Development of an immunochromatographic lateral flow dipstick for the detection of Mycobacterium tuberculosis 16 kDa antigen (Mtb-strip).

Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium that causes tuberculosis (TB). This contagious disease remains a severe health problem in the world. The disease is transmitted via inhalation of airborne droplets carrying Mtb from TB patients. Early detection of the disease is vital to prevent transmission of the infection to people in close contact with the patients. To date, there is a need of a simple, rapid, sensitive and specific diagnostic test for TB. Previous studies showed the potential of Mtb 16 kDa antigen (Ag16) in TB diagnosis. In this study, lateral flow immunoassay, also called simple strip immunoassay or immunochromatographic test (ICT) for detection of Ag16 was developed (Mtb-strip) and assessed as a potential rapid TB diagnosis method. A monoclonal antibody against Ag16 was optimized as the capturing and detection antibody on the Mtb-strip. Parameters affecting the performance of the Mtb-strip were also optimized before a complete prototype was developed. Analytical sensitivity showed that Mtb-strip was capable to detect as low as 125 ng of purified Ag16. The analytical sensitivity of Mtb-strip suggests its potential usefulness in different clinical applications.

Adaptación cultural al español del cuestionario sobre las dificultades para trabajar con esclerosis múltiple. Versión corta de 23 ítems (MSWDQ-23) / Spanish cultural adaptation of the short version of the Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23)

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Tuberculosis vaccine candidates based on mycobacterial cell envelope components.

Even after decades searching for a new and more effective vaccine against tuberculosis, the scientific community is still pursuing this goal due to the complexity of its causative agent, Mycobacterium tuberculosis (Mtb). Mtb is a microorganism with a robust variety of survival mechanisms that allow it to remain in the host for years. The structure and nature of the Mtb envelope play a leading role in its resistance and survival. Mtb has a perfect machinery that allows it to modulate the immune response in its favor and to adapt to the host's environmental conditions in order to remain alive until the moment to reactivate its normal growing state. Mtb cell envelope protein, carbohydrate and lipid components have been the subject of interest for developing new vaccines because most of them are responsible for the pathogenicity and virulence of the bacteria. Many indirect evidences, mainly derived from the use of monoclonal antibodies, support the potential protective role of Mtb envelope components. Subunit and DNA vaccines, lipid extracts, liposomes and membrane vesicle formulations are some examples of technologies used, with encouraging results, to evaluate the potential of these antigens in the protective response against Mtb.

Advantages of non-cryopreserved autologous hematopoietic stem cell transplantation against a cryopreserved strategy.

Autologous stem cell transplantation (auto-HSCT) is an effective treatment strategy for hematological malignancies. The standard mode of handling hematopoietic progenitors for the autologous procedure (CRYO) consists on its collection and freezing with dimethyl sulfoxide (DMSO) and its subsequent thawing and re-infusion. This process is toxic and expensive. Non-cryopreserved (non-CRYO) is a less expensive mode of auto-HSCT. We designed a comparative study between both strategies performed in two different centers to analyze the short-term complications. In total 111 auto-HSCT were performed from January/2015 to October/2016 (42 non-CRYO and 74 CRYO). There were 74 males and 69 (62%) patients had the underlying diagnosis of multiple myeloma. No differences were seen on the characteristics of the apheresis products and their viability. Engraftment was significantly faster in the non-CRYO group (p = 0.001). Febrile neutropenia and severe mucositis were lower in the non-CRYO group (40% vs 92% p = 0.0001 and 11% vs 64%, p = 0.001, respectively). In addition, length of hospitalization was 5 days shorter in the non-CRYO group (p = 0.0001). Overall responses and transplantation outcomes were similar. Our data demonstrate a clear advantage of the non-CRYO over CRYO auto-HSCT with faster engraftment, lower incidence of febrile neutropenia and shorter hospital stay after the transplantation procedure. These data are especially relevant for centers with high transplant activity or with limited resources.

Síndromes linfoproliferativos gastrointestinales / Gastrointestinal lymphoproliferative syndrome

The gastrointestinal lymphoid system plays a relevant role. The daily and continuous interaction between gastrointestinal lymphocytes with food and intestinal microbes requires precise functioning. The pathologic spectrum of lymphocyte malfunction results in lymphomas. MALT lymphoma is the most frequently diagnosed lymphoma, but there are other lymphoproliferative diseases such as diffuse large B cell lymphoma, mantle cell lymphoma and T associated lymphoma. The gastroenterologist and the endoscopist need to know these diseases in detail to achieve early diagnosis and treatment.

El sistema linfoide de defensa abdominal tiene un relevante rol en el buen funcionamiento sistémico. La interacción diaria y continua con patógenos alimentarios y microbios comensales intestinales precisa un estrecho funcionamiento. Las alteraciones linfoides clonales favorecen el desarrollo de linfomas de diversos tipos. Si bien, el linfoma asociado a tejido linfoide de mucosas (MALT) es el más conocido en contexto de su asociación con Helicobacter pylori, el tracto gastrointestinal se puede ver afectado por otros linfomas como el linfoma difuso de células grandes B y linfomas indolentes como el linfoma folicular, el linfoma del manto y el linfoma T asociado a enteropatía. El gastroenterólogo y endoscopista precisan conocer en detalle estas entidades para un oportuno diagnóstico y adecuado tratamiento.

Leucemia linfoblástica aguda con grave alteración hepática como manifestación inicial: presentación de dos casos y revisión de la literatura / Acute lymphoblastic leukemia causing hepatic failure: report of two cases

Hematological diseases may cause acute hepatic failure and are seldom sought. We report two cases illustrating this situation. A 16-year-old male presented with an acute liver failure: a bone marrow biopsy showed complete infiltration with lymphoid type blasts. A flow cytometry confirmed the presence of an acute lymphoblastic leukemia. The patient died days later. A 20-year-old female presented with acute liver failure: due to a pancytopenia, a bone marrow biopsy was performed, which confirmed the presence of an acute lymphoblastic leukemia. Chemotherapy was started immediately. The patient had a favorable evolution.

Más allá del nomograma de Briganti: individualización de la linfadenectomía utilizando la biopsia selectiva del ganglio centinela durante la prostatectomía radical por cáncer de próstata / Beyond the Briganti nomogram: Individualisation of lymphadenectomy using selective sentinel node biopsy during radical prostatectomy for prostate cancer

Objetivo: Validar la técnica de biopsia selectiva de ganglio centinela en el diagnóstico y estadificación del cáncer de próstata de riesgo intermedio y alto mediante comparación con la linfadenectomía extendida convencional (eLFD) en un estudio prospectivo longitudinal y comparativo. Métodos: Hemos aplicado la técnica a 45 pacientes. Previa inyección intraprostática de 99mTc-nanocoloide y SPECT-TC preoperatoria, se han extraído los ganglios centinela guiados con gammacámara portátil Sentinella® y sonda detectora de rayos gamma laparoscópica. Se completó la eLFD para establecer el valor predictivo negativo de la técnica. Resultados: La SPECT-TC mostró depósitos del radiotrazador fuera del territorio de la eLFD en el 73% de los pacientes y la gammasonda laparoscópica en el 60%. La media de focos activos por paciente en la SPECT-TC fue de 4,3 y con gammasonda laparoscópica de 3,2. La media de ganglios linfáticos centinelas extraídos fue 4,3 (0-14), el 26% fuera del territorio de la eLFD. En 10 pacientes (22%) se encontraron ganglios metastásicos, 6/40 (15%) cuando la prostatectomía fue el tratamiento primario. En todos los casos con ganglios metastásicos hubo, al menos, un ganglio centinela positivo. Se encontraron ganglios centinela metastásicos fuera del territorio de la eLFD en 3/10 pacientes (30%). La sensibilidad fue del 100%, la especificidad del 94,73%, el valor predictivo positivo del 81,81% y el valor predictivo negativo del 100%. Conclusión: La biopsia selectiva del ganglio centinela es superior a la eLFD en el diagnóstico de afectación ganglionar, y puede evitar la eLFD cuando no se encuentren ganglios centinela metastásicos (85%), con las consecuentes ventajas funcionales

Objective: To validate the technique of selective sentinel node biopsy for diagnosing and staging intermediate to high-risk prostate cancer by comparing the technique with conventional extended lymphadenectomy (eLFD) in a prospective, longitudinal comparative study. Methods: We applied the technique to 45 patients. After an intraprostatic injection of 99mTc-nanocolloid and preoperative single-photon emission computed tomography (SPECT/CT), we extracted the sentinel lymph nodes, guided by a portable Sentinella® gamma camera and a laparoscopic gamma-ray detection probe. The eLFD was completed to establish the negative predictive value of the technique. Results: SPECT/CT showed radiotracer deposits outside the eLFD territory in 73% of the patients and the laparoscopic gamma probe in 60%. The mean number of active foci per patient was 4.3 in the SPECT/CT and 3.2 in the laparoscopic gamma probe. The mean number of extracted sentinel lymph nodes was 4.3 (0-14), with 26% outside the eLFD territory. The lymph nodes were metastatic in 10 patients (22%), 6/40 (15%) when the prostatectomy was the primary treatment. In all cases with metastatic lymph nodes, there was at least one positive sentinel node. Metastatic sentinel lymph nodes were found outside the eLFD territory in 3/10 patients (30%). The sensitivity was 100%, the specificity was 94.73%, the positive predictive value was 81.81%, and the negative predictive value was 100%. Conclusion: Selective sentinel node biopsy is superior to eLFD for diagnosing lymph node involvement and can avoid eLFD when metastatic sentinel lymph nodes are not found (85%), with the consequent functional advantages

Beyond the Briganti nomogram: Individualisation of lymphadenectomy using selective sentinel node biopsy during radical prostatectomy for prostate cancer. / Más allá del nomograma de Briganti: individualización de la linfadenectomía utilizando la biopsia selectiva del ganglio centinela durante la prostatectomía radical por cáncer de próstata.

OBJECTIVE: To validate the technique of selective sentinel node biopsy for diagnosing and staging intermediate to high-risk prostate cancer by comparing the technique with conventional extended lymphadenectomy (eLFD) in a prospective, longitudinal comparative study. METHODS: We applied the technique to 45 patients. After an intraprostatic injection of 99mTc-nanocolloid and preoperative single-photon emission computed tomography (SPECT/CT), we extracted the sentinel lymph nodes, guided by a portable Sentinella® gamma camera and a laparoscopic gamma-ray detection probe. The eLFD was completed to establish the negative predictive value of the technique. RESULTS: SPECT/CT showed radiotracer deposits outside the eLFD territory in 73% of the patients and the laparoscopic gamma probe in 60%. The mean number of active foci per patient was 4.3 in the SPECT/CT and 3.2 in the laparoscopic gamma probe. The mean number of extracted sentinel lymph nodes was 4.3 (0-14), with 26% outside the eLFD territory. The lymph nodes were metastatic in 10 patients (22%), 6/40 (15%) when the prostatectomy was the primary treatment. In all cases with metastatic lymph nodes, there was at least one positive sentinel node. Metastatic sentinel lymph nodes were found outside the eLFD territory in 3/10 patients (30%). The sensitivity was 100%, the specificity was 94.73%, the positive predictive value was 81.81%, and the negative predictive value was 100%. CONCLUSION: Selective sentinel node biopsy is superior to eLFD for diagnosing lymph node involvement and can avoid eLFD when metastatic sentinel lymph nodes are not found (85%), with the consequent functional advantages.

Ajuste de intensidad para el trasplante hematopoyético alogénico en leucemia aguda / Intensity adjustment of hematopoietic alogeneic transplantation in acute leukemia

Background: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patient’s age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. Aim: To report our experience with HSCT in patients of different ages with acute leukemia. Material and Methods: Retrospective analysis of 115 allogeneic HSCT performed in patients with acute myeloid or lymphoblastic leukemia. Results: We analyzed the cohort of patients in groups according to age at transplantation: younger than 40 years (n = 74), 41 to 50 years (n = 25) and older than 51 years of age (n = 16). Overall survival (OS), Disease free survival (DFS) and relapse at five years were similar in both groups of patients younger than 50 years (OS 40 and 44% respectively, DFS 38 and 42% respectively and relapse 40% and 34% respectively, p = NS). Patients over 51 years had a five years OS of 12%. However when we analyzed those patients by date and conditioning we found that patients who were treated with MA regimens in the first decade of the transplant program (before 2000) had lower OS compared to those treated after 2000 with RIC (five years OS 49% and 12% respectively, p < 0.01). No significant differences in terms of OS, recurrence or incidence of graft-versus-host disease were found when comparing groups under 40 years, between 41 and 50 years and older than 51 years treated only with RIC. Conclusions: RIC provides the possibility of HSCT in older patients with rates comparable to those obtained in younger patients successfully treated with MA conditioning.

Thrombotic microangiopathy as first manifestation of acute human immunodeficiency virus infection: a case report and review of the literature.

BACKGROUND: We present the case of a patient with acute human immunodeficiency virus infection and a thrombotic microangiopathy as the first clinical manifestation, a presentation that has not, to the best of our knowledge, been previously reported. CASE PRESENTATION: A 35-year-old Bolivian man presented with epistaxis and thrombocytopenia. We found microangiopathic anemia, lymphopenia, elevated lactate dehydrogenase, progressive acute renal failure, negative direct antiglobulin test, and normal activity of ADAMTS13. An human immunodeficiency virus ELISA test was negative, with an human immunodeficiency virus viral load of 10,000,000 RNA copies/mL. Antiretroviral therapy and three sessions of therapeutic plasma exchange were able to control thrombotic microangiopathy. CONCLUSIONS: Hematologic manifestations of human immunodeficiency virus infection are frequent. However, the debut of acute human immunodeficiency virus infection with thrombotic microangiopathy is a rare event. A high index of suspicion and early treatment is required.

METODOLOGÍA PARA EL ANÁLISIS DE CASOS CLÍNICOS EN LOS COMITÉS DE BIOÉTICA: ENFOQUES Y PROPUESTAS DE APOYO / METHODOLOGY FOR ANALYZING CLINICAL CASES IN BIOETHICS COMMITTEES: APPROACHES AND PROPOSED SUPPORT / METODOLOGIA PARA A ANÁLISE DE CASOS CLÍNICOS NOS COMITÊS DE BIOÉTICA: ENFOQUES E PROPOSTA DE APOIO

El presente trabajo examina y evalúa los modelos y las metodologías más importantes para la resolución de casos clínicos: 1) el principialismo, 2) el deontologismo, 3) el consecuencialismo, 4) la casuística, 5) la ética de la virtud y 6) la ética centrada en la persona (o ética "personalista"). Se sopesan las fortalezas y debilidades de cada una y se propone, además, un instrumento que facilite este tipo de análisis. Como grupo, se opta por una metodología que articula tres modelos: el enfoque de la virtud, el enfoque centrado en la persona y estos dos en armonía con una ética centrada en los principios. Las razones para esta opción integral están basadas, fundamentalmente, en el reconocimiento de la supremacía de la dignidad de la persona humana y de que las situaciones clínicas complejas requieren de una mirada integral tanto de la persona como de la práctica clínica. Esta última requiere de virtudes, principios éticos y del reconocimiento del ser humano como un ser dotado de dignidad intrínseca y, a su vez, como fundamento de la ética y de la práctica clínica.

This paper examines and evaluates the models and the most important methods for solving clinical cases; namely, 1) principlism, 2) deontologism, 3) consequentialism, 4) casuistry, 5) virtue ethics and 6) ethics centered on the person (or "personalist" ethics). The strengths and weaknesses of each are weighed and an instrument is proposed to facilitate this type of analysis. As a group, the preference is for a methodology that articulates three models: the virtue approach, the person-centered approach, and these two in harmony with an ethics centered on principles. The reasons for this comprehensive option are based primarily on recognition of the primacy of the dignity of the human person and on acknowledgement that complex clinical situations require a comprehensive view of both the person and clinical practice. The latter requires virtues, ethical principles and recognition of the human person as being endowed with inherent dignity and, in turn, as the foundation of ethics and clinical practice.

Este trabalho examina e avalia os modelos e as metodologias mais importantes para a resolução de casos clínicos: 1) o principialismo; 2) a deontologia; 3) o consequencialismo; 4) a casuística; 5) a ética da virtude e 6) a ética centralizada na pessoa (ou ética "personalista"). Consideram-se as fortalezas e as debilidades de cada uma e propõe-se, além disso, um instrumento que facilite esse tipo de análise. Como grupo, opta-se por uma metodologia que articula três modelos: o enfoque da virtude, o enfoque centralizado na pessoa e esses dois em harmonia com uma ética focada nos princípios. As razões para essa opção integral estão baseadas, fundamentalmente, no reconhecimento da supremacia da dignidade da pessoa humana e de que as situações clínicas complexas requerem de um olhar integral tanto da pessoa quanto da prática clínica. Esta última exige virtudes, princípios éticos e reconhecimento do ser humano como um ser dotado de dignidade intrínseca e, por sua vez, como fundamento da ética e da prática clínica.

[Intensity adjustment of hematopoietic alogeneic transplantation in acute leukemia]. / Ajuste de intensidad para el trasplante hematopoyético alogénico en leucemia aguda.

BACKGROUND: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patient’s age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. AIM: To report our experience with HSCT in patients of different ages with acute leukemia. MATERIAL AND METHODS: Retrospective analysis of 115 allogeneic HSCT performed in patients with acute myeloid or lymphoblastic leukemia. RESULTS: We analyzed the cohort of patients in groups according to age at transplantation: younger than 40 years (n = 74), 41 to 50 years (n = 25) and older than 51 years of age (n = 16). Overall survival (OS), Disease free survival (DFS) and relapse at five years were similar in both groups of patients younger than 50 years (OS 40 and 44% respectively, DFS 38 and 42% respectively and relapse 40% and 34% respectively, p = NS). Patients over 51 years had a five years OS of 12%. However when we analyzed those patients by date and conditioning we found that patients who were treated with MA regimens in the first decade of the transplant program (before 2000) had lower OS compared to those treated after 2000 with RIC (five years OS 49% and 12% respectively, p < 0.01). No significant differences in terms of OS, recurrence or incidence of graft-versus-host disease were found when comparing groups under 40 years, between 41 and 50 years and older than 51 years treated only with RIC. CONCLUSIONS: RIC provides the possibility of HSCT in older patients with rates comparable to those obtained in younger patients successfully treated with MA conditioning.

HLA Class II Antibody Activation of Endothelial Cells Promotes Th17 and Disrupts Regulatory T Lymphocyte Expansion.

Kidney transplantation is the most successful treatment option for patients with end-stage renal disease, and chronic antibody-mediated rejection is the principal cause of allograft loss. Predictive factors for chronic rejection include high levels of HLA alloantibodies (particularly HLA class II) and activation of graft endothelial cells (ECs). The mechanistic basis for this association is unresolved. We used an experimental model of HLA-DR antibody stimulation of microvascular ECs to examine the mechanisms underlying the association between HLA class II antibodies, EC activation and allograft damage. Activation of ECs with the F(Ab')2 fragment of HLA-DR antibody led to phosphorylation of Akt, ERK and MEK and increased IL-6 production by ECs cocultured with allogeneic peripheral blood mononuclear cells (PBMCs) in an Akt-dependent manner. We previously showed that HLA-DR-expressing ECs induce polarization of Th17 and FoxP3(bright) regulatory T cell (Treg) subsets. Preactivation of ECs with anti-HLA-DR antibody redirected EC allogenicity toward a proinflammatory response by decreasing amplification of functional Treg and by further increasing IL-6-dependent Th17 expansion. Alloimmunized patient serum containing relevant HLA-DR alloantibodies selectively bound and increased EC secretion of IL-6 in cocultures with PBMCs. These data contribute to understanding of potential mechanisms of antibody-mediated endothelial damage independent of complement activation and FcR-expressing effector cells.

Amiloidosis por cadenas livianas de inmunoglobulina con compromiso gástrico al debut: revisión de la literatura basada en un caso clínico / Gastric AL amyloidosis as initial manifestation: literature review from a case report

Systemic amyloidosis comprises a group of diseases characterized by low molecular weight subunit protein deposit in organs, including the gastrointestinal tract. The most frequent clinical manifestations are gastrointestinal bleeding, malabsorption syndrome, protein-losing enteropathy and chronic intestinal dysmotility. The diagnosis is confirmed with gastrointestinal tissue biopsy positive to Congo red stain or recognizing the amyloid fibrils by electron microscopy. The treatment is based in the management of gastrointestinal symptoms and chemotherapeutic drugs, including melphalan and prednisone or cyclophosphamide, bortezomib and prednisone. The bone marrow transplant is reserved for 70-year-old patients or younger without advanced comorbidities. We present a case of a patient with weight loss, anorexia, nausea and early satiety.

La amiloidosis sistémica a un conjunto de enfermedades caracterizadas por el depósito de subunidades fibrilares proteicas de bajo peso molecular en órganos, incluyendo el sistema digestivo. Sus manifestaciones clínicas más frecuentes son la hemorragia digestiva, síndrome malabsortivo, gastro-enteropatía perdedora de proteínas y dismotilidad gastrointestinal crónica. El diagnóstico se confirma con una biopsia de tejido gastrointestinal positiva a tinción rojo Congo o la visualización de fibrillas de amiloide mediante microscopia electrónica. El tratamiento está basado el manejo de los síntomas gastrointestinales y el oncológico, donde destacan esquemas quimioterapéuticos que incluyen melfalan y prednisona o ciclofosfamida, bortezomib y prednisona. El trasplante de médula ósea está reservado a pacientes menores de 70 años sin comorbilidades avanzadas. Presentamos en este artículo el caso de un paciente con baja de peso, anorexia, náuseas y saciedad precoz.

[Acquired hemophagocytic syndrome treated with HLH 94-04 chemotherapy protocol: Report of four cases]. / Síndrome hemofagocítico adquirido: reporte de casos de cuatro pacientes adultos tratados con protocolo HLH 94-04 y revisión de la literatura.

Hemophagocytic syndrome is a severe condition of excessive immune activation that has a high mortality in the absence of treatment. The syndrome is classified as primary if associated with congenital or hereditary problems, or secondary/acquired if associated with infectious, autoimmune or oncology diseases. We report four adult cases of the syndrome, one with viral, two with autoimmune and one with idiopathic causes who were successfully treated with HLH 94-04 chemotherapy protocol. Our experience shows that a high index of suspicion, early diagnosis and an opportune therapy are essential in the treatment of this disease.

Síndrome hemofagocítico adquirido: reporte de casos de cuatro pacientes adultos tratados con protocolo HLH 94-04 y revisión de la literatura / Acquired hemophagocytic syndrome treated with HLH 94-04 chemotherapy protocol: Report of four cases

Hemophagocytic syndrome is a severe condition of excessive immune activation that has a high mortality in the absence of treatment. The syndrome is classified as primary if associated with congenital or hereditary problems, or secondary/acquired if associated with infectious, autoimmune or oncology diseases. We report four adult cases of the syndrome, one with viral, two with autoimmune and one with idiopathic causes who were successfully treated with HLH 94-04 chemotherapy protocol. Our experience shows that a high index of suspicion, early diagnosis and an opportune therapy are essential in the treatment of this disease.