Analysis of apheresis outcomes in a cohort of Chilean patients treated with autologous stem cell transplantation: A single center real-world experience.

Adequate stem cell harvesting is required for autologous hematopoietic transplantation. In deficient mobilizer patients, the collection of stem cells can be challenging because of the impossibility of achieving satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent and expensive drug that promotes the release of stem cells from the medullary niche to the peripheral blood and allows satisfactory harvests. We performed a retrospective analysis of 370 patients with myeloma and lymphoma harvested at our institution. 99 % of patients achieved satisfactory apheresis using Plerixafor in 45 %. Satisfactory harvests were obtained in patients mobilized with GCSF or plerixafor. In patients who used plerixafor, it was necessary to perform fewer apheresis procedures (P = 0.05). In multivariate analysis, the only factor that predicted the need for plerixafor was the presence of less than 30,000 CD34 / ul on the day of apheresis (OR 0.3. p < 0.001). Since we adopted the plerixafor protocol guided by CD34 counts, the number of patients with harvest failure has decreased. In conclusion, the rational and standardized use of plerixafor favors satisfactory harvest in patients who require autologous transplantation in South-American patients.

Análisis del manejo del linfoma de Hodgkin clásico durante 10 años en el Hospital Clínico Red Salud UC-Christus con énfasis en el uso del PET CT / Decade of Hodgkin lymphoma: PET CT vs biopsy in single Academic Chilean Center

INTRODUCCIÓN: El Linfoma de Hodgkin (LH) es una causa prevalente de morbilidad por Cáncer Hematológico en el mundo y también en nuestro entorno. OBJETIVOS: Mostrar la experiencia de diez años tratando el LH en un centro docente chileno. Adicionalmente, exponer el rendimiento de diagnóstico del PET CT y la Biopsia de Médula Ósea. MATERIAL Y MÉTODOS: Se realiza un estudio de Cohorte retrospectivo para recopilar datos y resultados de los pacientes tratados en nuestro centro. RESULTADOS: Se analizaron 82 pacientes (edad promedio 35 años. Razón entre hombres y mujeres de 1,9:1). La sobrevida libre de progresión de 88,6% y 66,4% para estadios localizados y avanzados respectivamente. El PET como estrategia de etapificación tuvo mejor sensibilidad al comparar con la Biopsia de Médula. CONCLUSIONES: El resultado clínico de los pacientes tratados en este centro docente chileno fueron comparables a la literatura internacional. Adicionalmente, el PET CT evidenció ser una herramienta superior en el diagnóstico y etapificación superior a la biopsia en nuestros pacientes.

INTRODUCTION: Hodgkin Lymphoma (HL) is a prevalent hematological cancer in the world and Chile. OBJECTIVES: Show the experience of 10 years treating HL in a Chilean academic center. Additionally, it exposes the diagnostic performance of PET CT and Bone Marrow Biopsy. MATERIAL AND METHODS: We conducted a retrospective cohort study to collect data and outcomes of patients treated in our center. RESULTS: 82 patients were analyzed (Average age, 35 years old; the ratio between men and women was 1.9:1). Progression-free survival was 88.6% and 66.4% for localized and advanced stages, respectively. PET as a staging strategy had better sensitivity than Marrow Biopsy. CONCLUSIONS: The clinical results of the patients treated in this Chilean teaching center were comparable to the international literature. Additionally, PET CT proved to be a superior tool in diagnosis and staging compared to biopsy in our patients.

[Decade of Hodgkin lymphoma: PET CT vs biopsy in single Academic Chilean Center]. / Análisis del manejo del linfoma de Hodgkin clásico durante 10 años en el Hospital Clínico Red Salud UC-Christus con énfasis en el uso del PET CT.

INTRODUCTION: Hodgkin Lymphoma (HL) is a prevalent hematological cancer in the world and Chile. OBJECTIVES: Show the experience of 10 years treating HL in a Chilean academic center. Additionally, it exposes the diagnostic performance of PET CT and Bone Marrow Biopsy. MATERIAL AND METHODS: We conducted a retrospective cohort study to collect data and outcomes of patients treated in our center. RESULTS: 82 patients were analyzed (Average age, 35 years old; the ratio between men and women was 1.9:1). Progression-free survival was 88.6% and 66.4% for localized and advanced stages, respectively. PET as a staging strategy had better sensitivity than Marrow Biopsy. CONCLUSIONS: The clinical results of the patients treated in this Chilean teaching center were comparable to the international literature. Additionally, PET CT proved to be a superior tool in diagnosis and staging compared to biopsy in our patients.

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.

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.

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.

Complementary and alternative medicines usage in bipolar patients from Argentina and Colombia: associations with satisfaction and adherence to treatment.

BACKGROUND: The use of Complementary and Alternative Medicines (CAM) has been reported by around half the patients undergoing medical treatment for chronic conditions. CAM use could be higher in people affected by bipolar disorders (BD). Some questions about CAM use in BD have not been investigated enough. We report here the results of an anonymous survey on CAM-use conducted among BD outpatients of two centers located in Argentina and Colombia. METHODS: an anonymous self-survey was administrated to bipolar euthymic outpatients treated at each center. The survey included a self-report measure of adherence to psychiatric treatment and a modified version of CGI to asses satisfaction with the current treatment. RESULTS: 200 patients completed the survey. Although samples differ in socio-economic profile, they do not differ in their reported CAM-usage (more than 40%). CAM-usage did not modify the adherence or satisfaction with the psychiatric treatment reported level. Thirty eight percent of those who were still resorting to CAM failed to inform it to their clinician. CAM-usage was rated as "useful" or "very useful" by 52% of patients. LIMITS: adherence to current medical treatment and satisfaction with current treatment were investigated by a self-reported instrument. DISCUSSION: the prevalence of CAM usage found is similar to that of other studies. CAM usage seems to be ubiquitous, which takes to posit that a subgroup of patients may be in need of treatment with greater magical-religious components. Half of these patients were reluctant to disclose CAM use. Clinicians may need to consider coexistence between "traditional" treatments and CAM for these patients.

Más allá de laseelección natural / Beyond Natural Selection

La explicación de la evolución de los organismos a través de selección natural es el núcleo del sistema conceptual de la biología gracias a su sencillez, a su poder explicativo así como a su coherencia con una cantidad impresionante de datos. No obstante, en algunos casos se ha transformado en un discurso por defecto que no permite penetrar y descubrir procesos mucho más complejos. Esta dificultad ha sido puntualizada por varios autores y el presente documento hace una síntesis de alternativas o delimitaciones al modelo de evolución por selección natural en varios niveles: se exploran las consecuencias del neutralismo genético. Se revisa cómo la complejidad de la relación genotipo y fenotipo puede dificultar la aplicación de un modelo genético simple de evolución por selección natural. Se discute la propuesta de extender la idea de neutralidad a los fenotipos mediante el modelo de equivalencia funcional. Se detallan algunos de los aspectos controversiales en la aplicación del concepto de adaptación y se discute cómo incluir la historia filogenética de los caracteres propuestos como adaptativos puede enriquecer la explicación de los mismos. Se revisan las consecuencias de estos análisis en cuatro áreas: adaptación, definición de especie, reconstrucción filogenética y conservación. Este documento en ningún momento niega el valor del modelo de evolución por selección natural, pero sí puntualiza la importancia de modelos distintos fuertemente afianzados en datos concretos rigurosamente analizados.

The explanation of the evolution of organisms through natural selection is the nucleus of the system of concepts of the biology thanks to is simplicity, its explanatory power and its coherence with an impressive amount of data. However, in some cases this model has become a by default discourse that does not allow to penetrate and discover much more complex processes. This difficulty has been pointed out by several authors and the present paper summarizes several of the alternatives or delimitations at several levels: the consequences of genetic neutralism are explored. The implications of the complex relationship between genotype and phenotype are studied since these may made difficult the use of simple genetic models for the study of evolution by natural selection. The proposal of extending a neutral model for morphological traits through the concept of functional equivalence is discussed. Some of the controversial aspects of the use of the concept of adaptation are analyzed and the insightful effect of including the phylogenetic history in the explanation of the origin of the proposed adaptive characters is discussed. The consequences of these analyses are reviewed in four areas: adaptation, species definition, phylogenetic reconstructions and conservation. At no point this document denies the value of the model of evolution by natural selection but points out the importance of alternative models strongly supported by data rigorously analyzed.

Study of KIR genes in tuberculosis patients.

A total of 97 patients with tuberculosis (TB) and 51 controls from Xalapa, Veracruz, Mexico, were studied for the presence and absence of killer cell immunoglobulin-like receptor (KIR) genes. The number of patients with either KIR2DL1 or KIR2DL3 differed significantly compared with the controls. However, only the difference in KIR2DL3 remained significant after correction for the number of factors analysed. We also found KIR2DS2 with its presumed C1 group ligand less prevalent in TB patients than in the control group, but this result lost significance after correction.

Violencia: prioritaria enfermedad que debe ser prevenida / Violence: high-priority disease that must be prevented

En este trabajo, el autor examina la problemática de la violencia como un fenómeno universal, sobre el que la OMS ha señalado una importante enfermedad de dimensiones globales. Además, ilustra las estrategias de prevención propuestas y hace un examen crítico de las mismas, para ofrecer nuevos elementos de análisis no considerados en torno al problema.

Mutagencity and antimutagencity studies of lipidic extracts from yellowtail fish (Seriola lalandi), lisa fish (Mugil cephalus) and cazón fish (Mustelus lunulatus).

Organic extracts from fresh and smoked yellowtail fish (Seriola lalandi), lisa fish (Mugil cephalus) and cazon fish (Mustelus lunulatus) were tested for mutagenicity using Ames Salmonella tester strains TA98 and TA100 with metabolic activation (S9). Also, the antimutagenicity of the organic extract from yellowtail fish was tested against aflatoxin B1 (AFB1). Yellowtail fish extract was sequentially fractionated by thin-layer chromatography (TLC) and each fraction was also tested for antimutagenicity. None of the fresh species showed mutagenicity. Extract from smoked yellowtail showed the highest mutagenic potential among the smoked species tested. Organic extract from fresh yellowtail reduced the number of revertants caused by AFB1 showing a dose response type of relationship. Sequential TLC fractionation of the antimutagenic extract produced four antimutagenic fractions from fresh yellowtail fish. These results that the lipidic fraction of the species tested contains at least four compounds with chemoprotective properties that reduce the mutagenicity of AFB1.