Epidemiology of infectious diseases in migrant populations from endemic or high-endemic countries: A multicentric primary care-based study in Spain.

OBJECTIVES: We aimed to evaluate the epidemiology of seven infections (Chagas disease, strongyloidiasis, schistosomiasis, human immunodeficiency virus, hepatitis B and C virus, and active tuberculosis) in migrant populations attended at primary care facilities in Catalonia, Spain. METHODS: This is a cross sectional study conducted from March to December 2018 at eight primary care centres in Catalonia, Spain where health professionals were recommended to systematically screen multiple infections in migrants considering the endemicity of the pathogens in their country of birth. Routine health data were retrospectively extracted from electronic health records of the primary care centres. The proportion of cases among individuals tested for each infection was estimated with its 95% confident interval (CI). Mixed-effects logistics regression models were conducted to assess any possible association between the exposure variables and the primary outcome. RESULTS: Out of the 15,780 migrants that attended primary care centres, 2410 individuals were tested for at least one infection. Of the 508 (21.1%) migrants diagnosed with at least one condition, a higher proportion originated from Sub-Saharan Africa (207, 40.7%), followed by South-East Europe (117, 23.0%) and Latin-America (88, 17.3%; p value <0.001). The proportion of migrants diagnosed with Chagas disease was 5/122 (4.1%, 95%CI 0.5-7.7), for strongyloidiasis 56/409 (13.7%, 95%CI 10.3-17.0) and for schistosomiasis 2/101 (2.0%, 95%CI 0.0-4.7) with very few cases tested. The estimated proportion for human immunodeficiency virus was 67/1176 (5.7%, 95%CI 4.4-7.0); 377/1478 (25.5%, 95%CI 23.3-27.7) for hepatitis B virus, with 108/1478 (7.3%, 95%CI 6.0-8.6) of them presenting an active infection, while 31/1433 (2.2%, 95%CI 1.4-2.9) were diagnosed with hepatitis C virus. One case of active tuberculosis was diagnosed after testing 172 migrant patients (0.6%, 95%CI 0.0-1.7). CONCLUSIONS: We estimated a high proportion of the studied infections in migrants from endemic areas. Country-specific estimations of the burden of infections in migrants are fundamental for the implementation of preventive interventions.

Screening and routine diagnosis of mental disorders among migrants in primary care: A cross-sectional study.

Background: Migrants in host countries are at risk for the development of mental health conditions. The two aims of the study were to describe routine diagnoses of mental disorders among migrant patients at primary healthcare level and the associated risk factors, and to test the utility of an innovative migrant mental health assessment by evaluating whether the health professionals followed the recommendations proposed by the clinical decision support system (CDSS) tool. Methods: A cross-sectional study was carried out in eight primary care centres (PCCs) in four non-randomly selected health regions of Catalonia, Spain from March to December 2018. Routine health data and mental health diagnoses based on the International Classification of Diseases (10th edition), including mental, behavioural and neuro developmental disorders (F01-F99), symptoms and signs involving emotional state (R45), and sleep disorders (G47), were extracted from the electronic health records. The proportion of mental health conditions was estimated and logistic regression models were used to assess any possible association with mental health disorders. The utility of the mental health assessment was assessed with the proportion of questionnaires performed by health professionals for migrants fulfilling the mental health screening criterion (country of origin with an active conflict in 2017) and the diagnoses given to the screened patients. Results: Of 14,130 migrants that visited any of the PCCs during the study period, 7,358 (52.1 %) were women with a median age of 38.0 years-old. There were 520/14,130 (3.7 %) migrant patients diagnosed with a mental disorder, being more frequent among women (342/7,358; 4.7 %, p-value < 0.001), migrants from Latin-America (177/3,483; 5.1 %, p < 0.001) and those who recently arrived in Spain (170/3,672; 4.6 %, p < 0.001). A lower proportion of mental disorders were reported in migrants coming from conflicted countries in 2017 (116/3,669, 3.2 %, p = 0.053).Out of the 547 mental health diagnoses reported in 520 patients, 69/14,130 (0.5 %) were mood disorders, 346/14,130 (2.5 %) anxiety disorders and 127/14,130 (0.9 %) sleeping disorders. Mood disorders were more common in migrants from Eastern Europe (25/2,971; 0.8 %, p < 0.001) and anxiety disorders in migrants from Latin-America (126/3,483; 3.6 %, p < 0.001), while both type of disorders were more often reported in women (p < 0.001).In the adjusted model, women (aOR: 1.5, [95 % CI 1.2-1.8, p < 0.001]), migrants with more than one visit to the health center during the study period (aOR: 4.4, [95 %CI 2.8-6.8, p < 0.001]) and who presented an infectious disease (aOR: 2.1, [95 %CI 1.5-3.1, p < 0.001]) had higher odds of having a mental disorder.Lastly, out of the 1,840 migrants coming from a conflicted country in 2017 who were attended in centres where the CDSS tool was implemented, 29 (1.6 %) had a mental health assessment performed and the tool correctly identified one individual. Conclusions: Mental health is a condition that may be overlooked in migrants at primary healthcare. Interventions at this level of care must be reinforced and adapted to the needs and circumstances of migrants to ensure equity in health services.

Improving the detection of infectious diseases in at-risk migrants with an innovative integrated multi-infection screening digital decision support tool (IS-MiHealth) in primary care: a pilot cluster-randomized-controlled trial.

BACKGROUND: There are major shortfalls in the identification and screening of at-risk migrant groups. This study aims to evaluate the effectiveness of a new digital tool (IS-MiHealth) integrated into the electronic patient record system of primary care centres in detecting prevalent migrant infections. IS-MiHealth provides targeted recommendations to health professionals for screening multiple infections, including human immunodeficiency virus (HIV), hepatitis B and C, active tuberculosis (TB), Chagas disease, strongyloidiasis and schistosomiasis, based on patient characteristics (including variables of country of origin, age and sex). METHODS: A pragmatic pilot cluster-randomized-controlled trial was deployed from March to December 2018. Eight primary care centres in Catalonia, Spain, were randomly allocated 1:1 to use of the digital tool for screening, or to routine care. The primary outcome was the monthly diagnostic yield of all aggregated infections. Intervention and control sites were compared before and after implementation with respect to their monthly diagnostic yield using regression models. This study is registered on international standard randomised controlled trial number (ISRCTN) (ISRCTN14795012). RESULTS: A total of 15 780 migrants registered across the eight centres had at least one visit during the intervention period (March-December 2018), of which 14 598 (92.51%) fulfilled the criteria to be screened for at least one infection. There were 210 (2.57%) individuals from the intervention group with new diagnoses compared with 113 (1.49%) from the control group [odds ratio: 2.08, 95% confidence interval (CI) 1.63-2.64, P < 0.001]. The intervention centres raised their overall monthly diagnosis rate to 5.80 (95% CI 1.23-10.38, P = 0.013) extra diagnoses compared with the control centres. This monthly increase in diagnosis in intervention centres was also observed if we consider all cases together of HIV, hepatitis B and C, and active TB cases [2.72 (95% CI 0.43-5.00); P = 0.02] and was observed as well for the parasitic infections' group (Chagas disease, strongyloidiasis and schistosomiasis) 2.58 (95% CI 1.60-3.57; P < 0.001). CONCLUSIONS: The IS-MiHealth increased screening rate and diagnostic yield for key infections in migrants in a population-based primary care setting. Further testing and development of this new tool is warranted in larger trials and in other countries.

Los avatares de la adolescencia en nuestra época, a ritmo de las nuevas tecnologías / The vicissitudes of adolescence in our time, to the rhythm of new technologies

Este trabajo es una invitación a la reflexión sobre nuestra escucha y quehacer en la clínica psicoanalítica contemporánea. Se parte de la base que los cambios socioculturales en nuestra sociedad postmoderna, entre ellos la irrupción e inmersión de las nuevas tecnologías, producen transformaciones y aparición de configuraciones subjetivas inéditas. Pensamos que este panorama nos convoca como profesionales a afinar nuestra escucha y ampliar nuestra mirada, si queremos acompañar y sostener a nuestros adolescentes. Somos partidarios del "uso" de dispositivos en la consulta si así lo solicitan, para facilitar la representación de su mundo interno, en la interacción continua entre el empuje pulsional y la relación objetal. Se presentan distintas viñetas clínicas, provenientes de casos del Programa de Apoyo a la Salud Mental Infanto Juvenil de Aragón (AAPIPNA), en las que se plasma el trabajo psicoterapéutico

This paper is an invitation to consider our listening and way of proceeding in our contemporary psychoanalytic clinical work. It takes as a starting point for reflection the sociocultural changes in our postmodern society, including the emergence and the immersion of new technologies, which produce transformations and the appearance of new types of subjective organizations. This scenario calls us as professionals to attune our listening and broaden our view, in order, to accompany and support our adolescents. We are in favor of the "use" of devices in the consultation room if we are requested to, to facilitate the representation of their internal world, in the continuous interaction between the drive and the object relationship. Different clinical vignettes are presented, all cases that belong to the Program of Support for Child and Adolescent Mental Health in Aragon (AAPIPNA), which shows the psychotherapeutic work

Identification and characterization of a cell wall porin from Gordonia jacobaea.

Gordonia jacobaea is a bacterium belonging to the mycolata group characterized by its ability to produce carotenoids. Mycolic acids in the cell wall contribute to reducing the permeability of their envelopes requiring the presence of channel-forming proteins to allow the exchange of hydrophilic molecules with the surrounding medium. Identification and purification of the channel-forming proteins was accomplished by SDS-PAGE, Mass spectrometry and Mass peptide fingerprinting and the channel-forming activity was studied by reconstitution in lipid bilayers. Here, we describe for the first time the presence of a cell-wall protein from G. jacobaea with channel-forming activity. Our results suggest that this protein bears a low similarity to other hypothetical proteins from the genus Gordonia of uncharacterized functions. The channel has an average single-channel conductance of 800 pS in 1 M KCl, is moderately anion-selective, and does not show any voltage dependence for voltages between +100 and -100 mV. The channel characteristics suggest that this protein could be of relevance in the import and export of negatively charged molecules across the cell wall. This could contribute to design treatments for mycobacterial infections, as well as being of interest in biotechnology applications.

Transcriptomics as a tool to discover new antibacterial targets.

The emergence of antibiotic-resistant pathogens, multiple drug-resistance, and extremely drug-resistant strains demonstrates the need for improved strategies to discover new drug-based compounds. The development of transcriptomics, proteomics, and metabolomics has provided new tools for global studies of living organisms. However, the compendium of expression profiles produced by these methods has introduced new scientific challenges into antimicrobial research. In this review, we discuss the practical value of transcriptomic techniques as well as their difficulties and pitfalls. We advocate the construction of new databases of transcriptomic data, using standardized formats in addition to standardized models of bacterial and yeast similar to those used in systems biology. The inclusion of proteomic and metabolomic data is also essential, as the resulting networks can provide a landscape to rationally predict and exploit new drug targets and to understand drug synergies.

Oculocutaneous albinism and consanguineous marriage among Spanish Gitanos or Calé--a study of 83 cases.

This paper studies 83 cases of oculocutaneous albinism (OCA) in family networks of Gitanos in southeastern Spain, and analyzes their sustained inbreeding patterns and complex genealogical relationships. It is based in the family and genealogy reconstitution of the Gitano population of 22 contiguous localities using ethnographic and historical demography methods. The study found a prevalence of OCA among Gitanos in the area of about 1: 1,200. Most of the cases belong to three extended kin networks in which consanguineous marriages have been common for generations. In these networks there are other cases of visual and auditive congenital anomalies, and other birth defects such as brachydactily, polydactily, neurological defects, Potter Sequence, etc. In 61 OCA cases it was possible to trace inbreeding links with a depth of three to nine generations. For these cases the estimated alpha (average of the inbreeding coefficient, F) is 0.0222. Relationships between the parents of people affected are of three types: close, as between first or second cousins; distant, as between third or fourth cousins, and non-existent, as in mixed marriages. In most cases, however, persons with albinism are linked by multiple consanguineous links. Albinism seems to be a visible example of a high prevalence of birth defects in this minority, associated with founder effects, sustained inbreeding and high fertility rates. These conditions derive from Gitano's marriage preferences and pronatalist strategies. In turn, these strategies have to be related to the exclusion, persecution and segregation that Spanish Gypsies have suffered for centuries.

Impact on quality of life by improving asthma control medication in patients with persistent asthma in a paediatric emergency department.

OBJECTIVE: To assess the impact of improving long-term control medications on quality of life in children with persistent asthma symptoms attended in a paediatric emergency department (PED). STUDY DESIGN/METHODS: Prospective study carried out in a Spanish PED from May to December 2010 including children 1-14 years of age with persistent asthma symptoms. At discharge, their long-term control medications was either initiated or improved on the basis of the National Asthma Education and Prevention Program. Three follow-up telephone interviews at 2 and 6 weeks and at 6 months after the PED visit were completed. Parents were asked about the presence of asthma symptoms and quality of life of the child, respectively, using a six-item paediatric asthma control tool and an eight-item asthma-related quality-of-life instrument. RESULTS: The study was completed in 124 patients. Asthma LCTM was initiated in 74 (59.7%), improved in the same step in 36 (29%) and stepped up in 14 (11.3%). Ninety-one (73.4%), 107 (86.3%) and 117 patients (94.4%) were free of persistent asthma symptoms at 2 and 6 weeks and 6 months at follow-up, respectively. Seventy-five (60.5%) and 93 patients (75%) experienced an improvement in their quality of life between 2 and 6 weeks and 6 months after the PED visit, respectively. The mean eight-item asthma-related quality-of-life scores at 6 weeks and 6 months were significantly higher than those registered at 2 weeks at follow-up (91.9 ± 11 and 93 ± 10 vs. 86.1 ± 14.3; P < 0.001). CONCLUSION: Children attended for acute asthma in PED where LCTM were initiated or stepped up showed a decrease in asthma persistent symptoms and an improvement in their quality of life.

Lymphocytic vasculitis of the prostate transition zone.

UNLABELLED: Study Type--Pathology (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Lymphocytic vasculitis of the prostate is an exceedingly rare form of localised vasculitis that presents without systemic involvement, and is illustrated with anecdotal case reports; often as localised polyarteritis nodosa-like vasculitis. True incidence and clinical significance of lymphocytic vasculitis of the prostate in surgical specimens is virtually unknown. The present findings support that lymphocytic vasculitis of the prostate was present in 67 (12.4%) of 540 specimens. Lymphocytic vasculitis of the prostate was present in 14 (93.3%) of 15 specimens with prostatic infarction (P < 0.001) with a risk of 124.68 (OR [odds ratio]; 95% CI [confidence interval] 16.07-967.07) as compared with BPH cases not associated with lymphocytic vasculitis. OBJECTIVE: • To present our experience of lymphocytic vasculitis of the prostate in men with benign prostatic hyperplasia (BPH) without systemic involvement, as this is an exceedingly rare form of localised vasculitis and the incidence in surgical specimens and clinical significance of lymphocytic vasculitis is virtually unknown. PATIENTS AND METHODS: • A sequential cohort series of 540 surgical specimens removed because of BPH-related symptoms, including simple prostatectomy (374 men) and transurethral resection of the prostate (166), comprised the study group. • All men had histological diagnosis of BPH and received surgical therapy only. None of the men had had previous surgery or granulomatous prostatitis. • The mean (range) age at diagnosis was 67.8 (38-89) years. RESULTS: • Lymphocytic vasculitis of the prostate was present in 67 (12.4 %) of 540 specimens. It was seen in a variable number of small- to medium-sized parenchyma arteries with segmental to transmural lymphocytic inflammation, within the morphological spectrum of a polyarteritis nodosa (PAN)-like lesion seen at the periphery of BPH nodules. • In four cases, focal fibrinoid necrosis was seen in vessels with otherwise typical lymphocytic vasculitis features. Immunohistochemical staining showed a T cell predominant polymorphic cellular infiltrate with a minor component of B cells and monocytes. Six cases additionally had eosinophils (<1% of inflammatory cells). • Lymphocytic vasculitis of the prostate was present in 14 (93.3%) of 15 specimens with prostatic infarction (P < 0.001) with a risk of 124.68 (odds ratio [OR]; 95% confidence interval [CI] 16.07-967.07) as compared with BPH cases not associated with lymphocytic vasculitis. Logistic regression multivariate analysis selected both lymphocytic vasculitis of the prostate and patient age as significant predictors of prostate infarction with lymphocytic vasculitis being the most significant (P < 0.001; OR 128.12; 95% CI 16.298-1007.202). Follow-up information was available in all cases, range 2-16 years, and none of the patients developed systemic disease. • A validation set of 1665 additional cases including radical prostatectomy, cystoprostatectomy, and needle biopsies showed lymphocytic vasculitis of the prostate being associated to prostate infarction on univariate and multivariate logistic regression (P < 0.001; OR 228.34; 95% CI 45.17-1154.22) analyses. CONCLUSIONS: • Lymphocytic vasculitis in men with BPH is associated with prostatic infarction and should be considered a form of localised vasculitis with PAN-like morphology that does not necessitate additional evaluation for systemic disease. • The potential clinical relevance of lymphocytic vasculitis warrants further investigation.

Applications of a general random-walk theory for confined diffusion.

A general random walk theory for diffusion in the presence of nanoscale confinement is developed and applied. The random-walk theory contains two parameters describing confinement: a cage size and a cage-to-cage hopping probability. The theory captures the correct nonlinear dependence of the mean square displacement (MSD) on observation time for intermediate times. Because of its simplicity, the theory also requires modest computational requirements and is thus able to simulate systems with very low diffusivities for sufficiently long time to reach the infinite-time-limit regime where the Einstein relation can be used to extract the self-diffusivity. The theory is applied to three practical cases in which the degree of order in confinement varies. The three systems include diffusion of (i) polyatomic molecules in metal organic frameworks, (ii) water in proton exchange membranes, and (iii) liquid and glassy iron. For all three cases, the comparison between theory and the results of molecular dynamics (MD) simulations indicates that the theory can describe the observed diffusion behavior with a small fraction of the computational expense. The confined-random-walk theory fit to the MSDs of very short MD simulations is capable of accurately reproducing the MSDs of much longer MD simulations. Furthermore, the values of the parameter for cage size correspond to the physical dimensions of the systems and the cage-to-cage hopping probability corresponds to the activation barrier for diffusion, indicating that the two parameters in the theory are not simply fitted values but correspond to real properties of the physical system.

Toward a predictive understanding of water and charge transport in proton exchange membranes.

An analytical model for water and charge transport in highly acidic and highly confined systems such as proton exchange membranes of fuel cells is developed and compared to available experimental data. The model is based on observations from both experiment and multiscale simulation. The model accounts for three factors in the system including acidity, confinement, and connectivity. This model has its basis in the molecular-level mechanisms of water transport but has been coarse-grained to the extent that it can be expressed in an analytical form. The model uses the concentration of H(3)O(+) ion to characterize acidity, interfacial surface area per water molecule to characterize confinement, and percolation theory to describe connectivity. Several important results are presented. First, an integrated multiscale simulation approach including both molecular dynamics simulation and confined random walk theory is capable of quantitatively reproducing experimentally measured self-diffusivities of water in the perfluorinated sulfonic acid proton exchange membrane material, Nafion. The simulations, across a range of hydration conditions from minimally hydrated to fully saturated, have an average error for the self-diffusivity of water of 16% relative to experiment. Second, accounting for three factors-acidity, confinement, and connectivity-is necessary and sufficient to understand the self-diffusivity of water in proton exchange membranes. Third, an analytical model based on percolation theory is capable of quantitatively reproducing experimentally measured self-diffusivities of both water and charge in Nafion across a full range of hydration.

Cyclin D3 gene amplification in bladder carcinoma in situ.

Carcinoma in situ (CIS) is a non-papillary high-grade, potentially aggressive, and unpredictable manifestation of bladder urothelial carcinoma. The aim of this study was to assess patterns of Cyclin D3 gene amplification in Bacillus Calmette-Guerin (BCG)-treated CIS and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 28 primary (isolated) or secondary (concomitant) bladder CIS samples in which there was enough tissue material to assess Cyclin D3 gene status by fluorescent in situ hybridization was the study group. Cyclin D3 gene amplification was present in 29% of secondary CIS; none of primary CIS samples had Cyclin D3 gene amplification. Cyclin D3 amplification was related to recurrence- (p = 0.046) and progression-free survival (p = 0.002). Type of bladder CIS (primary vs. secondary) was unrelated to recurrence- or progression-free survival in the current series. Cox's regression analysis selected Cyclin D3 as an independent predictor of progression-free survival (p = 0.041, relative risk = 61.503, 95% confidence interval = 1.1-274.710). None of primary CIS cases recurred on follow-up; nine secondary CIS recurred and four of them progressed to invasive bladder carcinoma HG T1 (n = 1), T2b N0M0 (n = 1), T3b N1M0 (n = 1) and T4aN1M1 (n = 1). Mean recurrence ± SD (months) occurred at 19.5 ± 2.06 (95% (confidence interval (CI)), 15.5-23.6); mean progression (months) occurred at 23.8 ± 1.46 (95% (CI), 20.9-26.7). Our study suggests that Cyclin D3 gene amplification might be a predictor of aggressiveness in BCG-treated CIS.

Papel de los bisfosfonatos en el tratamiento adyuvante del cáncer de mama / The role of bisphosphonates of adjuvant therapy in breast cancer

El cáncer de mama es la neoplasia maligna más frecuente en las mujeres. El hueso es la localización más común de diseminación mestastásica del cáncer de mama precoz y es además la causa de dolor, fracturas e hipercalcemia en estas mujeres. Esta diseminación depende de la liberación de sustancias osteolíticas por parte de las células tumorales. La consecuente activación de los osteoclastos produce, a su vez, la liberación de factores de crecimiento que estimulan la proliferación de las células neoplásicas. Los bisfosfonatos, agentes antiosteolíticos, han demostrado su capacidad para reducir la progresión de metástasis óseas ya establecida. Pero éste no es el único mecanismo por el que los bisfosfonatos ejercen su acción antitumoral. Su capacidad de interferir en la vía de la angiogénesis tumoral o de modular el sistema inmunitario son algunos de los mecanismos que han llevado al desarrollo de estudios con el objetivo de establecer su papel como tratamiento adyuvante adicional en mujeres con cáncer de mama temprano. El bisfosfonato oral clodronato (1,600mg/día) es eficaz para el tratamiento de pacientes con metástasis óseas. Cuando se usa como tratamiento adyuvante durante 2 años en mujeres operadas de cáncer de mama precoz demuestra una reducción significativa del riesgo de metástasis óseas durante este período, con una significativa reducción de la mortalidad. Este beneficio, junto con su baja toxicidad y seguridad, apoyan su uso como tratamiento adyuvante adicional en mujeres con cáncer de mama precoz. El zoledronato, un potente bisfosfonato nitrogenado de tercera generación y uso parenteral, ha demostrado mantener o incluso mejorar la densidad mineral ósea en mujeres con cáncer de mama precoz en tratamiento hormonal adyuvante, así como en mujeres posmenopáusicas con pérdidas de masa ósea. Estudios más recientes llevados a cabo con este bisfosfonato en el contexto de la (neo)adyuvancia del cáncer de mama precoz otorgan al zoledronato un beneficio en la mejoría de la supervivencia libre de recaída, una reducción de la mortalidad y efecto antitumoral directo basado en la capacidad de inducir regresión del tamaño tumoral y mejoría de la tasa de respuestas patológicas (AU)

Breast cancer is the most common neoplasm in women. Bone is the most common site of metastatic spread from primary operable breast cancer, causing pain, fractures and hypercalcemia. This spread depends on the release of osteolytic substances by the cancer cells. The osteoclasts also release growth factors that can act back on the cancer cells to activate growth. Biphosphonates, antiosteolytic agents, have been shown to reduce the progression of established bone metastases. Emerging evidence suggests that biphosphonates also have antitumor and antimetastatic properties, including the inhibition of angiogenesis, tumor-cell invasion, and adhesion in bone; the induction of apoptosis; antitumor sinergy with cytotoxic chemotherapy; and immunomodulatory effects through induction of γ/δ T cells. These findings were the background and rationale for ongoing clinical trials, in order to establish their role as a part of adjuvant treatment for early breast cancer. The oral biphosphonate clodronate (1600mg/d) is effective in patients with bone metastases. When used as adjuvant therapy, given to patients with operable breast cancer for two years, clodronate has been reported to reduce the risk of bone metastases during a 2-year study period with a significant reduction in mortality. This benefit supports its use as additional adjuvant therapy for patients with operable breast cancer. Zoledronic acid, a potent nitrogen-containing biphosphonate, has been shown to maintain or increase bone mineral density (BMD) in premenopausal women with early-stage breast cancer receiving adjuvant hormone therapies as well as healthy postmenopausal women with low BMD. Recent large clinical trials with biphosphonates in the (neo)adjuvant setting for early-breast cancer, demonstrate an improvement of disease-free and overall survival as well as increased pathologic rate responses (AU)

Biomarcadores de estrés oxidativo como indicadores de actividad en la enfermedad articular inflamatoria crónica / Oxidative stress biomarkers as indicator of chronic inflammatory joint diseases stage

Objetivo Evaluar la participación del estrés oxidativo (EO) en la enfermedad articular inflamatoria crónica (EAIC), así como su posible uso como biomarcador diagnóstico. Pacientes y métodos Se estudiaron 29 pacientes con EAIC: 18 con artritis reumatoide (AR): 13 activos/5 inactivos; y 11 con espondilitis anquilosante (EA): 7 activos/4 inactivos, y como grupo control, 13 sujetos sanos. Los pacientes fueron clasificados según los siguientes criterios de actividad: escala de actividad de la enfermedad (DAS-28) para AR, e índice de actividad de enfermedad (BASDAI) y la escala visual analógica (EVA) de dolor nocturno para EA. Las concentraciones plasmáticas de los biomarcadores de estrés oxidativo fueron cuantificadas mediante técnicas espectrofotométricas y el análisis estadístico realizado, mediante el programa estadístico SPSS. Resultados Los pacientes con EAIC activa presentan un intenso EO, caracterizado por elevación de los parámetros indicadores de daño oxidativo y disminución de los sistemas antioxidantes, junto con una mayor cantidad de mieloperoxidasa. En los pacientes con EAIC inactiva sólo encontramos cambios en los niveles de glutatión oxidado (GSSG) y en el cociente glutatión reducido (GSH)/GSSG, y no en los indicadores de daño oxidativo ni en los sistemas antioxidantes. Conclusiones Nuestros datos indican que: a) los pacientes con EAIC activa presentan un intenso EO; b) la EAIC inactiva cursa con producción de especies reactivas sin llegar a desencadenar daño oxidativo y manteniendo la homeostasis reducción-oxidación, y c) los biomarcadores de EO podrían ser utilizados como indicadores del estado de actividad-inactividad de la EAIC (AU)

Objective To evaluate the participation of oxidative stress (OS) on chronic inflammatory joint disease (CIJD), as well as its possible use as a diagnostic biomarker. Patients and methods The study population comprised 29 patients with CIJD: 18 with rheumatoid arthritis (RA: 13 active/5 inactive); 11 with ankylosing spondylitis (AS: 7 active/4 inactive) and 13 healthy subjects. Activity of the disease was assessed by: RA patients, Disease Activity Score (DAS 28) and AS patients by means of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Oxidative stress biomarkers were determined in plasma using spectrophotometrical techniques. The statistical analysis was carried out using the SSPS statistical package. Results Active CIJD showed a high oxidative stress characterized by increases in oxidative damage markers and a reduction in antioxidative systems, together with a higher myeloperoxidase (MPO) concentration. Inactive CIJD only showed changes in oxidized glutathione (GSSG) and reduced glutathione (GSH)/GSSG ratio levels, without changes in oxidative damage parameters or in antioxidative systems. Conclusions Our data revealed that: i) CIJD presents with a high oxidative stress; ii) inactive CIJD shows a production of reactive species without triggering oxidative damage and maintaining red-ox homeostasis, and iii) the combination of oxidative stress biomarkers may be used as markers of active-inactive stages of CIJD (AU)

[Oxidative stress biomarkers as indicator of chronic inflammatory joint diseases stage]. / Biomarcadores de estrés oxidativo como indicadores de actividad en la enfermedad articular inflamatoria crónica.

OBJECTIVE: To evaluate the participation of oxidative stress (OS) on chronic inflammatory joint disease (CIJD), as well as its possible use as a diagnostic biomarker. PATIENTS AND METHODS: The study population comprised 29 patients with CIJD: 18 with rheumatoid arthritis (RA: 13 active/5 inactive); 11 with ankylosing spondylitis (AS: 7 active/4 inactive) and 13 healthy subjects. Activity of the disease was assessed by: RA patients, Disease Activity Score (DAS 28) and AS patients by means of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Oxidative stress biomarkers were determined in plasma using spectrophotometrical techniques. The statistical analysis was carried out using the SSPS statistical package. RESULTS: Active CIJD showed a high oxidative stress characterized by increases in oxidative damage markers and a reduction in antioxidative systems, together with a higher myeloperoxidase (MPO) concentration. Inactive CIJD only showed changes in oxidized glutathione (GSSG) and reduced glutathione (GSH)/GSSG ratio levels, without changes in oxidative damage parameters or in antioxidative systems. CONCLUSIONS: Our data revealed that: i) CIJD presents with a high oxidative stress; ii) inactive CIJD shows a production of reactive species without triggering oxidative damage and maintaining red-ox homeostasis, and iii) the combination of oxidative stress biomarkers may be used as markers of active-inactive stages of CIJD.

[The role of bisphosphonates of adjuvant therapy in breast cancer]. / Papel de los bisfosfonatos en el tratamiento adyuvante del cáncer de mama.

Breast cancer is the most common neoplasm in women. Bone is the most common site of metastatic spread from primary operable breast cancer, causing pain, fractures and hypercalcemia. This spread depends on the release of osteolytic substances by the cancer cells. The osteoclasts also release growth factors that can act back on the cancer cells to activate growth. Biphosphonates, antiosteolytic agents, have been shown to reduce the progression of established bone metastases. Emerging evidence suggests that biphosphonates also have antitumor and antimetastatic properties, including the inhibition of angiogenesis, tumor-cell invasion, and adhesion in bone; the induction of apoptosis; antitumor sinergy with cytotoxic chemotherapy; and immunomodulatory effects through induction of γ/δ T cells. These findings were the background and rationale for ongoing clinical trials, in order to establish their role as a part of adjuvant treatment for early breast cancer. The oral biphosphonate clodronate (1600mg/d) is effective in patients with bone metastases. When used as adjuvant therapy, given to patients with operable breast cancer for two years, clodronate has been reported to reduce the risk of bone metastases during a 2-year study period with a significant reduction in mortality. This benefit supports its use as additional adjuvant therapy for patients with operable breast cancer. Zoledronic acid, a potent nitrogen-containing biphosphonate, has been shown to maintain or increase bone mineral density (BMD) in premenopausal women with early-stage breast cancer receiving adjuvant hormone therapies as well as healthy postmenopausal women with low BMD. Recent large clinical trials with biphosphonates in the (neo)adjuvant setting for early-breast cancer, demonstrate an improvement of disease-free and overall survival as well as increased pathologic rate responses.

Hepatoid adenocarcinoma of the stomach - a different histology for not so different gastric adenocarcinoma: a case report.

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.

Cutaneous apocrine cystic adenolipoma.

Adenolipoma is a rare microscopic variant of cutaneous lipoma composed of large lobules of mature adipocytic tissue admixed with eccrine ducts and glands. We report a new case of cutaneous adenolipoma, and the first showing an apocrine cystic glandular component. This lesion may not be a specific entity, and could represent entrapment of epithelial structures within a lipoma.

Hipoglicemia / Hypoglycemia

A hipoglicemia é um distúrbio bastante comum e que deve ter um manejo rápido e apropriado, assim que diagnosticado. Pretendemos, com este artigo, revisar os principais aspectos clínicos e laboratoriais da hipoglicemia, bem como seu tratamento, proporcionando um melhor manejo deste distúrbio