Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice.

The principal reason for failure of targeted cancer therapies is the emergence of resistant clones that regenerate the tumor. Therapeutic efficacy therefore depends on not only how effectively a drug inhibits its target, but also the innate or adaptive functional redundancy of that target and its attendant pathway. In this regard, the Myc transcription factors are intriguing therapeutic targets because they serve the unique and irreplaceable role of coordinating expression of the many diverse genes that, together, are required for somatic cell proliferation. Furthermore, Myc expression is deregulated in most-perhaps all-cancers, underscoring its irreplaceable role in proliferation. We previously showed in a preclinical mouse model of non-small-cell lung cancer that systemic Myc inhibition using the dominant-negative Myc mutant Omomyc exerts a dramatic therapeutic impact, triggering rapid regression of tumors with only mild and fully reversible side effects. Using protracted episodic expression of Omomyc, we now demonstrate that metronomic Myc inhibition not only contains Ras-driven lung tumors indefinitely, but also leads to their progressive eradication. Hence, Myc does indeed serve a unique and nondegenerate role in lung tumor maintenance that cannot be complemented by any adaptive mechanism, even in the most aggressive p53-deficient tumors. These data endorse Myc as a compelling cancer drug target.

Vascular access care in patients with multimorbidity.

BACKGROUND: More than half of patients with multimorbidity require intravenous therapy during their hospital stay. The aims of this study are to describe difficult intravenous access (DIVA) and vascular access care provided to this patient population and to explore the differences between easy and DIVA groups. METHODS: A cohort study was conducted in patients with multimorbidity admitted to 2 hospitals between March and November 2013. The variables used to describe vascular care included choice and placement of devices, catheter swell time, and occurrence of adverse events. The incidence of adverse events was expressed as number cases per 1000 catheter days and χ2, Student's t, or Mann-Whitney U tests were used to compare the care provided between both groups. Odds rates were calculated to determine the risk of complications associated with DIVA. RESULTS: We recruited 135 patients, of whom 34.8% were women. Overall, 59.3% had DIVA. A total of 224 catheters were inserted, patients with difficult access requiring a mean of 1.71 catheters and those with easy access 1.58 catheters. Two or more attempts were required to place catheters in 23% of cases in the difficult access group versus 2.50% in the easy access group. Mean catheter dwell time was 3.84 days and 3.99 days, and the adverse event rate was 111/1000 and 83.6/1000 catheter days, respectively. The odds ratio for complications was 1.596. CONCLUSIONS: Multimorbid patients with DIVA have a higher rate of complications as well as requiring more catheters and more placement attempts.

Prevalence of difficult venous access and associated risk factors in highly complex hospitalised patients.

AIMS AND OBJECTIVES: To estimate the prevalence of difficult venous access in complex patients with multimorbidity and to identify associated risk factors. BACKGROUND: In highly complex patients, factors like ageing, the need for frequent use of irritant medication and multiple venous catheterisations to complete treatment could contribute to exhaustion of venous access. DESIGN: A cross-sectional study was conducted. METHODS: 'Highly complex' patients (n = 135) were recruited from March 2013-November 2013. The main study variable was the prevalence of difficult venous access, assessed using one of the following criteria: (1) a history of difficulties obtaining venous access based on more than two attempts to insert an intravenous line and (2) no visible or palpable veins. Other factors potentially associated with the risk of difficult access were also measured (age, gender and chronic illnesses). Univariate analysis was performed for each potential risk factor. Factors with p < 0·2 were then included in multivariable logistic regression analysis. Odds ratios were also calculated. RESULTS: The prevalence of difficult venous access was 59·3%. The univariate logistic regression analysis indicated that gender, a history of vascular access complications and osteoarticular disease were significantly associated with difficult venous access. The multivariable logistic regression showed that only gender was an independent risk factor and the odds ratios was 2·85. CONCLUSIONS: The prevalence of difficult venous access is high in this population. Gender (female) is the only independent risk factor associated with this. Previous history of several attempts at catheter insertion is an important criterion in the assessment of difficult venous access. RELEVANCE TO CLINICAL PRACTICE: The prevalence of difficult venous access in complex patients is 59·3%. Significant risk factors include being female and a history of complications related to vascular access.

[Sentinel lymph node biopsy technique in colon cancer. Experience in 125 cases]. / Técnica del ganglio centinela en el cáncer de colon. Experiencia en 125 casos.

INTRODUCTION: The level of lymph node involvement is the most important factor in staging colorectal cancer without metastasis. Sentinel lymph node mapping identifies the node(s) that most accurately reflect the lymph node status of patients, and intensive techniques that improve staging can be focused on these nodes. The aim of this study was to assess the efficacy of ex vivo sentinel lymph node mapping in the staging of colon cancer. MATERIALS AND METHODS: A prospective study was conducted on 125 patients from the Alava-Txagorritxu University Hospital Health Region (Alava), who were diagnosed prior to surgery with colon cancer without distant metastasis from September 2009 to December 2011. Ex vivo sentinel lymph node mapping with methylene blue was use in these patients to study the sentinel nodes with multiple slices using immunohistochemical techniques and haematoxylin-eosin staining. A comparative study was also performed based on a control group of 170 patients staged with conventional techniques, and involving a single slice and haematoxylin-eosin staining. RESULTS: The sentinel lymph node identification rate was 98%, with 5.6% false negatives. Upstaging occurred in 14.2% of cases compared to the group studied using conventional techniques (P=.006). CONCLUSIONS: Ex vivo sentinel lymph node mapping with methylene blue accurately reflects the lymph node status of patients with colon cancer. This approach upstages patients classified as stages i and ii by conventional techniques to stage iii, indicating chemotherapy that may improve their prognosis.

Obstructive sleep apnea and systemic hypertension: longitudinal study in the general population: the Vitoria Sleep Cohort.

RATIONALE: Obstructive sleep apnea and systemic hypertension (SH) are highly prevalent. Although their association has been suggested in cross-sectional studies, conflicting evidence has emerged from longitudinal studies. OBJECTIVES: To assess the association between obstructive sleep apnea and SH in the middle-aged general population. METHODS: A total of 2,148 subjects were included in a longitudinal study of the Vitoria Sleep Cohort, a general population sample aged 30-70 years. We analyzed data on office blood pressure, anthropometric measures, health history, and home polygraphy. Out of 1,557 subjects who completed the 7.5-year follow-up, 377 were excluded for having SH at baseline. The odds ratios for the incidence of SH, according to the respiratory disturbance index (RDI) at baseline, were estimated in 1,180 subjects (526 men and 654 women) after adjustment for age; sex; body mass index; neck circumference; fitness level; and alcohol, tobacco, and coffee consumption. The RDI was divided into quartiles (0-2.9, 3-6.9, 7-13.9, and ≥ 14), using the first quartile as reference. MEASUREMENTS AND MAIN RESULTS: The crude odds ratio for incident hypertension increased with higher RDI category with a dose-response effect (P < 0.001), but was not statistically significant after adjustment for age (P = 0.051). Adjustments for sex (P = 0.342), body mass index (P = 0.803), neck circumference (P = 0.885), and fitness level and alcohol, tobacco, and coffee consumption (P = 0.708) further reduced the strength of the association between RDI and SH. No differences were observed between men and women. CONCLUSIONS: Our findings do not suggest an association between obstructive sleep apnea and the incidence of SH in the middle-aged general population. Long-term follow-up longitudinal studies are needed to better ascertain this association.

MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding.

MYC's role in promoting tumorigenesis is beyond doubt, but its function in the metastatic process is still controversial. Omomyc is a MYC dominant negative that has shown potent antitumor activity in multiple cancer cell lines and mouse models, regardless of their tissue of origin or driver mutations, by impacting on several of the hallmarks of cancer. However, its therapeutic efficacy against metastasis has not been elucidated yet. Here we demonstrate for the first time that MYC inhibition by transgenic Omomyc is efficacious against all breast cancer molecular subtypes, including triple-negative breast cancer, where it displays potent antimetastatic properties both in vitro and in vivo. Importantly, pharmacologic treatment with the recombinantly produced Omomyc miniprotein, recently entering a clinical trial in solid tumors, recapitulates several key features of expression of the Omomyc transgene, confirming its clinical applicability to metastatic breast cancer, including advanced triple-negative breast cancer, a disease in urgent need of better therapeutic options. Significance: While MYC role in metastasis has been long controversial, this manuscript demonstrates that MYC inhibition by either transgenic expression or pharmacologic use of the recombinantly produced Omomyc miniprotein exerts antitumor and antimetastatic activity in breast cancer models in vitro and in vivo, suggesting its clinical applicability.

Gallium nanoparticles as novel inhibitors of Aß40 aggregation.

Alzheimer's disease (AD) has been consistently related to the formation of senile amyloid plaques mainly composed of amyloid ß (Aß) peptides. The toxicity of Aß aggregates has been indicated to be responsible for AD pathology. One scenario to decrease Aß toxicity is the development of effective inhibitors against Aß amyloid formation. In this study, we investigate the effect of gallium nitride nanoparticles (GaN NPs) as inhibitors of Aß40 amyloid formation using a combination of biophysical approaches. Our results show that the lag phase of Aß40 aggregation kinetics is significantly retarded by GaN NPs in a concentration dependent manner, implying the activity of GaN NPs in interfering with the formation of the crucial nucleus during Aß aggregation. Our results also show that GaN NPs can reduce the amyloid fibril elongation rate in the course of the aggregation kinetics. It is speculated that the high polarization characteristics of GaN NPs may provoke a strong interaction between the particles and Aß40 peptide and in this way decrease self-association of the peptide monomers to form amyloids.

Calculation of prevalence with Markov models: budget impact analysis of thrombolysis for stroke.

OBJECTIVES: The objective is to develop a method for calculating the prevalence of stroke based on Markov models and to apply it to the assessment of the budget impact analysis of thrombolytic treatment. METHODS: A Markov model was used to reproduce the natural history of stroke. The first step was to run the model to build the sojourn matrix from the initial population vector. The second step was to ascertain the number of individuals in the origin of each annual cohort. Finally, prevalence figures were obtained, validated, and used to calculate the impact of treatment with thrombolysis in 10% of patients with stroke in the Basque Country as if thrombolysis had begun in 2000 and would continue to 2015. RESULTS: Stroke prevalence rates per 100,000 for the entire population are 898 for men and 686 for women, with a combined rate of 774 for men and women. Rates for stroke-related disability are 358 per 100,000 for men, 275 for women, and 309 for men and women combined. If 10% of the stroke patients would have received thrombolytic treatment from 2000 to 2015, the number of disabled in 2015 would be reduced by 328, and the net savings for the Basque society (2,100,000 inhabitants) would be 1.7 million euro. CONCLUSIONS: The budget impact analysis of thrombolysis for stroke starting in 2000 shows a positive impact on the health budget because it saves costs after 2006 and produces a net benefit in health from the beginning of treatment.

Derivation and validation of a clinical prediction rule for sleep apnoea syndrome for use in primary care.

BACKGROUND: Several clinical prediction rules (CPRs) are available for sleep apnoea-hypopnoea syndrome (OSAH), but they are difficult to apply in primary care (PC). AIM: Derivation and validation of a CPR using simple measurements available in PC. DESIGN & SETTING: A prospective study conducted in health centres from the area of influence of three Spanish hospitals. METHOD: Patients (aged 18-70 years) who attended for any reason; who presented with at least one of the three key symptoms for OSAH (snoring, breathing pauses while sleeping, and daytime sleepiness); and who were not undergoing non-invasive ventilation or prior treatment with continuous positive airway pressure (CPAP) were included. Anthropometric data, smoking habit, comorbidities, and Epworth test were collected. Patients were subsequently referred to the sleep unit (SU), where the decision was taken whether or not to instigate treatment. A multivariate logistic model was constructed using a sub-sample and scores assigned based on the regression coefficients; the CPR was validated with the remaining sample. Both receiver operating characteristic (ROC) curves were plotted and the sensitivity, specificity, and predictive values calculated. RESULTS: The derivation sample comprised 352 patients, with 260 in the validation sample. The final factors (arterial hypertension [AHT], age, body mass index [BMI], and sex) were used to develop a rule with scores ranging from 0.00-5.50. The cut-off point that optimises the area under the curve (AUC) is ≥2.50 points (AUC = 0.78; sensitivity = 86%; specificity = 54%; positive predictive value [PPV] = 45%; negative predictive value [NPV] = 90%; likelihood ratio [LR] = 0.26). The properties for the validation sample with this cut-off point are as follows: AUC = 0.68; sensitivity = 81%; specificity = 43%; PPV = 61%; NPV = 68%; LR = 0.44. CONCLUSION: As in similar cases, the specificity is low, meaning that healthy people are referred to a specialist. A negative result rules out the disease in most cases.

Ibrutinib exerts potent antifibrotic and antitumor activities in mouse models of pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stromal fibroinflammatory reaction that is a major obstacle to effective therapy. The desmoplastic stroma comprises many inflammatory cells, in particular mast cells as key components of the PDAC microenvironment, and such infiltration correlates with poor patient outcome. Indeed, it has been hypothesized that stromal ablation is critical to improve clinical response in patients with PDAC. Ibrutinib is a clinically approved Bruton's tyrosine kinase inhibitor that inhibits mast cells and tumor progression in a mouse model of ß-cell tumorigenesis. Here, we show that ibrutinib is highly effective at limiting the growth of PDAC in both transgenic mouse and patient-derived xenograft models of the disease. In these various experimental settings, ibrutinib effectively diminished fibrosis, extended survival, and improved the response to clinical standard-of-care therapy. Our results offer a preclinical rationale to immediately evaluate the clinical efficacy of ibrutinib in patients with PDAC.

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.

[Ultrasound-guided peripherally inserted central catheters (PICC) in cancer patients: success of the insertion, survival and complications]. / Inserción eco-guiada de catéteres centrales de inserción periférica (PICC) en pacientes oncológicos y hematológicos: éxito en la inserción, supervivencia y complicaciones.

OBJECTIVE: To evaluate the results of peripherally inserted central catheters (PICC) inserted by nurses using an ultrasound-guided technique at bed-side. METHODS: An observational and prospective study was conducted on all the PICC inserted at bed-side by an ultrasound-guided technique at the Araba University Hospital. The technique was introduced in June 2010, and the data collection period ended in November 2011. The main study variables were successful insertion, duration of PICC, incidences related to the catheter, devices reaching end of treatment and reasons for withdrawal. Patient sociodemographic data and PICC technical features were also registered. RESULTS: A total of 165 PICC were inserted, 73 are still in use, with 95.2% inserted in patients from oncology or haematology departments. Insertion was successful in the 89.7% (95% CI: 85.1%-94.3%) of the cases. The study included 16,234 catheter days, with a median dwell time of 92 days by PICC. The most frequent incidence was accidental removal in 0.986 per 1000 catheter days (95% CI=0.970-1.001). The thrombosis rate was 0.308 per 1,000 days (95% CI= 0.299-0.317), and the catheter-associated bloodstream infection rate was 0.062 per 1,000 catheter days (95% CI=0.058-0.065). CONCLUSION: Ultrasound-guided PICC insertion can be performed at bedside by trained nurses with a high probability of success. PICC, because of its low complication rate and long indwelling catheter survival, is a suitable central venous device for long-term treatment in oncology and haematology patients.

Knowledge, attitudes and perceptions of health professionals in relation to A/H1N1 influenza and its vaccine.

OBJECTIVE: To determine the intention of health professionals, doctors and nurses, concerning whether or not to be vaccinated against A/H1N1 influenza virus, and their perception of the severity of this pandemic compared with seasonal flu. MATERIAL AND METHODS: A cross-sectional study was carried out based on an questionnaire e-mailed to health professionals in public healthcare centres in Vitoria between 6 and 16 November 2009; the percentage of respondents who wanted to be vaccinated and who perceived the pandemic flu to carry a high risk of death were calculated. RESULTS: A total of 115 people completed the questionnaire of whom 61.7% (n=71) were doctors and 38.3% (n=44) were nurses. Of these, 33.3% (n=23) of doctors and 13.6% (n=6) of nurses intended to be vaccinated (p=0.019). Even among those who considered themselves to be at a high risk, 70.6% (n=48) of doctors and 31.7% (n=13) of nurses participating in the study (p=0.001) planned to have the vaccination. CONCLUSIONS: Most health professionals, and in particular nurses, had no intention to be vaccinated against A/H1N1 influenza virus at the beginning of the vaccination campaign.

Pentalogy of Cantrell: Forty-two Years of Experience in the Hospital Infantil de Mexico Federico Gomez.

Pentalogy of Cantrell is a rare disease. Approximately 185 cases have been reported around the world. The authors performed a retrospective study that reviewed the clinical files and pathological samples of 22 cases of pentalogy of Cantrell treated at the Hospital Infantil de México Federico Gómez. Thirteen patients had ectopia cordis associated with pentalogy of Cantrell (group I), and there were 9 cases without ectopia cordis (group II). In group I, the following types of congenital heart disease were found: single ventricle (4), double-outlet right ventricle (4), ventricular septal defect (3), aortic coarctation (1), and atrial septal defect (1). In group II, the following types of congenital heart disease were found: double-outlet right ventricle (3), double-inlet left ventricle (2), ventricular septal defect (2), tetralogy of Fallot (1), and hypoplastic right ventricle syndrome (1). Nine cases had a ventricular diverticulum (40%). Ten patients (45%) had some other congenital anomaly associated with pentalogy of Cantrell. Thirteen patients underwent surgery (59%), which included cardiac surgery in 10 cases (45%). Sixteen patients died (73%): 11 from group I and 5 from group II (P < .05). Little more than 50 years since it was first described, pentalogy of Cantrell remains a disease with high mortality, especially in patients with associated ectopia cordis.

Influenza A virus subtypes in wild birds in North-Eastern Spain (Catalonia).

Since the spread of H5N1 highly pathogenic avian influenza virus in 2005, many surveillance programmes have been initiated in poultry and wild birds worldwide. This study describes for the first time the detection of different subtypes of avian influenza viruses (AIV) in wild birds in the West Mediterranean area (Catalonia, North-Eastern Spain). During a 3-year period (from mid-2006 to mid-2009), 1374 birds from 16 different families were examined, and a total of 62 AIV were detected by means of a real-time reverse transcriptase PCR assay. AIV were more frequently detected in Anatidae, Phoenicopteridae, Rallidae and Laridae families. Of the 62 positive samples, 28 AIV could be isolated in embryonated eggs. All isolates were subtyped by haemagglutinin and neuraminidase inhibition techniques and 10 different haemagglutinins (HA) and 7 neuraminidases (NA) were found in 13 different subtype combinations. The most common combinations were H4N6 (22.2%) and H1N1 (18.5%). The HA and NA gene sequences of different AIV subtypes were compared and aligned with those available AIV strains from genome databases. Our studies on AIV phylogenetic analysis revealed that all AIV genes sequenced from wild birds in North-Eastern Spain clustered within Eurasian avian clades, including the sequences of H8, N4 and N5 genes analyzed for the first time in Europe. The results contribute to the understanding of AIV in the Mediterranean area and in Europe.

[Population-based cross sectional study about vaccine acceptability and perception of the severity of A/H1N1 influenza: opinion of the general population and health professionals]. / Estudio transversal basado en la población sobre la aceptabilidad de la vacuna y la percepción de la gravedad de la gripe A/H1N1: opinión de la población general y de los profesionales sanitarios.

OBJECTIVES: To determine the intention of general population and health professionals to vaccinate against the H1N1 influenza A virus. To determine the perception of severity of the H1N1 influenza A in both groups compared to that of seasonal influenza. METHODS: Cross-sectional telephone survey performed to a sample of population (obtained randomly from the Vitoria-Gasteiz telephone directory) and cross-sectional electronically-administered survey to a sample of health professionals from public health centres in Vitoria-Gasteiz, conducted between 6th and 16th November 2009. The relative and absolute frecuency of persons willing to be vaccinated and the proportion of those considering the H1N1 influenza A as a life-threatening risk were calculated in both groups. RESULTS: 219 (33%) persons out of 637 contacted telephone numbers answered the questionnaire, as well as 109 health professionals. 63.0% (n=138) of general population and 73.4% (n=80) of the professional group would not undergo vaccination, even if it was for free (p=0.595). If belonging to a high-risk group, the corresponding proportions of unwillingness were 14.6% (n=32) for general population and 40.4 (n=44) for professionals (p<0.001). The proportion of undecided persons is 25.6% (n=56) in general population, against 6.4% (n=7) among the professionals. CONCLUSIONS: At the beginning of the vaccination campaign, the majority of population is unwilling to undergo immunization against the H1N1 influenza A virus. The proportion in general population is similar to that among the health professionals. However, when belonging to a high-risk group, there is a high proportion of undecided persons in general population.

Estudio transversal basado en la población sobre la aceptabilidad de la vacuna y la percepción de la gravedad de la gripe A/H1N1: opinión de la población general y de los profesionales sanitarios / Population-based cross sectional study about vaccine acceptability and perception of the severity of A/H1N1 influenza: Opinion of the general population and health professionals

ObjetivosDeterminar la intención de la población general y de los profesionales sanitarios de vacunarse contra la gripe A/H1N1, así como la percepción que tienen de la gravedad de la gripe A/H1N1 en comparación con la gripe estacional.MétodosEstudio transversal mediante encuesta telefónica a una muestra de población general, a partir de la guía telefónica, y electrónica a profesionales sanitarios de los centros asistenciales públicos de Vitoria-Gasteiz, entre los días 6 y 16 de noviembre de 2009. En ambos colectivos se calcularon las frecuencias absolutas y relativas de los que se querían vacunar y de los que perciben la gripe como un riesgo alto para la vida.ResultadosContestaron al cuestionario el 33% (n=219) de las 637 personas contactadas y se obtuvieron 109 respuestas de profesionales. El 63,0% (n=138) de la población general y el 73,4% (n=80) de la población sanitaria no se vacunaría si la vacuna fuese gratis (p=0,595). En caso de pertenecer a alguno de los grupos de riesgo no se vacunaría el 14,6% (n=32) de la población ni el 40,4% (n=44) de los sanitarios (p<0,001). El porcentaje de indecisos entre la población general es del 25,6%, frente al 6,4% de los profesionales sanitarios.ConclusionesLa mayoría de la población no tiene, al inicio de la campaña de vacunación, intención de vacunarse contra la gripe A. La proporción es similar a la del colectivo de profesionales sanitarios, salvo bajo el supuesto de pertenecer a grupos de riesgo, en cuyo caso hay un importante grupo de indecisos entre la población (AU)

ObjectivesTo determine the intention of general population and health professionals to vaccinate against the H1N1 influenza A virus. To determine the perception of severity of the H1N1 influenza A in both groups compared to that of seasonal influenza.MethodsCross-sectional telephone survey performed to a sample of population (obtained randomly from the Vitoria-Gasteiz telephone directory) and cross-sectional electronically-administered survey to a sample of health professionals from public health centres in Vitoria-Gasteiz, conducted between 6th and 16th November 2009. The relative and absolute frecuency of persons willing to be vaccinated and the proportion of those considering the H1N1 influenza A as a life-threatening risk were calculated in both groups.Results219 (33%) persons out of 637 contacted telephone numbers answered the questionnaire, as well as 109 health professionals. 63.0% (n=138) of general population and 73.4% (n=80) of the professional group would not undergo vaccination, even if it was for free (p=0.595). If belonging to a high-risk group, the corresponding proportions of unwillingness were 14.6% (n=32) for general population and 40.4 (n=44) for professionals (p<0.001). The proportion of undecided persons is 25.6% (n=56) in general population, against 6.4% (n=7) among the professionals.ConclusionsAt the beginning of the vaccination campaign, the majority of population is unwilling to undergo immunization against the H1N1 influenza A virus. The proportion in general population is similar to that among the health professionals. However, when belonging to a high-risk group, there is a high proportion of undecided persons in general population (AU)

Plasmin activity is required for myogenesis in vitro and skeletal muscle regeneration in vivo.

Plasmin, the primary fibrinolytic enzyme, has a broad substrate spectrum and is implicated in biologic processes dependent upon proteolytic activity, such as tissue remodeling and cell migration. Active plasmin is generated from proteolytic cleavage of the zymogen plasminogen (Plg) by urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). Here, we have investigated the role of plasmin in C2C12 myoblast fusion and differentiation in vitro, as well as in skeletal muscle regeneration in vivo, in wild-type and Plg-deficient mice. Wild-type mice completely repaired experimentally damaged skeletal muscle. In contrast, Plg(-/-) mice presented a severe regeneration defect with decreased recruitment of blood-derived monocytes and lymphocytes to the site of injury and persistent myotube degeneration. In addition, Plg-deficient mice accumulated fibrin in the degenerating muscle fibers; however, fibrinogen depletion of Plg-deficient mice resulted in a correction of the muscular regeneration defect. Because we found that uPA, but not tPA, was induced in skeletal muscle regeneration, and persistent fibrin deposition was also reproducible in uPA-deficient mice following injury, we propose that fibrinolysis by uPA-dependent plasmin activity plays a fundamental role in skeletal muscle regeneration. In summary, we identify plasmin as a critical component of the mammalian skeletal muscle regeneration process, possibly by preventing intramuscular fibrin accumulation and by contributing to the adequate inflammatory response after injury. Finally, we found that inhibition of plasmin activity with alpha2-antiplasmin resulted in decreased myoblast fusion and differentiation in vitro. Altogether, these studies demonstrate the requirement of plasmin during myogenesis in vitro and muscle regeneration in vivo.

Técnica del ganglio centinela en el cáncer de colon. Experiencia en 125 casos / Sentinel lymph node biopsy technique in colon cancer. Experience in 125 cases

Introducción El estudio de los ganglios linfáticos supone el factor pronóstico más importante en el cáncer colorrectal sin metástasis. La técnica del ganglio centinela identifica el ganglio que mejor predice el estado ganglionar de un paciente y permite realizar en él técnicas de estudio intensivo que mejoran la estadificación. El objetivo del trabajo es estudiar la eficacia de la técnica del ganglio centinela en la estadificación del cáncer de colon.Material y métodos Estudio prospectivo con 125 pacientes diagnosticados preoperatoriamente de cáncer de colon sin metástasis a distancia desde septiembre de 2009 hasta diciembre de 2011 en el Hospital Universitario de Álava-Txagorritxu en Álava. Realizamos la técnica del ganglio centinela ex vivo y con azul de metileno. El ganglio centinela se estudió realizando secciones múltiples y técnicas de inmunohistoquímica, además de hematoxilina-eosina. Realizamos un estudio comparativo con un grupo control con 170 pacientes estudiado de forma convencional mediante sección única y tinción de hematoxilina-eosina. Resultados Identificamos el ganglio centinela en el 98% de los casos, con una tasa de falsos negativos del 5,6%. La supraestadificación lograda en el grupo con estudio del ganglio centinela se encuentra en el 14,2% con respecto al grupo estudiado convencionalmente (p = 0,006).Conclusiones El estudio del ganglio centinela realizado ex vivo y con azul de metileno predice el estado ganglionar de los pacientes con cáncer de colon. Esta técnica supraestadifica, pasando al estadio iii a pacientes que el estudio convencional determinaba como estadios i y ii , permitiendo que accedan a un tratamiento quimioterápico que podría mejorar su pronóstico (AU)

Introduction The level of lymph node involvement is the most important factor in staging colorectal cancer without metastasis. Sentinel lymph node mapping identifies the node(s) that most accurately reflect the lymph node status of patients, and intensive techniques that improve staging can be focused on these nodes. The aim of this study was to assess the efficacy of ex vivo sentinel lymph node mapping in the staging of colon cancer. Materials and methods A prospective study was conducted on 125 patients from the Alava-Txagorritxu University Hospital Health Region (Alava), who were diagnosed prior to surgery with colon cancer without distant metastasis from September 2009 to December 2011. Ex vivo sentinel lymph node mapping with methylene blue was use in these patients to study the sentinel nodes with multiple slices using immunohistochemical techniques and haematoxylin-eosin staining. A comparative study was also performed based on a control group of 170 patients staged with conventional techniques, and involving a single slice and haematoxylin-eosin staining. Results The sentinel lymph node identification rate was 98%, with 5.6% false negatives. Upstaging occurred in 14.2% of cases compared to the group studied using conventional techniques (P=.006).Conclusions Ex vivo sentinel lymph node mapping with methylene blue accurately reflects the lymph node status of patients with colon cancer. This approach upstages patients classified as stages i and ii by conventional techniques to stage iii , indicating chemotherapy that may improve their prognosis (AU)

Inserción eco-guiada de catéteres centrales de inserción periférica (PICC) en pacientes oncológicos y hematológicos: éxito en la inserción, supervivencia y complicaciones / Ultrasound-guided peripherally inserted central catheters (picc) in cancer patients: success of the insertion, survival and complications

Objetivo evaluar los resultados de los catéteres centrales de inserción periférica (PICC) insertados por enfermeras de la unidad de oncología y hematología con técnica ecoguiada en cuanto a éxito en la inserción, incidencias, dispositivos que llegan a fin de tratamiento y supervivencia de los catéteres. Método estudio observacional y prospectivo. Se incluyeron todos los PICC insertados mediante eco-guía a pie de cama en el Hospital Universitario Araba. La técnica se inició en junio de 2010. El estudio finalizó en noviembre de 2011. Se recogieron datos socio-demográficos, características del catéter, éxito en la inserción, duración, incidencias y motivo de retirada. Resultados Se insertaron 165 catéteres, el 95,2% a pacientes de oncología o hematología, 73 de ellos continúan aún en uso. Se obtuvo un éxito en la inserción del 89,7% (IC del 95%: 85,1%- 94,3%). Los días de uso total de los catéteres fueron 16.234 con una mediana de duración de 92 días por PICC. La incidencia más frecuente fue la extracción accidental 0,986/1.000 días de catéter (IC del 95%: 0,970-1,001/1.000). La tasa de trombosis fue de 0,308/1.000 días (IC del 95%: 0,299- 0,317) y la de bacteriemia relacionada con catéter de 0,062/1.000 días de catéter (IC del 95%: 0,058- 0,065).Conclusión la inserción del PICC eco-guiada a pie de cama puede ser realizada por enfermeras entrenadas con una elevada probabilidad de inserción exitosa. El PICC, por su baja tasa de complicaciones y su alta duración media, es un dispositivo válido como acceso venoso central de media y larga duración para pacientes oncológicos y hematológicos (AU)

Objective To evaluate the results of peripherally inserted central catheters (PICC) inserted by nurses using an ultrasound-guided technique at bed-side. Methods An observational and prospective study was conducted on all the PICC inserted at bed-side by an ultrasound-guided technique at the Araba University Hospital. The technique was introduced in June 2010, and the data collection period ended in November 2011. The main study variables were successful insertion, duration of PICC, incidences related to the catheter, devices reaching end of treatment and reasons for withdrawal. Patient sociodemographic data and PICC technical features were also registered. Results A total of 165 PICC were inserted, 73 are still in use, with 95.2% inserted in patients from oncology or haematology departments. Insertion was successful in the 89.7% (95% CI: 85.1%-94.3%) of the cases. The study included 16,234 catheter days, with a median dwell time of 92 days by PICC. The most frequent incidence was accidental removal in 0.986 per 1000 catheter days (95% CI=0.970-1.001). The thrombosis rate was 0.308 per 1,000 days (95% CI= 0.299-0.317), and the catheter-associated bloodstream infection rate was 0.062 per 1,000 catheter days (95% CI=0.058-0.065).Conclusion Ultrasound-guided PICC insertion can be performed at bedside by trained nurses with a high probability of success. PICC, because of its low complication rate and long indwelling catheter survival, is a suitable central venous device for long-term treatment in oncology and haematology patients (AU)