Prognostic importance of DNA from human papillomavirus in patients with oral squamous cell carcinoma

Background: Survival of patients with oral squamous cell carcinoma (OSCC) is generally low, with the likelihood of locoregional recurrence or disease progression (LR/DP). Knowledge of prognostic factors for survival is key to achieving an understanding and increased survival. The present study aimed to identify prognostic factors for patients with OSCC, especially the presence of DNA from human papillomavirus (HPV). Material and Methods: Retrospective cohort study including 119 patients with OSCC treated at the National Cancer Institute in Mexico City (2009-2013). Clinical information was obtained from patient records including LR/DP. Formalin-fixed, paraffin-embedded tissues were obtained and used for detecting DNA from different types of HPV. Potential prognostic factors for Overall Survival (OS) were analyzed using the Cox proportional hazards model. Results: After model adjustment, factors associated with longer OS were a pre-treatment platelet count above 400,000/mm3 (HR=0.09, p=0.026) and response to primary treatment (HR=0.26, p=0.001). HPV DNA was present in 23 (19.3%) of the patients and importantly, type 16 found in 19 of them. Although survival of HPV-positive patients was longer, difference was not significant. However, among patients with LR/DP, HPV positivity was significantly associated with increased survival (HR=0.23, p=0.034). Importantly, survival was significantly different for HPV-positive patients with LR/DP > 6 months (HR=0.20, p=0.002), had higher absolute lymphocyte count at start of treatment (HR=0.50, p=0.028) or had local rescue treatment (HR=0.24, p=0.019). Conclusions: Although HPV positivity was not associated with a longer OS of OSCC patients, a better prognosis was significantly associated with HPV positivity and recurring or progressing disease, particularly with HPV type 16.(AU)

PD-1 and PD-L1 gene expressions and their association with Epstein-Barr virus infection in chronic lymphocytic leukemia

PurposeThe PD-1 (programmed cell death-1) receptor is expressed on the surface of activated T cells. Its ligand, programmed cell death ligand-1 (PD-L1), is expressed on the surface of dendritic cells or macrophages. The PD-1/PD-L1 interaction ensures prevention of autoimmunity by activating the immune system only when needed. In cancers, PD-L1 expressed on the tumour cells binds to PD-1 receptors on the activated T cells, leading to inhibition of the cytotoxic T cells and immunosuppression. PD-1/PD-L1 pathway is upregulated in EBV infection that is known to worsen the CLL prognosis. Therefore, we aimed to study the association between PD-1 and PD-L1 expressions, EBV status and the CLL prognosis.Methods and patientsThe study was conducted on 80 newly diagnosed CLL patients and 80 controls. We analyzed PD-1 and PD-L1 expressions and EBV-DNA load by real-time PCR. The cytogenetic abnormalities and expression of ZAP70 and CD38 were detected by FISH and Flow cytometry, respectively.ResultsPD-1/PD-L1 expressions were significantly upregulated in CLL patients compared to controls. In addition, their mRNA levels were significantly higher in EBV( +) versus EBV( −) patients. High expression of PD-1/PD-L1 was associated with poor prognostic markers (RAI stages of CLL, del 17p13, ZAP70, and CD38 expression), failure of complete remission, shorter progression-free survival, and overall survival.ConclusionHigh expression of PD-1 and PD-L1, together with high EBD-DNA load were linked to worse prognosis in CLL. In addition, PD-1 and PD-L1 might represent suitable therapeutic targets for patients suffering from aggressive CLL. (AU)

The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer

Purpose To investigate the possibility of using the methylation level of PAX1/ZNF582 gene as molecular marker to differentiate the progression of cervical cancer. Methods From January 2016 to March 2018, 150 patients, who were admitted to Cervical Disease Diagnosis and Treatment Center of Xuzhu Maternity and Child Care Hospital, were enrolled in this study. Patients were classified into chronic cervicitis (for 19 cases), low-grade squamous intraepithelial lesion (LSIL) (18 cases), high-grade squamous intraepithelial lesion (HSIL) (37 cases) and squamous cell carcinoma (SCC) (31 cases). All patients underwent several tests including Thin-prep cytology test (TCT), HPV DNA detection and detection of methylation level of PAX1/ZNF582 genes. Results For diagnosis of HSIL, the area under curve (AUC) was 0.878 (95% CI 0.806 ~ 0.950); the threshold for PAX1 was 12.285, the sensitivity and specificity were 91.9% and 72.8%, respectively. The AUC of ZNF582 gene detection was 0.900 (95% CI 0.842 ~ 0.959), the threshold was 11.56, while the sensitivity and specificity were 97.3% and 76.7%, respectively. Among various tests we conducted, PAX gene detection methods showed the highest specificity (97.30%). PAX1/ZNF582 gene detection method demonstrated the highest accuracy. Conclusions For patients with high-grade cervical lesion and cervical cancer, the methylation level of PAX1/ZNF582 gene could be applied as a noteworthy biomarker for diagnosis and for cervical cancer classification (AU)

Efficacy of entecavir in treating hepatitis B virus-associated membranous nephropathy

OBJECTIVE: hepatitis B virus-associated membranous nephropathy (HBV-MN) is the most common pathological type of hepatitis B virus-associated glomerulonephritis. This study evaluated the efficacy of entecavir antiviral therapy for HBV-MN patients due to the intolerable side effects of interferon-alpha and high incidence rate of drug-resistance in lamivudine therapy. METHOD: thirty-two patients with HBV-MN were identified by biopsy and treated with entecavir for 52 weeks. These patients were followed up to evaluate outcomes of entecavir-treatment. Descriptive statistics were used to summarize patient demographics and treatment outcomes. RESULTS: entecavir treatment reduced 24-h urinary protein excretion. The total probability of partial proteinuria and complete remission at 24 and 52 weeks was 53.1 and 78.1 %, respectively. A decrease of circulating HBV-DNA was observed in all patients with active HBV replication. The significant decrease of 24-h urinary protein began at 12 weeks, as early as the decrease of serum HBV-DNA level. The serum HBV DNA titers at baseline and after 52 weeks of treatment were 4.3 ± 2.8 log10 and 2.3 ± 1.7 log10, respectively. Meanwhile, eGFR increased from 100.3 ± 20.5 ml/min/1.73 m2 at baseline to 107.7 ± 15.9 ml/min/1.73 m2 after 52 weeks of treatment. The serum alanine aminotransferase level (ALT) gradually decreased to normal during entecavir antiviral treatment. CONCLUSIONS: entecavir treatment in HBV-MN patients was carefully described. Complete remission and HBV replication suppression were induced by entecavir treatment in HBV-MN patients. Patients with high serum creatinine (Scr), ALT and low eGFR levels benefit more from entecavir treatment. Entecavir therapy is well tolerated by patients and no adverse reactions were observed

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Quantitative HBcrAg and HBcAb versus HBsAg and HBV DNA in predicting liver fibrosis levels of chronic hepatitis B patients / HBcrAg y HBcAb cuantitativos versus HBsAg y ADN del VHB en la predicción de los niveles de fibrosis hepática de los pacientes con hepatitis B crónica

OBJECTIVE: To evaluate the performance of the quantitative markers of hepatitis B core-related antigen (HBcrAg) and anti-hepatitis B core antigen antibodies HbcAb versus hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA) in predicting liver fibrosis levels in chronic hepatitis B patients. METHODS: Two hundred and fifty hepatitis B e antigen (HBeAg)-positive and 245 HBeAg-negative patients were enrolled. With reference to the Scheuer standard, stage 2 or higher and stage 4 liver disease were defined as significant fibrosis and cirrhosis, respectively. A receiver operating characteristic (ROC) curve was used to evaluate the performance of the HBV markers investigated. RESULTS: The areas under the ROC curves (AUCs) of HBcrAg in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.577 and 0.700) were both close to those of HBsAg (0.617 and 0.762) (both P> 0.05). In HBeAg-negative patients (0.797 and 0.837), they were both significantly greater than those of HBV DNA (0.723 and 0.738) (P=0.0090 and P=0.0079). The AUCs of HBcAb in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.640 and 0.665) were both close to those of HBsAg. In HBeAg-negative patients (0.570 and 0.621), they were both significantly less than those of HBcrAg (P <0.0001 and P=0.0001). Specificity in predicting significant fibrosis and sensitivity in predicting cirrhosis in HBeAg-positive patients, using a single cut-off of HBsAg ≤5,000 IU/ml, were 76.5% and 72.7%, respectively. In HBeAg-negative patients, using a single cut-off of HBcrAg>80kU/ml, they were 85.9% and 81.3%, respectively. CONCLUSIONS: HBsAg has good performance in predicting liver fibrosis levels in HBeAg-positive and HBeAg-negative patients, and HBcrAg has very good performance in predicting liver fibrosis levels in HBeAg-negative patients

OBJETIVO: Evaluar el rendimiento de los marcadores cuantitativos del antígeno central de la hepatitis B (HBcrAg) y los anticuerpos contra el antígeno central de la hepatitis B (HBcAb) frente al antígeno de superficie de la hepatitis B (HBsAg) y el ADN del virus de la hepatitis B (ADN del VHB) en la predicción de los niveles de fibrosis hepática de los pacientes con hepatitis B crónica. MÉTODOS: Se inscribieron 250 pacientes con HBsAg positivo y 245 pacientes con HBeAg negativo. Con referencia al estándar de Scheuer, la etapa patológica hepática 2 o superior y la etapa 4 se definieron como fibrosis y cirrosis significativas, respectivamente. Se utilizó la curva característica de funcionamiento del receptor (ROC) para evaluar el rendimiento de los marcadores del VHB investigados. RESULTADOS: Las áreas bajo la curva ROC (AUC) del HBcrAg en la predicción de la fibrosis y cirrosis significativa de los pacientes positivos para el HBeAg (0,577 y 0,700) fueron ambas cercanas a las del HBsAg (0,617 y 0,762) (ambas p > 0,05); de los pacientes negativos para el HBeAg (0,797 y 0,837) fueron ambas significativamente mayores que las del ADN del VHB (0,723 y 0,738) (p = 0,0090 y p = 0,0079); las AUC del HBcAb en la predicción de la fibrosis y cirrosis significativa de los pacientes positivos para el HBeAg (0,640 y 0,665) fueron ambas cercanas a las del HBsAg; de los pacientes negativos para el HBeAg (0,570 y 0,621) fueron ambas significativamente menores que las del HBcrAg (p < 0,0001 y p = 0,0001). La especificidad en la predicción de la fibrosis significativa y la sensibilidad en la predicción de la cirrosis de los pacientes positivos para el HBeAg, utilizando un solo corte de HBsAg ≤ 5.000 UI/mL fueron 76,5 y 72,7%, respectivamente; de los pacientes negativos para el HBeAg utilizando un solo corte de HBcrAg > 80 kU/mL fueron 85,9 y 81,3%, respectivamente. CONCLUSIONES: El HBsAg tiene un buen rendimiento en la predicción de los niveles de fibrosis hepática de los pacientes HBeAg positivos y negativos, mientras que HBcrAg tiene un muy buen rendimiento en la predicción de los niveles de fibrosis de los pacientes HBaAg negativos

Oral Human Papillomavirus: a multisite infection

BACKGROUND: The Human Papillomavirus (HPV) has different strategies for persist in the cells. This characteristic has led us to consider the presence of the virus in tissues of the oral cavity that had no clinical signs of infection. The aim of this study was to detect the presence of DNA-HPV at multiple sites of the oral cavity. MATERIAL AND METHODS: A case-control study was designed: Oral Squamous Carcinoma Group (OSCG), healthy n=72 and Control Group (CG), n=72, healthy volunteers paired by sex and age with OSCG. Four samples were taken from OSCG: saliva, biopsy, brush scraping of lesion and contralateral healthy side. In CG a saliva sample and a scratch of the posterior border of tongue were collected. HPV was detected by PCR using Bioneer Accuprep genomic DNA Extraction kit, and consensus primers MY09 and MY11. Chi square test was applied. RESULTS: 432 samples were obtained from 144 individuals. DNA-HPV was detected in 30 (42%) of OSCG subjects and 3 (4%) of CG. Two or more positive samples were obtained in 67% of the OSCG, 67% in saliva and 60% in biopsy; in CG 100% of the individuals were positive in the two samples. CONCLUSIONS: HPV is frequently present in oral cavity as a multifocal infection, even without the presence of clinical lesions

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Presence of HPV DNA in extracellular vesicles from HeLa cells and cervical samples / Presencia de ADN de VPH en vesículas extracelulares de células HeLa y muestras cervicales

INTRODUCTION: The main cause of cervical cancer is an infection of keratinocytes in the basal layer of the stratified epithelium of the cervix by human papillomavirus (HPV). Other than in cervical samples, HPV DNA has been found in serum and other fluids but its origin is unclear. Extracellular vesicles (EV) could be a conveyance of viral DNA given their emerging role in cellular communication. The content of EV derived from cervical cells has not been properly explored and it is not known whether or not they contain HPV DNA. METHODS: We evaluated the DNA content of exosomes purified from cultures of HeLa cells by Next Generation Sequencing (NGS) and confirmed its presence by PCR. The presence of HPV DNA was also evaluated by PCR and NGS in EV from HPV-positive cervical samples without apparent lesion or with LSIL. RESULTS: We detected the integrated form of viral-DNA in exosomes from HeLa cells by NGS and confirmed its presence by PCR. The search for HPV sequences in EV obtained from cervical exudate samples without apparent lesion or with LSIL, where we expected to find the viral genome as an episome, indicated that HPV DNA, including the E6 and E7 oncogenes, is present in these EV. CONCLUSIÓN: HPV DNA, including the viral oncogenes E6/E7, is found in exosomes regardless of the integration status of the virus in the infected cell

INTRODUCCIÓN: La principal causa del cáncer de cérvix es la infección de los queratinocitos de la capa basal del epitelio estratificado del cuello uterino por el virus del papiloma humano (VPH). El ADN del VPH se ha encontrado en muestras cervicales, pero también en suero y otros fluidos, aunque su origen en estos últimos no está claro. Las vesículas extracelulares (VE) podrían ser el medio de transporte del ADN viral considerando su papel emergente en la comunicación celular. El contenido de las VE derivadas de células cervicales ha sido poco explorado y la presencia en ellas de ADN de VPH sigue siendo desconocida. MÉTODOS: Evaluamos el ADN de exosomas purificados a partir de cultivos de células HeLa mediante secuenciación de nueva generación (NGS) y confirmamos su presencia a través de PCR. La presencia de ADN de VPH también se evaluó mediante PCR y NGS en VE de muestras cervicales positivas a VPH, sin lesión aparente o con LSIL. RESULTADOS: Detectamos la forma integrada del ADN viral en exosomas de células HeLa mediante NGS, y confirmamos su presencia a través de PCR. La búsqueda de secuencias de VPH en VE obtenidas a partir de muestras de exudado cervical sin lesión aparente o con LSIL, donde esperamos encontrar el genoma viral en forma episomal, indicó que el DNA de VPH incluyendo los oncogenes E6 y E7, está presente en estas VE. CONCLUSIÓN: El ADN del VPH incluyendo el correspondiente con los oncogenes virales E6/E7 se encuentra en exosomas independientemente del estado de integración del virus en la célula infectada

¿Cuándo puede ser útil buscar VHB oculto en pacientes en hemodiálisis? / When can it be useful to look for occult HBV in hemodialysis patients?

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Prevalence of human papillomavirus in the saliva of sexually active women with cervical intraepithelial neoplasias

BACKGROUND: The main objective of this study was to estimate the prevalence of human papillomavirus-DNA (HPV-DNA) in the saliva of sexually active women with HPV-related cervical intraepithelial neoplasias (CIN) and compare the findings with a healthy control group. The secondary objectives were: 1) to determine the concordance between genital and oral HPV types in sexually active women with HPV-related CIN; 2) to analyze whether sexual habits influence the presence of HPV-related CIN; 3) to determine whether sexual habits influence the presence of oral HPV. MATERIAL AND METHODS: Saliva samples were collected from 100 sexually active women, 50 with HPV-related CIN and 50 healthy subjects presenting normal cytology. PCR assay was used to detect HPV-DNA. RESULTS: The prevalence of oral HPV infection in saliva samples was 14% in women with HPV-related CIN, while in the healthy group it was 12%, without statistically significant difference (p = 0.766). As for the concordance between genital and oral HPV types in women with HPV-related CIN, concordance was only observed for HPV-16, whereby among 22 women with genital HPV-16, only one (4.54%) also presented oral HPV-16. Regarding the possible influence of sexual habits on the presence of cervical pathology and presence of oral HPV, it was found that marital status, age at first intercourse, number of lifetime sexual partners, and condom use are related with the presence of cervical pathology (p < 0.001; p = 0.017; p = 0.002; and p < 0.001, respectively); condom use was also found to be related to the presence of oral HPV (p < 0.001). CONCLUSIONS: The prevalence of HPV-DNA in the saliva of sexually active women with HPV-related CIN is similar to healthy women. The concordance between genital and oral HPV types is low. Both the presence of cervical pathology and the presence of oral HPV are related to sexual habits. Wider sample size is required to confirm this results

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Infecciones genitales por virus herpes tipo 1 y virus herpes tipo 2 en Valencia, España: estudio observacional retrospectivo / Genital Infection With Herpes Simplex Virus Type 1 and Type 2 in Valencia, Spain: A Retrospective Observational Study

INTRODUCCIÓN Y OBJETIVO: Se ha constatado un cambio en la epidemiología del herpes genital en los últimos años con un aumento de la incidencia del virus herpes (VHS) tipo 1. El objetivo de nuestro estudio es analizar las características clínico-epidemiológicas de los pacientes diagnosticados de un herpes genital. MATERIAL Y MÉTODOS: Se diseñó un estudio observacional retrospectivo donde se incluyeron todos los pacientes diagnosticados de herpes genital entre enero de 2016 y enero de 2019 en una Unidad de Infecciones de Transmisión Sexual (ITS) en Valencia, España. RESULTADOS: Se diagnosticaron 895 ITS, de las cuales 126 fueron un herpes genital (14%), 68 (54%) en mujeres y 58 (46%) en hombres. En 110 de ellos (87,3%) se confirmó el herpes genital por la detección de ADN viral por técnicas moleculares. Se diagnosticaron 52 casos de VHS tipo 1 (47,3%) y 58 casos de VHS tipo 2 (52,7%). En el 69,5% de los hombres se detectó el VHS tipo 2, mientras que en el 59,3% de las mujeres se detectó el VHS tipo 1. La edad media de las mujeres diagnosticadas de VHS tipo 1 fue de 26 años, mientras que la de las mujeres diagnosticadas de VHS tipo 2 fue de 34 años (p = 0,015). Las recurrencias de las lesiones en los pacientes con VHS tipo 1 y VHS tipo 2 fue del 13% y del 40%, respectivamente. CONCLUSIÓN: Destacamos un aumento de la prevalencia del VHS tipo 1 en nuestro medio como agente causante de herpes genital, especialmente en mujeres jóvenes. Esto tiene un valor pronóstico importante dado el menor riesgo de recurrencias que tiene

INTRODUCTION AND OBJECTIVE: The epidemiology of genital herpes has changed in recent years with an increase in the incidence of herpes simplex virus type 1 (HSV-1) infection. The aim of this study was to analyze the clinical and epidemiological characteristics of patients diagnosed with genital herpes. MATERIAL AND METHODS: A retrospective observational study was designed. All patients diagnosed with genital herpes between January 2016 and January 2019 in a Sexually Transmitted Infections Unit (ITS) in Valencia, Spain, were included. RESULTS: We identified 895 STI diagnoses. Of these, 126 (14%) were genital herpes; 68 (54%) of these cases were in women and 58 (46%) in men. Diagnosis was confirmed by molecular detection of HSV DNA in 110 cases (87.3%). Of these, 52 were cases of HSV-1 infection (47.3%) and 58 were HSV-2 infection (52.7%). HSV-2 was more common in men (69.5%), while HSV-1 was more common in women (59.3%). In the subgroup of women, mean age at diagnosis was 26 years for HSV-1 and 34 years for HSV-2 (P = .015). Recurrent genital herpes rates were 13% for HSV-1 and 40% for HSV-2. CONCLUSIONS: There has been an increase in the number of cases of genital herpes caused by HSV-1 in our setting, with young women in particular being affected. This has important prognostic implications because genital herpes caused by HSV-1 is less likely to recur

Teorías del origen del SARS-COV-2, claves e incógnitas de una enfermedad emergente / Origin of SARS-CoV-2 theories, keys and unknowns of an emerged disease

En el contexto de la actual pandemia puede resultar de especial interés el esclarecimiento de importantes aspectos relativos al origen del nuevo virus SARS-CoV-2 e identificar los mecanismos que han permitido a este agente zoonótico atravesar la barrera especie y colonizar al nuevo hospedador humano de un modo tan eficaz, objetivos ambos de este trabajo. Dudas cuya respuesta puede ser reveladora a la hora de entender ciertos aspectos patológicos y epidemiológicos del nuevo agente, facilitar la toma de decisiones e identificar posibles rebrotes.Las investigaciones llevadas a cabo hasta la fecha permiten establecer al murciélago como el huésped origen, valorar la posible presencia de un hospedador intermediario, todavía desconocido, y fijar la teoría de la selección natural como la más probable. Aun así, es pronto para determinar si las mutaciones que incrementaron la virulencia del virus o permitieron la inclusión de cadenas proteicas implicadas en el reconocimiento del receptor humano se produjeron antes o después de haber atravesado la barrera especie. Son necesarios estudios adicionales que ayuden a resolver éstas y otras incógnitas e insistir en la necesidad de aplicar a nivel mundial estrategias One Health para facilitar una gestión integrada de la salud humana, en coordinación con la sanidad animal, y prevenir así posibles eventos emergentes futuros

In the midst of the SARS-CoV-2 public-health pandemic emergency, it is important to understand its zoonotic origin and how an animal virus finally infects humans. Identifying the circumstances in which a virus jumps species boundaries to infect humans so productively is objective of this work and will help us to determine the epidemiology and pathogenisis of this agent. Nowadays, it is known that bats serve as reservoir hosts for virus progenitor, but determine the possibility of a potential intermediate host of SARS-CoV-2 is still a challenge. Scientific investigations stablish the natural selection theory as the most probable (natural selection in an animal host before zoonotic transfer or acquired mutations in humans following crossing species barrier). It is necessary to find out how SARS-CoV-2 emerged, its rapidly spreads within a community and the optimal context in which this virus binds to human receptor. One Health is a multisectoral, collaborative and transdisciplinary approach which allows a cooperative working between animal and human health that will help us to introduce some possible control measures that might reduce the spread of the virus; improving sanitary management, identifying new outbreaks and preventing future zoonotic and pandemic events

Prevalencia y características clínicas y anatomopatológicas de los pacientes con diagnóstico de linfoma difuso de células B grandes y positivo al virus Epstein-Barr en un hospital de alta complejidad en Cali (Colombia) / Prevalence and clinico-pathological characteristics in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma in a high complexity hospital in Cali, Columbia

INTRODUCCIÓN: El linfoma difuso de células B grandes (LDCBG) constituye el 35% de los linfomas no Hodgkin y su incidencia aumenta con la edad. El virus Epstein-Barr (VEB) está ampliamente distribuido a nivel mundial. La asociación entre el LDCBG y VEB está cerca del 10% en pacientes inmunocompetentes; este tipo de linfoma tiene alta prevalencia en países de Latinoamérica. OBJETIVO: Conocer la frecuencia del LDCBG asociado al VEB y describir sus características demográficas, clínicas, inmunofenotípicas y desenlace de los pacientes en un centro de alta complejidad en Cali (Colombia). MATERIALES Y MÉTODOS: Estudio observacional descriptivo de una cohorte histórica. Se revisaron los registros clínicos y de anatomía patológica de pacientes con diagnóstico de LDCBG y se realizó la hibridación in situ para la detección del VEB (EBER). Se realizó un análisis descriptivo. RESULTADOS: Entre 2011 y 2017 se revisó la historia clínica de 55 pacientes con diagnóstico de LDCBG. El 16% fueron VEB positivos, los cuales fueron en su mayoría del subtipo no centro germinal (89%), con presentación nodal (56%); hubo mayor prevalencia en hombres (68%), menor edad de presentación (mediana 48 años) y muerte en el 56% de los casos. CONCLUSIONES: Los pacientes con LDCBG y VEB positivo presentan con mayor frecuencia el subtipo no centro germinal, el cual, según nuestros hallazgos, se presenta en pacientes más jóvenes y se asocia a peor pronóstico. El EBER no es un examen que se hace de rutina, por lo cual se recomienda realizar pruebas para la detección del VEB en pacientes con diagnóstico de LDCBG

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) accounts for 35% of non-Hodgkin lymphoma and its incidence increases with age. Epstein Barr virus (EBV) is widely spread worldwide. There is a 10% association between EBV and DLBCL in immunocompetent patients; this type of malignancy has a high prevalence in Latin American countries. OBJECTIVE: Estimate the percentage of association between DLBCL and EBV patients, describing demographics, clinical and immunological features, as well as phenotype and clinical outcome in a high complexity healthcare institution in Colombia. MATERIALS AND METHODS: This is an analytic observational study from an historical cohort. Clinical and pathological records were revised among DLBCL patients and subsequent in-situ hybridization was performed for EBV detection. A descriptive analysis of the data was carried out. RESULTS: From 2011 to 2017, 55 DLBCL patients were identified.16% were positive on ISH for EBV, most of which belonged to the non-germinal center B-cell immunophenotype (89%), with a nodal presentation (56%). DLBCL EBV positive was more prevalent among males (67%) and in younger patients (median of 48 years) where the mortality rate was 56%. CONCLUSIONS: DLBCL patients positive for EBV are more prone to belong to the non-germinal center B-cell immunophenotype which, according to our findings, is associated with a younger age and worse prognosis. Presently, EBER in-situ hybridization is not a part of routine tests, but we recommend its inclusion in the pathology package for DLBCL patients, as it can influence clinical outcomes

Pitiriasis liquenoide y varioliforme aguda asociada al virus herpes humano tipo 7 / Pitiryasis lichenoides et varioliformis acuta associated with human herpesvirus 7

Tanto la pitiriasis liquenoide y varioliforme aguda como la pitiriasis liquenoide crónica representan 2 extremos de un espectro de enfermedad de etiología desconocida. En este trabajo se describen 2 casos de pitiriasis liquenoide y varioliforme aguda, en los que se detectó ADN de virus herpes humano tipo 7 en muestras de piel mediante la metodología de reacción en cadena de la polimerasa, una asociación no descrita previamente. Este manuscrito puede apoyar la participación de la infección viral en la etiopatogenia de esta enfermedad

Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica represent 2 ends of a disease spectrum of unknown etiology. Herein we describe 2 cases of pityriasis lichenoides et varioliformis acuta, in which human herpesvirus 7 DNA was detected in skin samples by polymerase chain reaction methodology, an association not previously described. This report may support the involvement of viral infection in the etiopathogeny of this disease

Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo / Characteristics and course of chronic hepatitis B e antigen-negative infection

OBJETIVO: Describir las características epidemiológicas, analíticas, histológicas y evolutivas de pacientes con infección crónica por VHB AgHBe-negativo. MATERIAL Y MÉTODOS: Estudio observacional de cohorte retrospectivo de pacientes diagnosticados de infección crónica VHB AgHBe-negativo (2005-2012) sin otras hepatopatías. RESULTADOS: Se incluyeron 138 pacientes con edad media de 40,5 ± 12,2 años, de los cuales el 54% eran mujeres. El 38% eran extranjeros, con incremento de estos en los últimos años (p < 0,001). Las transaminasas en el momento del diagnóstico eran normales en casi el 75% y el ADN-VHB < 2.000 UI/ml en el 56%. En los portadores inactivos existe una disminución progresiva de los niveles de ADN-VHB en el periodo de estudio. En el 47% se evaluó la fibrosis hepática por Fibroscan ® o biopsia hepática: el 55,4% resultó normal y el 6,1% reportó cirrosis. El 77,77% eran portadores inactivos. Precisaron tratamiento el 15,5% (20% por cirrosis y 80% por HBC AgHBe-negativo). Aclararon el AgHBs 5 pacientes (tasa anual 0,94%), presentando todos al diagnóstico ADN-VHB < 2.000 UI/ml. Cinco pacientes desarrollaron alguna complicación (3,6%), 4 de ellos carcinoma hepatocelular (CHC) (solo 2 presentaban cirrosis). Hubo un fallecimiento relacionado con el VHB (0,72%). CONCLUSIÓN: Entre los enfermos con infección crónica por VHB AgHBe-negativo predominan los portadores inactivos. Se produce un progresivo descenso de ADN-VHB en los primeros años tras el diagnóstico. Desarrollan poca morbimortalidad, especialmente si existe GPT normal y ADN-VHB bajo al diagnóstico. Un número no despreciable de pacientes precisa tratamiento. El CHC es la complicación más frecuente, incluso en pacientes sin cirrosis

OBJECTIVE: To describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen. MATERIAL AND METHODS: Observational, retrospective cohort study of HBV carriers with negative HBe antigen (2005-2012), with no other causes of liver disease. RESULTS: One hundred and thirty-eight patients were included, with mean age 40.5 ± 12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (P < .001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was < 2,000 IU/ml in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan ® or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA <2,000IU/ml at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%). CONCLUSION: Among HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis

Monitoring of airborne biological particles in outdoor atmosphere. Part 2: Metagenomics applied to urban environments

The air we breathe contains microscopic biological particles such as viruses, bacteria, fungi and pollen, some of them with relevant clinic importance. These organisms and/or their propagules have been traditionally studied by different disciplines and diverse methodologies like culture and microscopy. These techniques require time, expertise and also have some important biases. As a consequence, our knowledge on the total diversity and the relationships between the different biological entities present in the air is far from being complete. Currently, metagenomics and next-generation sequencing (NGS) may resolve this shortage of information and have been recently applied to metropolitan areas. Although the procedures and methods are not totally standardized yet, the first studies from urban air samples confirm the previous results obtained by culture and microscopy regarding abundance and variation of these biological particles. However, DNA-sequence analyses call into question some preceding ideas and also provide new interesting insights into diversity and their spatial distribution inside the cities. Here, we review the procedures, results and perspectives of the recent works that apply NGS to study the main biological particles present in the air of urban environments (AU)

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Mecanismo de acción, farmacología e interacciones de dolutegravir / Mechanisms of action, pharmacology and interactions of dolutegravir

Dolutegravir es un inhibidor de la integrasa de segunda generación, con un potencial y una semivida de unión en la integrasa muy superiores a los de raltegravir o elvitegravir, que le confieren unas características únicas en cuanto a barrera genética y actividad frente a virus con alguna mutación de resistencia en la integrasa. Las propiedades farmacocinéticas de dolutegravir permiten administrarlo 1 vez al día (50 mg), con o sin alimentos, manteniendo concentraciones muy superiores a las eficaces para virus sensibles. En presencia de mutaciones en la integrasa se recomienda administrar 50 mg/12 h. La difusión de dolutegravir al líquido cefalorraquídeo es buena y también se alcanzan concentraciones eficaces en tracto genital femenino y masculino. Dolutegravir es metabolizado por UGT1A1 y en menor grado por CYP3A4, sin que sea inductor ni inhibidor de los sistemas metabólicos habituales. Su potencial de interacciones es muy escaso y puede administrarse a las dosis habituales con la mayoría de fármacos. No es preciso ajustar la dosis de dolutegravir ni en pacientes con insuficiencia renal ni con insuficiencia hepática leve o moderada. Los únicos fármacos con los que se recomienda aumentar la dosis de dolutegravir (50 mg/12 h) son efavirenz, nevirapina, fosamprenavir/r, tipranavir/r, rifampicina, carbamazepina, fenitoína y fenobarbital. No se recomienda coadministrar dolutegravir con etravirina sin un inhibidor de la proteasa, ni con hipérico. Dolutegravir debe administrarse 2 h antes o 6 h después de antiácidos o productos con cationes polivalentes. Dolutegravir puede disminuir la secreción tubular renal de sustancias que se excretan vía OCT2, con un ligero incremento inicial de creatinina, sin que ello suponga toxicidad renal. También podría aumentar las concentraciones de metformina recomendándose vigilancia por si se requiere ajuste de dosis. En definitiva, dolutegravir tiene un excelente perfil farmacocinético y de interacciones con otros fármacos

Dolutegravir is a second-generation integrase strand transfer inhibitor (INSTI), whose potential and binding half-life in the integrase are far superior to those of raltegravir and elvitegravir, conferring it with unique characteristics in terms of its genetic barrier to resistance and activity against viruses with one or more mutations in the integrase. The pharmacokinetic properties of dolutegravir allow once-daily dosing (50 mg), with or without food, maintaining concentrations far above those effective against wild-type viruses. If integrase resistance mutations are present, the recommended dosing regimen is 50 mg/12 h. The distribution of dolutegravir in cerebrospinal fluid is good and effective concentrations are also reached in the male and female genital tracts. Dolutegravir is metabolized by UGT1A1 and, to a lesser extent, by CYP3A4, without being an inducer or inhibitor of the usual metabolic systems. It has a very low potential for drug interactions and can be administered in routine doses with most drugs. Dose adjustment is not required, even in patients with renal insufficiency or mild or moderate liver failure. Increasing the dose of dolutegravir (50 mg/12 h) is only recommended when administered with efavirenz, nevirapine, fosamprenavir/r, tipranavir/r, rifampicin, carbamazepine, phenytoin and phenobarbital. Coadministration of dolutegravir with etravirine is not recommended without a protease inhibitor or with Hypericum perforatum. Dolutegravir should be administered 2 h before or 6 h after antacids or products with polyvalent cations. Dolutegravir can reduce renal tubule secretion of substances excreted via OCT2, with a slight initial increase in creatinine, with no risk of renal toxicity. The drug can also increase metformin concentrations and consequently monitoring is recommended in case dose adjustment is required. In summary, dolutegravir has excellent pharmacokinetic and drug interaction profiles