Kidney transplantation outcomes in lupus nephritis: A 37-year single-center experience from Latin America.

OBJECTIVE: We assessed patient and graft outcomes and prognostic factors in kidney transplantation in patients with end-stage kidney disease (ESKD) secondary to lupus nephritis (LN) undergoing kidney transplantation from August 1977 to December 2014 in a Latin American single center. METHODS: The primary endpoint was patient survival, and the secondary endpoints were death-censored graft survival for the first renal transplant and the rate of recurrent LN (RLN). Kaplan-Meier method was used for survival analysis. Factors predicting patient and death-censored graft survivals were examined by Cox proportional-hazards regression analyses. RESULTS: 185 patients were retrospectively evaluated. Patient survival rates were 88% at one year, 82% at three years, 78% at five years, and 67% at ten years. Death-censored graft survival for the first renal transplant was 93% at one year, 89% at three years, 87% at five years, and 80% at ten years. RLN was diagnosed in 2 patients (1.08%), but no graft was lost because of RLN. Thirty-nine (21.1%) patients died, and 65 (35.1%) patients experienced graft loss during the follow-up. By multivariable analyses, older recipient age and 1-month posttransplantation eGFR <45 ml/min/1.73m2 were associated with lower patient survival and an increased risk of graft loss, while induction immunosuppressive therapy exerted a protective effect on patients' survival. In the subgroup of patients in whom disease activity was measured at the time of transplantation, a higher SLEDAI score was also associated with lower patient survival and an increased risk of graft loss. CONCLUSION: In a mostly Mestizo population, kidney transplantation is an excellent therapeutic alternative in LN patients with ESKD. Older recipient age, an eGFR <45 ml/min/1.73m2 at one month posttransplantation, and disease activity at the time of transplantation are predictive of a lower patient and death-censored graft survival, while induction immunosuppressive therapy has a protective effect on patient survival. RLN is rare and does not influence the risk of graft loss.

Dexamethasone vs methylprednisolone high dose for Covid-19 pneumonia.

BACKGROUND: There is no effective therapy for the severe acute respiratory syndrome by coronavirus 2 (SARS-CoV2) responsible for the Coronavirus disease 2019 (Covid-19). To date, dexamethasone has shown a decrease in mortality in patients who require oxygen, especially those with invasive mechanical ventilation. However, it is unknown if another corticosteroid can be used, the optimal dose and its duration, to achieve a better clinical outcome. The objective of the study was to compare the differences in clinical outcome and laboratory results in hospitalized patients with severe SARS-CoV2 Pneumonia treated with dexamethasone at 6 mg doses versus patients treated with high-dose methylprednisolone. MATERIALS AND METHODS: Ambispective cohort study with survival analysis of 216 patients diagnosed with severe Covid-19 pneumonia confirmed by polymerase chain reaction for SARS-CoV2 by Berlin protocol, who were hospitalized in a high-complexity clinic in Medellín, Colombia. The patients should also have supplementary oxygen and radiological confirmation of Pneumonia by chest tomography. Sample size was not calculated since the total population that met the inclusion criteria was evaluated. 111 patients were treated with the institutional protocol with intravenous dexamethasone 6 mg QD for seven to 10 days if they required oxygen. Since September 15, 2020, the hospitalization protocol of the clinic was modified by the Infectious Diseases and Pulmonology service, recommending a high dose of methylprednisolone of 250 to 500 mg every day for three days with a subsequent change to oral prednisone 50 mg every day for 14 days. The protocol was not applied in the intensive care unit, where dexamethasone continued to be administered. The clinical outcome and differences in laboratory results of the patients who received dexamethasone vs. the prospective cohort that received methylprednisolone from September 15 to October 31, 2020, were evaluated. Follow-up was carried out by outpatient consultation one month after discharge or by telephone, inquiring about readmission or living-dead status. RESULTS: 216 patients had Covid-19 pneumonia documented by ground-glass imaging and alveolar pressure / inspired oxygen fraction (PaFi) less than 300. 111 patients received dexamethasone (DXM) and 105 received methylprednisolone (MTP). Patients in the DXM group evolved to severe ARDS in a higher proportion (26.1% vs 17.1% than the MTP group). Upon completion 4 days of treatment with parenteral corticosteroid, laboratory markers of severity decreased significantly in the group that received MTP, CRP 2.85 (2.3-3.8) vs 7.2 (5.4-9.8), (p-value < 0.0001), D-dimer 691 (612-847) vs 1083 (740-1565) (p-value = 0.04) and DHL 273 (244-289) vs 355 (270.6-422) (p-value = 0.01). After starting the corticosteroid, transfer to the intensive care unit (4.8% vs. 14.4%) and mortality (9,5% vs. 17.1%) was lower in the group that received MTP. Recovery time was shorter in patients treated with MTP, three days (3-4) vs. DXM 6 days (5-8) (p-value < 0.0001). At 30-day follow-up, 88 (92.6%) were alive in MTP vs 58 (63.1%) of those who received dexamethasone. CONCLUSIONS: In this study, the treatment of severe Covid-19 Pneumonia with high-dose methylprednisolone for three days followed by oral prednisone for 14 days, compared with 6 mg dexamethasone for 7 to 10 days, statistically significantly decreased the recovery time, the need for transfer to intensive care and the severity markers C-reactive protein (CRP), D-dimer and LDH. Randomized controlled studies with methylprednisolone are required to corroborate its effect, and studies in a population hospitalized in intensive care wards.

[Effect of opportunistic infections on the frequency of leukocyte subpopulations from type-1 human immunodeficiency virus infected individuals]. / Efecto de las infecciones oportunistas sobre las subpoblaciones de leucocitos en individuos infectados con el virus de inmunodeficiencia humana tipo 1.

INTRODUCTION: The presence of opportunistic infections in patients with acquired immunodeficiency syndrome favors the progression of HIV-1 infection. Despite the key role that several leukocyte subpopulations exhibit during the anti-infectious response, few studies have focused on the role of these cells in HIV-1-infected patients with active opportunistic infections. OBJECTIVE: The quantity of several innate and adaptive cell subpopulations was evaluated in whole peripheral blood of HIV-1-infected patients, with and without a history of opportunistic infections. MATERIALS AND METHODS: The absolute number of each leukocyte subpopulation was evaluated by flow cytometry, and for each cell subpopulation, this number was correlated with viral load, CD4+ T cell count and the expression of activation markers on CD4+ and CD8+ T lymphocytes. RESULTS: Chronically HIV-1 infected patients exhibited a quantitative deficiency in several leukocyte subpopulations; this effect was more pronounced in individuals suffering an active opportunistic infection. This indicated that the coinfection by HIV-1 and opportunistic microorganisms potentiated the immunodeficiency by reducing significantly the frequency of different subpopulations of leukocytes. CONCLUSIONS: This finding underlines the importance of an early diagnose of HIV-1 infection, and the need for the rational use of antiretroviral medications to avoid the development of opportunistic infections. In addition, it points to the necessity of developing immunotherapy strategies for HIV-1-infected patients in order to re-establish the immune competence.

Efecto de las infecciones oportunistas sobre las subpoblaciones de leucocitos en individuos infectados con el virus de inmunodeficiencia humana tipo 1 / Effect of opportunistic infections on the frequency of leukocyte subpopulations from type-1 human immunodeficiency virus infected individuals

Introducción. La presencia de infecciones por patógenos oportunistas en pacientes con síndrome de inmunodeficiencia adquirida representa un coestímulo para acelerar la progresión de la infección por el VIH-1. A pesar del papel preponderante que varias subpoblaciones de leucocitos tienen en la respuesta antiinfecciosa, poco se ha estudiado el comportamiento de esas células en pacientes positivos para VIH-1 que presentan infecciones oportunistas. Objetivo. Evaluar cuantitativamente las subpoblaciones celulares más importantes de la inmunidad innata y adaptativa en sangre periférica de adultos infectados con el VIH-1 (con antecedentes de infecciones oportunistas y sin ellos). Materiales y métodos. El número absoluto de las diferentes subpoblaciones de leucocitos fue determinado por citometría de flujo; para cada subpoblación, este número se correlacionó con la carga viral, el recuento de linfocitos T CD4+ y la expresión de marcadores de activación inmunológica en células T CD4+ y CD8+. Resultados. Los pacientes crónicamente infectados por el VIH-1 presentan deficiencia cuantitativa de varias subpoblaciones de leucocitos, que es más significativa en aquellos pacientes con una infección oportunista activa al momento de la evaluación, lo cual indica que la coinfección VIH-1/agentes oportunistas puede potenciar la inmunodeficiencia al asociarse con una reducción significativa de las diferentes subpoblaciones de leucocitos. Conclusiones. Estos hallazgos sugieren la necesidad de hacer un diagnóstico temprano de la infección por el VIH-1 y un uso racional de la terapia antirretroviral de manera que se impida que los pacientes lleguen a desarrollar infecciones oportunistas, así como la necesidad de establecer estrategias de inmunoterapia para pacientes positivos para VIH-1 con el fin de reestablecer más integralmente la competencia inmune.

Invariant NKT cells from HIV-1 or Mycobacterium tuberculosis-infected patients express an activated phenotype.

The frequency, subsets and activation status of peripheral blood invariant NKT (iNKT) cells were evaluated in pulmonary tuberculosis (TB) patients and in chronically HIV-1-infected subjects. The absolute numbers of iNKT cells were significantly decreased in TB patients and in HIV-1+ individuals who were antiretroviral therapy naive or had detectable viremia despite receiving HAART. iNKT cell subset analysis demonstrated a decreased percentage of CD4(+) iNKT cells in HIV-1+ subjects, and a decreased percentage of double negative iNKT cells in TB patients. Peripheral blood iNKT cells from HIV-1+ and TB patients had significantly increased expression of CD69, CD38, HLA-DR, CD16, CD56, and CD62L. The expression of CD25 was significantly increased only on iNKT cells from TB patients. These findings indicate that peripheral blood iNKT cells in these two chronic infections show an up-regulated expression of activation markers, suggesting their role in the immune response to infection.

Origen no infeccioso del sida: ¿mito o realidad? / The non-infectious aetiology of AIDS: Myth or reality?

El síndrome de inmunodeficiencia adquirida, o sida,fue reconocido al principio de la década de los ochenta y hasta el momento ha causado más de 20 millones de muertes, por lo que se ha convertido en la peor pandemia de todos los siglos. Inicialmente se postularon varias hipótesis etiológicas pero en 1983, con el descubrimiento del virus de inmunodeficiencia humana (VIH), se creyó que la polémica llegaría a su fin y que este virus sería reconocido mundialmentecomo el agente etiológico del sida. Sin embargo hoy, después de muchos años de investigación, aún se promueve el origen no infeccioso del sida, negando la existencia del VIH-1 y postulando como agente causal una variedad de factores tóxico-nutricionales que pueden actuar solos o en conjunto para ®estresar¼ el sistema inmune y producir la inmunodeficiencia grave, característica del sida. La existencia del VIH-1 y su asociación causal con el sida han sido corroboradas a lo largo de estos veinte años por diferentes grupos de investigación independientes. Además de satisfacer los postulados de Koch y los postulados clásicos de causalidad, los más de veinte millones de muertes, 42 millones de infectados,14 millones de huérfanos y 15 mil nuevos infectados diariamente hablan por sí solos, demostrando una vez más el origen infectocontagioso del sida. Este artículo se propone evaluar, con la información científica disponible, cada uno de los puntos que soportan la hipótesis no infecciosa del sida y mostrar cómo, el conocimiento actual del VIH-1 y de la enfermedad permite satisfacer los postulados clásicos de causalidad.

Situaciones clínicas importantes en niños infectados por el Virus de la Inmunodeficiencia Humana (VIH) / Important clinical situations in pediatric HIV infection

La infección por el virus de la inmunodeficiencia humana (VIH) en los niños se comporta en forma diferente a la infección en adultos, no sólo por sus manifestaciones clínicas sino por la forma de hacer el diagnóstico y el tratamiento. Los niños tienen un sistema inmune en desarrollo y no poseen inmunidad previa para la mayoría de los agentes infecciosos, a diferencia de los pacientes adultos, cuyo sistema inmune ya es competente. Por lo tanto, las infecciones oportunistas de los adultos generalmente corresponden a reactivaciones, mientras que las de los niños usualmente son el resultado de infecciones primarias. El examen físico del neonato infectado por el VIH-1 puede ser normal pero, a medida que avanza la infección, van apareciendo manifestaciones clínicas que sugieren un compromiso inmunológico. Los hallazgos más frecuentes en los niños, a diferencia de los adultos, son: infecciones bacterianas recurrentes, edema parotídeo crónico, neumonía intersticial linfoide y deterioro neurológico prematuro. Ciertos sistemas, como el respiratorio y el nervioso central, son atacados con frecuencia y gravedad y enfermedades como la tuberculosis revisten características especiales en los niños infectados por el VIH-1

Presentation of HIV infection in children differs from than in adults: there are different clinical manifestations and, therefore, diagnosis and treatment have their own particularities. Unlike adults, children have a developing immune system without previous immunity for many infectious agents; consequently, opportunistic infections in children correspond to primary infections while those in adults usually result from reactivations.Physical examination in HIV-infected newborns is usually normal, but as the infection progresses clinical manifestations of immunological incompetence appear. In contrast to adults, the most frequent findings in children are recurrent bacterial infections, parotid chronic edema, lymphoid interstitial pneumonia and early neurological deterioration. Respiratory and central nervous systems are frequently and severely involved during HIV-1 infection; diseases such as tuberculosis have special characteristics in HIV-1 infected children