Long-term evolution in liver fibrosis and immune profile after direct-acting antivirals therapy in hepatitis C virus-human immunodeficiency virus co-infected patients.

OBJECTIVE: Hepatitis C virus (HCV) therapy with direct-acting antivirals (DAA) achieves high rates of sustained virological response in people living with human immunodeficiency virus (HIV) (PLWH). Information on its long-term clinical impact is scarce. The aim of this study was to analyse liver fibrosis and immune response evolution after DAA treatment. METHODS: Retrospective, single centre cohort study of HIV-HCV co-infected patients treated with DAA between June 2013 and June 2018. We analysed the changes during follow up in liver fibrosis (assessed by transient elastography (TE), aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 scores) and immunity (CD4 and CD8 cells counts and CD4/CD8 ratio). RESULTS: We included 410 patients; 75% (308/407) men with a mean age of 50 years (SD 8); 78% (318/410) had long chronic HCV infection (median 21 years, interquartile range (IQR) 6-27 years) and 27% (107/393) had liver cirrhosis. Liver fibrosis improvement based on the decrease in TE value compared with the baseline occurred in 43% (131/302) of patients and 31% of patients based on biological scores (APRI: 124/398; FIB-4: 104/398) (p < 0.0001), being more frequent in those with advanced baseline fibrosis (83/144). The higher decrease was observed at 6 months after DAA therapy (-0.23; 95% CI -0.29 to -0.18), but a continuum in fibrosis regression of at least 30% from baseline value of TE was observed along the follow up (32% of patients at month 6, 51% at month 24 and 55% at month 48). Regarding the immunological profile, there was a significant decrease in CD8 counts at month 48 (-62.38; 95% CI -106.77 to -17.99; p 0.0001) and a progressive rise in the CD4/CD8 ratio after 24 months of follow up reaching an increment of +0.07 (95% CI 0.03-0.10, p 0.0001) at month 48. CONCLUSIONS: HCV treatment with DAA in PLWH is associated with significant progressive improvement in liver fibrosis and recovery of the immune system with an increase in the CD4/CD8 ratio in long-term follow up.

Low-intensity continuous ultrasound to inhibit cancer cell migration.

In recent years, it has been verified that collective cell migration is a fundamental step in tumor spreading and metastatic processes. In this paper, we demonstrate for the first time how low-intensity ultrasound produces long-term inhibition of collective migration of epithelial cancer cells in wound healing processes. In particular, we show how pancreatic tumor cells, PANC-1, grown as monolayers in vitro respond to these waves at frequencies close to 1 MHz and low intensities (<100 mW cm-2) for 48-72 h of culture after some minutes of a single ultrasound irradiation. This new strategy opens a new line of action to block the spread of malignant cells in cancer processes. Despite relevant spatial variations of the acoustic pressure amplitude induced in the assay, the cells behave as a whole, showing a collective dynamic response to acoustic performance. Experiments carried out with samples without previous starving showed remarkable effects of the LICUs from the first hours of culture, more prominent than those with experiments with monolayers subjected to fasting prior to the experiments. This new strategy to control cell migration demonstrating the effectiveness of LICUS on not starved cells opens a new line of action to study effects of in vivo ultrasonic actuation on tumor tissues with malignant cells. This is a proof-of-concept study to demonstrate the physical effects of ultrasound stimulation on tumor cell migration. An in-depth biological study of the effects of ultrasounds and underlying biological mechanisms is on-going but out of the scope of this article.

Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis.

Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the cell, requiring the use of carriers to protect them from degradation and transporting them across the cell membrane. There is no information about which is the most efficient endocytosis route for high siRNA transfection efficiency. One of the most promising carriers to efficiently deliver siRNA are cyclodextrin derivatives. We have used nanocomplexes composed of siRNA and a ß-cyclodextrin derivative, AMC6, with a very high transfection efficiency to selectively knockdown clathrin heavy chain, caveolin 1, and p21 Activated Kinase 1 to specifically block clathrin-mediated, caveolin-mediated and macropinocytosis endocytic pathways. The main objective was to identify whether there is a preferential endocytic pathway associated with high siRNA transfection efficiency. We have found that macropinocytosis is the preferential entry pathway for the nanoparticle and its associated siRNA cargo. However, blockade of macropinocytosis does not affect AMC6-mediated transfection efficiency, suggesting that macropinocytosis blockade can be functionally compensated by an increase in clathrin- and caveolin-mediated endocytosis.

[Our eight-year experience in home parenteral nutrition for adult patients]. / Nuestra experiencia de ocho años en nutrición parenteral domiciliaria de pacientes adultos.

INTRODUCTION: Background: home parenteral nutrition (HPN) is a technique that allows increasing the survival of patients with intestinal failure. Aim: to study the evolution of home parenteral nutrition over the last 8 years in our center. Methods: a retrospective study of adult patients receiving HPN between 2011 and 2019. Study variables are expressed as frequency and mean ± SD (range). Parametric, non-parametric tests, and a survival analysis (p < 0.05) were applied. Results: the use of HPN showed a substantial increase (up to 154 %). A total of 76 patients received HPN, 76.32 % had an oncological pathology, and consequently the main indication was intestinal obstruction (56.58 %). Average duration was 11.12 ± 23.38 months (0.17-139.17). In all, 44.74 % experienced one or several complications, primarily catheter-related bacteremia (CRB) (27.63 %), and metabolic disorders (40.79 %), mainly of hepatic type. CRB rate was 2.25/1,000 days of HPN. The main cause of death was the underlying disease. Overall survival in case of benign conditions at 1, 3, and 5 years was 65.5 %, 53.6 %, and 40.2 %, respectively. In case of malignancy overall survival at 3 months was 55.1 %, at 6 months 28.7 %, and at 1 years 19.1 %. Conclusions: oncological disease was the primary condition that led to an indication in our center. It is the underlying pathology what determines prognosis, which must be taken into account at the time of selecting patients. The BRC rate obtained is susceptible to improvement, so it is essential that health education and a correct technique be encouraged.

INTRODUCCIÓN: Introducción: la nutrición parenteral domiciliaria (NPD) es una técnica que permite incrementar la supervivencia de los pacientes con fallo intestinal. Objetivos: estudiar la evolución de la NPD en los últimos 8 años en nuestro centro. Métodos: estudio retrospectivo de pacientes adultos con NPD entre 2011 y 2019. Las variables se expresan como frecuencias y media ± DE (rango). Se realizaron pruebas paramétricas, no paramétricas y análisis de la supervivencia (p < 0,05). Resultados: el uso de NPD mostró un sustancial incremento (hasta un 154 %). Un total de 76 pacientes recibieron NPD, el 76,32 % tenían patología oncológica y, en consecuencia, la principal indicación fue la obstrucción intestinal (56,58 %). La duración media fue de 11,12 ± 23,38 meses (0,17-139,17). El 44,74 % experimentaron una o varias complicaciones, siendo las principales la bacteriemia relacionada con el catéter (BRC) (27,63 %) y las metabólicas (40,79 %), fundamentalmente de tipo hepático. La tasa de BRC fue de 2,25/1000 días de NPD. La principal causa de muerte fue la enfermedad de base. La supervivencia global en caso de patología benigna a los 1, 3 y 5 años fue del 65,5 %, 53,6 % y 40,2 %, respectivamente. En caso de patología maligna, la supervivencia global a los 3 meses fue del 55,1 %, a los 6 meses del 28,7 %, y al año del 19,1 %. Conclusiones: la enfermedad oncológica fue la principal patología que motivó la indicación en nuestro centro. Es la patología de base la que determina el pronóstico, lo que debe tenerse en cuenta en la selección de pacientes. La tasa de BRC obtenida es susceptible de mejora, por lo que es fundamental reforzar la educación sanitaria y la técnica correcta.

[Evolution of patients with home parenteral nutrition: a systematic review of available studies]. / Evolución de los pacientes con nutrición parenteral domiciliaria: una revisión sistemática de los estudios disponibles.

INTRODUCTION: Introduction: home parenteral nutrition (HPN) is a fundamental treatment for patients with intestinal failure who do not require hospitalization. We aimed to conduct an epidemiological and clinical practice analysis of HPN through a systematic review. Methods: the systematic review was conducted according to the PRISMA guidelines. A search was performed using the Healthcare Databases Advanced Search of PubMed® and EMBASE®, to identify articles which followed patients treated with HPN for at least 5 years, published between 2009 and 2019 in English or Spanish language. In addition, we manually retrieved other publications of interest. We excluded articles about subgroups of patients with a specific pathology, cancer or pregnant patients. We excluded studies collecting exclusively HPN complications. Results: a total of 267 references were identified, of which 9 met criteria (3 of pediatric population and 6 of adults). In adults, the main difference found between publications was the underlying pathologies. The most common indication was short bowel syndrome and the main cause of exitus was the underlying pathology. Most of the pediatric patients received this support in the first months of life. In addition, children showed a higher conversion rate to oral intake and a lower number of deaths when compared to adults. Conclusions: the use of HPN in cancer pathology is subject to wide geographic variability. It would be advisable to establish indication guidelines in patients with cancer and conduct quality studies, which provide rigorous and homogeneous information.

INTRODUCCIÓN: Introducción: la nutrición parenteral domiciliaria (NPD) constituye el tratamiento de elección para pacientes con fallo intestinal que no requieren ingreso hospitalario. En esta revisión sistemática, nuestro objetivo fue realizar un análisis epidemiológico y de práctica clínica en NPD. Métodos: la revisión se realizó siguiendo la guía PRISMA. Para ello, se hizo una búsqueda bibliográfica en PubMed® y EMBASE® de los estudios publicados entre 2009 y 2019 en inglés o español que realizaran el seguimiento de pacientes con NPD durante al menos 5 años. Esta búsqueda se completó manualmente. Se excluyeron los artículos centrados únicamente en pacientes oncológicos, una patología específica o embarazadas o bien en complicaciones. Resultados: se identificaron 267 artículos, de los que cumplieron los criterios 9 (3 de población pediátrica y 6 de adultos). En adultos, la principal diferencia entre los estudios fue la patología de base. La indicación mayoritaria fue el síndrome de intestino corto y la causa de exitus, la enfermedad primaria. La mayor parte de la población pediátrica recibió este apoyo en los primeros meses de vida. Además, destaca el mayor porcentaje de conversión a vía oral y el menor número de fallecimientos frente a población adulta. Conclusiones: la utilización de la NPD en patología oncológica está sometida a una amplia variabilidad geográfica. Sería recomendable establecer directrices de uso en enfermos oncológicos y la realización de estudios de calidad que aporten información rigurosa y homogénea.

mRNA Detection in Anal Cytology: A Feasible Approach for Anal Cancer Screening in Men Who Have Sex with Men Living With HIV.

There is growing interest in anal cancer screening strategies. However, cytological/molecular evaluation of anal samples is challenging. We aimed to determine the feasibility of detecting, in anal liquid-based cytologies, the expression of biomarkers involved in the cell cycle disturbance elicited by human papillomavirus (HPV). The accuracy of this approach in the identification of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia grade2-3 (HSIL/AIN2-3) was also evaluated. 215 anal cytologies from men having sex with men living with human immunodeficiency virus were evaluated. Patients showing concordant cytological and anoscopy-directed biopsy diagnosis were selected: 70 with negative cytology and HPV test, 70 with low-grade SIL (LSIL/AIN1) cytology and biopsy, and 75 with cytology and biopsy of HSIL/AIN2-3. CDKN2A/p16, MKI67 and TOP2A mRNA expression was analyzed. HPV detection was performed with Xpert HPV Assay (Cepheid, Sunnyvale, CA, USA). HSIL/AIN2-3 showed higher expression for the biomarkers than LSIL/AIN1 or negative samples. The specificity for HSIL/AIN2-3 detection for a sensitivity established at 70% was 44.7% (95%confidence interval [CI] 36.5-53.2) for TOP2A and MKI67 and 54.5% (95%CI 46.0-62.8%) for CDKN2A/p16. mRNA detection of cell biomarkers in anal liquid-based cytology is feasible. Further studies are warranted to confirm if strategies based on mRNA detection have any role in anal cancer screening.

Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

Analysis of known amyotrophic lateral sclerosis and frontotemporal dementia genes reveals a substantial genetic burden in patients manifesting both diseases not carrying the C9orf72 expansion mutation.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a clinical, pathological and genetic continuum. OBJECTIVES: The purpose of the present study was to assess the mutation burden that is present in patients with concurrent ALS and FTD (ALS/FTD) not carrying the chromosome 9 open reading frame 72 (C9orf72) hexanucleotide repeat expansion, the most important genetic cause in both diseases. METHODS: From an initial group of 973 patients with ALS, we retrospectively selected those patients fulfilling diagnostic criteria of concomitant ALS and FTD lacking the repeat expansion mutation in C9orf72. Our final study group consisted of 54 patients clinically diagnosed with ALS/FTD (16 with available postmortem neuropathological diagnosis). Data from whole exome sequencing were used to screen for mutations in known ALS and/or FTD genes. RESULTS: We identified 11 patients carrying a probable pathogenic mutation, representing an overall mutation frequency of 20.4%. TBK1 was the most important genetic cause of ALS/FTD (n=5; 9.3%). The second most common mutated gene was SQSTM1, with three mutation carriers (one of them also harboured a TBK1 mutation). We also detected probable pathogenic genetic alterations in TAF15, VCP and TARDBP and possible pathogenic mutations in FIG4 and ERBB4. CONCLUSION: Our results indicate a high genetic burden underlying the co-occurrence of ALS and FTD and expand the phenotype associated with TAF15, FIG4 and ERBB4 to FTD. A systematic screening of ALS and FTD genes could be indicated in patients manifesting both diseases without the C9orf72 expansion mutation, regardless of family history of disease.

Extracellular Volume Detects Amyloidotic Cardiomyopathy and Correlates With Neurological Impairment in Transthyretin-familial Amyloidosis.

INTRODUCTION AND OBJECTIVES: Cardiac involvement determines prognosis and treatment options in transthyretin-familial amyloidosis. Cardiac magnetic resonance T1 mapping techniques are useful to assess myocardial extracellular volume. This study hypothesized that myocardial extracellular volume allows identification of amyloidotic cardiomyopathy and correlates with the degree of neurological impairment in transthyretin-familial amyloidosis. METHODS: A total of 31 transthyretin-familial amyloidosis patients (19 mean age, 49 ± 12 years; 26 with the Val30Met mutation) underwent a T1 mapping cardiac magnetic resonance study and a neurological evaluation with Neuropathy Impairment Score of the Lower Limb score, Norfolk Quality of Life questionnaire, and Karnofsky index. RESULTS: Five patients had cardiac amyloidosis (all confirmed by 99mTc-DPD scintigraphy). Mean extracellular volume was increased in patients with cardiac amyloidosis (0.490 ± 0.131 vs 0.289 ± 0.035; P = .026). Extracellular volume correlated with age (R = 0.467; P = .008), N-terminal pro-B-type natriuretic peptide (RS = 0.846; P < .001), maximum wall thickness (R = 0.621; P < .001), left ventricular mass index (R = 0.685; P < .001), left ventricular ejection fraction (R = -0.378; P = .036), Neuropathy Impairment Score of the Lower Limb (RS = 0.604; P = .001), Norfolk Quality of Life questionnaire (RS = 0.529; P = .003) and Karnofsky index (RS= -0.517; P = .004). A cutoff value of extracellular volume of 0.357 was diagnostic of cardiac amyloidosis with 100% sensitivity and specificity (P < .001). Extracellular volume and N-terminal pro-B-type natriuretic peptide were the only cardiac parameters that significantly correlated with neurologic scores. CONCLUSIONS: Extracellular volume quantification allows identification of cardiac amyloidosis and correlates with the degree of neurological impairment in transthyretin-familial amyloidosis. This noninvasive technique could be a useful tool for early diagnosis of cardiac amyloidosis and to track cardiac and extracardiac amyloid disease.

Aproximación a los encuadres de salud en noticieros de la televisión mexicana / Approach to framings health in Mexican television newscasts

Resumen Propósitos del estudio: Los encuadres sobre salud en los medios de comunicación inciden tanto en las percepciones y conductas de las audiencias como en los procesos de construcción, comunicación e interpretación del problema y asuntos de salud. El objetivo de este artículo es mostrar cómo tres informativos de la televisión mexicana (TVAzteca, Televisa y C7) abordan el tópico de la salud. Se presentan avances del estudio, en proceso, sobre encuadres de salud. Metodología: Se recurrió al análisis de contenido de una muestra de 62 piezas, identificando como principales variables a los actores -personas e instituciones-, acciones, lugares geográficos, espacios físicos, temáticas, posibles razones y enfoques de la noticia, así como la perspectiva de género adoptada. Resultados: Los resultados preliminares de la investigación muestran una reducida agenda centrada en la prevención de enfermedades infectocontagiosas y en el tratamiento clínico de problemas biomédicos (físicos y fisiológicos) de salud. También cabe destacar la mayor frecuencia de informaciones institucionales distribuidas por la Secretaría de Salud y del IMSS. Conclusiones: Se sugiere ampliar la cobertura temática y territorial de asuntos/perspectivas sobre salud a partir del cuidado de la calidad y la precisión en el tratamiento informativo e incorporar la perspectiva de género, hoy ausente.

Abstract Aims: Framing health in media impact in perceptions and behavior of audiences, also in the construction processes, communication and interpretation of health issues and questions. The aim of this paper is to show how the news in Mexican television (TVAzteca, Televisa and C7) address issues related to health; it present a preview of study in progress on framing health. Methodology: It´s resorted to a content analysis of a sample of 62 pieces, identifying the main variables -people actors and institutions, actions, geographic locations, physical spaces, thematic, possible reasons and approaches to news and gender approach adopted. Results: Preliminary research results show a reduced agenda focused on preventing infectious diseases and clinical treatment of biomedical problems (physical and psychological) health. Also should be noted the greater frequency of information institutional distributed by the Ministry of Health and IMSS. Conclusions: It's suggested expanding the thematic and territorial coverage of issues/perspectives on health from the quality care and precision in the informative treatment and incorporate the, now absent, gender perspective.

CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular and pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of which TDP-43 is a major component, are a characteristic pathological feature of most ALS and FTD patients. Here we use genome-wide linkage analysis in a large ALS/FTD kindred to identify a novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified a CCNF missense mutation at this locus. Interrogation of international cohorts identified additional novel CCNF variants in familial and sporadic ALS and FTD. Enrichment of rare protein-altering CCNF variants was evident in a large sporadic ALS replication cohort. CCNF encodes cyclin F, a component of an E3 ubiquitin-protein ligase complex (SCF(Cyclin F)). Expression of mutant CCNF in neuronal cells caused abnormal ubiquitination and accumulation of ubiquitinated proteins, including TDP-43 and a SCF(Cyclin F) substrate. This implicates common mechanisms, linked to protein homeostasis, underlying neuronal degeneration.

Trehalose- and glucose-derived glycoamphiphiles: small-molecule and nanoparticle Toll-like receptor 4 (TLR4) modulators.

An increasing number of pathologies have been linked to Toll-like receptor 4 (TLR4) activation and signaling, therefore new hit and lead compounds targeting this receptor activation process are urgently needed. We report on the synthesis and biological properties of glycolipids based on glucose and trehalose scaffolds which potently inhibit TLR4 activation and signaling in vitro and in vivo. Structure-activity relationship studies on these compounds indicate that the presence of fatty ester chains in the molecule is a primary prerequisite for biological activity and point to facial amphiphilicity as a preferred architecture for TLR4 antagonism. The cationic glycolipids here presented can be considered as new lead compounds for the development of drugs targeting TLR4 activation and signaling in infectious, inflammatory, and autoimmune diseases. Interestingly, the biological activity of the best drug candidate was retained after adsorption at the surface of colloidal gold nanoparticles, broadening the options for clinical development.

Overcoming the slow recovery of MOX gas sensors through a system modeling approach.

Metal Oxide Semiconductor (MOX) gas transducers are one of the preferable technologies to build electronic noses because of their high sensitivity and low price. In this paper we present an approach to overcome to a certain extent one of their major disadvantages: their slow recovery time (tens of seconds), which limits their suitability to applications where the sensor is exposed to rapid changes of the gas concentration. Our proposal consists of exploiting a double first-order model of the MOX-based sensor from which a steady-state output is anticipated in real time given measurements of the transient state signal. This approach assumes that the nature of the volatile is known and requires a precalibration of the system time constants for each substance, an issue that is also described in the paper. The applicability of the proposed approach is validated with several experiments in real, uncontrolled scenarios with a mobile robot bearing an e-nose.

Polycationic amphiphilic cyclodextrins as gene vectors: effect of the macrocyclic ring size on the DNA complexing and delivery properties.

A collection of homologous monodisperse facial amphiphiles consisting of an α-, ß- or γ-cyclodextrin (α, ß or γCD) platform exposing a multivalent display of cationic groups at the primary rim and bearing hexanoyl chains at the secondary hydroxyls have been prepared to assess the influence of the cyclooligosaccharide core size in their ability to complex, compact and protect pDNA and in the efficiency of the resulting nanocondensates (CDplexes) to deliver DNA into cells and promote transfection in the presence of serum. All the polycationic amphiphilic CDs (paCDs) were able to self-assemble in the presence of the plasmid and produce transfectious nanoparticles at nitrogen/phosphorous ratios ≥5. CDplexes obtained from ßCD derivatives generally exhibited higher transfection capabilities, which can be ascribed to their ability to form inclusion complexes with cholesterol, thereby enhancing biological membrane permeability. The presence of thiourea moieties as well as increasing the number of primary amino groups then favour cooperative complexation of the polyphosphate chain, enhancing the stability of the complex and improving transfection. In the α and γCD series, however, only the presence of tertiary amino groups in the cationic clusters translates into a significant improvement of the transfection efficiency, probably by activating endosome escape by the proton sponge mechanism. This set of results illustrates the potential of this strategy for the rational design and optimisation of nonviral gene vectors.

Prevalence and clinical relevance of occult hepatitis B in the fibrosis progression and antiviral response to INF therapy in HIV-HCV-coinfected patients.

Occult hepatitis B virus (HBV) infection is diagnosed when HBc antibodies (HBcAb) and HBV DNA are detectable in serum while hepatitis B surface antigen (HBsAg) is not. This situation has been frequently described in patients with chronic hepatitis C virus (HCV) infection. The objective of this study was to evaluate the prevalence of occult hepatitis B in HIV-HCV-coinfected patients and its clinical relevance in liver histology and viral response after interferon therapy for HCV. A total of 238 HIV-HCV-infected patients,negative for HBsAg, were included. Serum samples were analyzed for the presence of HBV DNA and HBcAb.HBV DNA quantification was determined with the Cobas TaqMan HBV Test (detection limit 6 IU/ml). Data from liver biopsy and laboratory tests were also analyzed. HBcAb resulted in 142 (60%) patients, being the independent associated factors: male gender, previous history of intravenous drug use, age, CD4 count,and HAV antibody presence. Among 90 HBcAb patients that we could analyze, HBV DNA was positive in 15 (16.7% of occult hepatitis B infection in this group, and 6.3% in the whole HIV-HCV cohort studied). No baseline factors, liver histology, or HCV therapy response were related to the presence of HBV DNA. We found that occult hepatitis B is a frequent condition present in at least 6.3% of our HCV-HIV patients and in more than 16% of those with HBcAb. Despite the high prevalence, this phenomenon does not seem to affect the clinical evolution of chronic hepatitis C or modify the viral response to interferon-based HCV therapies

Noninvasive diagnosis of hepatic fibrosis in HIV/HCV-coinfected patients.

BACKGROUND: Several serum markers reflecting extracellular matrix status have been correlated with liver fibrosis in non-HIV-infected patients with chronic hepatitis C infection. These indexes have been less examined in HIV/HCV-coinfected individuals. OBJECTIVE: We aimed to evaluate the predictive value of serum markers for liver fibrosis in HIV-infected patients with chronic hepatitis C virus (HVC). METHODS: Serum levels of metalloproteinases 1 and 2 (MMP-1 and -2), tissue inhibitors of matrix metalloproteinases (TIMP-1), procollagen type III N-terminal peptide (PIIINP), and hyaluronic acid (HA) were measured in HIV-infected patients with chronic hepatitis C at the time of obtaining a liver biopsy and before the consideration of anti-hepatitis C therapy. RESULTS: One hundred and nineteen consecutive HIV-HVC coinfected patients were included. TIMP-1 (r = 0.6; P < 0.001), TIMP-1/MMP-1 ratio (r = 0.5; P < 0.001), TIMP-1/MMP-2 ratio (r = 0.3; P < 0.001), MMP-2 (r = 0.2; P = 0.044), PIIINP (r = 0.4; P < 0.001), and HA (r = 0.5; P < 0.001) were positively and significantly correlated with the fibrosis stage. In the multivariate analysis, TIMP-1 (odds ratio [OR] = 1.004, 95% confidence interval [CI]: 1.002 to 1.006, P = 0.001) and HA >95 microg/dL (OR = 6.041, 95% CI: 1.184 to 30.816, P = 0.031) were independently associated with liver fibrosis. The area under the curve of score to discriminate mild (F0-F1) from significant (F2-F4) fibrosis in the received-operating analysis using the variables TIMP-1 and HA was 0.84, with a sensitivity of 72.9% and a specificity of 83.1%. CONCLUSION: TIMP-1 and HA were quite sensitive and specific for predicting the degree of liver fibrosis in HIV-infected patients with chronic hepatitis C. These parameters may become a noninvasive alternative to liver biopsy when the degree of liver fibrosis needs to be estimated.

Occipital condyle syndrome guiding diagnosis to metastatic prostate cancer.

Occipital condyle syndrome (OCS) results from a unilateral occipital pain associated with an ipsilateral paresis of the 12th cranial nerve (hypoglossal), and is typically caused by metastasis of the skull base. OCS diagnosis occurred, in all cases described in the published literature, when metastatic prostate cancer (MPC) was previously known. We present a case of a patient whose initial manifestation of MPC was OCS. The patient was treated with complete hormonal blockade and non-steroidal anti-inflammatory drugs as opposed to locoregional radiotherapy applied in other cases. After 18 month follow-up, the patient had a complete neurological and biochemical response.

[Expression of multidrug resistance (MDR)-associated proteins in solid tumors]. / Expresión de proteínas relacionadas con resistencia a múltiples fármacos (MDR-proteínas) en tumores sólidos.

The causes of drug resistance in tumor cells vary widely. The present study aims to provide an update of multidrug resistance in tumor cells and, in particular, of multidrug resistance-associated proteins.