Resumen La enfermedad por COVID-19 fue detectada a finales de 2019 en Wuhan, China. Debido a su rápida propagación fue declarada emergencia sanitaria de forma inicial y luego de identificar casos fuera de China con transmisión autóctona y caracterizado por una mortalidad considerablemente alta en países como Italia y España, fue declarada pandemia por la Organización Mundial de la Salud. Se ha evidenciado que los pacientes mayores y con antecedentes de enfermedades crónicas incluido el cáncer desarrollan una enfermedad severa, presentando mayor riesgo de mortalidad por SARS-CoV2/ COVID-19. Lo anterior es por supuesto especialmente importante en el manejo de pacientes con Mieloma Múltiple (MM), generando en el personal Médico nuevos desafíos, oportunidades de mejora y aprendizajes, que aporten al análisis riesgo-beneficio del tratamiento inmunodepresor en este tipo de patologías. El consenso tiene como objetivo brindar orientación sobre el manejo de pacientes con MM en estos momentos donde el profesional de la salud requiere información para llevar a cabo terapias eficientes en el cuidado del paciente.

Abstract COVID-19 disease was detected in late 2019 in Wuhan, China. Due to its rapid spread, it was initially declared a health emergency, but after cases with indigenous transmission were identified outside China, characterized by considerably high mortality in countries such as Italy and Spain, it was declared a pandemic by the World Health Organization. It has been shown that elderly patients with a history of chronic diseases, including cancer, develop a severe disease, presenting a higher risk of mortality from SARS-CoV2 / COVID-19. This becomes especially important in the management of patients with Multiple Myeloma (MM), generating new challenges, opportunities for improvement and learning opportunities in the health professionals, which will contribute to the risk-benefit analysis of immunosuppressive treatment for this type of pathology. The consensus aims to provide guidance for the management of patients with MM in these times when the health professional requires information to deliver efficient therapies in patient care.

ABSTRACT Non-Hodgkin's lymphoma is the second most common neoplasm in patients with AIDS. Its systemic clinical forms associated with the human immunodeficiency virus almost always have a high degree of malignancy. Involvement of the central nervous system is a frequent occurrence in patients with this type of lymphoma. The purpose of the study is to describe an atypical presentation of non-Hodgkin's lymphoma in a patient with AIDS. A case is reported of a male 28-year-old HIV-positive patient with diffuse large B-cell non-Hodgkin's lymphoma who presented with isolated cranial nerve III palsy as the main initial manifestation. The disease progressed rapidly and had a fatal outcome some days later. It is concluded that it is necessary to consider the diagnosis of non-Hodgkin's lymphoma in patients with AIDS and cranial nerve III palsy, in order to make an early diagnosis and initiate timely treatment, in view of the rapid evolution and poor prognosis of the disease.

RESUMEN El linfoma no Hodgkin es la segunda neoplasia más frecuente en pacientes con sida. Sus formas clínicas sistémicas asociadas con el virus de inmunodeficiencia humana casi siempre tienen un alto grado una malignidad. La participación del sistema nervioso central es un hecho frecuente en pacientes con este tipo de linfoma. El objetivo es describir una forma atípica de presentación del linfoma no Hodgkin en un paciente con sida. Se informa acerca de un paciente de 28 años, VIH positivo, con linfoma no Hodgkin de células grandes B difuso que se presentó con parálisis aislada del III par craneal como principal manifestación inicial, la enfermedad progresó rápidamente y en pocos días tuvo un desenlace fatal. Se concluye que es necesario considerar el diagnóstico de linfoma no Hodgkin en pacientes con sida y parálisis del III par craneal, para de esta forma realizar un diagnóstico temprano e iniciar tratamiento oportuno debido a la rápida evolución y mal pronóstico de la enfermedad.

Abstract INTRODUCTION: Interferon-γ (IFN-γ) plays a crucial role in resistance to mycobacterial diseases; accordingly, variants of the gene encoding this cytokine may be associated with elevated risk of contracting pulmonary tuberculosis (TB). METHODS: Blood samples were collected from 135 Warao indigenous individuals with newly diagnosed sputum culture-positive TB. Of these, 24 were diagnosed with active tuberculosis (ATB). The study comprised 111 participants, who were grouped as follows: 1) 14 tuberculin skin test (TST)-positive Warao indigenous individuals and 4 that were QuantiFERON-TB?Gold In-Tube (QFT-IT) test-positive, collectively comprising the latent TB infection group (LTBI), n = 18), and 2) healthy controls who were QFT-IT- and TST-negative, comprising the control group (CTRL, n = 93). Detection of the IFN γ gene (IFNG) +874A/T polymorphism was performed via PCR and quantification of IFNG expression via qPCR. RESULTS: Relative to indigenous and white Americans, ATB and CTRL groups had a higher frequency of the IFNG SNP (+874A): 23 (95.8%) and 108 (97.3%), respectively. Indigenous Warao individuals homozygous for the IFNG (+874) A allele exhibited 3.59-fold increased risk of developing TB (95% confidence interval, 2.60-4.96, p =0.0001). A decreased frequency of the AT genotype was observed in individuals with pulmonary TB (4.16%) and controls (0.90%). The frequency of the TT genotype was decreased among controls (1.80%); none of the patients with TB were found to have this genotype. The differences in IFNG expression between the groups, under unstimulated and stimulated conditions, were not statistically significant. CONCLUSIONS: Preliminary results demonstrate concordance between IFNG +874 A/A genotype and low expression of IFNG.

The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection.

Recientemente existe un gran interés hacia un mejor y más rápido diagnóstico de tuberculosis (TB), especialmente de tuberculosis pleural, el cual es difícil. Al presente las principales herramientas diagnósticas son la baciloscopia y el cultivo de líquido pleural; desafortunadamente, las sensibilidades de estos métodos son bajas, por lo que el desarrollo de nuevas herramientas diagnósticas es necesario. El objetivo del presente estudio consistió en encontrar un algoritmo que permita la rápida identificación de la mayoría de los pacientes con TB pleural que ingresan en el Hospital Vargas de Caracas a un buen costo-beneficio. Para esto se evaluaron los niveles de las citocinas Interferón-gamma (IFN-g) y la Interleucina 12p40 (IL-12p40) en líquido pleural y suero, así como la reactividad de anticuerpos contra antígenos de Mycobacterium tuberculosis. Se estudiaron 60 individuos con derrame pleural; 20 individuos con líquido pleural tuberculoso (LPT) conformaron el grupo de pacientes y 40 individuos con líquido pleural no tuberculoso (LPNT) el grupo de controles. La técnica de inmunoensayo de ELISA fue utilizada para medir los niveles de IFN-g y IL-12p40; así como las reactividades de los diversos isotipos y subclases de inmunoglobulina G (IgG) frente a antígenos del bacilo. La utilidad de los métodos fue evaluada utilizando el análisis de las curvas ROC (receiver operating characteristic). Los resultados de los 11 métodos inmunológicos evaluados mostraron que el método IgG2 anti-PPD alcanzó la mayor especificidad de 95%, (CI: 88,3-101,8) con un valor predictivo positivo (VPP) de 75. La sensibilidad de los métodos estuvo entre 30% y 95%; dos métodos alcanzaron altas sensibilidades: los altos niveles de IFN-g en líquido pleural, con sensibilidad de 95% (CI: 85,5-104,5), con un valor predictivo negativo (VPN) de 97, seguido de los bajos niveles de IL-12p40 en suero, con una sensibilidad de 95% (CI: 85,5-104,5) con un VPN de 95,2. En contraste, los métodos microbiológicos mostraron una baja sensibilidad, en el caso de la baciloscopia sólo del 20%; mientras que la combinación baciloscopia más el cultivo alcanzó 70%. Considerando que las LPT representan el 15% de todos los casos de TB diagnosticados en el Hospital Vargas de Caracas; aquellos pacientes con una microbiología preliminar negativa en líquido pleural, la realización del análisis de IFN-g en líquido y el método serológico IgG2 anti-PPD podrían constituir un algoritmo diagnóstico rápido y efectivo, previo al resultado del cultivo para micobacteria, lo cual permitiría iniciar el tratamiento antituberculoso de forma más precoz o considerar la realización de la biopsia

In recent years, better diagnostics for tuberculosis (TB) has received increasing attention, especially the diagnosis of tuberculous pleural effusion, which is difficult and at present the main tool in TPE diagnostic is pleural effusion smear and culture, but unfortunately, sensitivities are low, therefore better TPE diagnostic tools are needed. The aim of this study was to find a diagnostic algorithm to assess the progress in TPE diagnostic at the Hospital Vargas de Caracas, that permits identification of the majority of patients, at a satisfactory cost-benefit ratio, evaluating the levels of IFN-g and IL-12p40 in pleural effusion and serum, as well as the antibody reactivity in order to compare it with microbiological tests. A total of 60 individuals with pleural effusion were studied; 20 patients with tuberculous pleural effusion (TPE) formed the patient group and 40 patients with non-tuberculous pleural effusion (NTPE) formed the control group. The levels of IFN-g and IL-12p40 in effusion and serum and class and subclasses of IgG reactivity to Mycobacterium tuberculosis antigens were measured by ELISA. The utility of these methods for diagnosis of TPE was evaluated using receiver operating characteristic (ROC) curve analysis. The results of the 11 immunological methods evaluated showed that the anti-PPD IgG2 method was able to reach the highest specificity of 95% (CI: 88.3-101.8), positive predictive value (PPV)=75 (at 30% sensitivity); while that the overall sensitivity of methods was between 95% and 30%, of these, two methods reached higher sensitivities; increased levels of pleural IFN-g, with a sensitivity of 95% (CI: 85.5-104.5) with the highest negative predictive value (NPV)=97, (at 82.5% specificity), followed by decreased levels of serum IL-12p40 with a sensitivity of 95% (CI: 85.5-104.5), NPV=95.2 (at 50% specificity). In contrast, microbiological methods showed that smear had a sensitivity of only 20%, while smear plus culture had, a sensitivity of 70%. Considering that TPE represents approximately 15 percent of all the TB clinically diagnosed at the Hospital Vargas de Caracas, in those patients with preliminary microbiology negativity in the effusion, the combined analysis of pleural IFN-g and anti-PPD IgG2 could represent a fast and effective diagnostic algorithm for improving the diagnosis previous to obtain culture results. In this way treatment against TB could be initiated or the need to cytological and pleural biopsy could be considered

La tuberculosis (TB) es una de las principales causas de muerte por infección con Mycobacterium tuberculosis en seres humanos en el ámbito mundial, y es preocupante que su incidencia esté aumentado en los últimos años, debido principalmente a la infección por el virus de inmunodeficiencia humano (VIH). Considerando que los métodos diagnósticos utilizados actualmente para detectar la enfermedad no son totalmente efectivos y rápidos, debido a que el cultivo no es útil como primera opción diagnóstica porque ya que requiere más de 4 semanas y el examen microscópico tiene una sensibilidad de 50 a 60% y es aún más baja en pacientes pediátricos, múltiples esfuerzos se realizan con el objetivo de caracterizar cada vez más los antígenos de M. tuberculosis asociados con protección y para desarrollar rápidos y mejores métodos de diagnóstico. Entre los antígenos secretados de M. tuberculosis y que han sido descritos como inductores de la secreción de mediadores asociados a protección contra la infección por M. tuberculosis están CPF-10, ESAT-6, 27 kDa y 38 kDa, por inducir la producción de IFN-γ, TNF-α y óxido nítrico, todos estos relacionados con una respuesta inmunitaria protectora. A través del estudio de las funciones y composición de estos antígenos, se hacen esfuerzos por encontrar métodos más efectivos en el diagnóstico de la enfermedad, en sus diversas etapas de evolución. La presente revisión tiene como finalidad describir los antígenos que han sido reportados como antígenos relevantes de M. tuberculosis por participar en la respuesta inmunitaria protectora frente a la infección y su posible utilidad en el diagnóstico.

Tuberculosis (TB) is one of the main causes of death by M. tuberculosis infection in humans worldwide and, it is worrying that the number of cases have been increasing in recent years, largely due to HIV infection. Since the diagnostic methods for detecting the disease are not totally effective because of their lack of specificity and sensitivity, efforts are being made to characterize the M. tuberculosis antigens associated with protection and, thereby develop better diagnostic methods. Among the antigens which are secreted by M. tuberculosis -and which have been described as inducers of the secretion of mediators associated with protection- are CPF-10, ESAT-6, 27 kDa and 38 kDa, which induce the production of IFN-γ; TNF-α and nitric oxide. By means of the study of the functions and composition of these antigens, which are mainly secreted by the bacteria, efforts are being made to find more effective methods of diagnosing the disease in its different stages of evolution. The present review aims to describe the antigens which have been reported as being relevant in the case of M. tuberculosis, since they participate in the immune response to infection and therefore, may be important in terms of diagnosis.

Foram dosados anticorpos sIgA anti-Purified Protein Derivative e 38kDa da saliva de 127 crianças, das quais 31 eram de pacientes altamente suspeitos de tuberculose e 96 eram provenientes de crianças saudáveis, que tiveram contato com pacientes. Os resultados referentes à porcentagem de crianças, reativas ao PPD e ao antígeno 38kDa, mostraram que destes dois antígenos, o 38kDa induziu maior reatividade em pacientes positivos e negativos ao Tuberculin Skin Test (28% e 16,6%, respectivamente), em comparação aos controles positivos e negativos ao TST (11,7% e 7,1%, respectivamente). Houve diferença estatisticamente significativa entre pacientes positivos e controles negativos ao Tuberculin Skin Test. Em relação ao antígeno PPD, enquanto 14,2% de pacientes positivos ao TST mostraram anticorpos reativos ao antígeno Purified Protein Derivative, nenhum paciente negativo ao TST foi reativo ao antígeno. Os achados sugerem que, aparentemente, estes dois antígenos estão associados a desenvolvimento distinto dos mecanismos de defesa da mucosa mediados por sIgA contra Mycobacterium tuberculosis.

We report on the measurement of saliva anti-Purified Protein Derivative sIgA and 38kDa antibodies from 127 children, of whom 31 were strong tuberculosis suspects and 96 were healthy contact children. The results concerning the percentage of children with antibody reactivity to PPD and 38kDa antigens showed that, of these 2 antigens, 38kDa induced higher reactivity in patients positive and negative for the Tuberculin Skin Test (28% and 16.6%, respectively) in comparison to controls positive and negative for the TST (11.7% and 7.1%, respectively). There was a statistically significant difference between patients positive and controls negative for the TST. In relation to the Purified Protein Derivative antigen, while 14.2% of patients positive for the TST showed antibody reactivity to the PPD antigen, no patients negative for the TST had reactivity to this antigen. The findings suggest that these two antigens seem be associated with a different development of the mucosal defence mechanisms mediated by sIgA against Mycobacterium tuberculosis.

El sistema respiratorio se encuentra en contacto con patógenos, sin embargo, gracias a la respuesta inmune innata de este, solo en raras ocasiones se establece la enfermedad. Las células epiteliales del tracto respiratorio juegan un papel importante para evitar la colonización del pulmón por agentes infecciosos, identificando a los microorganismos a través de receptores especializados, como los Toll-like,. Las células epiteliales son capaces de secretar citocinas, péptidos antimicrobianos y otras moléculas proinflamatorias las cuales evitan el establecimiento de patógenos.

Resumen. En una población de niños Warao menores de 15 años con una tasa de prevalencia de tuberculosis (TBC) de 3190/100.000 se planteó como objetivo, estudiar ciertos parámetros de la respuesta inmunitaria en una población de 107 niños, de éstos, 32 presentaban TBC (27 PPD positivos y 5 PPD negativos) y 75 eran controles sin clínica de TBC (45 PPD positivos y 30 PPD negativos). Se evaluaron la inmunidad humoral, celular y algunos aspectos de la inmunidad innata. Entre los niños pacientes y controles, no se encontraron diferencias significativas en los componentes C3 y C4 del complemento. En cuanto a la inmunidad humoral, el grupo de pacientes presentó un alto porcentaje de niños con niveles totales de IgA e IgG elevados (13,8% y 79,3%, respectivamente) en comparación con los niños controles (0% y 69,2%). En el grupo control, un alto porcentaje de niños presentaron niveles totales de IgM e IgAs elevados (69,2% y 56,16%, respectivamente) en comparación con los pacientes (48,3% y 31,25%). El 100% de los niños presentó altos niveles séricos de IgE. Los estudios de la respuesta celular retardada mostraron que los niños de mayor edad presentaron las mayores medidas de induraciones. Los niños menores de 7 años presentaron similar reactividad positiva al PPD independientemente de la presencia o no de cicatriz de BCG. Un alto porcentaje de niños sin y con cicatriz (46,8% y 27,6% respectivamente) presentaron medidas de induraciones a la tuberculina de 0 mm. La reactividad a Candida mostró un 80% de niños con estados de anergia no específica. Sin embargo, el mayor porcentaje de niños con TBC estaba vacunado y presentaba positividad a la prueba de tuberculina. En conclusión, en los niños Warao se observó un aumento en los niveles de los componentes C3 y C4 del complemento y una hipergammaglobulinemia. Los resultados de los isotipos mostraron que, la disminución de IgAs podría ser un marcador de enfermedad activa, mientras que el aumento de IgM un marcador de infección reciente. La policlonalidad fue independiente de la reactividad al PPD.

Abstract. The present study was carried out in a Warao childhood population with extremely high tuberculosis (TB) rate of 3190/100,000 in 0-15 years old children. One hundred seven serum and saliva samples were tested, 32 from patients with active TB (27 positive and 5 negative for the tuberculin skin test, TST) and 75 apparently healthy contact children (45 positive and 30 negative for the TST). The innate, immunoglobulin and cellular responses were studied. The results showed that both, patients and controls, had a high percentage of children with increased levels of complement C3 and C4 components. A high percentage of children with increased total serum IgA and IgG (13.8% and 79.3% respectively) was observed in children with TB in comparison to control children (0% and 69.2%). A high percentage of control children had increased levels of IgM and sIgA (69.2% and 56.16%, respectively) in comparison to patients (48.3% and 31.25%). Both groups showed children with increased levels of IgE. The results concerning to the cellular immune response to PPD and the BCG vaccination status showed that there was a correlation between an increase in PPD reactivity and age. The PPD reactivity in children less than 7 years old was similar and also independent of the BCG vaccination status. A significant number of children without or with scars (46.8% and 27.6%, respectively) showed induration values of 0 mm to tuberculin skin test. The Candida reactivity showed a high percentage of children (80%) with anergy status. In conclusion, an increase in the levels of complement components C3 and C4 and hypergammaglobulinemia was observed in Warao children, and these results were independent from PPD reactivity and BCG vaccination. The isotype results showed that the decrease in sIgA could be and active disease marker, while the increase in IgM levels could represent a marker of recent disease.

Lumbar hernias are extremely -+rare and they are occasionally reported. The hernias occurred through the superior lumbar space or triangle of Grynfeltt-Lesshaft, which is more constant and larger, appear more often than those developed through the lumbar triangle of Petit. 2 patients who were diagnosed and surgically treated due to this affection are reported

Las hernias lumbares son sumamentes raras, y se reportan en pocas ocasiones. Las hernias que se producen a través del espacio lumbar superior o de Grynfelt-Lesshaft, por ser éste más constante y de mayor tamaño, suelen aparecer con más frecuencia que las que se producen a través del triángulo de Petit. Se reportan 2 pacientes diagnosticados y tratados quirúrgicamente a causa de esta afección

El diagnóstico definitivo de tuberculosis (TBC) infantil no es fácil en zonas rurales con difícil acceso a centros de salud con una infraestructura adecuada. El presente trabajo consistió en aplicar una metodología simple para diagnosticar TBC infantil en un área con alta prevalencia de Tuberculosis en adultos, la población indígena Warao en Delta Amacuro, Venezuela. La metodología tomó en cuenta parámetros epidemiológicos (contacto intradomiciliario y reactividad a la tuberculina) y criterios clínicos. La aplicación de esta metodología permitió, que a partir de una población total de 502 niños Warao provenientes de San Francisco de Guayo y comunidades vecinas, se seleccionaran 27 niños menores de 15 años con una clínica compatible con TBC, de los cuales 16 (60%) fueron confirmados por radiología, de padecer TBC pulmonar. De estos pacientes, 13 (81%) resultaron positivos a la prueba de tuberculina (PPD). Adicional a la confirmación radiológica, se encontró que de los niños con radiología patológica, 7 (43%) tenían una o más confirmaciones adicionales: 3 pacientes fueron positivos por BK/cultivo (2 PPD negativo) y 5 por serología (1 PPD negativo). Se registró una prevalencia de TBC infantil de 3,2% en la zona en estudio. En conclusión, la aplicación de esta metodología simple permite diagnosticar TBC en poblaciones infantiles con una alta eficiencia y puede ser una herramienta útil para controlar esta patología en poblaciones infantiles en comunidades rurales aisladas.

It is difficult to establish a definitive diagnosis of tuberculosis in rural areas where there is no access to a large hospital. The Warao people of the Delta Amacuro State in Venezuela, have a very high prevalence of adult TB, and we suspected that the Warao children would also have a high prevalence of the disease, almost entirely undiagnosed. We applied a simple methodology to select children suspicious for tuberculosis that is based on a rating system using clinical criteria, reactivity to tuberculin and intradomicilliary contacts. Of the 502 children under the age of 15 that were evaluated with this rating system, 27 were determined to be suspicious of TB and were further evaluated by a chest X-ray. Radiologic confirmation of TB was found in 16 (60%) of the 27 suspicious children. Of these 16 patients, 13 (81%) were PPD positive and 3 were PPD negative. Additionally, 7 of the 16 children with pathologic x-ray changes had one or more confirmatory findings: 3 were positive by culture or smear examination and 5 had a positive serologic B diagnostic test. In conclusion this methodology proved to be highly efficient in diagnosing childhood tuberculosis in this population, and should also be useful in other rural populations with a high prevalence of adult TB