Considering Bone Marrow Blasts From Nonerythroid Cellularity Improves the Prognostic Evaluation of Myelodysplastic Syndromes.

PURPOSE: WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts ≥ 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are ≥ 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. PATIENTS AND METHODS: We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Español de Síndromes Mielodisplásicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. RESULTS: By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. CONCLUSION: Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future WHO classification reviews.

Use of newer prognostic indices for patients with myelodysplastic syndromes in the low and intermediate-1 risk categories: a population-based study.

BACKGROUND: We aimed to compare the ability of recently developed prognostic indices for myelodysplastic syndromes to identify patients with poor prognoses within the lower-risk (low and intermediate-1) categories defined by the International Prognosis Scoring System (IPSS). METHODS: We included patients with de-novo myelodysplastic syndromes diagnosed between Nov 29, 1972, and Dec 15, 2011, who had low or intermediate-1 IPSS scores and were in the Spanish Registry of Myelodysplastic Syndromes. We reclassified these patients with the new prognostic indices (revised IPSS [IPSS-R], revised WHO-based Prognostic Scoring System [WPSS-R], Lower Risk Scoring System [LRSS], and the Grupo Español de Síndromes Mielodisplásicos [Spanish Group of Myelodysplastic Syndromes; GESMD]) and calculated the overall survival of the different risk groups within each prognostic index to identify the groups of patients with overall poor prognoses (defined as an expected overall survival <30 months). We calculated overall survival with the Kaplan-Meier method. FINDINGS: We identified 2373 patients. None of the prognostic indices could be used to identify a population with poor prognoses (median overall survival <30 months) for the patients with low IPSS scores (1290 individuals). In the group with intermediate-1 scores (1083 individuals), between 17% and 47% of patients were identified as having poor prognoses with the new prognostic indices. The LRSS had the best model fit with the lowest value in the Akaike information criteria test, whereas the IPSS-R identified the largest proportion of patients with poor prognoses (47%). Patients with intermediate-1 scores who were classified as having poor prognoses by one or more prognostic index (646 [60%] individuals) had worse median overall survival (33·1 months, 95% CI 28·4-37·9) than did patients who were classified as having low risk by all prognostic indices (63·7 months, 49·5-78·0], HR 1·9, 95% CI 1·6-2·3, p<0·0001) INTERPRETATION: Recently proposed prognostic indices for myelodysplastic syndromes can be used to improve identification of patients with poor prognoses in the group of patients with intermediate-1 IPSS scores, who could potentially benefit from a high-risk treatment approach. FUNDING: None.

Results of treatment with azacitidine in patients aged ≥ 75 years included in the Spanish Registry of Myelodysplastic Syndromes.

The tolerability of azacitidine (AZA) allows its administration in elderly patients. The objective of this study was to analyze the clinical and biological characteristics, transfusion independence (TI), overall survival (OS) and toxicity in a series of 107 patients ≥ 75 years of age from the Spanish Registry of Myelodysplastic Syndromes (MDS) treated with AZA. The median age (range) was 78 (75-90) years. According to the World Health Organization (WHO) classification, 86/102 (84%) had MDS, 10/102 (10%) had mixed myeloproferative/myelodysplastic disorder and 6/102 (6%) had acute myeloblastic leukemia. Regarding MDS by the International Prognostic Scoring System on initiation of AZA, 38/84 (45%) were low-intermediate-1 risk and 46/84 (55%) were intermediate-2-high risk. Ninety-five patients (89%) were red blood cell or platelet transfusion dependent. The AZA schedule was 5-0-0 in 39/106 (37%) patients, 5-2-2 in 36/106 (34%) patients and 7 consecutive days in 31/106 (29%) patients. The median number of cycles administered was 8 (range, 1-30). Thirty-eight out of 94 (40%) patients achieved TI. Median OS (95% confidence interval [CI]) was significantly better in patients achieving TI (n = 38) compared to patients who did not (n = 56) (22 [20.1-23.9] months vs. 11.1 [4.8-17.5] months, p = 0.001). No significant differences were observed in TI rate and OS among the three different schedules. With a median follow-up of 14 (min-max, 1-50) months, the median OS (95% CI) of the 107 patients was 18 (12-23) months and the probability of OS (95% CI) at 2 years was 34% (22-46%). Cycles were delayed in 31/106 (29%) patients and 47/101 patients (47%) were hospitalized for infection. These results show that treatment with AZA was feasible and effective in this elderly population, with 40% achieving TI, having a better OS than patients not achieving it. The schedule of AZA administration did not affect efficacy and toxicity.

Complex, not monosomal, karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome.

PURPOSE: Complex karyotype (CK) is the poorest risk factor in patients with myelodysplastic syndrome (MDS). It has recently been reported that monosomal karyotype (MK) worsens the prognosis of patients with CK. PATIENTS AND METHODS; We analyzed 1,054 adult patients with MDS with an abnormal karyotype from the Spanish Registry of MDS. The aim of the study was to describe the incidence, characteristics, and prognosis of MK; the main end points were overall survival (OS) and leukemia-free survival. RESULTS: MK was identified in 172 patients (16%), most of whom (88%) presented with CK. Variables significantly associated with OS were age (hazard ratio [HR], 1.90; P < .001), bone marrow (BM) blast percentage (HR, 1.05; P < .001), hemoglobin level (HR, 1.71; P < .001), platelet count (HR, 1.41; P < .001), karyotype complexity (CK [three abnormalities]: HR, 1.81; P = .003; very CK [> three abnormalities]: HR, 2; P < .001), and abnormalities of chromosome 5 and/or 7 (HR, 1.89; P < .001). Variables significantly related to the risk of transformation to acute myeloid leukemia (AML) were higher BM blast percentage (HR, 1.12; P < .001) and karyotype complexity (CK: HR, 2.53; P = .002; very CK: HR, 2.77; P < .001). CONCLUSION: After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.

Cytogenetic risk stratification in chronic myelomonocytic leukemia.

BACKGROUND: The prognostic value of cytogenetic findings in chronic myelomonocytic leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic myelomonocytic leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes. DESIGN AND METHODS: We studied 414 patients with chronic myelomonocytic leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid leukemia. RESULTS: Patients with abnormal karyotype (110 patients, 27%) had poorer overall survival (P=0.001) and higher risk of acute myeloid leukemia evolution (P=0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively (P<0.001). Multivariate analysis confirmed that this new CMML-specific cytogenetic risk stratification was an independent prognostic variable for overall survival (P=0.001). Additionally, patients belonging to the high-risk cytogenetic category also had a higher risk of acute myeloid leukemia evolution on univariate (P=0.001) but not multivariate analysis. CONCLUSIONS: Cytogenetic findings have a strong prognostic impact in patients with chronic myelomonocytic leukemia.

Trauma contuso de artéria carótida interna após acidente automobilístico: apresentação de um caso / Blunt internal carotid artery injury after a motor vehicle crash: presentation of a case

Este estudo relata o caso de uma paciente vítima de acidente automobilístico, que desenvolveu quadro de hemiplegia poucas horas depois do trauma. Na propedêutica diagnosticou-se acidente vascular cerebral isquêmico (AVCi) secundário à trombose da artéria carótida interna direita. O objetivo é alertar para o trauma contuso vascular como diagnóstico diferencial de injúrias neurológicas.

This work relates a occurrence of a patient victim of a motor vehicle crash that developed signs of unilateral paralysis few hours after the trauma. At investigation a diagnosis of ischemic stroke due a right carotid artery thrombosis was made. The objective of this article is to alert about the blunt vascular trauma as a differential diagnostic of neurologic injuries.

Accidental subarachnoid administration of 4 mg of morphine: case report / Administração inadvertida de 4 mg de morfina por via subaracnóidea: relato de caso / Administración inadvertida de 4 mg de morfina por vía subaracnoidea: relato de caso

JUSTIFICATIVA E OBJETIVOS: A administração de morfina por via subaracnóidea é técnica bem estabelecida para analgesia pós-operatória devido a sua eficácia, segurança e baixo custo. A administração inadvertida de 4 mg de morfina por via subaracnóidea complicada por fibrilação atrial após administração de naloxona foi o objetivo desse relato. RELATO DO CASO: Paciente do sexo masculino, 45 anos, 75 kg, 1,72 m, estado físico ASA II, hipertenso, a ser submetido à reconstrução do ligamento cruzado anterior do joelho esquerdo. Após a realização da raquianestesia, foi constatada troca da ampola de morfina, com administração de 4 mg (0,4 mL da ampola de 10 mg) por via subaracnóidea. A freqüência respiratória oscilou entre 12 e 16 incursões respiratórias por minuto e o paciente manteve-se estável hemodinamicamente sem queixas no intra-operatório. Após 30 minutos da admissão na SRPA, apresentou vômitos e sudorese, tratados com 0,4 mg de naloxona seguidos de infusão contínua de 0,2 mg.h-1 até o desaparecimento dos sintomas. A infusão contínua de naloxona foi mantida na Unidade de Terapia Intensiva (UTI), onde a pressão arterial, freqüência cardíaca, freqüência respiratória, saturação de oxigênio foram monitoradas, assim como a presença de náusea, prurido, vômito, sedação, dor e retenção urinária observadas. Após 2 horas de admissão na UTI, o paciente apresentou fibrilação atrial aguda sem instabilidade hemodinâmica. O ritmo sinusal foi restabelecido após 150 mg de amiodarona e interrupção da infusão de naloxona. Nas 18 horas seguintes apresentou estabilidade hemodinâmica e evoluiu sem outras intercorrências até a alta hospitalar. CONCLUSÕES: O presente relato alerta para o risco de troca de medicamentos durante o ato anestésico e ressalta a importância do encaminhamento dos pacientes em tratamento de sobredose de opióides à UTI em virtude de seus potenciais efeitos adversos.

BACKGROUND AND OBJECTIVES: The subarachnoid administration of morphine is a well-established anesthetic technique of postoperative analgesia due to its efficacy, safety and low cost. The objective of this paper was to report the accidental subarachnoid administration of 4 mg of morphine complicated by atrial fibrillation after administration of naloxone. CASE REPORT: A 45-year old male patient with 75 kg, 1.72 m, physical status ASA II, hypertensive, was scheduled for reconstruction of the anterior cruciate ligament of the left knee. After spinal anesthesia, it was noticed that the vial of morphine had been changed resulting in the accidental subarachnoid administration of 4 mg of morphine (0.4 mL of the 10 mg vial). Respiratory rate varied from 12 to 16 bpm and the patient remained hemodynamically stable without intraoperative complaints. Thirty minutes after admission to the post-anesthesia recovery unit the patient developed vomiting and diaphoresis being treated with 0.4 mg of naloxone followed by continuous infusion of 0.2 mg.h-1 until the symptoms had subsided. Continuous naloxone infusion was maintained in the Intensive Care Unit (ICU), where blood pressure, heart rate, respiratory rate and oxygen saturation were monitored as well as the presence of nausea, pruritus, vomiting, sedation, pain and urinary retention. Two hours after arriving at the ICU the patient developed acute atrial fibrillation without hemodynamic instability. Sinus rhythm was reestablished after the administration of 150 mg of amiodarone and discontinuation of the naloxone infusion. During the following 18 hours the patient remained hemodynamically stable and did not experience any other intercurrence until his discharge from the hospital. CONCLUSIONS: The present report is an alert for the risk of inadvertently switching of drugs during anesthesia, stressing the importance of referring patients being treated for opiate overdose to the ICU, due to the potential...

JUSTIFICATIVA Y OBJETIVOS: La administración de morfina por vía subaracnoidea es la técnica bien establecida para la analgesia postoperatoria debido a su eficacia, seguridad y bajo costo. La administración inadvertida de 4 mg de morfina por vía subaracnoidea complicada por fibrilación atrial después de la administración de naloxona fue el objetivo de este relato. RELATO DEL CASO: Paciente del sexo masculino, 45 años, 75 kg, 1,72 m, estado físico ASA II, hipertenso, a ser sometido a la reconstrucción del ligamento cruzado anterior de la rodilla izquierda. Después de la realización de la raquianestesia, fue constatado cambio de la ampolla de morfina, con administración de 4 mg (0,4 mL de la ampolla de 10 mg) por vía subaracnoidea. La frecuencia respiratoria osciló entre 12 y 16 incursiones respiratorias por minuto y el paciente se mantuvo estable hemodinámicamente sin quejarse en el intraoperatorio. Después de 30 minutos de la admisión en la SRPA, presentó vómitos y sudor, tratados con 0,4 mg de naloxona seguidos de infusión continua de 0,2 mg.h-1 hasta el desaparecimiento de los síntomas. La infusión continua de naloxona se mantuvo en la Unidad de Cuidados Intensivos (UCI), donde la presión arterial, frecuencia cardíaca, frecuencia respiratoria, saturación de oxígeno se monitorearon. También se comprobó la presencia de náusea, prurito, vómito, sedación, dolor y retención urinaria. Después de 2 horas de admisión en la UCI, el paciente presentó fibrilación atrial aguda sin inestabilidad hemodinámica. El ritmo sinusal fue reestablecido después de 150 mg de amiodarona e interrupción de la infusión de naloxona. En las 18 horas siguientes presentó estabilidad hemodinámica y evolucionó sin otras intercurrencias hasta su alta. CONCLUSIONES: El presente relato nos avisa sobre el riesgo del cambio de medicamentos durante la anestesia y resalta la importancia del envío de los pacientes en tratamiento de sobredosis de opioides a la UCI a causa de...

Accidental subarachnoid administration of 4 mg of morphine. Case report.

BACKGROUND AND OBJECTIVES: The subarachnoid administration of morphine is a well-established anesthetic technique of postoperative analgesia due to its efficacy safety and low cost. The objective of this paper was to report the accidental subarachnoid administration of 4 mg of morphine complicated by atrial fibrillation after administration of naloxone. CASE REPORT: A 45-year old male patient with 75 kg, 1.72 m, physical status ASA II, hypertensive, was scheduled for reconstruction of the anterior cruciate ligament of the left knee. After spinal anesthesia, it was noticed that the vial of morphine had been changed resulting in the accidental subarachnoid administration of 4 mg of morphine (0.4 mL of the 10 mg vial). Respiratory rate varied from 12 to 16 bpm and the patient remained hemodynamically stable without intraoperative complaints. Thirty minutes after admission to the post-anesthesia recovery unit the patient developed vomiting and diaphoresis being treated with 0.4 mg of naloxone followed by continuous infusion of 0.2 mg x (-1) until the symptoms had subsided. Continuous naloxone infusion was maintained in the Intensive Care Unit (ICU), where blood pressure, heart rate, respiratory rate and oxygen saturation were monitored as well as the presence of nausea, pruritus, vomiting, sedation, pain and urinary retention. Two hours after arriving at the ICU the patient developed acute atrial fibrillation without hemodynamic instability. Sinus rhythm was reestablished after the administration of 150 mg of amiodarone and discontinuation of the naloxone infusion. During the following 18 hours the patient remained hemodynamically stable and did not experience any other intercurrence until his discharge from the hospital. CONCLUSIONS: The present report is an alert for the risk of inadvertently switching of drugs during anesthesia, stressing the importance of referring patients being treated for opiate overdose to the ICU, due to the potential adverse reactions.

Schistosoma mansoni: the effect of dexamethasone on the cercaria schistosomullum transformation, in vivo

O tratamento com dexametasona (DMS) nas fases iniciais da infeccao experimental com S. mansoni leva a um efeito indireto sobre o processo de transformacao da cercaria em esquistossomulo, quando camundongos isentos de infeccao sao tratados com esta droga (50 mg/kg, subcutaneamente) e, 01 hora depois, sao infectados intraperitonealmente com cerca de 500 cercarias de S. mansoni (cepa LE). Foi observada uma significativa reducao na adesao de celulas do hospedeiro as larvas, com um atraso simultaneo no processo de transformacao das cercarias em esquistossomulos...

Oogram studies in mice infected with Schistosoma mansoni and treated with dexamethasone

Camundongos infectados com cerca de 90 cercarias da cepa Le de Schistosoma mansoni foram tratados durante 5 dias consecutivos com dexametasona (50mg/kg, subcutaneamente) a partir do 42§ dia de infeccao. Grupos de cinco camundongos foram sacrificados diariamente apos o primeiro dia do inicio do tratamento ate o primeiro dia apos o termino. A perfusao do sistema porta foi feita e fragmentos do intestino foram processados para a realizacao de oogramas qualitativos e quantitativos....

Estudo histopatológico do teste cutâneo em cäes de área endêmica de leishmaniose tegumentar, utilisando dois antígenos: leishvacin e o P10.000G / Comparative histopathologic study of the skin test in dogs from an endemic of area tegumentary leishmaniosis , using two antigens: leishvacin and P10.000G

A intradermorreaçäo de Montenegro, um teste de hipersensibilidade tardia, é um método muito utilizado no diagnóstico auxiliar da leishmaniose tegumentar americana (LTA) humana. Entretanto, säo escassos os relatos a respeito das alteraçöes induzidas experimentalmente pelo teste cutâneo, sobretudo no cäo. Frente a isso, a nível de campo, foram comparados dois testes cutâneos para diagnóstico da leishmaniose tegumentar canina (LTC), utilizando-se o leishvacin e o P10.000G como antígenos. Nos cäes que receberam o P10.000G, constatou-se reaçäo inflamatória mais evidente e difusa que nos testados com o Leishvacin

Kinectics of the pulmonary phase of Schistosoma mansoni in mice treated with dexamethasone

Na esquistossomose mansoni experimental, os glicocorticóides causam uma reduçäo na carga de vermes quando administradoss na semana da infecçäo, ou, no mais tardar, na semana seguinte. A fim de determinar o(s) provável(is) sítio(s) de reduçäo da carga de vermes, camundongos foram infectados com cercárias da cepa LE de S. mansoni e dexametasona foi administrada diariamente (50 mg/Kg, subcutaneamente), iniciando 1 hora antes da infecçäo e prosseguindo até o 8§ dia. Os camundongos foram sacrificados diariamente, do 3§ ao 9§ dia pós-infecçäo, e os esquistossômulos foram coletados. Os camundongos remanescentes foram sacrificados seis semanas após a infecçäo e perfundidos para recuperaçäo dos vermes adultos. A análise dos resultados apresentavam números maiores de larvas pulmonares que os tratados, sendo que esta diferença foi também encontrada mais tarde na carga de vermes do sistema porta. Esta diferença pode representar a morte precoce das larvas nos animais tratados, no período pelepulmäo de seu desenvolvimento