Neonatal alloimmune thrombocytopenia due to anti-HPA 5a in a HPA-5a homozygous neonate.

The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Cases of FNAIT caused by HPA-5a antigen are extremely rare, and usually not severe. We report a case of FNAIT caused by anti-HPA antibodies directed to the HPA-5a antigen. The thrombocytopenia was moderate with a minimal platelet count of 36 × 109/L by day 3, and spontaneously resolved by day 10. The pregnancy had been obtained by in vitro fertilization using embryo donation, creating a complete genetic disparity between the HPA 5b5b mother and the HPA 5a5a homozygous neonate. The use of ART with gamete donation can increase the risk and the severity of alloimmune thrombocytopenia and must be considered in new and subsequent pregnancies.

Factores de riesgo de ocurrencia y gravedad de malformaciones congénitas / Identification of risk factors for congenital malformations

Background: The relative importance of congenital malformations as a cause of death in the first year of life is increasing along with the control of preventable causes of perinatal mortality. Aim: To identify risk factors for congenital malformations. Patients and Methods: Retrospective case-control study of births registered in the database of The Latin American Collaborative Study of Congenital Malformations (ECLAMC), in the period 2001-2010. Results: Birth weight and gestational age were significantly lower in cases than controls, behaving as risk factors and associated with a greater severity of congenital malformations. The risk and severity of congenital malformations increased along with mother’s age. Fetal growth retardation, a history of congenital malformations in the family, physical factors and acute illnesses of the mother in the first trimester of pregnancy were also significant risk factors for congenital malformations and their severity. The educational level of the mother was a protective factor for congenital malformations and their severity. Conclusions: Variables previously identified as risk factors for congenital malformations, were significantly related with the occurrence of congenital malformations and their severity.

Matched unrelated donor allogeneic transplantation provides comparable long-term outcome to HLA-identical sibling transplantation in relapsed diffuse large B-cell lymphoma.

The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiving URD-HCT between 2000 and 2007 and reported to the European Group for Blood and Marrow Transplantation, was compared with that of 301 subjects, allografted from sib-HCT. With a median follow-up of 45 months, 3-year PFS approached 35% for both groups; overall survival (OS) was 42% for sib-HCT versus 37% for URD (NS). Multivariate analyses confirmed that donor type was not associated with differences in non-relapse mortality (NRM), relapse rate (RR), PFS or OS. Poor performance status (PS) and refractory disease adversely affected PFS and OS. Prior auto-SCT and multiple previous therapies predicted for shorter PFS. NRM was adversely affected by older age (⩾50 years), poor PS and refractory disease, and RR by time from diagnosis to allo-HCT of <36 months, prior auto-SCT, refractory disease, poor PS and in vivo T-cell depletion with alemtuzumab. This large study shows for the first time that URD-HCT is not inferior to sib-HCT, providing a reasonable therapeutic approach for DLBCL patients, having no HLA-identical sibling available.

Role of serum holotranscobalamin (holoTC) in the diagnosis of patients with low serum cobalamin. Comparison with methylmalonic acid and homocysteine.

Plasma holotranscobalamin (holoTC) transports active cobalamin. Decreased levels of holoTC have been considered to be the earliest marker of cobalamin (Cbl) deficiency. In this work, holoTC was evaluated in low or borderline serum Cbl (LB12) and a concordance analysis was carried out with methylmalonic acid (MMA) and homocysteine (Hcy). Levels of Cbl, holoTC, MMA, and Hcy were investigated in a reference group in 106 patients with LB12 (≤200 pmol/l) and in 27 with folate deficiency (FOL). HoloTC levels were evaluated by an automated immunoassay (Active B12, Abbott Lab, Abbott Park, IL, USA). Lower levels of holoTC were observed in both LB12 and FOL groups (reference group vs LB12; p < 0.0001. Reference group vs FOL; p = 0.002). HoloTC levels were lower in LB12 than in FOL (p = 0.001). In LB12, concordance between Hcy and MMA was 82.1 % (chi-square test, p < 0.001; Kappa Index, 0.64, p < 0.0001). Concordance between Hcy and holoTC was 62 % (chi-square test, p = 0.006; Kappa index, 0.245, p = 0.006). Concordance between holoTC and MMA was 55.6 % (p = 0.233). Some cases with LB12 and elevated MMA did not show decreased holoTC. By contrast, MMA and Hcy were not increased in some patients with low holoTC and LB12. In conclusion, levels of holoTC were decreased in LB12 and FOL. In LB12 patients, holoTC concordance with MMA was poor. MMA/Hcy levels were not increased in a significant number of subjects with LB12 and low holoTC. This profile was found in iron deficiency. The significance of these changes remains to be clarified.

[Identification of risk factors for congenital malformations]. / Factores de riesgo de ocurrencia y gravedad de malformaciones congénitas.

BACKGROUND: The relative importance of congenital malformations as a cause of death in the first year of life is increasing along with the control of preventable causes of perinatal mortality. AIM: To identify risk factors for congenital malformations. PATIENTS AND METHODS: Retrospective case-control study of births registered in the database of The Latin American Collaborative Study of Congenital Malformations (ECLAMC), in the period 2001-2010. RESULTS: Birth weight and gestational age were significantly lower in cases than controls, behaving as risk factors and associated with a greater severity of congenital malformations. The risk and severity of congenital malformations increased along with mother's age. Fetal growth retardation, a history of congenital malformations in the family, physical factors and acute illnesses of the mother in the first trimester of pregnancy were also significant risk factors for congenital malformations and their severity. The educational level of the mother was a protective factor for congenital malformations and their severity. CONCLUSIONS: Variables previously identified as risk factors for congenital malformations, were significantly related with the occurrence of congenital malformations and their severity.

The outcome of reduced intensity allogeneic stem cell transplantation and autologous stem cell transplantation when performed as a first transplant strategy in relapsed follicular lymphoma: an analysis from the Lymphoma Working Party of the EBMT.

Both auto-SCT and reduced intensity allo-SCT (RIST) are employed in the treatment of relapsed follicular lymphoma (FL). We have analysed the outcome of these two transplant procedures when used as a first transplant in this setting. We conducted a retrospective comparison of 726 patients who underwent an auto-SCT and 149 who underwent a RIST as a first transplant procedure for relapsed FL as reported to the Lymphoma Working Party of the European Bone Marrow Transplant. The non-relapse mortality (NRM) was significantly worse for patients undergoing a RIST (relative risk (RR) 4.0, P<0.001). The 1-year NRM was 15% for those undergoing a RIST compared with 3% for those undergoing an auto-SCT. Disease relapse or progression were significantly worse for those receiving an auto-SCT (RR 3.1, P<0.001). Patients undergoing a RIST had a 5-year relapse rate of 20% compared with 47% for those undergoing an auto-SCT. The PFS at 5 years was 57% for patients receiving a RIST compared with 48% for those receiving an auto-SCT. There was no significant difference in OS between the two groups. RIST is associated with a higher NRM and lower relapse rate in patients with relapsed FL.

Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.

Consenso chileno sobre Abobotulinumtoxina A (Dysport®): indicaciones, técnicas / Chilean Consensus for on abobotulinumtoxin A (Dysport®): indications, techniques

Botulinum neurotoxin is widely used to treat a variety of movement disorders, especially dystonia and spasticity. There botúlica different preparations of botulinum type A, that because biologics are difficult to compare. AbobotulinumtoxinA (Dysport ®) has recently been introduced in Chile for treating dystonia and spasticity. The aim of this paper is to provide a review by experts on the existing evidence and propose a practical guide to the use of the drug. Methods and Results: A group of Chilean experts met on 6 and 7 July 2012 to review AbobotulinumtoxinA doses along with injection protocols for dystonia, spasticity and other movement disorders. We worked in two groups, one composed of neurologists who reviewed the on dystonias and other by physiatrists who reviewed the indications for spasticity. Conclusions: Finally, there is a proposal in terms of dose, injection points and recommendations for dystonia and spasticity...

La neurotoxina botulínica es ampliamente usada para tratar una variedad de trastornos del movimiento, especialmente la distonía y la espasticidad. Existen diferentes preparados de toxina botúlica tipo A, que por ser productos biológicos resultan difícilmente comparables. La abobotulinumtoxinA (Dysport®) ha sido introducida en Chile recientemente para el tratamiento de la distonía y la espasticidad. El objetivo de este trabajo es entregar una revisión hecha por expertos sobre la evidencia existente y plantear una guía práctica para el uso del medicamento. Métodos y Resultados: Un grupo de expertos chilenos se reunieron el 6 y 7 julio de 2012 para revisar las dosis abobotulinumtoxin A, junto con los protocolos de inyección para la distonía, la espasticidad y otros trastornos del movimiento. Se trabajó en dos grupos, uno compuesto por neurólogos que revisaron las indicaciones en distonías y otro por fisiatras que revisaron las indicaciones para espasticidad. Conclusiones: Finalmente, se realiza una propuesta en cuanto a dosis, puntos a inyectar y recomendaciones para la distonia y espasticidad...

Combined cobalamin and iron deficiency anemia: a diagnostic approach using a model based on age and homocysteine assessment.

Macrocytosis, the hallmark of cobalamin/folate deficiency anemia, is frequently absent. Clinicians have to be aware of coexisting conditions that can mask the macrocytosis expression of megaloblastic anemia, especially iron deficiency. The objective of this work was to investigate the degree of overlap between iron deficiency anemia (IDA) and cobalamin deficiency and to develop a predictive model for differentiating IDA from combined deficiency. A prospective case and control study was carried out to investigate vitamin B12 and folate status in iron deficiency anemia. A total of 658 patients were recruited, 41 of whom (6.2 %) were excluded. The remaining 617 subjects consisted of 130 controls and 487 with IDA. Low vitamin B12 (LB12) was considered when serum vitamin B12 was ≤200 pmol/L. High serum homocysteine (Hcy) was defined by Hcy >17 µM/L. A multivariate analysis (including a logistic regression) was performed to develop a diagnostic model. Low vitamin B12 levels were found in 17.8 % of IDA subjects. Ten out of 11 subjects (91 %) with IDA and serum vitamin B12 (B12) ≤100 pmol/L showed vitamin B12 deficiency. Moreover, vitamin B12 deficiency was demonstrated in 48 % of cases with IDA and B12 between 101 and 150 pmol/L and in 40 % with IDA and B12 between 151 and 200 pmol/, respectively. As a result of multivariate logistic analysis, neutrophil counts and age predicted subjects with vitamin B12 ≤200 and Hcy >17 µmol/L, [Formula: see text]. Using the age of 60 as a cutoff, sensitivity was 91 % (39 out of the 43 patients with vitamin B12 deficiency and IDA were identified). In summary, low vitamin B12 was found in 18 % of patients with IDA. Vitamin B12 deficiency was demonstrated in many patients with LB12 and IDA. Age over 60 years was used to separate patients with combined deficiency (sensitivity 91 %). Therefore, for a diagnostic purpose, serum vitamin B12 should be evaluated in IDA patients over 60 years. This diagnostic model needs to be validated in a different population.

Autologous stem-cell transplantation in patients with mantle cell lymphoma beyond 65 years of age: a study from the European Group for Blood and Marrow Transplantation (EBMT).

BACKGROUND: Limited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years. DESIGN AND METHODS: We analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients>65 years were compared with patients<65 years for the end points non-relapse mortality (NRM), relapse incidence, progression-free survival (PFS), and overall survival (OS). RESULTS: Seventy-nine patients were ≥65 years old. Median time from diagnosis to ASCT was longer in the elderly patients (11 versus 9 months, P=0.005); they had more commonly received at least two treatment lines (62.0% versus 47.9%, P=0.02) and were less commonly in first complete remission at ASCT (35.4% versus 51.2%, P=0.002). Median follow-up after ASCT was 19 and 25 months, respectively. NRM was comparable at 3 months (3.8% versus 2.5%) and at 5 years (5.6% versus 5.0%). There were no differences in relapse rate (66% versus 55% at 5 years), PFS (29% versus 40%) and OS (61% versus 67%) between both populations of patients. CONCLUSION: ASCT beyond 65 years of age is feasible in selected patients with MCL and results in similar disease control and survival as in younger patients.

[Bacteremia in patients with liver cirrhosis]. / Bacteriemia en daño hepático crónico.

UNLABELLED: Bacteremic infections are more frequent in patients with cirrhosis, as their immune system is compromised. Series of cirrhotic patients with bacteremia has seldom been reported in Chile. We retrospectively collected, from 2005 to 2008, 59 episodes of bacteremia in cirrhotics representing 9% of the overall number of bacteremic episodes seen in our center in the period. Spontaneous bacteremia accounted for 29% followed by those of pulmonary origin (22%). Grampositive cocci and gramnegative bacilli were responsible in 52% and 48% respectively, however gramnegative rods predominated in nosocomial bacteremias. Overall, the most frequent organisms were Staphylococcus aureus (24%) and Escherichia col i (22%). Mortality in bacteremic patients was significantly higher compared with all cirrhotic patients hospitalized in the period (37.0 vs 9.4%; p < 0.001) and MELD score was significantly correlated with mortality. CONCLUSION: bacteremia is a severe complication of cirrhosis and MELD score could be a useful tool to stratify risk in these patients.

Bacteriemia en daño hepático crónico / Bacteremia in patients with liver cirrhosis

Las infecciones bacteriémicas son más frecuentes en el paciente cirrótico que en la población general. Se identificaron retrospectivamente 59 pacientes cirróticos con bacteriemia, hospitalizados entre los años 2005 y 2008. La bacteriemia sin foco fue la más frecuente (29 por ciento), seguida de aquellas de origen pulmonar (22 por ciento). Cincuenta y dos por ciento de los agentes aislados correspondieron a cocáceas grampositivas y 48 por ciento a bacilos gramnegativos, siendo estos últimos los agentes predominantes en las bacteriemias nosocomiales. Los principales agentes aislados fueron Staphylococcns aureus (24 por ciento) y Escherichia col i (22 por ciento). La mortalidad de los pacientes cirróticos bacteriémicos fue mayor que la del total de cirróticos hospitalizados (37 vs 9,4 por ciento; p < 0,001) y la medición del puntaje de MELD a las 72 horas se correlacionó significativamente con la mortalidad. Conclusión: La bacteriemia es una complicación grave del paciente cirrótico y el MELD podría ser útil en su categorización de riesgo.

Bacteremic infections are more frequent in patients with cirrhosis, as their immune system is compromised. Series of cirrhotic patients with bacteremia has seldom been reported in Chile. We retrospectively collected, from 2005 to 2008, 59 episodes of bacteremia in cirrhotics representing 9 percent of the overall number of bacteremic episodes seen in our center in the period. Spontaneous bacteremia accounted for 29 percent followed by those of pulmonary origin (22 percent). Grampositive cocci and gramnegative bacilli were responsible in 52 percent and 48 percent respectively, however gramnegative rods predominated in nosocomial bacteremias. Overall, the most frequent organisms were Staphylococcus aureus (24 percent) and Escherichia col i (22 percent). Mortality in bacteremic patients was significantly higher compared with all cirrhotic patients hospitalized in the period (37.0 vs 9.4 percent; p < 0.001) and MELD score was significantly correlated with mortality. Conclusion: bacteremia is a severe complication of cirrhosis and MELD score could be a useful tool to stratify risk in these patients.

Valor de la secuencia de difusión en el estudio de cáncer de próstata en pacientes con antígeno prostático específico elevado / Value of diffusion-weighted sequences in the study of prostate cancer in patients with increased prostate specific antigen levels

En el carcinoma prostático la arquitectura glandular es reemplazada por células cancerosas, produciendo barreras al movimiento del agua, que pueden ser estudiadas con resonancia magnética potenciada en difusión. Para evaluar el aporte de estas secuencias en el estudio de la próstata, realizamos estudio descriptivo e inferencia!, utilizando difusión en 26 pacientes con tacto rectal anormal y antígeno prostático elevado. Se analizó sensibilidad, especificidad y curvas ROC basadas en coeficiente aparente de difusión (CAD). Se realizó biopsia prostática en 14 pacientes; 7 resultaron positivos. Con CAD <1000 um2/s, se encontraron altas sensibilidades con bajas especificidades y valores predictivos moderados. Incorporando T2 mejoraron: certeza diagnóstica, especificidad y valores predictivos. Al comparar los valores CAD en zonas con y sin cáncer, obtuvimos diferencias para CAD promedio y mínimo. Las curvas ROC mostraron áreas elevadas y significativas, sugiriéndose valores de corte de 1059 um2/s y 969 um2/s entre "normales" y con cáncer; LR(+) para valores de corte: 6,97 y 5,23 respectivamente. Nuestros resultados permiten proponer que se obtiene mayor ganancia diagnóstica en la interpretación conjunta de imágenes T2 y secuencias de difusión y que CAD permite diferenciar entre tejido normal y cáncer, por lo que se debiera incorporar en el estudio prostático.

In prostatic carcinoma, the glandular architecture is replaced by cancer cells producing barriers to water motion, anomaly that can be studied through diffusion-enhanced MRI technique. To assess the contribution of these sequences in the prostate cancer exploration, we conducted a descriptive and inferential study using diffusion-enhanced MRI technique in 26 patients with abnormal digital rectal examination (DRE) and increased prostate specific antigen (PSA) values. We analyzed sensitivity, specificity and ROC curves based on apparent diffusion coefficient (ADC). Seven out of 14 biopsies were positive in patients undergoing prostate biopsy. When applying ADC <1000 _m2/se, high sensitivity with low specificity levels, as well as moderate predictive values were obtained. By incorporating T2-weighted images, improved diagnostic accuracy, specificity and predictive values were achieved. When comparing ADC values in tissues with and without cancer, average and minimum ADC appeared to exhibit different values. ROC curves depicted increased and significant values, suggesting cutoff values of 1059 um2/s and 969/um2/s for healthy and malignant tissues, respectively; LR (+) for cut-off value: 6.97 and 5.23, respectively. Our results enable us to propose that improved diagnostic outcomes are attained through combined interpretation of T2-weighted images and diffusion-weighted sequences and that the ADC permits discrimination between normal and malignant tissues. Therefore, we strongly support that these criteria should be taken into account when performing prostate explorations.

Evaluación de la ventilación mecánica no invasiva en pacientes con insuficiencia respiratoria aguda / Evaluation of non-invasive ventilation in patients with acute respiratory failure

Antecedentes: Existe evidencia que avala la utilidad de la ventilación mecánica no invasiva (VMNI) en el manejo de la insuficiencia respiratoria aguda (IRA), no obstante, la definición de variables que permitan predecir el éxito o fracaso de este recurso terapéutico es controversial. Objetivo: Evaluar el comportamiento de parámetros clínicos y de laboratorio en relación con el éxito o fracaso de la VMNI en pacientes con IRA. Metodología: Estudio prospectivo de cohorte descriptivo que incluye pacientes consecutivos que cumplieron con criterios de conexión a VMNI e ingresaron a la UPC de Clínica Alemana de Santiago entre marzo de 2005 y julio de 2007. Los pacientes se dividieron en dos grupos, aquellos que fracasan con VMNI y requirieron intubación, grupo fracaso (GF) y los que no la requirieron, grupo éxito (GE). Se registraron variables demográficas, APACHE II, diagnóstico de ingreso. La mecánica respiratoria, gasometría arterial y hemodinámica se obtuvieron en tres momentos de la evolución evolución: previo a la conexión, a las dos horas y al término del uso de VMNI (preintubación y destete de VMNI). Resultados: De los 132 pacientes incluidos se logró evitar la intubación en 99 de ellos (75 por ciento), 33 fueron intubados (25 por ciento), de los cuales 1 falleció. El pH fue menor en el GF (7,42+/-0,06 v/s 7,39+/-0,08; p =0,04). La saturación de oxígeno por pulsioximetría (SpO2) también fue menor en el GF tanto a las dos horas (96+/-2 v/s 95+/-3; p=0,01) como al final del uso de VMNI (96+/-2 v/s 95+/-3; p =0,04). La PaO2/FiO2 fue menor en el mismo grupo, en los tres momentos de medición: previo a la conexión (196+/-66 v/s 144+/-59; p =0,001), a las dos horas (223+/-92 v/s 179+/-88;p =0,022) y al término del uso de VMNI (252+/-78 v/s 208+/-104; p =0,021). Al final del uso de VMNI, tanto la frecuencia cardiaca (FC) (86+/-16 v/s 94+/-20; p =0,03) como el nivel de IPAP (12+/-2 v/s 13+/-3; p =0,02) fueron mayores en el GF. Conclusiones: El GF muestra..

Background: There is evidence supporting the benefits of non-invasive ventilation (NIV) in the treatment of acute respiratory failure (ARF), however, the role of different variables in the evaluation of this technique’s success are controversial. Objective: To evaluate the performance of the different clinical parameters and relate them with the success and failure of NIV in patients with ARF. Methodology: Prospective study of descriptive cohort that includes consecutive patients who fulfilled criteria of connection to NIV and entered to the ICU (Intensive Care Unit)of Clínica Alemana de Santiago between March of 2005 to July 2007. These patients were divided into two groups, those presenting failure with NIV and required intubation, failure group (GF) and those that did not require it, success sgroup (GE). The demographic registered variables measured were APACHE II, diagnosis of entrance were registered. The respiratory mechanics, arterial gasometry and haemodynamics were obtained at three moments of the evolution: previous to the connection, the two hours and at the end of the use of NIV (pre-intubation and weaning of NIV). Results: From the 132 patients included, intubation was avoided in 99 of them (75 percent) 33 percent were entubated from which only 1 died. The pH was lower in the FG (7.42 +/- 0.06v/s 7.39 +/- 0.08; p = 0.04). The oxygen saturation by pulsometry (SpO2), was also lower in the GF after two hours (96+/-2 v/s 95+/-3; p =0.01) and at the end of NIV use (96+/-2 v/s 95+/-3; p =0.04). The PaO2/FiO2 was lower in the same group, at the three moments of measurement: previous to the connection (196+/-66 v/s 144+/-59; p =0.001), two hours post connection (223+/-92 v/s 179+/-88; p =0.022) and at the end of the NIV use (252+/-78 v/s 208+/-104; p =0.021). At the end of the NIV use both, the cardiac frequency (FC) (86+/-16 v/s94+/-20; p =0.03) and the IPAP level (12+/-2 v/s 13+/-3; p=0.02)...