Efectividad de los glucocorticoides en pacientes hospitalizados por neumonía grave por SARS-CoV-2 / Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia

Introducción: Se han comunicado varios trabajos donde se ha demostrado un efecto beneficioso de los glucocorticoides como tratamiento de la tormenta de citocinas que se asocia a los cuadros graves por SARS-CoV-2, plateándose diferentes pautas de glucocorticoides.MétodosEstudio observacional retrospectivo que incluye pacientes con neumonía grave por SARS-CoV-2 y compara el ingreso en una unidad de cuidados intensivos (UCI) o fallecimiento durante la hospitalización en 3 grupos de pacientes: sin tratamiento con glucocorticoides, uso de dosis diarias de glucocorticoides equivalentes menores a 250mg de prednisona y dosis diarias equivalentes mayores o iguales a 250mg de prednisona. Se realizó un análisis multivariante mediante regresión logística, utilizando el índice de propensión como covariante.ResultadosDe los 259 pacientes incorporados al estudio 67 (25,9%) tuvieron una evolución desfavorable, falleciendo o precisando ingreso en UCI. Los análisis comparativos entre diferentes tratamientos con glucocorticoides, y la asociación con ingreso en UCI o fallecimiento fueron: tratamiento con glucocorticoides (cualquier dosis) versus sin tratamiento con glucocorticoides (OR: 0,71 [0,30-1,66]), tratamiento con glucocorticoides (≥250mg de prednisona al día) versus sin tratamiento con glucocorticoides (OR: 0,35 [0,11-1,08]) y tratamiento con glucocorticoides (≥250mg de prednisona al día) versus pacientes con dosis de glucocorticoides<250mg de prednisona o sin tratamiento con glucocorticoides (OR: 0,30 [0,10-0,88]).ConclusiónLos resultados de este estudio muestran que los paciente con neumonía grave por SARS-CoV-2 tratados con pulsos con glucocorticoides con dosis equivalentes de prednisona mayor o igual de 250mg tienen una evolución más favorable (menos mortalidad e ingreso en UCI). (AU)

Introduction: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed.MethodsRetrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250mg of prednisone daily and use of equivalent doses greater than or equal to 250mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant.ResultsOf the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250mg prednisone daily) versus patients with glucocorticoids doses <250mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]).ConclusionThe results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250mg have a more favorable evolution (less mortality and less admission to ICU). (AU)

Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia.

BACKGROUND: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250 mg of prednisone daily and use of equivalent doses greater than or equal to 250 mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250 mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250 mg prednisone daily) versus patients with glucocorticoids doses <250 mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250 mg have a more favorable evolution (less mortality and less admission to ICU).

INTRODUCCIÓN: Se han comunicado varios trabajos donde se ha demostrado un efecto beneficioso de los glucocorticoides como tratamiento de la tormenta de citocinas que se asocia a los cuadros graves por SARS-CoV-2, plateándose diferentes pautas de glucocorticoides. MÉTODOS: Estudio observacional retrospectivo que incluye pacientes con neumonía grave por SARS-CoV-2 y compara el ingreso en una unidad de cuidados intensivos (UCI) o fallecimiento durante la hospitalización en 3 grupos de pacientes: sin tratamiento con glucocorticoides, uso de dosis diarias de glucocorticoides equivalentes menores a 250 mg de prednisona y dosis diarias equivalentes mayores o iguales a 250 mg de prednisona. Se realizó un análisis multivariante mediante regresión logística, utilizando el índice de propensión como covariante. RESULTADOS: De los 259 pacientes incorporados al estudio 67 (25,9%) tuvieron una evolución desfavorable, falleciendo o precisando ingreso en UCI. Los análisis comparativos entre diferentes tratamientos con glucocorticoides, y la asociación con ingreso en UCI o fallecimiento fueron: tratamiento con glucocorticoides (cualquier dosis) versus sin tratamiento con glucocorticoides (OR: 0,71 [0,30­1,66]), tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus sin tratamiento con glucocorticoides (OR: 0,35 [0,11­1,08]) y tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus pacientes con dosis de glucocorticoides < 250 mg de prednisona o sin tratamiento con glucocorticoides (OR: 0,30 [0,10­0,88]). CONCLUSIÓN: Los resultados de este estudio muestran que los paciente con neumonía grave por SARS-CoV-2 tratados con pulsos con glucocorticoides con dosis equivalentes de prednisona mayor o igual de 250 mg tienen una evolución más favorable (menos mortalidad e ingreso en UCI).

[Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia]. / Efectividad de los glucocorticoides en pacientes hospitalizados por neumonía grave por SARS-CoV-2.

INTRODUCTION: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250mg of prednisone daily and use of equivalent doses greater than or equal to 250mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250mg prednisone daily) versus patients with glucocorticoids doses <250mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250mg have a more favorable evolution (less mortality and less admission to ICU).

Tratamiento de la enfermedad tuberculosa pulmonar y extrapulmonar / Treatment of pulmonary and extrapulmonary tuberculosis

El tratamiento de la enfermedad tuberculosa busca un doble beneficio: un beneficio individual, centrado en la curación del paciente afecto de tuberculosis, y un beneficio colectivo, de la comunidad en la cual reside el paciente. Se exponen los diferentes regímenes de tratamiento tanto de la tuberculosis sensible a fármacos antituberculosos de primera línea como de la tuberculosis resistente. Se comentan las peculiaridades en cuanto al manejo de la tuberculosis pulmonar y extrapulmonar

The purpose of tuberculosis treatment is twofold: to provide an individual benefit centred on healing the patient with TB, and to provide a collective benefit to the community in which the patient resides. The different treatment regimens for tuberculosis sensitive to first-line antituberculosis drugs as well as resistant tuberculosis are examined and the peculiarities in the management of pulmonary and extrapulmonary tuberculosis are discussed

Comentarios al tratamiento de la tuberculosis con resistencia / Comments On The Treatment Of Resistant Tuberculosis

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Treatment of pulmonary and extrapulmonary tuberculosis. / Tratamiento de la enfermedad tuberculosa pulmonar y extrapulmonar.

The purpose of tuberculosis treatment is twofold: to provide an individual benefit centred on healing the patient with TB, and to provide a collective benefit to the community in which the patient resides. The different treatment regimens for tuberculosis sensitive to first-line antituberculosis drugs as well as resistant tuberculosis are examined and the peculiarities in the management of pulmonary and extrapulmonary tuberculosis are discussed.

Retrospective study of tolerability and efficacy of linezolid in patients with multidrug-resistant tuberculosis (1998-2014) / Estudio retrospectivo sobre la tolerabilidad y eficacia de linezolid en pacientes con tuberculosis multirresistente (1998-2014)

INTRODUCTION: Although linezolid is known to be effective when used as an adjunct therapy in the treatment of patients with multidrug-resistant tuberculosis (MDR-TB), the clinical experience is limited. In this study the efficacy and adverse effects of linezolid treatment were evaluated. METHODS: A retrospective study of tolerability and efficacy of linezolid in MDR-TB patients was performed in Madrid, Spain. Demographic characteristics, microbiological and clinical features and data on treatment tolerability were collected. Regimens were constructed with a target of prescribing, at least, five anti-tuberculosis agents likely to be effective. Linezolid, at a dosage of 1200 or 600 mg daily, was included to complete the treatment if no other sensitive drugs were available. Vitamin B6 was used to reduce toxicity. Treatment outcome and clinical status at last contact were compared between patients with linezolid-containing regimens and with those without linezolid-containing regimens. RESULTS: During the period 1998-2014, 55 patients with MDR-TB received treatment. In 21 of these patients, linezolid was added. The median of linezolid administration was 23.9 months (IQT 13.1-24.7). Patients using linezolid showed a greater resistance to drugs, with a median of 6 (IQR 5-7) compared with those who did not use it, with a median of 4 drugs (IQR 3-5) (p < 0.001). The median time to sputum culture conversion of the patients in the linezolid group (73.5 days) did not differ significantly from those in the non-linezolid group (61 days) (p = 0.29). There were no significant differences in the outcomes of the two patient groups. There were no reported adverse events in 81% of patients assigned to linezolid therapy. Only four patients developed toxicity attributed to linezolid. The most serious adverse event in these patients was anemia observed in the two patients treated with 1200 mg per day. One of them also developed moderate paresthesia. In both cases the dosage was reduced to 600 mg per day, with improvement of the anemia and paresthesias. No patients stopped linezolid therapy. CONCLUSION: A daily dosage of 600 mg of linezolid was well tolerated without stopping treatment in any case. The efficacy of the treatment and the outcomes were similar in both the linezolid and non-linezolid group

INTRODUCCIÓN: Aunque es conocida la utilidad y la eficacia de linezolid cuando se administra para el tratamiento de pacientes con tuberculosis multirresistente (TB-MR), la experiencia clínica actual sigue siendo limitada. En este estudio se analiza la evolución, la eficacia y los efectos adversos del tratamiento con linezolid en pacientes con diagnostico de TB-MR. MÉTODO: Se realizó un estudio retrospectivo sobre la tolerabilidad y la eficacia de linezolid en pacientes diagnosticados de TB-MR en Madrid, España. Los regimenes de tratamiento se constituyeron con al menos 5 fármacos antituberculosos efectivos. Linezolid (a dosis de 1200 o 600 mg por día) se añadió para completar el tratamiento en los pacientes en los que no existían otros fármacos alternativos sensibles. Se utilizó vitamina B6 para reducir la toxicidad al tratamiento. Se comparó la evolución clínica de los pacientes y los resultados del tratamiento entre el grupo de pacientes tratados con linezolid y el grupo de pacientes que no fueron tratados con este fármaco. RESULTADOS: Entre 1998 y 2014, 55 pacientes fueron diagnosticados de TB-MR y recibieron tratamiento. En 21 pacientes fue necesaria la administración de linezolid. La media de tiempo de administración de linezolid fue de 23.9 meses (IQR 13.1-24.7). Los pacientes del grupo de linezolid presentaron mayor número de resistencias a fármacos con una mediana de 6 (IQR 5-7), respecto al grupo que no tomó Linezolid [4 fármacos (IQR 3-5)] (p < 0,001). No hubo diferencias significativas entre el tiempo de conversión del cultivo de esputo de los pacientes del grupo de linezolid (73,5 días) frente al del grupo sin linezolid (61 días) (p = 0,29). Tampoco hubo diferencias significativas en la evolución de los dos grupos de pacientes. El 81% de los pacientes que tomaron linezolid no experimentaron efectos adversos atribuidos a la administración de Linezolid. Sólo cuatro pacientes desarrollaron toxicidad secundaria al uso de linezolid. El efecto adverso más importante fue anemia que se presentó en los dos pacientes tratados con 1200 mg al día. Uno de ellos también desarrolló parestesias de grado moderado en miembros inferiores. En ambos casos, la dosis se redujo a 600 mg al día, con mejoría de la anemia y de las parestesias. CONCLUSIÓN: La dosis de 600 mg al día de linezolid fue bien tolerada sin necesidad de interrumpir el tratamiento en ningún caso. La eficacia del tratamiento y la evolución de los pacientes fueron similares en ambos grupos

Retrospective study of tolerability and efficacy of linezolid in patients with multidrug-resistant tuberculosis (1998-2014).

INTRODUCTION: Although linezolid is known to be effective when used as an adjunct therapy in the treatment of patients with multidrug-resistant tuberculosis (MDR-TB), the clinical experience is limited. In this study the efficacy and adverse effects of linezolid treatment were evaluated. METHODS: A retrospective study of tolerability and efficacy of linezolid in MDR-TB patients was performed in Madrid, Spain. Demographic characteristics, microbiological and clinical features and data on treatment tolerability were collected. Regimens were constructed with a target of prescribing, at least, five anti-tuberculosis agents likely to be effective. Linezolid, at a dosage of 1200 or 600 mg daily, was included to complete the treatment if no other sensitive drugs were available. Vitamin B6 was used to reduce toxicity. Treatment outcome and clinical status at last contact were compared between patients with linezolid-containing regimens and with those without linezolid-containing regimens. RESULTS: During the period 1998-2014, 55 patients with MDR-TB received treatment. In 21 of these patients, linezolid was added. The median of linezolid administration was 23.9 months (IQT 13.1-24.7). Patients using linezolid showed a greater resistance to drugs, with a median of 6 (IQR 5-7) compared with those who did not use it, with a median of 4 drugs (IQR 3-5) (p<0.001). The median time to sputum culture conversion of the patients in the linezolid group (73.5 days) did not differ significantly from those in the non-linezolid group (61 days) (p=0.29). There were no significant differences in the outcomes of the two patient groups. There were no reported adverse events in 81% of patients assigned to linezolid therapy. Only four patients developed toxicity attributed to linezolid. The most serious adverse event in these patients was anemia observed in the two patients treated with 1200 mg per day. One of them also developed moderate paresthesia. In both cases the dosage was reduced to 600 mg per day, with improvement of the anemia and paresthesias. No patients stopped linezolid therapy. CONCLUSION: A daily dosage of 600 mg of linezolid was well tolerated without stopping treatment in any case. The efficacy of the treatment and the outcomes were similar in both the linezolid and non-linezolid group.

Nuevos fármacos antituberculosos en la tuberculosis resistente y multirresistente / New tuberculosis drugs in resistant and multiresistant tuberculosis

La tuberculosis resistente a fármacos es un problema emergente en todo el mundo, con una incidencia cada vez mayor. Según la OMS, en el año 2008, el 17% de las cepas de Mycobacterium tuberculosis, en los casos no tratados, eran resistentes al menos a un fármaco, y el 3,6% eran resistentes a rifampicina e isoniacida, lo que se denomina tuberculosis multirresistente. El problema es mucho mayor en pacientes previamente tratados y en algunos países, donde las tasas de multirresistencia pueden llegar hasta el 60%. Aproximadamente el 5% de los pacientes con tuberculosis multirresistente son también resistentes a alguna fluoroquinolona y al menos a un fármaco inyectable, denominándose tuberculosis extremadamente resistente. El tratamiento de estas formas de tuberculosis requiere el empleo de fármacos de segunda línea, que ocasionan un mayor corte, elevada toxicidad y un aumento de la duración de los tratamientos. Existe una necesidad de nuevos compuestos con perfiles de seguridad y eficacia mejores que los actualmente utilizados para el tratamiento de estas formas de tuberculosis. En la última década están siendo reevaluados diferentes fármacos ya conocidos y además han aparecido nuevos compuestos que están siendo investigados y se encuentran en diferentes fases de su desarrollo (AU)

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[New tuberculosis drugs in resistant and multiresistant tuberculosis]. / Nuevos fármacos antituberculosos en la tuberculosis resistente y multirresistente.

Drug-resistant tuberculosis is a globally emerging problem with a rising incidence. According to the WHO in 2008, 17% of strains of Mycobacterium tuberculosis, in untreated cases were resistant to at least one drug and 3.6% were resistant to rifampicin and isoniazid, which is called multidrug-resistant tuberculosis. The problem is greater in patients previously treated and in some countries, where rates of multidrug resistance reach 60%. Approximately 5% of multidrug-resistant tuberculosis patients are also resistant to any fluoroquinolone and at least one injectable drug, being called extensively drug-resistant tuberculosis. The treatment of these forms of tuberculosis requires the use of second-line drugs, which causes higher cost, higher toxicity and a longer duration of treatment. There is a need for new compounds with efficacy and safety profiles better than those currently used to treat these forms of tuberculosis. In the last decade different drugs have being reassessed and appeared, which are at different stages of development.

Evolución y tratamiento de pacientes con tuberculosis multirresistente / Outcome and treatment among patients with multidrug-resistant tuberculosis

Fundamento y objetivo: A pesar de los avances en reducir la incidencia de la tuberculosis, la emergencia de la tuberculosis multirresistente durante las últimas décadas amenaza con limitar estos resultados. El objetivo de este estudio es evaluar las características epidemiológicas, clínicas y microbiológicas y los resultados del tratamiento de una serie española de pacientes con tuberculosis multirresistente. Pacientes y método: Estudio retrospectivo realizado entre enero de 1998 y diciembre de 2010 en la Unidad de Aislamiento de Medicina Interna del Hospital de Cantoblanco-La Paz de Madrid. Resultados: Un total de 47 pacientes fueron evaluados. La edad media fue de 36 años y 33 eran varones. Un 64% eran extranjeros. Hubo 26 casos nuevos (55,3%). Los pacientes fueron resistentes a 5 fármacos de mediana y 3 cumplieron criterios de tuberculosis extremadamente resistente. La mediana de tiempo hasta la negativización del cultivo fue de 68,5 días (rango intercuartil [RIQ] 49,5-91,8) y la de hospitalización 2,75 meses (RIQ 1,3-4,6). Los pacientes recibieron tratamiento durante 22,4 meses de mediana (RIQ 15,3-24,3). Se obtuvo respuesta favorable al tratamiento en el 93%. Se realizó tratamiento directamente observado en el 79%. El 68% presentaron algún efecto adverso, que fueron leves o moderados en el 75%. Se pudo realizar seguimiento tras la finalización del tratamiento en 14 pacientes, con una mediana de 40,5 meses (RIQ 7,4-55), y no se objetivó ninguna recidiva clínica ni microbiológica. Conclusión: La mayoría de los pacientes con tuberculosis multirresistente pueden alcanzar la curación con el uso de pautas de tratamiento adecuadas, un control exhaustivo de los efectos adversos y la aplicación de estrategias para mejorar la adherencia al tratamiento (AU)

Background and objective: Although progress has been made to reduce the global incidence of tuberculosis, the emergence of multidrug-resistant tuberculosis during the past decade threatens to limit these results. The aim of this study is to evaluate the geographic distribution, clinical and microbiological characteristics and outcomes of multidrug-resistant tuberculosis patients in Spain. Patients and methods: Retrospective study between January 1998 and December 2010 of patients attended in Cantoblanco-La Paz Hospital Isolation Internal Medicine Unit. Results: Forty-seven patients were studied, with a mean age of 36 years. There were 33 male. Sixty-four per cent were immigrants and the mean residence time in Spain was 12 months. Twenty-six patients (55.3%) were new cases. Patients were resistant to a median of 5 drugs (interquartile range [IQR] 3-7) and 3 patients had extensively drug-resistant tuberculosis. Cultures became negative after a median of 68.5 days (IQR 49.5-91.8). The median length of hospitalization was 2.75 months (IQR 1.3-4.6). They were treated during a median of 22.4 months (IQR 15.3-24.3). The overall success rate was 93%. A directly observed treatment was carried out in 79% of patients. Sixty-eight per cent patients presented side effects. In 75% of the cases the effects were mild and moderate with no need to replace the drug. Fourteen patients were followed up for a median of 40.5 months (IQR 7.4-55) and no clinical or bacteriological manifestation of disease was detected. Conclusions: Most patients with multidrug-resistant tuberculosis can be cured with the use of appropriate and intensive regimens, management of side effects and implementation of strategies to improve adherence to treatment (AU)

[Outcome and treatment among patients with multidrug-resistant tuberculosis]. / Evolución y tratamiento de pacientes con tuberculosis multirresistente.

BACKGROUND AND OBJECTIVE: Although progress has been made to reduce the global incidence of tuberculosis, the emergence of multidrug-resistant tuberculosis during the past decade threatens to limit these results. The aim of this study is to evaluate the geographic distribution, clinical and microbiological characteristics and outcomes of multidrug-resistant tuberculosis patients in Spain. PATIENTS AND METHODS: Retrospective study between January 1998 and December 2010 of patients attended in Cantoblanco-La Paz Hospital Isolation Internal Medicine Unit. RESULTS: Forty-seven patients were studied, with a mean age of 36 years. There were 33 male. Sixty-four per cent were immigrants and the mean residence time in Spain was 12 months. Twenty-six patients (55.3%) were new cases. Patients were resistant to a median of 5 drugs (interquartile range [IQR] 3-7) and 3 patients had extensively drug-resistant tuberculosis. Cultures became negative after a median of 68.5 days (IQR 49.5-91.8). The median length of hospitalization was 2.75 months (IQR 1.3-4.6). They were treated during a median of 22.4 months (IQR 15.3-24.3). The overall success rate was 93%. A directly observed treatment was carried out in 79% of patients. Sixty-eight per cent patients presented side effects. In 75% of the cases the effects were mild and moderate with no need to replace the drug. Fourteen patients were followed up for a median of 40.5 months (IQR 7.4-55) and no clinical or bacteriological manifestation of disease was detected. CONCLUSIONS: Most patients with multidrug-resistant tuberculosis can be cured with the use of appropriate and intensive regimens, management of side effects and implementation of strategies to improve adherence to treatment.

Detection and quantification of the K103N mutation in HIV reverse transcriptase by pyrosequencing.

Prolonged treatment of human immunodeficiency virus (HIV)-infected patients with nonnucleoside reverse transcriptase inhibitors (NNRTIs) might result in the selection of resistant mutants, the most frequent being the K103N mutation in reverse transcriptase. Resistance mutations are routinely detected by Sanger sequencing of the whole viral population, which does not detect sequence variants with frequencies below 20%. We have developed a pyrosequencing approach for the analysis of codon 103 of the HIV reverse transcriptase gene in the circulating viral population that detects variants below the limit of conventional sequencing. The method was tested with samples from 5 controls (not exposed to NNRTIs), 6 from patients exposed to NNRTIs and having a K103N mutant virus population detected by conventional sequencing, and 9 from patients previously exposed to NNRTIs that had a wild-type virus population by conventional sequencing. In 7 of 9, samples the mutation could not be detected by either the standard assay or pyrosequencing, while in 2 samples persistence of the mutation could be detected by pyrosequencing. The method might be of practical use in detecting minority variants of HIV in the clinical setting, in epidemiological studies with large numbers of samples, or as a complement to more complex approaches.

Undetectable serum calcidiol: not everything that glitters is gold.

There is an increased awareness of the adverse consequences of nutritional vitamin D deficiency. We report a patient with chronic tophaceous gout, chronic kidney disease (CKD) Stage 3/4 and undetectable serum calcidiol who developed severe hypercalcaemia upon vitamin D supplementation despite serum 25(OH) vitamin D within the normal range. Upon recovery, serum 1,25(OH)2 vitamin D remained in the normal range despite CKD and serum 25(OH) vitamin D 6 ng/mL. Gout tophi biopsies from additional patients showed macrophage expression of 25(OH) vitamin D 1α-hydroxylase. This case illustrates the dangers of supplementing vitamin D in patients with low serum 25(OH) vitamin D and increased 1α-hydroxylase activity due to granulomatous disease.

[Factors associated with hepatic steatosis in human immunodeficiency virus and hepatits C virus coinfected patients]. / Factores asociados con esteatosis hepática en pacientes coinfectados por los virus de la inmunodeficiencia humana y de la hepatitis C.

BACKGROUND AND OBJECTIVE: To determinate the prevalence and factors associated with hepatic steatosis and severity of steatosis in human immunodeficiency virus (HIV) and hepatits C virus (HCV) coinfected patients. PATIENTS AND METHOD: Liver histology was assessed in 163 HIV-HCV coinfected patients. Exclusion criteria included positive hepatitis B surface antigen and prior anti-HCV therapy. Steatosis was scored by a single pathologist according to the percentage of affected hepatocytes. Necroinflammatory activity and fibrosis was scored by the Scheuer system. Logistic regression analyses were used to evaluate variables associated with hepatic steatosis. RESULTS: Steatosis was present in 65% of biopsy samples. Moderate-severe steatosis (>30% of hepatocytes) was detected in 17% of patients. 78.5% of patients were under high active antiretroviral therapy at the time of biopsy. In a multivariate analysis, steatosis was associated with body weight, alcohol, advanced fibrosis, stavudine use and non-use of lopinavir/ritonavir. In a multivariate analysis, severity of steatosis (>30% of hepatocytes) was associated with alcohol, HCV genotype 3, HCV load >1,400,000 copies/ml and advanced fibrosis. CONCLUSIONS: The presence of hepatic steatosis and severity of steatosis were associated with advanced fibrosis in patients coinfected with HIV and HCV. Body weight, consumption of alcohol and antiretroviral therapy (stavudine use and absence of exposure to lopinavir/ritonavir) were modifiable factors associated with the presence of steatosis. Characteristics of HCV infection were associated with the severity of steatosis in this population.

Factores asociados con esteatosis hepática en pacientes coinfectados por los virus de la inmunodeficiencia humana y de la hepatitis C / Factors associated with hepatic steatosis in human immunodeficiency virus and hepatits C virus coinfected patients

Fundamento y objetivo: determinar la prevalencia y los factores asociados con la presencia de esteatosis hepática y con su intensidad en los pacientes coinfectados por los virus de la inmunodeficiencia humana (VIH) y de la hepatitis C (VHC).Pacientes y método: se han evaluado las biopsias hepáticas de 163 pacientes coinfectados por el VIH y VHC. Se excluyó a aquéllos con antígeno de superficie del virus de la hepatitis B y tratamiento previo del VHC. El grado de esteatosis se evaluó según el porcentaje de hepatocitos afectados. La actividad necroinflamatoria y el grado de fibrosis se clasificaron según el sistema de Scheuer. Mediante regresión logística se valoraron los factores asociados con la presencia e intensidad de la esteatosis en la biopsia. Resultados: un 65% de las biopsias presentaba esteatosis, que era moderada-intensa (>30% de los hepatocitos) en un 17%. Un 78,5% de los pacientes recibía tratamiento antirretroviral de gran actividad en el momento de realizar la biopsia. Los factores asociados con la presencia de esteatosis fueron: el peso corporal, el consumo de alcohol, la presencia de fibrosis avanzada, la exposición a estavudina y la ausencia de exposición a lopinavir/ritonavir. Los factores asociados con la intensidad de la esteatosis (>30% de hepatocitos) fueron: el consumo de alcohol, el genotipo 3 del VHC, la carga vírica del VHC mayor de 1.400.000 copias de ARN/ml y la presencia de fibrosis avanzada. Conclusiones: la presencia de esteatosis y su intensidad se asociaron a un mayor grado de fibrosis hepática en los pacientes coinfectados por el VIH y VHC. El peso, el consumo de alcohol y el tratamiento antirretroviral (tratamiento con estavudina y ausencia de tratamiento con lopinavir/ritonavir) son factores modificables que se asociaron a la presencia de esteatosis. Las características de la infección del VHC estaban asociadas a la intensidad de la esteatosis en esta población (AU)

Background and objective: To determinate the prevalence and factors associated with hepatic steatosis and severity of steatos is in human immunodeficiency virus (HIV) and hepatits C virus (HCV) coinfected patients. Patients and method: Liver histology was assessed in 163 HIV-HCV coinfected patients. Exclusion criteria included positive hepatitis B surface antigen and prior anti-HCV therapy. Steatosis was scored by a single pathologist according to the percentage of affected hepatocytes. Necroinflammatory activity and fibrosis was scored by the Scheuer system. Logistic regression analyses were used to evaluate variables associated with hepatic steatosis. Results: Steatosis was present in 65% of biopsy samples. Moderate-severe steatosis (>30% of hepatocytes) was detected in 17% of patients. 78.5% of patients were under high active antiretroviral therapy at the time of biopsy. In a multivariate analysis, steatosis was associated with body weight, alcohol, advanced fibrosis, stavudine use and non-use of lopinavir/ritonavir. In a multivariate analysis, severity of steatosis (>30% of hepatocytes) was associated with alcohol, HCV genotype 3, HCV load >1,400,000 copies/ml and advanced fibrosis. Conclusions: The presence of hepatic steatosis and severity of steatosis were associated with advanced fibrosis in patients coinfected with HIV and HCV. Body weight, consumption of alcohol and antiretroviral therapy (stavudine use and absence of exposure to lopinavir/ritonavir) were modifiable factors associated with the presence of steatosis. Characteristics of HCV infection were associated with the severity of steatosis in this population (AU)