Tribuna. Reorientar el diagnóstico

Las técnicas de diagnóstico por imagen han revolucionado muchas especialidades, como la oncología, donde su uso ha permitido reducir la morbi-mortalidad de lesiones detectadas precozmente. Sin embargo, ni todas las técnicas ni todos los tumores son iguales.

How reliable is an undetectable viral load?

OBJECTIVES: An article by the Swiss AIDS Commission states that patients with stably suppressed viraemia [i.e. several successive HIV-1 RNA plasma concentrations (viral loads, VL) below the limits of detection during 6 months or more of highly active antiretroviral therapy (HAART)] are unlikely to be infectious. Questions then arise: how reliable is the undetectability of the VL, given the history of measures? What factors determine reliability? METHODS: We assessed the probability (henceforth termed reliability) that the n+1 VL would exceed 50 or 1000 HIV-1 RNA copies/mL when the nth one had been <50 copies/mL in 6168 patients of the Swiss HIV Cohort Study who were continuing to take HAART between 2003 and 2007. General estimating equations were used to analyse potential factors of reliability. RESULTS: With a cut-off at 50 copies/mL, reliability was 84.5% (n=1), increasing to 94.5% (n=5). Compliance, the current type of HAART and the first antiretroviral therapy (ART) received (HAART or not) were predictive factors of reliability. With a cut-off at 1000 copies/mL, reliability was 97.5% (n=1), increasing to 99.1% (n=4). Chart review revealed that patients had stopped their treatment, admitted to major problems with compliance or were taking non-HAART ART in 72.2% of these cases. Viral escape caused by resistance was found in 5.6%. No explanation was found in the charts of 22.2% of cases. CONCLUSIONS: After several successive VLs at <50 copies/mL, reliability reaches approximately 94% with a cut-off of 50 copies/mL and approximately 99% with a cut-off at 1000 copies/mL. Compliance is the most important factor predicting reliability.

Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals.

OBJECTIVES: Toll-like receptors (TLRs) are innate immune sensors that are integral to resisting chronic and opportunistic infections. Mounting evidence implicates TLR polymorphisms in susceptibilities to various infectious diseases, including HIV-1. We investigated the impact of TLR single nucleotide polymorphisms (SNPs) on clinical outcome in a seroincident cohort of HIV-1-infected volunteers. DESIGN: We analyzed TLR SNPs in 201 antiretroviral treatment-naive HIV-1-infected volunteers from a longitudinal seroincident cohort with regular follow-up intervals (median follow-up 4.2 years, interquartile range 4.4). Participants were stratified into two groups according to either disease progression, defined as peripheral blood CD4(+) T-cell decline over time, or peak and setpoint viral load. METHODS: Haplotype tagging SNPs from TLR2, TLR3, TLR4, and TLR9 were detected by mass array genotyping, and CD4(+) T-cell counts and viral load measurements were determined prior to antiretroviral therapy initiation. The association of TLR haplotypes with viral load and rapid progression was assessed by multivariate regression models using age and sex as covariates. RESULTS: Two TLR4 SNPs in strong linkage disequilibrium [1063 A/G (D299G) and 1363 C/T (T399I)] were more frequent among individuals with high peak viral load compared with low/moderate peak viral load (odds ratio 6.65, 95% confidence interval 2.19-20.46, P < 0.001; adjusted P = 0.002 for 1063 A/G). In addition, a TLR9 SNP previously associated with slow progression was found less frequently among individuals with high viral setpoint compared with low/moderate setpoint (odds ratio 0.29, 95% confidence interval 0.13-0.65, P = 0.003, adjusted P = 0.04). CONCLUSION: This study suggests a potentially new role for TLR4 polymorphisms in HIV-1 peak viral load and confirms a role for TLR9 polymorphisms in disease progression.

Bridging basic science and clinical research - The EASL Monothematic Conference on Translational Research in Viral Hepatitis.

The EASL Monothematic Conference on Translational Research in Viral Hepatitis brought together a group of leading scientists and clinicians working on both, basic and clinical aspects of viral hepatitis, thereby building bridges from bench to bedside. This report recapitulates the presentations and discussions at the conference held in Lyon, France on November 29-30, 2013. In recent years, great advances have been made in the field of viral hepatitis, particularly in hepatitis C virus (HCV) infection. The identification of IL28B genetic polymorphisms as a major determinant for spontaneous and treatment-induced HCV clearance was a seminal discovery. Currently, hepatologists are at the doorstep of even greater advances, with the advent of a wealth of directly acting antivirals (DAAs) against HCV. Indeed, promising results have accumulated over the last months and few years, showing sustained virological response (SVR) rates of up to 100% with interferon-free DAA combination therapies. Thus, less than 25years after its identification, HCV infection may soon be curable in the vast majority of patients, highlighting the great success of HCV research over the last decades. However, viral hepatitis and its clinical complications such as liver cirrhosis and hepatocellular carcinoma (HCC) remain major global challenges. New therapeutic strategies to tackle hepatitis B virus (HBV) and hepatitis D virus (HDV) infection are needed, as current therapies have undeniable limitations. Nucleoside/nucleotide analogues (NUC) can efficiently control HBV replication and reduce or even reverse liver damage. However, these drugs have to be given for indefinite periods in most patients to maintain virological and biochemical responses. Although sustained responses off treatment can be achieved by treatment with (pegylated) interferon-α, only about 10-30% of patients effectively resolve chronic hepatitis B. It was the goal of this conference to review the progress made over the last years in chronic viral hepatitis research and to identify key questions that need to be addressed in order to close the gap between basic and clinical research and to develop novel preventive and treatment approaches for this most common cause of liver cirrhosis and HCC.

Diagnóstico diferencial del tobillo doloroso

El propósito de ésta comunicación es hacer un pequeño repaso de las diferentes patologías que pueden ocasionar dolor a nivel de la articulación del tobillo para poder establecer un diagnóstico diferencial de las mismas. Si bien las más frecuentes suelen producirse durante la práctica deportiva sobre todo en niños, adolescentes y adultos jóvenes, no hemos de olvidar las diversas patologías articulares que afectan dicha articulación y que en muchas ocasiones son procesos secundarios a enfermedades sistémicas, que se manifiestan con mayor frecuencia en la edad adulta. Se trata pues de una breve descripción de cada patología, la exploración clínica, pruebas complementarias y tratamientos más indicados, para cada una de ellas.

Dynamic models of viral replication and latency.

PURPOSE OF REVIEW: HIV targets primary CD4(+) T cells. The virus depends on the physiological state of its target cells for efficient replication, and, in turn, viral infection perturbs the cellular state significantly. Identifying the virus-host interactions that drive these dynamic changes is important for a better understanding of viral pathogenesis and persistence. The present review focuses on experimental and computational approaches to study the dynamics of viral replication and latency. RECENT FINDINGS: It was recently shown that only a fraction of the inducible latently infected reservoirs are successfully induced upon stimulation in ex-vivo models while additional rounds of stimulation make allowance for reactivation of more latently infected cells. This highlights the potential role of treatment duration and timing as important factors for successful reactivation of latently infected cells. The dynamics of HIV productive infection and latency have been investigated using transcriptome and proteome data. The cellular activation state has shown to be a major determinant of viral reactivation success. Mathematical models of latency have been used to explore the dynamics of the latent viral reservoir decay. SUMMARY: Timing is an important component of biological interactions. Temporal analyses covering aspects of viral life cycle are essential for gathering a comprehensive picture of HIV interaction with the host cell and untangling the complexity of latency. Understanding the dynamic changes tipping the balance between success and failure of HIV particle production might be key to eradicate the viral reservoir.

Competencias interculturales transversales: su diagnóstico en equipos de trabajo de baja qualificación

La competencia intercultural es la competencia profesional que permite un correcto desempeño y una adecuada integración en la empresa culturalmente diversa. El Modelo CIT de Competencias Interculturales Transversales describe el conjunto de conocimientos, comportamientos y actitudes a través de dos macro competencias como Diagnosticar Interculturalmente y Afrontar los requerimientos derivados de la interculturalidad. La presente investigación se plantea dos objetivos: a) Identificar las competencias interculturales de Diagnosticar y b) Identificar las competencias interculturales de Afrontar en 12 grupos de trabajo multiculturales de baja cualificación. El estudio de naturaleza cualitativa ha mostrado que la jerarquía y las normas organizativas son los elementos más diagnosticados como sensibles a la diferencia cultural. En relación a la competencia de Afrontar, se han identificado competencias de resolución de problemas, trabajo en equipo y comunicación intercultural; aplicados indistintamente tanto por los supervisores y responsables de los grupos como por parte de los operarios y personal de base. Las estrategias aplicadas por las personas participantes en el estudio, valoradas como competentes por sus empresas, han permitido la apreciación y estudio de la diferencia cultural y la adaptación del comportamiento a la nueva realidad organizacional.

Competencias interculturales transversales: su diagnóstico en equipos de trabajo de baja qualificación

La competencia intercultural es la competencia profesional que permite un correcto desempeño y una adecuada integración en la empresa culturalmente diversa. El Modelo CIT de Competencias Interculturales Transversales describe el conjunto de conocimientos, comportamientos y actitudes a través de dos macro competencias como Diagnosticar Interculturalmente y Afrontar los requerimientos derivados de la interculturalidad. La presente investigación se plantea dos objetivos: a) Identificar las competencias interculturales de Diagnosticar y b) Identificar las competencias interculturales de Afrontar en 12 grupos de trabajo multiculturales de baja cualificación. El estudio de naturaleza cualitativa ha mostrado que la jerarquía y las normas organizativas son los elementos más diagnosticados como sensibles a la diferencia cultural. En relación a la competencia de Afrontar, se han identificado competencias de resolución de problemas, trabajo en equipo y comunicación intercultural; aplicados indistintamente tanto por los supervisores y responsables de los grupos como por parte de los operarios y personal de base. Las estrategias aplicadas por las personas participantes en el estudio, valoradas como competentes por sus empresas, han permitido la apreciación y estudio de la diferencia cultural y la adaptación del comportamiento a la nueva realidad organizacional.

Diagnóstico rápido e dialogado em estudos de desenvolvimento rural sustentável

O principal objetivo deste trabalho foi verificar se a suposição de predominância da agricultura familiar na microbacia do Taquara Branca, Sumaré, SP, poderia ser sustentada com base em informações concretas. Foi possível a utilização de amostragem probabilística, pois estava disponível um mapa com os limites das 106 propriedades da microbacia, sendo sorteadas 33 delas para a aplicação de questionários do tipo cross-section. A técnica multivariada empregada foi a análise de agrupamentos, para a qual foi utilizado o procedimento PROC CLUSTER do SAS. Nessa análise só foram considerados os dados referentes aos 22 respondentes que exerciam atividade agrícola. Após a análise unidimensional, algumas perguntas foram selecionadas com base na variabilidade entre as respostas e, a partir destas, construíram-se as variáveis necessárias para se proceder à análise multidimensional. A análise de agrupamento permitiu identificar claramente três grupos naturais entre as 22 propriedades. De acordo com as características dos componentes de cada grupo, foi possível classificá-los em: grupo 1, doze propriedades de agricultura familiar; grupo 2, seis propriedades de agricultura não familiar em pequenas áreas; e grupo 3, quatro propriedades de agricultura não familiar em grandes áreas. Embora não seja predominante (apenas 36%), a agricultura familiar é o grupo mais freqüente na microbacia do Taquara Branca.

Viral genotype-specific role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis.

BACKGROUND & AIMS: Steatosis is a prominent feature of hepatitis C, especially in patients infected with genotype 3. The analysis of genetic polymorphisms influencing steatosis in chronic hepatitis C has been limited by the studies' small sample size, and important single nucleotide polymorphisms (SNPs), such as those in the patatin-like phospholipase family 3 protein (PNPLA3), were never evaluated. METHODS: We analyzed the role of SNPs, from 19 systematically selected candidate genes, on steatosis in 626 Caucasian hepatitis C virus (HCV) infected patients. SNPs were extracted from a genome-wide association-generated dataset. Associations of alleles with the presence and/or different severity of steatosis were evaluated by univariate and multivariate logistic regression, accounting for all relevant covariates. RESULTS: The risk of steatosis was increased by carriage of I148M in PNPLA3, but only in patients with HCV genotypes non-3 (odds ratio [OR]=1.9, 95% confidence interval [CI]=1.6-2.3, p<0.001) and similar, albeit weaker associations were found for SNPs in peroxisome proliferator-activated receptor-γ (PPARG) and interleukin-28B (IL28B). Carriage of a SNP in the microsomal triglyceride transfer protein (MTTP) increased the risk of steatosis, but only in patients with HCV genotype 3 (rs1800803, OR=3.4, 95% CI=2.4-4.9, p=0.001). CONCLUSIONS: The rs738409 SNP in PNPLA3 is associated with an increased risk of steatosis in patients infected with HCV genotypes non-3. Host genes affect steatosis depending on the infecting HCV genotype, suggesting their interaction with viral factors.

Xerostomía: diagnóstico y tratamiento

La xerostomía o disminución de la cantidad de saliva en la cavidad bucal suele tener una serie de consecuencias: unas directas, tales como el aumento en la incidencia de caries y enfermedad periodontal, y otras indirectas, como la dificultad en la masticación o la mala adaptación de las prótesis. De ahí la importancia de una correcta lubrificación salival de la cavidad bucal. En el presente trabajo se realiza una revisión de los problemas ocasionados por la xerostomía, así como de su diagnóstico y tratamiento, aspectos éstos un tanto conflictivos, debido a la dificultad de objetivar la sintomatología y de conseguir resultados duraderos.

Mesiodens: concepto, evaluación clínica, diagnóstico y tratamiento

La presencia de dientes supernumerarios en la línea media maxilar, conocidos bajo el término de mesiodens, puede causar diferentes alteraciones tales como malposición de dientes vecinos, erupción anómala o retraso de erupción de los incisivos centrales superiores permanentes, diastema interincisal y formación de quistes, entre otros. En este artículo presentamos una revisión bibliográfica exhaustiva de este tipo de patología y evaluamos los aspectos clínico, etiológico, diagnóstico y terapéutico.

Diagnóstico radiológico de un cuerpo extraño en fosas nasales. A propósito de un caso con retraso de erupción de incisivos laterales.

Se presenta el caso de un paciente con un objeto inanimado en fosa nasal izquierda, que acudió a la Clínica Odontológica de Bellvitge, por la ausencia de los incisivos laterales permanentes en el maxilar superior. Al confirmar la presencia de los incisivos, a partir de una radiografía oclusal, descubrimos, de forma casual, un objeto radiopaco al que acompañaba una específica sintomatología. Después de la intervención del otorrinolaringólogo, dicha sintomatología desapareció. Referimos el manejo de los cuerpos extraños en fosas nasales y aprovechamos la ocasión para revisar las pautas generales de orientación diagnóstico-terapéuticas frente a esta patología.

Deletion of the viral anti-apoptotic gene F1L in the HIV/AIDS vaccine candidate MVA-C enhances immune responses against HIV-1 antigens.

Vaccinia virus (VACV) encodes an anti-apoptotic Bcl-2-like protein F1 that acts as an inhibitor of caspase-9 and of the Bak/Bax checkpoint but the role of this gene in immune responses is not known. Because dendritic cells that have phagocytosed apoptotic infected cells cross-present viral antigens to cytotoxic T cells inducing an antigen-specific immunity, we hypothesized that deletion of the viral anti-apoptotic F1L gene might have a profound effect on the capacity of poxvirus vectors to activate specific immune responses to virus-expressed recombinant antigens. This has been tested in a mouse model with an F1L deletion mutant of the HIV/AIDS vaccine candidate MVA-C that expresses Env and Gag-Pol-Nef antigens (MVA-C-ΔF1L). The viral gene F1L is not required for virus replication in cultured cells and its deletion in MVA-C induces extensive apoptosis and expression of immunomodulatory genes in infected cells. Analysis of the immune responses induced in BALB/c mice after DNA prime/MVA boost revealed that, in comparison with parental MVA-C, the mutant MVA-C-ΔF1L improves the magnitude of the HIV-1-specific CD8 T cell adaptive immune responses and impacts on the CD8 T cell memory phase by enhancing the magnitude of the response, reducing the contraction phase and changing the memory differentiation pattern. These findings reveal the immunomodulatory role of F1L and that the loss of this gene is a valid strategy for the optimization of MVA as vaccine vector.