Prevalencia, factores de riesgo y características patogénicas diferenciales de EPOC y enfisema en pacientes con infección VIH

Antecedentes: Las anomalías pulmonares están a menudo presentes en pacientes infectados con el virus de la inmunodeficiencia humana (VIH). Objetivos: Determinar la prevalencia, las características patogénicas y los factores de riesgo de anormalidades pulmonares en pacientes VIH +. Métodos: Se incluyeron en el estudio 275 pacientes VIH +, con una media (± desviación estandar) de edad de 48,5 (± 6,6) años y en su mayoría (95,6%) tratados con terapia antirretroviral de gran actividad (TARGA), Se determinó: (1) pruebas funcionales respiratorias completas, (2) enfisema pulmonar medido por TAC, y, (3) estado inmune e inflamatorio, en muestras de esputo y de sangre periférica. Resultados: La limitación del flujo aéreo (LFA) estaba presente en el 17,2%, la baja capacidad de difusión pulmonar en el 52,2%, y el enfisema en el 10,5% y el 37,7% de los pacientes, dependiendo del método utilizado para la cuantificación. La mayoría de estas anomalías no habían sido diagnosticadas o tratadas previamente Para la LFA, los principales factores de riesgo fueron la exposición al tabaco y la historia previa de tuberculosis, mientras que para el enfisema pulmonar y la baja capacidad de difusión, además de la exposición al tabaco, se observaron factores relacionados con la infección porel VIH. Conclusiones: A pesar de la TARGA, son frecuentes las anormalidades estructurales y funcionales pulmonares en los pacientes VIH +, probablemente debido a factores relacionados con el medio ambiente y el VIH. La mayoría de ellos pasan desapercibidos y no son tratados. Dada la relativa edad joven de estos pacientes, estos resultados anticipan un problema de salud importante en los próximos años cuando, debido a la eficacia del TARGA, envejezcan

Increased rate of FEV1 decline in HIV patients despite effective treatment with HAART

Introduction: Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immune-viral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. Methods: We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. Results: We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. Discussion: Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population

Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

Background and Aims This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. Methods The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. Results As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant. Conclusions In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism

Acute gastric volvulus presenting as a pseudo cardiac tamponade

[eng] Gastric volvulus is defined as rotation of the stomach or part of the stomach by more than 180°, creating a closed loop obstruction. Typically, its clinical presentation includes abdominal pain, distension, nausea and vomiting. Diagnosis requires a high suspicion index as it can be easily misdiagnosed with other abdominal problems such as stomach distension or subocclusive syndrome. CT scan has proven to be both highly sensitive and specific when differentiating these processes.1 A woman in their early 80s with no relevant medical background presented at out hospital with nausea and progressive dyspnoea for 3 days. She did not mention chest pain, cough, fever or other symptoms. Physical examination revealed tachycardia (122 bpm), tachypnoea (35 bpm), low arterial pressure (90/67mm Hg), diminished heart sounds, jugular ingurgitation and basal left hypophonesis. Chest radiography (figure 1) showed massive hiatal hernia and urgent tomography (figure 2) confirmed hiatal hernia and an intrathoracic gastric volvulus, which partially compressed the heart. A nasogastric catheter was inserted, obtaining a drainage of 800mL, which rapidly improved the haemodynamic state of the patient. She was then referred for surgery that comprised Nissen fundoplication and reduction of the hiatal hernia with good outcome. Emergent surgery in these cases is required in order to re-establish transit and perfusion as the volvulus can lead to ischaemia, perforation and death. Pseudo cardiac tamponade due to external compression is a rare form of presentation of intrathoracic masses where patients present with typical tamponade symptoms such as the Beck's triad,2 namely low arterial blood pressure, dilated neck veins and muffled heart sounds, in the absence of pericardial effusion. Most often, it is caused by malignant neoplasms, but sometimes it can appear associated with non-tumorous masses as in the case we present

Análisis del ratio arteria pulmonar - aorta como factor pronóstico de mortalidad en población infectada por el VIH

Background: Prevalence of chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) in high in HIVinfected patients. Pulmonary artery to aorta (PA:A) ratio ≥1 has been proposed as diagnostic of PH and predictive of mortality and hospitalary admissions in COPD patients. Up to date this ratio has not been validated in HIV-infected populations. Objective: To assess PA:A ratio predictive role of mortality and admissions in a HIV-infected sample. Methods: Prospective cohort study including a randomly selected sample of adult HIV- infected patients aged 40-69 and clinical stable excluding those with heart, liver o renal advanced disease. Patients underwent high resolution CT chest scan with quantitative emphysema measure and PA:A estimation and lung function tests. Statistical analysis included ROC curve and Cox multivariate survival regression to analyze PA:A ratio predictive capacity. Results: We included 187 patients, 7.65 years mean followup and mortality rate of 18.8/1000 patients-year. 22.36% of the patients had COPD. Mean PA:A ratio was 0.83±0.11, 4.3% had ≥1 ratio. No ratio differences were observed in patients according to mortality or COPD. In multivariate survival analysis only DLCO and diabetes were associated with mortality. Conclusions: PA:A ratio is not predictive of mortality or hospital admissions in a sample of HIV infected patients.Antecedentes: La prevalencia de enfermedad pulmonar crónica obstructiva (EPOC) e hipertensión pulmonar (HTP) en pacientes infectados por el VIH es elevada. En pacientes con EPOC el ratio arteria pulmonar-aorta (AP:A) ≥1 podría ser un marcador diagnóstico de HTP y pronóstico de mortalidad e ingresos, sin embargo este ratio no ha sido estudiado en población infectada por el VIH. Objetivos: Valorar el ratio AP:A como predictor de mortalidad o ingreso en una cohorte de pacientes infectados por el VIH. Materiales y métodos: Estudio de cohorte prospectiva incluyendo una muestra aleatorizada de pacientes infectados por el VIH con edad 40-69 años, estables clínicamente y sin antecedentes de cardiopatía, nefropatía o hepatopatía avanzada. Se realiza TC torácico de alta resolución con cálculo de ratio AP:A, estimación del enfisema cuantitativo, pruebas funcionales respiratorias. Se realiza análisis estadístico de la relación entre AP:A y mortalidad mediante curva COR y análisis de supervivencia multivariante de Cox. Resultados: Se incluyen 187 pacientes, con seguimiento medio de 7.65 años, mortalidad observada de 18.8 /1000 pacientesaño. El 22.36% de los pacientes presentaban EPOC. El ratio AP:A medio fue 0.83±0.11, el 4,3% de pacientes presentó ratio ≥1 y no se apreciaron diferencias en función de mortalidad ni en la muestra global ni en subgrupo de pacientes con EPOC. En el análisis de supervivencia solo la DLCO y la presencia de diabetes resultaron significativas. Conclusiones: El ratio AP:A no resulta un marcador pronóstico de mortalidad o ingreso hospitalario

Interatrial blocks prevalence and risk factors for human immunodeficiency virus-infected persons.

BACKGROUND:Interatrial blocks are considered a new important risk factor for atrial fibrillation and cerebrovascular events. Their prevalence and clinical implications have been reported in general population and several subgroups of patients but no data from HIV-infected populations, with a non-negligible prevalence of atrial fibrillation, has been previously reported. METHODS:We conducted a cross-sectional study in a previously enrolled cohort of randomly selected middle-aged HIV-infected patients who attended our hospital and were clinically stable. Patients underwent both a 12-lead rest electrocardiogram and clinical questionnaires while epidemiological, clinical and HIV-related variables were obtained from electronic medical records and interviews with the patients. Electrocardiograms were then analyzed and codified using a standardized form by two trained members of the research team who were blinded to clinical variables. RESULTS:We obtained electrocardiograms from 204 patients with a mean age of 55.22 years, 39 patients (19.12%) presented an interatrial block, 9 (4.41%) advanced and 30 (14.71%) partial. Patients with interatrial block had a lower nadir lymphocyte CD4 count (124 vs 198 cells, p = 0.02) while advanced interatrial blocks were associated to older age (62.16 vs. 54.95 years, p = 0.046) and hypertension (77.8% vs. 32.3%, p = 0.009). We did not find differences regarding baseline CD4 lymphocyte count or CD4/CD8 lymphocyte ratio. Clinical variables and functional capacity among patients with or without interatrial block were similar. CONCLUSIONS:In a cohort of clinically stable HIV infected patients the prevalence of interatrial blocks, specially advanced, is high and associated to previously known factors (age, hypertension) and novel ones (nadir CD4 lymphocyte count)

Interatrial blocks prevalence and risk factors for human immunodeficiency virus-infected persons

[eng] Background Interatrial blocks are considered a new important risk factor for atrial fibrillation and cerebrovascular events. Their prevalence and clinical implications have been reported in general population and several subgroups of patients but no data from HIV-infected populations, with a non-negligible prevalence of atrial fibrillation, has been previously reported. Methods We conducted a cross-sectional study in a previously enrolled cohort of randomly selected middle-aged HIV-infected patients who attended our hospital and were clinically stable. Patients underwent both a 12-lead rest electrocardiogram and clinical questionnaires while epidemiological, clinical and HIV-related variables were obtained from electronic medical records and interviews with the patients. Electrocardiograms were then analyzed and codified using a standardized form by two trained members of the research team who were blinded to clinical variables. Results We obtained electrocardiograms from 204 patients with a mean age of 55.22 years, 39 patients (19.12%) presented an interatrial block, 9 (4.41%) advanced and 30 (14.71%) partial. Patients with interatrial block had a lower nadir lymphocyte CD4 count (124 vs 198 cells, p = 0.02) while advanced interatrial blocks were associated to older age (62.16 vs. 54.95 years, p = 0.046) and hypertension (77.8% vs. 32.3%, p = 0.009). We did not find differences regarding baseline CD4 lymphocyte count or CD4/CD8 lymphocyte ratio. Clinical variables and functional capacity among patients with or without interatrial block were similar. Conclusions In a cohort of clinically stable HIV infected patients the prevalence of interatrial blocks, specially advanced, is high and associated to previously known factors (age, hypertension) and novel ones (nadir CD4 lymphocyte count)

Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

BACKGROUND AND AIMS:This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. METHODS:The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. RESULTS:As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant. CONCLUSIONS:In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism

Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

Background and Aims This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. Methods The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. Results As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant. Conclusions In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism