Risk factors for early-onset basal cell carcinomas and the trend towards their female predominance.

BACKGROUND: A dramatic rise in the incidence rates of basal cell carcinoma (BCC) in young women has been reported. OBJECTIVES: We investigate potential risk factors (RF) for sporadic BCC in young patients and the current distribution of such RF in the general population of Catalonia, comparing the differences among men and women. PATIENTS AND METHODS: A case-control study was performed, 69 BCCs diagnosed in patients ≤ 45 years of age vs. 69 healthy controls. Afterward, 1,078 participants from the general population completed an RF questionnaire. RESULTS: Repeated sunburns were more frequent in instances of early-onset BCC in covered skin than in sun-exposed skin (P  =  0.029). In the general population, 39.1 % of participants reported sunbed use (50.1 % in women, 10.9 % in men). Sunbed use was the only relevant RF more predominant in women than men, favoring the trend to female predominance of BCCs above other RF. Additionally, we found a significant trend in young participants for reduced sunbed use (P < 0.001), although they had the same percentage of repeated sunburns. Repeated sunburns are the most relevant RF for early-onset BCCs that can be targeted in prevention campaigns. CONCLUSIONS: We should be aware of the more relevant RF for early-onset BCCs and their distribution among the general population to address preventive campaigns.

El tratamiento antiviral no mejora la ateromatosis subclínica en pacientes con hepatitis crónica por virus de la hepatitis C / Antiviral treatment does not improve subclinical atheromatosis in patients with chronic hepatitis caused by hepatitis C virus

Introducción: La infección crónica por el virus de la hepatitis C (VHC) es un factor de riesgo para desarrollar placas de ateroma, aunque se desconoce el posible efecto al eliminar el virus. Nuestro objetivo fue analizar si tras 12 meses de la erradicación del VHC por antivirales de acción directa (AAD) mejoraba la ateromatosis subclínica y existía modificación en la composición de las placas. Materiales y métodos: Estudio prospectivo que incluyó 85 pacientes con infección crónica por VHC en diferentes estadios de fibrosis, sometidos a AAD. Se excluyeron pacientes con antecedentes cardiovasculares, diabetes y enfermedad renal. Se realizó ecografía arterial (carótidas y femorales) para diagnosticar placa de ateroma (definida como grosor íntima-media≥1,5mm) y se analizó su composición (porcentaje de lípidos, fibrosis y calcio con software HEMODYN4) al inicio del estudio y tras 12 meses de finalizar la terapia. Resultados: Tras el seguimiento no se detectaron cambios en el grosor íntima-media (0,65mm vs. 0,63mm, p=0,240) ni en la presencia de placas (65,9%vs. 71,8%, p=0,063). Tampoco hubo modificación significativa en la composición de las mismas ni del territorio vascular afecto, observándose un aumento del perfil lipídico en sangre (p<0,001) tras 12 meses del tratamiento. Estos resultados se confirmaron en subgrupos por gravedad de enfermedad hepática. Discusión: La erradicación del VHC por AAD no mejora las placas de ateroma ni varía su composición, independientemente de la fibrosis hepática. Se precisan más estudios prospectivos que evalúen el riesgo residual cardiovascular tras la erradicación viral

Introduction: Chronic infection with hepatitis C virus is a risk factor for developing atheromatous plaques, although the possible effect of virus clearance is unknown. Our aim was to determine whether or not subclinical atheromatosis improved and there was any modification in the composition of the plaques 12 months after eradication of hepatitis C virus by direct-acting antiviral agents. Materials and methods: Prospective study that included 85 patients with chronic hepatitis C virus infection in different stages of fibrosis who were on direct-acting antiviral agents. Patients with a cardiovascular history, diabetes and kidney disease were excluded. An arterial ultrasound (carotid and femoral) was performed to diagnose atheromatous plaques (defined as intima-media thickness ≥1.5mm) and the composition (percentage of lipids, fibrosis and calcium with HEMODYN4 software) was analysed at the beginning of the study and 12 months after stopping the therapy. Results: After follow-up no changes were detected in the intima-media thickness (0.65mm vs. 0.63mm, P=.240) or in the presence of plaques (65.9% vs 71.8%, P=.063). There was also no significant change in their composition or affected vascular territory, with an increase in blood lipid profile (P<.001) after 12 months of treatment. These results were confirmed in subgroups by severity of liver disease. Discussion: The eradication of hepatitis C virus by direct-acting antiviral agents does not improve the atheroma plaques and nor does it vary their composition, regardless of liver fibrosis. More prospective studies are needed to evaluate residual cardiovascular risk after virus eradication

Antiviral treatment does not improve subclinical atheromatosis in patients with chronic hepatitis caused by hepatitis C virus. / El tratamiento antiviral no mejora la ateromatosis subclínica en pacientes con hepatitis crónica por virus de la hepatitis C.

INTRODUCTION: Chronic infection with hepatitis C virus is a risk factor for developing atheromatous plaques, although the possible effect of virus clearance is unknown. Our aim was to determine whether or not subclinical atheromatosis improved and there was any modification in the composition of the plaques 12 months after eradication of hepatitis C virus by direct-acting antiviral agents. MATERIALS AND METHODS: Prospective study that included 85 patients with chronic hepatitis C virus infection in different stages of fibrosis who were on direct-acting antiviral agents. Patients with a cardiovascular history, diabetes and kidney disease were excluded. An arterial ultrasound (carotid and femoral) was performed to diagnose atheromatous plaques (defined as intima-media thickness ≥1.5mm) and the composition (percentage of lipids, fibrosis and calcium with HEMODYN4 software) was analysed at the beginning of the study and 12 months after stopping the therapy. RESULTS: After follow-up no changes were detected in the intima-media thickness (0.65mm vs. 0.63mm, P=.240) or in the presence of plaques (65.9% vs 71.8%, P=.063). There was also no significant change in their composition or affected vascular territory, with an increase in blood lipid profile (P<.001) after 12 months of treatment. These results were confirmed in subgroups by severity of liver disease. DISCUSSION: The eradication of hepatitis C virus by direct-acting antiviral agents does not improve the atheroma plaques and nor does it vary their composition, regardless of liver fibrosis. More prospective studies are needed to evaluate residual cardiovascular risk after virus eradication.

Fluorescence in situ hybridization of TP53 for the detection of chromosome 17 abnormalities in myelodysplastic syndromes.

Conventional G-banding cytogenetics (CC) detects chromosome 17 (chr17) abnormalities in 2% of patients with de novo myelodysplastic syndromes (MDS). We used CC and fluorescence in situ hybridization (FISH) (LSI p53/17p13.1) to assess deletion of 17p in 531 patients with de novo MDS from the Spanish Group of Hematological Cytogenetics. FISH detected - 17 or 17p abnormalities in 13 cases (2.6%) in whom no 17p abnormalities were revealed by CC: 0.9% of patients with a normal karyotype, 0% in non-informative cytogenetics, 50% of patients with a chr17 abnormality without loss of 17p and 4.7% of cases with an abnormal karyotype not involving chr17. Our results suggest that applying FISH of 17p13 to identify the number of copies of the TP53 gene could be beneficial in patients with a complex karyotype. We recommend using FISH of 17p13 in young patients with a normal karyotype or non-informative cytogenetics, and always in isolated del(17p).

A non-digestible fraction of the common bean (Phaseolus vulgaris L.) induces cell cycle arrest and apoptosis during early carcinogenesis.

We have previously demonstrated that the non-digestible fraction (NDF) from common cooked beans (P. vulgaris L., cv Negro 8025) inhibits azoxymethane (AOM)-induced colon cancer and influences the expression of genes involved in the induction of apoptosis and cell cycle arrest through the action of butyrate. The objective of this study was to identify cell cycle alterations and morphological changes induced by treatment with AOM and to examine the formation of colonic aberrant crypt foci (ACF) in male Sprague Dawley rats fed with these beans. Rats were fed control diets upon arrival and were randomly placed into four groups after one week of acclimatization: control, NDF (intragastric administration), NDF + AOM and AOM. Rats treated with NDF + AOM exhibited a significantly lower number of total colonic ACF with a notable increase in the number of cells present in the G1 phase (83.14%); a decreased proliferation index was observed in the NDF + AOM group when compared to AOM group. NDF + AOM also displayed a higher number of apoptotic cells compared to AOM group. NDF of cooked common beans inhibited colon carcinogenesis at an early stage by inducing cell cycle arrest of colon cells and morphological changes linked to apoptosis, thus confirming previous results obtained with gene expression studies.

Characterization and prognostic implication of 17 chromosome abnormalities in myelodysplastic syndrome.

The prognosis of chromosome 17 (chr17) abnormalities in patients with primary myelodysplastic syndrome (MDS) remains unclear. The revised International Prognostic Scoring System (IPSS-R) includes these abnormalities within the intermediate cytogenetic risk group. This study assessed the impact on overall survival (OS) and risk of acute myeloid leukemia transformation (AMLt) of chr17 abnormalities in 88 patients with primary MDS. We have compared this group with 1346 patients with primary MDS and abnormal karyotype without chr17 involved. The alterations of chr17 should be considered within group of poor prognosis. The different types of alterations of chromosome 17 behave different prognosis. The study confirms the intermediate prognostic impact of the i(17q), as stated in IPSS-R. The results of the study, however, provide valuable new information on the prognostic impact of alterations of chromosome 17 in complex karyotypes.

The advantages of therapeutic drug monitoring in patients receiving antiretroviral treatment and experiencing medication-related problems.

BACKGROUND: Therapeutic drug monitoring (TDM) of antiretroviral drugs (ARVs) is used to improve the efficacy and safety of ARVs, but there is little interest for the systematic or random TDM of ARVs in the medical management of patients with acquired immune deficiency syndrome. This study aimed to evaluate a different approach and test the potential advantages of TDM as part of medical treatments when clinical problems are identified in human immunodeficiency virus-infected patients. METHODS: The authors conducted a prospective, noncontrolled, cohort study on 544 human immunodeficiency virus-positive patients treated either with a protease inhibitor (PI), atazanavir/lopinavir, or with a nonnucleoside reverse transcriptase inhibitor (NNRTI), efavirenz/nevirapine. Patients who had virological failure, clinical signs of toxicity, or a risk of pharmacokinetic interactions were identified as having medication-related problems (MRPs), and they were scheduled for TDM of the PIs or NNRTIs. Cases with drug levels outside the range were subjected to intervention, and a second determination of plasma levels and viral load was scheduled to assess their response to the intervention. RESULTS: Of the 521 treatment courses analyzed, 173 (32.4%) presented at least 1 MRP during the study. The TDM yielded abnormal results in 52.5% of the 198 identified MRP cases (95% CI: 45%-59%). The patients treated with PIs had an increased risk for having drug plasma levels that fell outside the normal range compared to those treated with NNRTIs (relative risk =1.36, 95% CI: 1.04-1.79). The TDM-guided interventions contributed to the resolution of 52.1% of the cases that involved treatment courses with MRPs and abnormal drug plasma levels. CONCLUSIONS: MRPs, including therapeutic failure, were common in the patients who were included in the study. A high proportion of the treatment courses involving such MRPs also presented abnormal plasma drug levels. The TDM-guided interventions are advantageous under these situations because they allow the continuation of treatments that would otherwise be substituted by more complex and costly alternatives.

Open-label, randomized comparison trial of long-term outcomes of levofloxacin versus standard antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: This study investigated whether treating acute exacerbations of COPD (AE-COPD) with levofloxacin modifies the long-term outcome of COPD patients in comparison with standard antibiotic regimens. METHODS: A 6-month open-label clinical trial of AE-COPD patients compared the outcomes of treating with levofloxacin versus standard therapy (clarithromycin, cefuroxime, or amoxicillin/clavulanate) at recommended doses for 10 days. Several variables were analysed: pulse oximetry, FEV1, health-related quality of life, infection-free interval, number of exacerbations, hospitalizations due to an exacerbation and mortality. RESULTS: Of the 116 patients initially enrolled, completion or withdrawal information was available for 50 patients in the levofloxacin arm and 52 in the standard therapy arm. At the end of the study, there were no differences in mortality (17.8% vs. 22.9%, P = 0.53), number of exacerbations (33 vs. 41, P = 0.40), pulse oximetry (median 91.71% vs. 92.46%, P = 0.18), FEV1 (median 51.31% vs. 47.14%, P = 0.30), health-related quality of life (median 8.63 vs. 10.75, P = 0.94) and infection-free interval (median 112 vs. 101 days, P = 0.72), for the levofloxacin and standard therapy, respectively. However, 12 out of 33 (33.6%) exacerbations treated with levofloxacin required in-hospital management versus 27 out of 41 (65.8%) treated with standard therapy (P = 0.02). CONCLUSION: This preliminary study suggests that 10-day treatment of AE-COPD with levofloxacin is associated with a reduction in hospitalizations compared with standard antibiotics despite there being no significant benefit in other outcome variables.

Caspase 8/10 are not mediating apoptosis in neuroblastoma cells treated with CDK inhibitory drugs.

Olomoucine and Roscovitine are pharmacological inhibitors of cyclin-dependent kinases (CDK) displaying a promising profile as anticancer agents. Both compounds are effective inductors of apoptosis in a human neuroblastoma cell line, SH-SY5Y. The characterization of this process had suggested the involvement of an extrinsic pathway [Ribas, J., Boix, J., 2004. Cell differentiation, Caspase inhibition, and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two CDK inhibitory drugs. Exp. Cell Res. 295 9-24.], which depends on either Caspase 8 or Caspase 10 activation. However, neither Caspase 8 nor Caspase 10 is expressed in SH-SY5Y cells because of gene silencing. Upon Olomoucine or Roscovitine treatment, no re-expression of Caspase 8 or Caspase 10 was found. Therefore, in SH-SY5Y cells, this type of drugs is not triggering a canonical, Caspase 8/10-mediated, extrinsic apoptotic pathway.

Investigación en especialidades quirúrgicas / Surgical Research

En este artículo los autores revisan las características específicas de la investigación en las especialidades quirúrgicas, sus problemas y diferencias en relación al resto de la investigación biomédica. Hacen especial hincapié en los temas más frecuentes a investigar en cirugía, sus defectos y la metodología. Argumentan que los estudios prospectivos randomizados a doble ciego no deben ser sobredimensionados, ya que presentan problemas metodológicos y bioéticos al aplicarlos a la cirugía. Los estudios prospectivos son los más utilizados por los cirujanos para el avance de las especialidades quirúrgicas (AU)

In this article authors review the specific characteristics of surgical research. Its problems and differences from other biomedical research. Specially they specify the main topics for surgical investigation, its pitfalls and methodologies. They argue that randomised prospective double blind studies must not be over dimensioned, as for surgery they present many difficulties, specially ethical and practical. Prospective studies are been more used by surgeons for the advance of the different surgical specialities (AU)

Lactancia maternal en el Pla d´Urgell / Breastfeeding at Pla d´Urgell, Catalonia

Fundamento. Con la aparición de las leches artificiales se produjo una disminución de la lactancia materna que se ha ido corrigiendo gracias a las campañas de promoción. Para mejorar la prevalencia y duración de la lactancia materna es fundamental conocer la situación actual y los factores que la condicionan. Estos datos varían según los estudios. Objetivo. Conocer la evolución de la prevalencia y los factores que influyen en la instauración y el mantenimiento de la lactancia materna en nuestra área. Método. Estudio retrospectivo revisando las historias clínicas de los recién nacidos de los periodos 1998-1999 y 2000-2001. Se analizaron las variables: edad materna, paridad, duración, motivo de abandono, motivo de no inicio y tipo de trabajo materno. Resultados. Se registraron 517 historias, 236 del primer periodo y 281 del segundo. Iniciaron lactancia materna el 68.6% y el 71.9% respectivamente. La duración media de la lactancia materna fue de 90.9 y 104.7 días. Las causas más frecuentes de no instauración de lactancia materna fueron las indicaciones médicas y la voluntad materna. Los factores que condicionan de manera más importante la duración fueron las indicaciones médicas al inicio, el trabajo entre los 2 y los 4 meses y la voluntad materna después. Conclusiones. Hemos apreciado que en nuestra área la prevalencia de lactancia materna presenta una discreta tendencia a aumentar tanto en porcentage de inicio como en duración, y que los factores que más influyen en la decisión de iniciar o mantener la lactancia materna son la voluntad materna, las indicaciones médicas y el trabajo (AU)

Background. The introduction of formula feeding resulted in a significant decrease in the use of breastfeeding, which has been partially corrected recently as a result of public health campaigns. In order to improve the prevalence and duration of breastfeeding, it is necessary to evaluate the current feeding practices and the determining factors in our population. Objective. To describe the trends in the prevalence of breastfeeding, and to evaluate the factors that influence its practice and maintenance in our population. Method. In this retrospective study, we reviewed the charts of all infants born in two periods, 1998-1999, and 2000-2001. The following variables were analyzed: maternal age, parity, feeding practice, duration, cause for discontinuation, cause for not using breastfeeding, and maternal work. Results. We reviewed 517 charts (first period, 236 infants; second period, 281 infants). Breastfeeding was started in 68.6% and 71.9% of the infants, respectively. The mean duration of breastfeeding was 90.9 and 104.7 days, respectively. The most common reasons for not starting breastfeeding were medical indications and maternal preference. The factors that conditioned the duration of breastfeeding were medical indications at the beginning, maternal work between 2 and 4 months, and maternal choice thereafter. Conclusions. We have documented an increase in the practice and duration of breastfeeding in our area. The factors that determine its use and duration are maternal preferences, medical indications, and maternal work (AU)