General care in the management of severe traumatic brain injury: Latin American consensus. / Cuidados generales en el manejo del traumatismo craneoencefálico grave: consenso latinoamericano.

Severe traumatic brain injury (sTBI) remains prevalent in the young adult population. Indeed, far from descending, the incidence of sTBI remains high. One of the key bases of treatment is to avoid, detect and correct secondary injuries of systemic origin, which aggravate the primary lesion. Much of this can be achieved by maintaining an adequate physiological microenvironment allowing recovery of the damaged brain tissue. General care measures are nonspecific actions designed to meet that objective. The available guidelines on the management of sTBI have not included the topics contemplated in this consensus. In this regard, a group of members of the Latin American Brain Injury Consortium (LABIC), involved in the different aspects of the acute management of sTBI (neurosurgeons, intensivists, anesthesiologists, neurologists, nurses and physiotherapists) were gathered. An exhaustive literature search was made of selected topics in the LILACS, PubMed, Embase, Scopus, Cochrane Controlled Register of Trials and Web of Science databases. To establish recommendations or suggestions with their respective strength or weakness, the GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was applied. Additionally, certain recommendations (included in complementary material) were not assessed by GRADE, because they constitute a set of therapeutic actions of effective compliance, in which it was not possible to apply the said methodology. Thirty-two recommendations were established, 16 strong and 16 weak, with their respective levels of evidence. This consensus attempts to standardize and establish basic general care measures in this particular patient population.

[Analysis of the medical prescription in institutionalised patients]. / Analisis de la prescripción farmacológica en pacientes institucionalizados.

OBJECTIVES: To evaluate/assess the therapeutic concordance/agreement with prescribed medication in patients institutionalized diagnoses in two periods of time as well as the characteristics of this prescription. MATERIAL AND METHODS: Observational and descriptive study. Prescribing and clinical diagnoses of institutionalized patients were analyzed. These patients were treated by the same physicians during the period of time with a one-year interval (2010-2011), offering prescribing information in this period. RESULTS: A total of 81 patients (78% women), mean age 84±7 years, and 5±2 diagnoses per patient. The number of drugs per patient was more than 8 in the 2 periods, being higher in 2011 compared to 2010. From all the prescription, we found that 8.88% in 2010 and 9.3% in 2011 are included as "limited clinical value" drugs. In 2010, it sees a concordance of 86.71±13.75 against 87.17±14.58 in 2011, it means, 87% of patients are treated with drugs in agreement with their diagnoses, representing an increase of 0.47 in 2011 regarding 2010. No statistically significant differences between the 2 years. CONCLUSIONS: The prescriptions in institutionalized patients are very high and the number of drugs per patient increased after information. When we analyzed prescriptions we underline a high percentage of drugs included in the group of limited clinical value (citicoline). A significant percentage of prescriptions don't correspond with diagnoses avaiable in their clinical history.

Virtual treatment of basilar aneurysms using shape memory polymer foam.

Numerical simulations are performed on patient-specific basilar aneurysms that are treated with shape memory polymer (SMP) foam. In order to assess the post-treatment hemodynamics, two modeling approaches are employed. In the first, the foam geometry is obtained from a micro-CT scan and the pulsatile blood flow within the foam is simulated for both Newtonian and non-Newtonian viscosity models. In the second, the foam is represented as a porous media continuum, which has permeability properties that are determined by computing the pressure gradient through the foam geometry over a range of flow speeds comparable to those of in vivo conditions. Virtual angiography and additional post-processing demonstrate that the SMP foam significantly reduces the blood flow speed within the treated aneurysms, while eliminating the high-frequency velocity fluctuations that are present within the pre-treatment aneurysms. An estimation of the initial locations of thrombus formation throughout the SMP foam is obtained by means of a low fidelity thrombosis model that is based upon the residence time and shear rate of blood. The Newtonian viscosity model and the porous media model capture similar qualitative trends, though both yield a smaller volume of thrombus within the SMP foam.

Efectividad y seguridad del régimen FLAG-IDA en leucemias agudas resistentes o recidivantes / Effectiveness and safety of the FLAG-IDA regimen in acute refractory or recurrent leukaemia

Objetivo: Evaluar la efectividad y seguridad del esquema FLAG-IDA en pacientes con leucemias agudas refractarias o recidivantes. Método Estudio observacional descriptivo retrospectivo en el que se revisaron las historias clínicas de pacientes con el esquema FLAG-IDA en el periodo 2005-2010. La efectividad se evaluó mediante la respuesta objetiva, el intervalo libre de progresión y la supervivencia global. La seguridad se midió según el sistema de clasificación NCI, Criterios comunes de Toxicidad para Acontecimientos Adversos. Resultados Fueron 12 pacientes (52,17 ± 8,26 años entre las mujeres y 54,83 ± 7,22 años en los hombres), 11casos fueron leucemias mieloides agudas (5 resistentes, 3 en recaída, una secundaria a leucemia mieloide crónica (LMC) resistente y 2 secundarias a síndrome mielodisplásico (SMD), de las que una fue resistente y la otra no había sido tratada previamente) y un caso de leucemia linfoide aguda (LLA) resistente. Seis pacientes (50%) alcanzaron una respuesta completa (RC). Un paciente consiguió una respuesta parcial (RP) tras la cual se administró otro protocolo indicado consiguiendo posteriormente una RC, 2 fallecieron por progresión de la enfermedad y 3 por complicaciones secundarias al tratamiento. El intervalo libre de progresión para los pacientes que alcanzaron la RC fue de 24,38 semanas (6 meses). La mediana de supervivencia global fue de 8,4 semanas. La media del tiempo necesario para la recuperación de la neutropenia fue de 23 y 37 días en el primer y segundo ciclo respectivamente. La media del tiempo necesario para la recuperación de la trombocitopenia fue de 24 y 35 días en cada ciclo. Conclusiones El esquema de inducción FLAG-IDA para el tratamiento de pacientes con leucemias de alto riesgo es un esquema establecido, bien tolerado y con una toxicidad aceptable que ofrece una oportunidad para optar al trasplante de progenitores hematopoyéticos (AU)

Objective: To evaluate the effectiveness and safety of the FLAG-IDA regimen in patients with acute refractory and/or recurrent leukaemia. Method: Descriptive, retrospective, observational study of the clinical histories of patients with the FLAG-IDA regimen during the period of 2005-2010. Effectiveness was measured using objective response, progression-free interval, and global survival. Safety was measured using the NCI classification system of common toxicity criteria for adverse events. Results: We registered 12 patients (52.17±8.26 years in women, and 54.83±7.22 years in men),11 cases were acute myeloid leukaemia (5 refractory, 3 in recurrence, 1 secondary to chronicre fractory myeloid leukaemia (CML) and 2 secondary to myelodysplastic syndrome (MDS), one of which was refractory and the other had not been previously treated) and one case was acuterefractory lymphoblastic leukaemia (ALL). Six patients (50%) reached a complete response (CR).One patient reached a partial response (PR), which was followed by another protocol that produced a CR, two died due to disease progression, and three due to secondary complications from treatment. The progression-free interval for patients that reached a CR was 24.38 weeks (6 months).Median global survival was 8.4 weeks. Mean time needed for the recovery of neutropenia was 23 and 37 days in the first and second cycle, respectively. The mean time required for recuperation of thrombocytopenia was 24 and35 days in each cycle. Conclusions: The FLAG-IDA induction regimen for the treatment of high-risk leukaemia patients is an established protocol, with good tolerance and acceptable toxicity levels that offers an opportunity for facilitating the transplantation of haematopoietic progenitors (AU)

Prognostic significance of FLT3 mutational status and expression levels in MLL-AF4+ and MLL-germline acute lymphoblastic leukemia.

There is barely any information about the prognostic significance of FLT3 expression and mutational status in cytogenetically distinct subgroups of acute lymphoblastic leukemia (ALL). We analyzed the presence of FLT3-tyrosine kinase domain (TKD) and FLT3-internal tandem duplication (ITD) mutations as well as FLT3 expression levels in 54 newly diagnosed patients with B-ALL (n=49) or T-ALL (n=5). All B/T-ALL samples tested negative for the presence of FLT3-TKD or FLT3-ITD. None of the T-ALL and E2A-PBX1+ B-ALL overexpressed FLT3. In contrast, mainly MLL-AF4+ B-ALL but also ETV6-RUNX1+, BCR-ABL+ or B-ALL displaying normal cytogenetics exhibited significantly higher FLT3 expression levels than normal bone marrow, supporting that aberrantly increased transcription of FLT3, rather than activating FLT3 mutations, contributes to the pathogenesis of these B-ALL. Using the median FLT3 expression as cut-off value we found that high-level FLT3 expression is associated with an extremely poor 1-year overall survival (OS; 0 vs 71%; P=0.002) and disease-free survival (DFS; 0 vs 43%; P=0.03) in MLL-AF4+ B-ALL but not in MLL-germline B-ALL. Cox regression analysis with OS/DFS as end points showed that age>14 years and high-level FLT3 expression were independent prognostic factors when all ALL patients were analyzed together. Importantly, when the MLL-AF4+ B-ALL subgroup was analyzed separately, high-level FLT3 expression was the only independent prognostic factor for OS and treatment outcome. These findings indicate that high FLT3 expression identifies MLL-AF4+ ALL patients at very high risk of treatment failure and poor survival, emphasizing the value of ongoing/future clinical trials for FLT3 inhibitors.

[Effectiveness and safety of the FLAG-IDA regimen in acute refractory or recurrent leukaemia]. / Efectividad y seguridad del régimen FLAG-IDA en leucemias agudas resistentes o recidivantes.

OBJECTIVE: To evaluate the effectiveness and safety of the FLAG-IDA regimen in patients with acute refractory and/or recurrent leukaemia. METHOD: Descriptive, retrospective, observational study of the clinical histories of patients with the FLAG-IDA regimen during the period of 2005-2010. Effectiveness was measured using objective response, progression-free interval, and global survival. Safety was measured using the NCI classification system of common toxicity criteria for adverse events. RESULTS: We registered 12 patients (52.17±8.26 years in women, and 54.83±7.22 years in men), 11 cases were acute myeloid leukaemia (5 refractory, 3 in recurrence, 1 secondary to chronic refractory myeloid leukaemia (CML) and 2 secondary to myelodysplastic syndrome (MDS), one of which was refractory and the other had not been previously treated) and one case was acute refractory lymphoblastic leukaemia (ALL). Six patients (50%) reached a complete response (CR). One patient reached a partial response (PR), which was followed by another protocol that produced a CR, two died due to disease progression, and three due to secondary complications from treatment. The progression-free interval for patients that reached a CR was 24.38 weeks (6 months). Median global survival was 8.4 weeks. Mean time needed for the recovery of neutropenia was 23 and 37 days in the first and second cycle, respectively. The mean time required for recuperation of thrombocytopenia was 24 and 35 days in each cycle. CONCLUSIONS: The FLAG-IDA induction regimen for the treatment of high-risk leukaemia patients is an established protocol, with good tolerance and acceptable toxicity levels that offers an opportunity for facilitating the transplantation of haematopoietic progenitors.

Production of polyhydroxyalkanoates (PHAs) with canola oil as carbon source.

Wautersia eutropha was able to synthesize medium chain length polyhydroxyalkanoates (PHAs) when canola oil was used as carbon source. W. eutropha was cultivated using fructose and ammonium sulphate as carbon and nitrogen sources, respectively, for growth and inoculum development. The experiments were done in a laboratory scale bioreactor in three stages. Initially, the biomass was adapted in a batch culture. Secondly, a fed-batch was used to increase the cell dry weight and PHA concentration to 4.36 g L(-1) and 0.36 g L(-1), respectively. Finally, after the addition of canola oil as carbon source a final concentration of 18.27 g L(-1) PHA was obtained after 40 h of fermentation. With canola oil as carbon source, the polymer content of the cell dry matter was 90%. The polymer was purified from dried cells and analyzed by FTIR, NMR and DSC using PHB as reference. The polymer produced by W. eutropha from canola oil had four carbon monomers in the structure of the PHA and identified by 1H and 13C NMR analysis as 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), 3-hydroxyoctanoate (3HO), and 3-hydroxydodecanoate (3HDD).

The Andalusian population from Huelva reveals a high diversification of Y-DNA paternal lineages from haplogroup E: Identifying human male movements within the Mediterranean space.

BACKGROUND: Gene flow among human populations is generally interpreted in terms of complex patterns, with the observed gene frequencies being the consequence of the entire genetic and demographic histories of the population. AIMS: This study performs a high-resolution analysis of the Y-chromosome haplogroup E in Western Andalusians (Huelva province). The genetic information presented here provides new insights into migration processes that took place throughout the Mediterranean space and tries to evaluate its impact on the current genetic composition of the most southwestern population of Spain. SUBJECTS AND METHODS: 167 unrelated males were previously typed for the presence/absence of the Y-chromosome Alu polymorphism (YAP). The group of YAP (+) Andalusians was genotyped for 16 Y-SNPs and also characterized for 16 Y-STR loci. RESULTS: The distribution of E-M81 haplogroup, a Berber marker, was found at a frequency of 3% in our sample. The distribution of M81 frequencies in Iberia seems to be not concordant with the regions where Islamic rule was most intense and long-lasting. The study also showed that most of M78 derived allele (6.6%) led to the V13* subhaplogroup. We also found the most basal and rare paragroup M78* and others with V12 and V65 mutations. The lineage defined by M34 mutation, which is quite frequent in Jews, was detected as well. CONCLUSIONS: The haplogroup E among Western Andalusians revealed a complex admixture of genetic markers from the Mediterranean space, with interesting signatures of populations from the Middle East and the Balkan Peninsula and a surprisingly low influence by Berber populations compared to other areas of the Iberian Peninsula.

[Information and worry among patients with non-oncohematological pathologies upon arrival at the hematology clinic]. / Información y preocupación de los pacientes con patología no oncohematológica al llegar a la consulta de hematología.

PURPOSE: Patients are frequently referred to the haematologist to be studied due to the presence of processes that are not properly haematological. We have studied the group of outpatients with non-oncohaematological pathologies referred to our external haematology clinic to evaluate their knowledge about the reason for consultation, the existence or not of worry upation and its degree at the arrival. PATIENTS AND METHODS: We have made a prospective study including all patients with non-oncohaematological processes (n = 204) who were referred for the first time to our external consultation between April and October 1997. We evaluated in each patient, using an inquest, the following data: age, sex, origin (hospital consultations or urban or rural health centres), reason for consultation, knowledge of the reason for consultation (yes/partially/no), existence or not of worry (yes/no) and when present, its degree (low, moderate, high). The inquiry was made to the parents in those patients aged under 12 years. We have analyzed all adults, each group of adult patients (rural, urban, hospital) separately and compared one group to each other, all pediatric patients and we have compared as well the overall results obtained with adult patients with those from the parents of pediatric patients. RESULTS: 1) Adult patients (n = 169; 78 referred from hospital, 59 from urban and 32 from rural health centres): with respect to the knowledge of the reason for consultation 49.7% of them knew it perfectly, 20.1% partially, and 30.2% did not know about it. 48.5% of patients arrived worried to the clinic, 16.6% of them with a high degree, 17.8% moderate and 14.2% low. 2) Adults referred from primary health care (urban versus rural health centres): We have found neither significant differences in the knowledge of the reason for consultation, worry or its degree with respect to age, sex or origin (urban or rural), nor in the worry or its degree with respect to the patient knowledge of the reason for consultation. 3) Adults referred from other hospital units: The mean age of patients who knew the reason for consultation was significatively lower than that observed in the group who did not (respectively 43.3 and 57 years) (p = 0.003). These differences did not exist with respect to sex. Differences in the existence or not of worry with respect to sex were almost significant, women arrive more worried than men (57.1% and 31.8% respectively, p = 0.07). No significant differences were found in the existence or not of worry and its degree with respect to age or knowledge of the reason for consultation. 4) Comparison between both groups of adults patients (hospital consultation and health centres): No significant differences in the knowledge of the reason for consultation, existence or not of worry and its degree have been found with respect to the other parameters studied. 5) Paediatric patients (n = 35; 8 referred from hospital, 14 from urban and 13 rural health centres): With respect to the knowledge of the reason for consultation 62.9% of them knew it perfectly, 17.1% partially and 20% did not know about it. 80% of patients' parents arrived worried at consultation, 45.7% with a high degree, 20% moderate and 14.3% low. 6) Comparison between paediatrics and adult patients: we have only found significative differences in the existence or not of worry (80% and 48.5% respectively, p = 0.001) and its degree (65.7% of parents with moderate or high worry and 34.4% of adults, p = 0.0004). Parents of paediatric patients arrive at our consultation more worried and with a higher worry degree than the other adults. CONCLUSION: We consider that patients referred to our external consultation of haematology for the first time arrive with a poor knowledge of their reason for consultation. This observation does not seem to have any relation with age, sex or origin (hospital consultations, urban or rural health centres). (ABSTRACT TRUNCATED)

rHuEpo for the treatment of anemia in myelofibrosis with myeloid metaplasia. Experience in 6 patients and meta-analytical approach.

BACKGROUND AND OBJECTIVE: Experience with recombinant human erythropoietin (rHuEPO) in the treatment of the anemia secondary to myelofibrosis with myeloid metaplasia (MMM) is slight up to now. We present our results of the treatment of 6 patients and a review of the literature in search of possible parameters predicting response to this treatment. DESIGN AND METHODS: From January 1994 to June 1996 all transfusion-dependent patients with MMM diagnosed in our hospital were included in this study. We established a minimum period of 4 weeks of treatment and a maximum of 12 if no response was observed. Initial dosages used were 100 U/kg s.c. 3 times weekly, increasing by 50 U/kg every 4 weeks where no response was observed. Response was defined as a reduction > or = 30% of the previous transfusional needs. The review of the literature was made using a MEDLINE search (January 1990-December 1996) on the keywords erythropoietin, myelofibrosis, and agnogenic myeloid metaplasia. A statistical study was made in search of possible parameters to predict response. The parameters studied include age, sex, hemoglobin, serum erythropoietin (sEPO) levels, transfusional dependency, transfusional requirements per month prior to treatment, maximum dosages used and dosage at which response was obtained. RESULTS: Only 2 of our 6 patients responded, both at a dosage of 600 U/kg/week (200 U/kg 3 times weekly s.c.). In addition to our 6 patients we have found only 28 other patients in the literature. For statistical calculation 2 of our patients were not considered as they did not complete the period of study. The overall rate of response was 17/32 (53.1%). In the univariate analysis comparing responders and non-responders we found a tendency to significance with respect to sex (p = 0.07), sEPO (p = 0.07) and transfusional needs in units of packed red blood cells per month (PRBC/m) (p = 0.13). In this way patients with low sEPO, females and those with low transfusional needs (< 3 PRBC/m) respond better. This better response in females could be explained by the fact that their disease situation was more stable (with both lower sEPO levels and transfusional dependency). The best cut-off point in the sEPO to predict response was 123 mU/mL. No important side-effects have been observed except three cases of aggravation of splenomegaly. In two cases this condition improved when the rHuEPO was discontinued. The association of rHuEPO with hydroxyurea or interferon does not seem to affect the response. INTERPRETATION AND CONCLUSIONS: Though the number of patients is low, our data suggest that some MMM patients, in particular females and individuals with low sEPO levels and with low transfusional needs, might benefit from rHuEPO in terms of elevation of hemoglobin levels. Unfortunately, transfusion dependent-patients, i.e. those in whom a beneficial effect of rHuEPO would be most welcome, are unlikely to respond, and more generally, treatment is not cost effective in medically responsive patients.

[Acute myeloid leukemia in those over 70 years of age. Experience using low-dose ara-C treatment]. / Leucemia mieloide aguda en mayores de 70 años. Experiencia utilizando tratamiento con Ara-C a bajas dosis.

PURPOSE: The treatment of elderly patients with acute myeloid leukaemia (AML) remains controversial. We present the results of the treatment of a group of patients aged above 70 years with AML diagnosed in our Hospital since 1990. PATIENTS AND METHODS: We have studied retrospectively the cases of AML in patients older than 70 years diagnosed in our Service since January 1990 to June 1996. Induction treatment was performed, in all cases but one, with two cycles of Ara-C 10 mg/m2/12 h s.c. for 21 days and after haematological recuperation, if complete remission had been achieved, monthly maintenance treatment with Ara-C (25 mg/m2/12 h oral x 5 days), prednisone (40 mg/m2/day x 5 days) y vincristine (1 mg/m2 i.v. x 1 day) was begun. RESULTS: During the period of study 48 patients with AML have been diagnosed in our Service, among them 22 (45.8%) were older than 70 years. One of them could not be considered for the study as not all data from him could be compiled. Among the other 21 patients 5 presented previous haematological processes (4 myelodysplastic syndrome and 1 Waldenström's macroglobulinemia). Initial diagnosis according to FAB classification for AML was as follows: 7 M1, 6 M2, 4 M4, 2 M5 and 2 M6. From these 21 patients 2 received no treatment due to rapid progression and death, among the other 19, one was directly treated with a modification of the maintenance treatment with vincristine and prednisone without response (survival 2 months). The other 18 patients were treated with low-dose Ara-C (described above), among them 3 (16.7%) were not evaluable as they did not finish the first cycle of induction treatment; 8 (44.4%) showed no response; 2 (11.1%) achieved partial remission and 5 (27.8%) complete remission. One patient did not show any response after two cycles of low-dose Ara-C but she obtained complete remission when treated with Ara-C and idaurubicin. Overall mean survival was 5.7 months (median 2; 95% confidence interval 1.6-9.8 months). In the group of patients treated with low-dose Ara-C mean survival was 6.6 months (median 3.5; 95% confidence interval 1.9-11.2 months). CONCLUSION: We consider that the treatment with low-dose Ara-C is a valid option in the treatment of elderly patients (aged 70 or above) with AML because 28% complete remissions can be achieved, specially in those ones in which other more aggressive treatments are not possible.

Waldenström's macroglobulinemia complicated with acute myeloid leukemia. Report of a case and review of the literature.

The evolution of Waldenström's macroglobulinemia (WM) into chronic or acute myeloid leukemia (AML) is a rare event. Most of these cases have occurred after treatment with alkylating agents. We herein report a case of WM terminating in an acute myelomonocytic leukemia after treatment with prednimustine and chlorambucil and present a review of the literature.