The Pulmonary Endothelial Glycocalyx Modifications in Glypican 1 Knockout Mice Do Not Affect Lung Endothelial Function in Physiological Conditions.

The endothelial glycocalyx is a dynamic signaling surface layer that is involved in the maintenance of cellular homeostasis. The glycocalyx has a very diverse composition, with glycoproteins, proteoglycans, and glycosaminoglycans interacting with each other to form a mesh-like structure. Due to its highly interactive nature, little is known about the relative contribution of each glycocalyx constituent to its overall function. Investigating the individual roles of the glycocalyx components to cellular functions and system physiology is challenging, as the genetic manipulation of animals that target specific glycocalyx components may result in the development of a modified glycocalyx. Thus, it is crucial that genetically modified animal models for glycocalyx components are characterized and validated before the development of mechanistic studies. Among the glycocalyx components, glypican 1, which acts through eNOS-dependent mechanisms, has recently emerged as a player in cardiovascular diseases. Whether glypican 1 regulates eNOS in physiological conditions is unclear. Herein, we assessed how the deletion of glypican 1 affects the development of the pulmonary endothelial glycocalyx and the impact on eNOS activity and endothelial function. Male and female 5-9-week-old wild-type and glypican 1 knockout mice were used. Transmission electron microscopy, immunofluorescence, and immunoblotting assessed the glycocalyx structure and composition. eNOS activation and content were assessed by immunoblotting; nitric oxide production was assessed by the Griess reaction. The pulmonary phenotype was evaluated by histological signs of lung injury, in vivo measurement of lung mechanics, and pulmonary ventilation. Glypican 1 knockout mice showed a modified glycocalyx with increased glycocalyx thickness and heparan sulfate content and decreased expression of syndecan 4. These alterations were associated with decreased phosphorylation of eNOS at S1177. The production of nitric oxides was not affected by the deletion of glypican 1, and the endothelial barrier was preserved in glypican 1 knockout mice. Pulmonary compliance was decreased, and pulmonary ventilation was unaltered in glypican 1 knockout mice. Collectively, these data indicate that the deletion of glypican 1 may result in the modification of the glycocalyx without affecting basal lung endothelial function, validating this mouse model as a tool for mechanistic studies that investigate the role of glypican 1 in lung endothelial function.

Survival in Elderly Patients Diagnosed With Acute Myeloid Leukemia: A Hospital-Based Study.

Background: Acute myeloid leukemia (AML) is a hematological neoplasm that is more frequent in elderly patients. The objective of this study was to evaluate elderly patients' survival with de novo AML and acute myeloid leukemia myelodysplasia-related (AML-MR), treated with intensive and less-intensive chemotherapy and supportive care. Methods: A retrospective cohort study was conducted in Fundacion Valle del Lili (Cali, Colombia), between 2013 and 2019. We included patients ≥ 60 years old diagnosed with AML. The statistical analysis considered the leukemia type (de novo vs. myelodysplasia-related) and treatment (intensive chemotherapy regimen, less-intensive chemotherapy regimen, and without chemotherapy). Survival analysis was performed using Kaplan-Meier method and Cox regression models. Results: A total of 53 patients were included (31 de novo and 22 AML-MR). Intensive chemotherapy regimens were more frequent in patients with de novo leukemia (54.8%), and 77.3% of patients with AML-MR received less-intensive regimens. Survival was higher in the chemotherapy group (P = 0.006), but with no difference between chemotherapy modalities. Additionally, patients without chemotherapy were 10 times more likely to die than those who received any regimen, independent of age, sex, Eastern Cooperative Oncology performance status, and Charlson comorbidity index (adjusted hazard ratio (HR) = 11.6, 95% confidence interval (CI) 3.47 - 38.8). Conclusions: Elderly patients with AML had longer survival time when receiving chemotherapy, regardless of the type of regimen.

Patch clamp studies on TRPV4-dependent hemichannel activation in lens epithelium.

ATP release from the lens via hemichannels has been explained as a response to TRPV4 activation when the lens is subjected to osmotic swelling. To explore the apparent linkage between TRPV4 activation and connexin hemichannel opening we performed patch-clamp recordings on cultured mouse lens epithelial cells exposed to the TRPV4 agonist GSK1016790A (GSK) in the presence or absence of the TRPV4 antagonist HC067047 (HC). GSK was found to cause a fast, variable and generally large non-selective increase of whole cell membrane conductance evident as a larger membrane current (Im) over a wide voltage range. The response was prevented by HC. The GSK-induced Im increase was proportionally larger at negative voltages and coincided with fast depolarization and the simultaneous disappearance of an outward current, likely a K+ current. The presence of this outward current in control conditions appeared to be a reliable predictor of a cell's response to GSK treatment. In some studies, recordings were obtained from single cells by combining cell-attached and whole-cell patch clamp configurations. This approach revealed events with a channel conductance 180-270 pS following GSK application through the patch pipette on the cell-attached side. The findings are consistent with TRPV4-dependent opening of Cx43 hemichannels.

Development of a Scale to Measure Healthy Behaviors in Spanish-Speaking University Students.

Chronic non-communicable diseases (NCDs) are a public health problem that affect the quality of life and well-being of people, especially the youth, who have been identified as a high-risk population. Physical inactivity is a key risk factor for NCDs, and an unhealthy diet is a significant driver of NCDs. On the other hand, physical exercise and healthy habits are effective methods of prevention. Although there are scales that measure different behaviors related to NCDs, most of them have been developed in another language (e.g., English) or only focus on one aspect of NCDs. The present study aimed to develop a scale to assess healthy behaviors (i.e., healthy eating and physical exercise) in Spanish-speaking university students, using an instrumental design, with a sample of 369 Chilean university students between 18 and 25 years of age. The results presented show evidence of validity through an exploratory structural equation model (ESEM), reliability estimation through McDonald's omega and Cronbach's alpha, evidence of invariance by sex, and evidence of validity in relation to other variables with an SEM model. It is concluded that the Healthy Behavior Scale, consisting of nine items to measure healthy eating and physical exercise, is a brief instrument with evidence of reliability and validity (CFI = 0.998; TLI = 0.995; and RMSEA = 0.063) for application in a Spanish-speaking university population, offering potential applications in research instruments, screening studies, and the development of new studies for other contexts.

Haploidentical and Matched Sibling Transplantation for Acute Myeloid Leukemia: A Hospital-Based Study.

Background: Allogeneic peripheral blood stem cell transplantation (PBSCT) has been increasing for the last years in Latin America. The objective of this study was to describe clinical outcomes in acute myeloid leukemia (AML) receiving allogeneic PBSCT between 2013 and 2019 in a single center of Cali, Colombia. Methods: A retrospective cohort study was conducted in Fundacion Valle del Lili. Patients diagnosed with AML who received an allogeneic PBSCT between 2013 and 2019 using human leukocyte antigen (HLA)-matched sibling donors (MSDs) or haploidentical related donors (HRDs) with myeloablative conditioning regimen were included. Cases with diagnosis of promyelocytic leukemia, myelodysplastic syndrome-related AML and therapy-related AML were excluded. Data were obtained directly from the hospital PBSCT database and clinical records. Results: A total of 50 patients were included (HRD, n = 32; MSD, n = 18). Sixty-two percent was in the first complete remission (CR1) at the time of the transplant, of which 26% were MSD and 74% were HRD. The European Group for Blood and Marrow Transplantation (EBMT) risk score was: 44% vs. 50% low, 28% vs. 28% intermediate and 28% vs. 22% high for MSD vs. HRD, respectively. Overall survival at 5 years for MSD was 62% (95% confidence interval (CI): 31-83%) and 43% (95% CI: 25-60%) for HRD. Event-free survival was 56% (95% CI: 26-78%) and 35.6% (95% CI: 18-53%), respectively. Non-relapse mortality at day-100 was 6% (95% CI: 0.8-35%) and 20% (95% CI: 9-39%). Relapse at5 years was 18% (95% CI: 4-58%) and 25% (95% CI: 10-52%). Overall mortality rate was 46%. The grade II-IV, III-IV acute graft-versus-host disease and severe chronic graft-versus-host disease was 44%, 11% and 12% for MSD, and 43%, 9% and 0% for HRD. Conclusion: These results underline that MSD remains the first donor choice for AML patients in CR1 when available. HRDs are still our next option among alternative donors. It is necessary to find strategies that have a positive impact on those outcomes that markedly affect the quality of allogeneic PBSCT and the prognosis of patients. Comparative, randomized, prospective studies with longer follow-up of haploidentical allogeneic PBSCT with other donor types are required to definitely establish its role among alternative donors.

Activation of Piezo1 Increases Na,K-ATPase-Mediated Ion Transport in Mouse Lens.

Lens ion homeostasis depends on Na,K-ATPase and NKCC1. TRPV4 and TRPV1 channels, which are mechanosensitive, play important roles in mechanisms that regulate the activity of these transporters. Here, we examined another mechanosensitive channel, piezo1, which is also expressed in the lens. The purpose of the study was to examine piezo1 function. Recognizing that activation of TRPV4 and TRPV1 causes changes in lens ion transport mechanisms, we carried out studies to determine whether piezo1 activation changes either Na,K-ATPase-mediated or NKCC1-mediated ion transport. We also examined channel function of piezo1 by measuring calcium entry. Rb uptake was measured as an index of inwardly directed potassium transport by intact mouse lenses. Intracellular calcium concentration was measured in Fura-2 loaded cells by a ratiometric imaging technique. Piezo1 immunolocalization was most evident in the lens epithelium. Potassium (Rb) uptake was increased in intact lenses as well as in cultured lens epithelium exposed to Yoda1, a piezo1 agonist. The majority of Rb uptake is Na,K-ATPase-dependent, although there also is a significant NKCC-dependent component. In the presence of ouabain, an Na,K-ATPase inhibitor, Yoda1 did not increase Rb uptake. In contrast, Yoda1 increased Rb uptake to a similar degree in the presence or absence of 1 µM bumetanide, an NKCC inhibitor. The Rb uptake response to Yoda1 was inhibited by the selective piezo1 antagonist GsMTx4, and also by the nonselective antagonists ruthenium red and gadolinium. In parallel studies, Yoda1 was observed to increase cytoplasmic calcium concentration in cells loaded with Fura-2. The calcium response to Yoda1 was abolished by gadolinium or ruthenium red. The calcium and Rb uptake responses to Yoda1 were absent in calcium-free bathing solution, consistent with calcium entry when piezo1 is activated. Taken together, these findings point to stimulation of Na,K-ATPase, but not NKCC, when piezo1 is activated. Na,K-ATPase is the principal mechanism responsible for ion and water homeostasis in the lens. The functional role of lens piezo1 is a topic for further study.

Cytomegalovirus disease in patients with hematopoietic stem cell transplantation, experience over 8 years

Abstract Objective Cytomegalovirus infection and disease are significant causes of morbidity and mortality among patients with hematopoietic stem cell transplantation. The aim of this study was to assess the frequency of cytomegalovirus infection and characterize the patients who developed the disease. Methods A retrospective cohort study was performed among adult patients, recipients of allogeneic HSTC between 2008 and 2015. Taking into account the institutional protocol of prophylaxis infections in hematopoietic stem cell transplantation, patients received either preemptive therapy or prophylaxis with valganciclovir. Infection was defined as a positive pp65 antigenemia assay or PCR higher than 500 copies/mL. Disease was defined as viremia with evidence of end organ damage. Results Seventy patients were included, the median age was 36 years old (IQR 17-62). A total of 93% of the recipients had a positive serology. The Cytomegalovirus infection occurred in 59% of the patients. Eleven patients developed disease (16%), the most frequent manifestation being colitis, followed by pneumonitis and a single case of retinitis. There were no differences between the preemptive therapy or prophylaxis groups. The mean time of onset of the disease was day 94 post-transplant. Three patients developed disease with a viral load lower than 1000 copies/mL. Conclusion The incidence of cytomegalovirus infection after transplantation at our institution is high. It was found that the disease can occur with any level of viral load and is associated with high mortality.

Cytomegalovirus disease in patients with hematopoietic stem cell transplantation, experience over 8 years.

OBJECTIVE: Cytomegalovirus infection and disease are significant causes of morbidity and mortality among patients with hematopoietic stem cell transplantation. The aim of this study was to assess the frequency of cytomegalovirus infection and characterize the patients who developed the disease. METHODS: A retrospective cohort study was performed among adult patients, recipients of allogeneic HSTC between 2008 and 2015. Taking into account the institutional protocol of prophylaxis infections in hematopoietic stem cell transplantation, patients received either preemptive therapy or prophylaxis with valganciclovir. Infection was defined as a positive pp65 antigenemia assay or PCR higher than 500copies/mL. Disease was defined as viremia with evidence of end organ damage. RESULTS: Seventy patients were included, the median age was 36 years old (IQR 17-62). A total of 93% of the recipients had a positive serology. The Cytomegalovirus infection occurred in 59% of the patients. Eleven patients developed disease (16%), the most frequent manifestation being colitis, followed by pneumonitis and a single case of retinitis. There were no differences between the preemptive therapy or prophylaxis groups. The mean time of onset of the disease was day 94 post-transplant. Three patients developed disease with a viral load lower than 1000copies/mL. CONCLUSION: The incidence of cytomegalovirus infection after transplantation at our institution is high. It was found that the disease can occur with any level of viral load and is associated with high mortality.

Trasplante haploidéntico de progenitores hematopoyéticos en pacientes con diagnóstico de leucemia mieloide aguda / Haploidentical transplantation of hematopoietic progenitors in patients diagnosed with acute myeloid leukemia

Resumen Introducción: En pacientes con leucemia mieloide aguda (LMA) el trasplante de progenitores hematopoyético (TPH) es el único tratamientoz curativo. El objetivo de este estudio es presentar la experiencia y resultados del trasplante haploidéntico en pacientes adultos con LMA en la Fundación Valle del Lili, Cali - Colombia. Materiales y métodos: Estudio de cohorte retrospectivo de pacientes que recibieron trasplante haploidéntico entre 2013 y 2017, con acondicionamiento mieloablativo y ciclofosfamida postrasplante, en Fundación Valle del Lili, Cali (Colombia). Resultados: Se realizaron 47 trasplantes en pacientes con leucemia mieloide aguda en la fecha de estudio, se incluyeron en el análisis 21 pacientes con donante haploidéntico, a 3 años tanto la supervivencia global y libre de eventos fue del 38%. La incidencia acumulada de mortalidad relacionada al trasplante fue del 26% a 100 días y del 38,3%, a 38 meses de seguimiento. La incidencia acumulada de recaída a 38 meses fue del 19%. Con respecto a la enfermedad injerto versus huésped (EICH) se encontró que la incidencia acumulada de EICH aguda grado II-IV, grado III-IV y EICH crónico fue del 19%, 5% y 19% respectivamente. Conclusión: Los resultados de este estudio sugieren que el trasplante haploidéntico es una alternativa factible como tratamiento para pacientes con diagnóstico de LMA en nuestro medio.

Abstract Introduction: In patients with acute myeloid leukemia (AML), hematopoietic progenitor transplantation (PHT) is the only curative treatment. The objective of this study is to present the experience and results of haploidentical transplantation in adult patients with AML at the Valle del Lili Foundation, Cali - Colombia. Materials and methods: Retrospective cohort study of patients who received haploidentical transplantation between 2013 and 2017, with myeloablative conditioning and post-transplant cyclophosphamide, in Fundación Valle del Lili, Cali (Colombia). Results: 47 transplants were performed in patients with acute myeloid leukemia on the study date, 21 patients with haploidentical donors were included in the analysis, at 3 years both overall and event-free survival was 38%. The cumulative incidence of transplant-related mortality was 26% at 100 days and 38.3% at 38 months of follow-up. The cumulative incidence of relapse at 38 months was 19%. Regarding graft versus host disease (GVHD), it was found that the cumulative incidence of acute GVHD grade II-IV, grade III-IV and chronic GVHD was 19%, 5% and 19% respectively. Conclusion: The results of this study suggest that haploidentical transplantation is a feasible alternative as a treatment for patients diagnosed with AML in our environment.

Trasplante autólogo de células madre hematopoyéticas en pacientes con diagnóstico de mieloma múltiple, experiencia en 9 años / Autologous stem cell transplant in patients with multiple myeloma, experience of 9 years

Resumen Objetivo: El mieloma múltiple representa la primera causa de trasplante autólogo de células madre hematopoyéticas (TCMH). El objetivo del presente trabajo es describir los resultados del TCMH en pacientes con diagnóstico de mieloma múltiple en la Fundación Valle del Lili. Materiales y métodos: Se realizó un estudio observacional, descriptivo de una cohorte retrospectiva, se incluyeron pacientes mayores de 18 años con TCMH autólogo tratados entre 2008 y 2016. Los desenlaces fueron: supervivencia global, supervivencia libre de progresión y la respuesta de la enfermedad postrasplante. Se realizó un análisis estadístico descriptivo y el análisis de supervivencia se hizo con el método Kaplan-Meier. Resultados: Durante el periodo de estudio se trasplantaron 103 pacientes. La mediana de la edad fue 57 años. El subtipo de inmunoglobulina secretada fue: 75% de IgG, 18% de IgA, 5% no secretor y 2% oligosecretor. El estadio Durie Salmon en la mayoría fue IIIA (43,7%). Previo al trasplante la mayoría de los pacientes estaba en muy buena respuesta parcial (31%), seguido por respuesta completa (25,2%) y respuesta parcial (19,4%). La supervivencia global y libre de progresión a 5 años fue de 71% y de 40%, respectivamente. Posterior al trasplante: el 33% de los pacientes estaba en muy buena respuesta parcial, el 25% en respuesta completa estricta, el 22% en respuesta completa, el 12% en respuesta parcial y el 8% en enfermedad progresiva o recaída. Conclusión: El TCMH autólogo es una estrategia que se asocia a buenas tasas de supervivencia, baja toxicidad y adecuada respuesta de la enfermedad postrasplante.

Abstract Objective: Multiple myeloma in Colombia is the one of the main reasons for autologous hematopoietic stem cell transplantation (HSCT). The aim of this study is to describe the results of the HSCT in adult patients diagnosed with multiple myeloma in the Fundación Valle del Lili. Materials and methods: An observational, descriptive study of a retrospective cohort was carried out. Patients older than 18 years with a diagnosis of multiple myeloma with autologous HSCT between 2008 and 2016 were included. The outcomes were overall survival, progression-free survival, and post-transplant disease response. A descriptive statistical analysis was carried out for all the variables considered in the analysis. The survival analysis was performed using the Kaplan-Meier method. Results: During the study period, transplants were performed on 103 patients with a diagnosis of multiple myeloma. The median age was 57 years. The subtype of secreted immunoglobulin was 75% IgG, 18% IgA, 5% non-secretor, and 2% oligo-secretor. The majority of patients were in Durie Salmon stage was IIIA (43.7%). Prior to transplantation 31% had a very good partial response, 25.2% complete response, 19.4% partial response, 10.7% progressive disease, 6.8% stable disease, 2.9% complete strict response, and in 3.9% of the patients the report of the disease status was not found. The 5-year overall survival was 71% (95% CI: 53-83) and progression-free survival was 40% (95% CI 25-54). After transplantation 33% of the patients were in very good partial response, 25% in strict complete response, 22% in complete response, 12% partial response, and 8% progressive disease or relapse. Conclusion: Autologous HSCT is a strategy that is associated with good survival rates, low toxicity, and an adequate post-transplant disease response.

Disseminated histoplasmosis as a first clinical manifestation in a patient with small lymphocytic lymphoma: A case report

The small lymphocytic lymphoma is a mature B cell neoplasm with a broad spectrum of clinical presentations. Opportunistic infections that are not related to the treatment, even in advanced stages, have a low incidence rate. There are few case reports in the medical literature of patients who have not received immunosuppressive therapy and present with small lymphocytic lymphoma associated with disseminated histoplasmosis at diagnosis. A female 82-year-old patient was admitted due to an intermittent dry cough, asthenia, and adynamia that had persisted for one month. Multiple studies to detect infections and immuno-rheumatic conditions were performed and an extensive cervical, thoracic and peritoneal adenopathic syndrome was diagnosed. A flow cytometry and a cervical lymph node biopsy were performed reporting CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg, and CD10neg phenotypes with restriction in the light kappa chain compatible with a small lymphocytic lymphoma. Epithelioid granulomas without necrosis were observed in the lymph node histopathology and special colorations showed no microorganisms. The culture from the lymph node was positive for Histoplasma capsulatum. We initiated treatment with amphotericin B and itraconazole with an adequate response. In the absence of compliance with oncology treatment criteria, the patient was managed on a "watch and wait" basis. Opportunistic infections could be the initial clinical manifestation in patients with low-grade lymphoproliferative syndromes. This case report shows that they can develop even in the absence of chemotherapy.

Histoplasmosis diseminada como manifestación inicial del linfoma linfocítico de células pequeñas / Disseminated histoplasmosis as a first clinical manifestation in a patient with small lymphocytic lymphoma: A case report

RESUMEN El linfoma linfocítico de células pequeñas es una neoplasia de células B maduras con un amplio espectro de presentaciones clínicas. Las infecciones por gérmenes oportunistas no asociadas con el tratamiento, incluso en estadios avanzados de la enfermedad, tienen baja incidencia. Se han reportado muy pocos casos de pacientes con linfoma linfocítico de células pequeñas asociado a histoplasmosis diseminada que no habían recibido quimioterapia en el momento del diagnóstico. Se presenta el caso de una paciente de 82 años que fue hospitalizada por presentar tos seca intermitente, astenia y adinamia de un mes de evolución. Se le practicaron múltiples estudios para detectar infecciones o compromiso inmunológico o reumático, y se diagnosticó un síndrome adenopático extenso con compromiso cervical, torácico y retroperitoneal. En la citometría de flujo y en la biopsia de ganglio linfático cervical, se reportaron los fenotipos CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg y CD10neg, con restricción de la cadena ligera kappa, lo cual confirmó un linfoma linfocítico de células pequeñas. En la histopatología del ganglio, se observaron granulomas epitelioides sin necrosis, pero las coloraciones especiales no mostraron la presencia de microorganismos, en tanto que el cultivo del ganglio fue positivo para Histoplasma capsulatum. Se inició el tratamiento antifúngico con anfotericina B e itraconazol, y la paciente tuvo una adecuada evolución. Dado que no se cumplían los criterios para el tratamiento oncológico, se continuó con su observación mediante controles periódicos. Las infecciones oportunistas pueden ser la manifestación clínica inicial en pacientes con síndromes linfoproliferativos de bajo grado. Este caso demuestra que pueden desarrollarse, incluso, en ausencia de quimioterapia.

ABSTRACT The small lymphocytic lymphoma is a mature B cell neoplasm with a broad spectrum of clinical presentations. Opportunistic infections that are not related to the treatment, even in advanced stages, have a low incidence rate. There are few case reports in the medical literature of patients who have not received immunosuppressive therapy and present with small lymphocytic lymphoma associated with disseminated histoplasmosis at diagnosis. A female 82-year-old patient was admitted due to an intermittent dry cough, asthenia, and adynamia that had persisted for one month. Multiple studies to detect infections and immuno-rheumatic conditions were performed and an extensive cervical, thoracic and peritoneal adenopathic syndrome was diagnosed. A flow cytometry and a cervical lymph node biopsy were performed reporting CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg, and CD10neg phenotypes with restriction in the light kappa chain compatible with a small lymphocytic lymphoma. Epithelioid granulomas without necrosis were observed in the lymph node histopathology and special colorations showed no microorganisms. The culture from the lymph node was positive for Histoplasma capsulatum. We initiated treatment with amphotericin B and itraconazole with an adequate response. In the absence of compliance with oncology treatment criteria, the patient was managed on a "watch and wait" basis. Opportunistic infections could be the initial clinical manifestation in patients with low-grade lymphoproliferative syndromes. This case report shows that they can develop even in the absence of chemotherapy.

Enfermedad de Gaucher, diagnostico en el embarazo, reporte de caso y consideraciones de su tratamiento en Colombia / Gaucher disease, diagnosis in pregnancy, report case study and considerations of its treatment in Colombia

RESUMEN Introducción y Objetivo: La enfermedad de Gaucher es una condición autosómica recesiva de baja prevalencia, de difícil diagnóstico y manejo, especialmente en embarazo. Reportamos una gestante con enfermedad de Gaucher manejada desde la semana 15,3 hasta el término del embarazo con Taliglucerasa en la Unidad de Alta Complejidad Obstétrica, en la Fundación Valle del Lili en Cali, Colombia. Métodos: Reporte de caso de gestante con diagnóstico de enfermedad de Gaucher diagnosticada durante el embarazo, con exacerbación de síntomas, quien presento severa pancitopenia y esplenomegalia. Resultados: El manejo medico interdiscilplinario permitió el control del severo deterioro clínico de la paciente durante el parto, presentó hemorragia postparto con choque hipovolémico, con adecuada respuesta al manejo médico. La madre y el neonato fueron dados de alta sin otras complicaciones asociadas. Conclusión: El manejo interdisciplinario es indispensable en gestantes con esta entidad para lograr buenos resultados maternos y perinatales.

ABSTRACT Introduction and Objective: Gaucher disease is a low prevalence autosomal recessive condition, difficult to diagnose and manage especially during pregnancy. We reported a pregnant woman with Gaucher disease managed with Taliglucerase in a critical care obstetric unit from week 15.3 until the end of her pregnancy, at the Fundación Valle del Lili, Cali, Colombia. Methods: A case report of a pregnant woman diagnosed during her pregnancy with Gaucher disease, who presented severe pancytopenia and splenomegaly. Results: The interdisciplinary medical management allowed the control of the severe clinical deterioration of the patient. During the delivery, she presented postpartum hemorrhage with hypovolemic shock, which resolved with medical management. The mother and the newborn were discharged without other associated complications. Conclusion: Interdisciplinary management is essential for handling a critically ill obstetric patient with Gaucher disease, and to achieve good maternal and perinatal outcomes.

Training in Goal-Oriented Attention Self-Regulation Improves Executive Functioning in Veterans with Chronic Traumatic Brain Injury.

Deficits in executive control functions are some of the most common and disabling consequences of both military and civilian brain injury. However, effective interventions are scant. The goal of this study was to assess whether cognitive rehabilitation training that was successfully applied in chronic civilian brain injury would be effective for military veterans with traumatic brain injury (TBI). In a prior study, participants with chronic acquired brain injury significantly improved after training in Goal-Oriented Attentional Self-Regulation (GOALS) on measures of attention/executive function, functional task performance, and goal-directed control over neural processing on functional magnetic resonance imaging. The objective of this study was to assess effects of GOALS training in veterans with chronic TBI. A total of 33 veterans with chronic TBI and executive difficulties in their daily life completed either 5 weeks of manualized GOALS training or Brain-Health Education (BHE) matched by time and intensity. Evaluator-blinded assessments at baseline and post-training included neuropsychological and complex functional task performance and self-report measures of emotional regulation. After GOALS, but not BHE training, participants significantly improved from baseline on primary outcome measures of Overall Complex Attention/Executive Function composite neuropsychological performance score (F = 7.10, p = 0.01; partial η2 = 0.19), and on overall complex functional task performance (Goal Processing Scale Overall Performance; F = 6.92, p = 0.01, partial η2 = 0.20). Additionally, post-GOALS participants indicated significant improvement on emotional regulation self-report measures (Profile of Mood States Confusion Score; F = 6.05, p = 0.02, partialη2 = 0.20). Training in attentional self-regulation applied to participant-defined goals may improve cognitive functioning in veterans with chronic TBI. Attention regulation training may not only impact executive control functioning in real-world complex tasks, but also may improve emotional regulation and functioning. Implications for treatment of veterans with TBI are discussed.

Fatal Blastoid Variant Mantle Cell Lymphoma in a Patient with Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disorder of the exocrine glands presenting with progressive ocular and oral dryness, parotid gland enlargement, and often with extraglandular manifestations. In this group of patients the risk of development of non-Hodgkin's lymphoma is 16-fold compared to healthy population, mainly of the MALT lymphoma type. This case reports a 52-year-old woman with pSS developing a progressively growing mass at face and neck compatible with blastoid variant mantle cell lymphoma and a fatal outcome.

Time of progression to osteopenia/osteoporosis in chronically HIV-infected patients: screening DXA scan.

BACKGROUND: Algorithms for bone mineral density (BMD) management in HIV-infected patients are lacking. Our objective was to assess how often a dual-energy x-ray absorptiometry (DXA) scan should be performed by assessing time of progression to osteopenia/osteoporosis. METHODS: All DXA scans performed between 2000 and 2009 from HIV-infected patients with at least two DXA were included. Time to an event (osteopenia and osteoporosis) was assessed using the Kaplan-Meier method. Strata (tertiles) were defined using baseline minimum T scores. Differences between strata in time to an event were compared with the log-rank test. RESULTS: Of 391 patients (1,639 DXAs), 49.6% had osteopenia and 21.7% osteoporosis at their first DXA scan. Of the 112 (28.6%) with normal BMD, 35.7% progressed to osteopenia; median progression time was 6.7 years. These patients were stratified: "low-risk" (baseline minimum T score >-0.2 SD), "middle-risk" (between -0.2 and -0.6 SD), and "high-risk" (from -0.6 to -1 SD); median progression time to osteopenia was 8.7, >7.2, and 1.7 years, respectively (p<0.0001). Of patients with osteopenia, 23.7% progressed to osteoporosis; median progression time was >8.5 years. Progression time was >8.2 years in "low-risk" tertile (T score between -1.1 and -1.6 SD), >8.5 years in "middle-risk" (between -1.6 and -2), and 3.2 years in "high-risk" (from -2 to -2.4) (p<0.0001). CONCLUSIONS: Our results may help to define the BMD testing interval. The lowest T score tertiles would suggest recommending a subsequent DXA in 1-2 years; in the highest tertiles, ≥6 years. Early intervention in patients with bone demineralization could reduce fracture-related morbidity/mortality.

Primary extranodal, extralymphatic hodgkin lymphoma of the mandible.

Primary extranodal, extralymphatic Hodgkin lymphomas (PEEHLs) are a rare occurrence. When they are encountered, they become diagnostic challenges. We are describing the uniqueness of a case of PEEHL affecting the mandible with his early response to the available chemotherapy.

How much fat loss is needed for lipoatrophy to become clinically evident?

The objective of this study was to evaluate how much limb fat is needed to be lost for lipoatrophy to become clinically evident. Antiretroviral drug-naive patients from a randomized trial comparing stavudine or abacavir plus lamivudine and efavirenz, who had subjective assessment to detect clinically evident lipoatrophy (standardized questionnaire) and objective measurements of limb fat (dual X-ray absorptiometry) at baseline, 48 weeks, and 96 weeks were included. ROC curves were used to assess the sensitivity and specificity of several cut-off values of absolute and percent limb fat loss for diagnosing lipoatrophy. Of 54 patients included, 13 (24%) had subjective lipoatrophy at 96 weeks. After 96 weeks, median limb fat change was -2.3 kg (interquartile range: -5.2, +0.2) and 0.4 kg (interquartile range: -7.2, +3.4) in patients with and without lipoatrophy, respectively. Median percent limb fat change was -45.5% (interquartile range: -78.0, +3.7) and 5.5% (interquartile range: -62.8, +95.6), respectively. The cut-off values of absolute and percent limb fat loss showing the best sensitivity and specificity values were -1.5 kg (sensitivity, 77%; specificity, 76%) and -30% (sensitivity, 85%; specificity, 73%). At least 30% limb fat is needed to be lost in HIV-infected patients for lipoatrophy to become clinically evident.

Consenso sobre diagnóstico y tratamiento de Leucemia Mieloide Crónica En Colombia / Consensus on diagnosis and treatment of chronic Myeloid Leukemia in Colombia

Objetivo: Unificar criterios para organizar el diagnóstico de la Leucemia Mieloide Crónica (LMC) y racionalizar el uso de nuevos medicamentos para su tratamiento. Métodos: se realizó una búsqueda estructurada de la literatura médica en la base de datos Medline en el Registro de Estudios Clínicos (CCTR) de la Biblioteca Cochrane y EMBSE, usando la plataforma OVID. Todoso los artículos fueron revisados por un comité central y los resultados fueron validados por hematólogos, oncólogos y otros especialistas en una reunión de consenso. Resultados: Se generaron 11 recomedaciones sobre diagnóstico (criterios definitorios), tratamiento (fase crónica, fase acelerada, crisis molecular, evolución clonal, etc), y seguimiento según fase y tratamiento base (remisión hematológica, respuesta citogenética, respuesta molecular, evolución clonal, etc). Conclusiones. los esquemas de tratamiento disponibles permiten mejorar la supervivencia y calidad de vida de los pacientes. Todo paiente con LMC requiere confirmación histológica y citogenética de su enfermedad. El inicio temprano del tratamiento con inhibidores de la tirosina-quinasa y el seguimiento estricto de las respuestas hematológica, citogenética y molecular permitirán adecuar o modificar la terapia de manera oportuna en pacientes resistentes primarios o secundarios.

Leucemia mieloide crónica en crisis: blástica bases moleculares y diagnóstico / Chronic myelogenous leukemia in blastic crisis: molecular basis and diagnostic

La leucemia mieloide crónica es una enfermedad con comportamiento bifásico o trifásico, 90 por ciento de los pacientes debuta en fase crónica, 50 por ciento asintomáticos al diagnóstico. Un porcentaje con enfermedad crónica desarrollan en tiempo variable una enfermedad más agresiva definida por un período intermedio y crisis blástica. Se diagnostica al encontrar más del 20 por ciento de blastos en médula ósea, 30 por ciento en sangre periférica o enfermedad extramedular. El pronóstico es pobre, al lograr respuesta completa, con una mediana de sobrevida de 3-12 meses, independiente del fenotipo. El 50 por ciento de los pacientes tendrán una mieloide, 25 por ciento linfoide y 25 por ciento fenotipo indiferenciado. Un grupo de expertos clínicos de Bogotá, Colombia, revisaron la mejor evidencia sobre diagnóstico y tratamiento. La información se obtuvo de búsquedas estructuradas y varios registros de experimentos clínicos en curso. Presentamos conclusiones y recomendaciones para la toma de decisiones basadas en la mejor evidencia.