko , Ishigatsubo Yoshiaki , Tamura Tomohiko 
Published: November 2013

Abstract
BCR-ABL tyrosine kinase inhibitors (TKI) have dramatically improved therapy for chronic myelogenous leukemia (CML). However, several problems leading to TKI resistance still impede a complete cure of this disease. IFN regulatory factor-8 (IRF8) is a transcription factor essential for the development and functions of immune cells, including dendritic cells. Irf8−/− mice develop a CML-like disease and IRF8 expression is downregulated in patients with CML, suggesting that IRF8 is involved in the pathogenesis of CML. In this study, by using a murine CML model, we show that BCR-ABL strongly inhibits a generation of dendritic cells from an early stage of their differentiation in vivo, concomitant with suppression of Irf8 expression. Forced expression of IRF8 overrode BCR-ABL (both wild-type and T315I-mutated) to rescue dendritic cell development in vitro, indicating that the suppression of Irf8 causes dendritic cell deficiency. Gene expression profiling revealed that IRF8 restored the expression of a significant portion of BCR-ABL–dysregulated genes and predicted that BCR-ABL has immune-stimulatory potential. Indeed, IRF8-rescued BCR-ABL–expressing dendritic cells were capable of inducing CTLs more efficiently than control dendritic cells. Altogether, our findings suggest that IRF8 is an attractive target in next-generation therapies for CML. Cancer Res; 73(22); 6642–53. ©2013 AACR.
MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer
Authors: MacNeil Adam J. , Jiao Shun-Chang , McEachern Lori A. , Yang Yong Jun , Dennis Amanda , Yu Haiming , Xu Zhaolin , Marshall Jean S. , Lin Tong-Jun 
Published: November 2013

Abstract
Cancers are initiated as a result of changes that occur in the genome. Identification of gains and losses in the structure and expression of tumor-suppressor genes and oncogenes lies at the root of the understanding of cancer cell biology. Here, we show that the mitogen–activated protein kinase (MAPK) MKK3 suppresses the growth of breast cancer, in which it varies in copy number. A pervasive loss of MKK3 gene copy number in patients with breast cancer is associated with an impairment of MKK3 expression and protein level in malignant tissues. To assess the functional role of MKK3 in breast cancer, we showed in an animal model that MKK3 activity is required for suppression of tumor growth. Active MKK3 enhanced expression of the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27Kip1, leading to increased cell-cycle arrest in G1 phase of the cell cycle. Our results reveal the functional significance of MKK3 as a tumor suppressor and improve understanding of the dynamic role of the MAPK pathway in tumor progression. Cancer Res; 74(1); 162–72. ©2013 AACR.
Small-Molecule Intramimics of Formin Autoinhibition: A New Strategy to Target the Cytoskeletal Remodeling Machinery in Cancer Cells
Authors: Lash L. Leanne , Wallar Bradley J. , Turner Julie D. , Vroegop Steven M. , Kilkuskie Robert E. , Kitchen-Goosen Susan M. , Xu H. Eric , Alberts Arthur S. 
Published: November 2013

Abstract
Although the cancer cell cytoskeleton is a clinically validated target, few new strategies have emerged for selectively targeting cell division by modulating the cytoskeletal structure, particularly ways that could avoid the cardiotoxic and neurotoxic effects of current agents such as taxanes. We address this gap by describing a novel class of small-molecule agonists of the mammalian Diaphanous (mDia)-related formins, which act downstream of Rho GTPases to assemble actin filaments, and their organization with microfilaments to establish and maintain cell polarity during migration and asymmetric division. GTP-bound Rho activates mDia family members by disrupting the interaction between the DID and DAD autoregulatory domains, which releases the FH2 domain to modulate actin and microtubule dynamics. In screening for DID–DAD disruptors that activate mDia, we identified two molecules called intramimics (IMM-01 and -02) that were sufficient to trigger actin assembly and microtubule stabilization, serum response factor-mediated gene expression, cell-cycle arrest, and apoptosis. In vivo analysis of IMM-01 and -02 established their ability to slow tumor growth in a mouse xenograft model of colon cancer. Taken together, our work establishes the use of intramimics and mDia-related formins as a new general strategy for therapeutic targeting of the cytoskeletal remodeling machinery of cancer cells. Cancer Res; 73(22); 6793–803. ©2013 AACR.
Helicobacter pylori Seropositivities and Risk of Pancreatic Carcinoma
Authors: Risch Harvey A. , Lu Lingeng , Kidd Mark S. , Wang Jing , Zhang Wei , Ni Quanxing , Gao Yu-Tang , Yu Herbert 
Published: November 2013

Abstract
Background: Pathophysiologic actions of Helicobacter pylori colonization on gastric acidity have been hypothesized to modulate the effect of pancreatic carcinogens, through CagA-negative organism strain type, hyperchlorhydria and increased risk of pancreatic cancer, or CagA-positive strain, hypochlorhydria and decreased risk of pancreatic cancer. We aimed to determine H. pylori strain–specific associations with pancreatic cancer in a population in which colonization by CagA-positive strains is common.
Methods: We carried out a large population-based case–control study of pancreatic carcinoma in Shanghai, China. Venipuncture specimens were obtained from a representative sample of 761 case patients and 794 randomly selected control subjects matched by category of age and gender. Antibody seropositivity for H. pylori and its virulence protein CagA were determined by commercial enzyme-linked immunosorbent IgG assays.
Results: Compared with individuals seronegative for both H. pylori and CagA, decreased pancreas-cancer risk was seen for CagA seropositivity [adjusted OR, 0.68; 95% confidence interval (CI), 0.54–0.84], whereas some increased risk was suggested for CagA-negative H. pylori seropositivity (OR, 1.28; 95% CI, 0.76–2.13). No risk interactions were observed between CagA seropositivity and gender, cigarette smoking, or age-21 body mass index.
Conclusions: Similar to what has been seen in animal models, our results provide suggestive evidence in humans for the involvement of gastric acidity, through its bidirectional modification according to colonization by H. pylori CagA strain type, in the risk of pancreatic carcinoma.
Impact:H. pylori colonization may have diverse effects on cancer risk, depending on the organism strain type as well as on the particular cancer site. Cancer Epidemiol Biomarkers Prev; 23(1); 172–8. ©2013 AACR.
Fragmented QRS Complex in Adult Patients With Ebstein Anomaly and Its Association With Arrhythmic Risk and the Severity of the Anomaly
Authors: Park Seung-Jung , Chung Seungmin , On Young Keun , Kim June Soo , Yang Ji-Hyuk , Jun Tae-Gook , Jang Shin Yi , Lee Ok Jung , Song Jinyoung , Kang I-Seok , Huh June 
Published: November 2013

Background—
Fragmented QRS complex (fQRS) on 12-lead ECG, a marker of myocardial scar, is a predictor of arrhythmic events in patients with ischemic and nonischemic cardiomyopathy. We investigated whether the presence of fQRS is associated with the severity of the anomaly and with increased arrhythmic events in adult patients with Ebstein anomaly (EA).

Methods and Results—

In 51 consecutive adult patients with EA (median age, 37 years; 18 males), the severity index of EA calculated from echocardiographic data and clinical arrhythmic events were analyzed. The extent of fQRS in each patient was measured by counting the number of ECG leads showing fQRS. There were 35 (68.6%) patients with fQRS (fQRS group) and 16 (31.4%) patients without fQRS (non-fQRS group). fQRS was observed more frequently in the inferior (n=26) and precordial (n=25) leads versus the lateral leads (n=5). The patients in the fQRS group had a worse functional class, greater cardiothoracic ratios, more severe tricuspid regurgitation, larger atrialized right ventricular areas, higher EA severity scores, and more frequent arrhythmic events compared with those in the non-fQRS group. The atrialized right ventricular area showed a positive correlation with the fQRS extent (
r
=0.51;
P
<0.001). In multivariable Cox regression models, the presence of fQRS was independently associated with arrhythmic events (
P
=0.036).

Conclusions—
Fragmented QRS on 12-lead ECG was associated with larger atrialized right ventricular area and an increased risk of arrhythmic events in adult patients with EA.