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1.
Clin Lymphoma Myeloma Leuk ; 22(9): e844-e852, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35688793

RESUMO

INTRODUCTION: Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). MATERIALS AND METHODS: We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a "resistance" parameter that reflects the stagnation in the response after an initial descent. RESULTS: Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P = .02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P = .02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P < .002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. CONCLUSION: This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Neoplasia Residual/diagnóstico , Paraproteínas , Prognóstico , Resultado do Tratamento
4.
Cytotherapy ; 20(9): 1110-1123, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30170815

RESUMO

BACKGROUND: The regenerative and immunomodulatory properties of human mesenchymal stromal cells (hMSCs) have raised great hope for their use in cell therapy. However, when intravenously infused, hMSCs fail to reach sites of tissue injury. Fucose addition in α(1,3)-linkage to terminal sialyllactosamines on CD44 creates the molecule known as hematopoietic cell E-/L-selectin ligand (HCELL), programming hMSC binding to E-selectin that is expressed on microvascular endothelial cells of bone marrow (BM), skin and at all sites of inflammation. Here we describe how this modification on BM-derived hMSCs (BM-hMSCs) can be adapted to good manufacturing practice (GMP) standards. METHODS: BM-hMSCs were expanded using xenogenic-free media and exofucosylated using α(1,3)-fucosyltransferases VI (FTVI) or VII (FTVII). Enforced fucosylation converted CD44 into HCELL, and HCELL formation was assessed using Western blot, flow cytometry and cell-binding assays. Untreated (unfucosylated), buffer-treated and exofucosylated BM-hMSCs were each analyzed for cell viability, immunophenotype and differentiation potential, and E-selectin binding stability was assessed at room temperature, at 4°C, and after cryopreservation. Cell product safety was evaluated using microbiological testing, karyotype analysis, and c-Myc messenger RNA (mRNA) expression, and potential effects on genetic reprogramming and in cell signaling were analyzed using gene expression microarrays and receptor tyrosine kinase (RTK) phosphorylation arrays. RESULTS: Our protocol efficiently generates HCELL on clinical-scale batches of BM-hMSCs. Exofucosylation yields stable HCELL expression for 48 h at 4°C, with retained expression after cell cryopreservation. Cell viability and identity are unaffected by exofucosylation, without changes in gene expression or RTK phosphorylation. DISCUSSION: The described exofucosylation protocol using xenogenic-free reagents enforces HCELL expression on hMSCs endowing potent E-selectin binding without affecting cell viability or native phenotype. This described protocol is readily scalable for GMP-compliant clinical production.


Assuntos
Biotecnologia/métodos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Biotecnologia/normas , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Criopreservação , Selectina E/metabolismo , Células Endoteliais/metabolismo , Fucose/metabolismo , Fucosiltransferases/metabolismo , Glicosilação , Humanos , Receptores de Hialuronatos/metabolismo , Imunofenotipagem , Transcriptoma
5.
Future Cardiol ; 14(3s): 31-37, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29848091

RESUMO

AIM: To evaluate the clinical profile and effectiveness/safety of patients taking rivaroxaban in clinical practice. METHODS: Retrospective study that included patients with nonvalvular atrial fibrillation treated with rivaroxaban for the prevention of stroke between January 2012 and December 2016 in a tertiary hospital in Spain. RESULTS: A total of 142 patients (median age 78 years, 40.1% men, 32.4% creatinine clearance <50 ml/min; 96.5% CHA2DS2-VASc ≥2; 44.3% HAS-BLED ≥3) were included. Only two patients had a thromboembolic event (in both cases ischemic stroke) and three patients had major bleeding (rates of 1.3 and 1.9 events/100 patient years, respectively). CONCLUSION: Data regarding effectiveness and safety in our cohort were consistent with previous studies, showing that rivaroxaban can be effective and safely used in our setting.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Hemorragia/epidemiologia , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Feminino , Humanos , Masculino , Padrões de Prática Médica , Estudos Retrospectivos , Espanha , Acidente Vascular Cerebral/etiologia , Centros de Atenção Terciária
6.
Rev. esp. cardiol. (Ed. impr.) ; 70(11): 907-914, nov. 2017. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-168316

RESUMO

Introducción y objetivos: Los pacientes con síndrome de QT largo (SQTL) tienen una adaptación anormal del QT a los cambios bruscos de la frecuencia cardiaca producidos con la bipedestación. Este trabajo estudia la utilidad del test de bipedestación en una cohorte de pacientes con SQTL y evalúa si el fenómeno de «mala adaptación» del QT se normaliza con el tratamiento con bloqueadores beta. Métodos: Se realizó un electrocardiograma basal y otro inmediatamente tras la bipedestación a 36 pacientes con SQTL (6 [17%] con QTL1, 20 [56%] con QTL2, 3 [8%] con QTL7 y 7 [19%] con genotipo no identificado) y 41 controles. Se midió el intervalo QT corregido (QTc) basal (QTcdecúbito) y tras la bipedestación (QTcbipedestación) y el incremento del QTc (ΔQTc = QTcbipedestación - QTcdecúbito). Se repitió el test en 26 de los pacientes bajo tratamiento con bloqueadores beta. Resultados: El QTcbipedestación y el ΔQTc fueron mayores en el grupo de SQTL que en el grupo control (QTcbipedestación, 528 ± 46 frente a 420 ± 15 ms; p < 0,0001; ΔQTc, 78 ± 40 frente a 8 ± 13 ms; p < 0,0001). No hubo diferencias significativas entre los pacientes con QTL1 y QTL2. Los pacientes con SQTL presentaron patrones típicos del segmento ST-onda T tras la bipedestación. Las curvas receiver operating characteristic del QTcbipedestación y ΔQTc mostraron un incremento significativo del valor diagnóstico comparadas con la del QTcdecúbito(área bajo la curva de ambos, 0,99 frente a 0,85; p < 0,001). El tratamiento con bloqueadores beta atenuó la respuesta a la bipedestación de los pacientes con SQTL (en tratamiento, QTcbipedestación, 440 ± 32 ms [p < 0,0001] y ΔQTc, 14 ± 16 ms [p < 0,0001]). Conclusiones: La evaluación del intervalo QTc tras la bipedestación proporciona un alto rendimiento diagnóstico y podría ser de gran utilidad en la monitorización del tratamiento con bloqueadores beta en los pacientes con SQTL (AU)


Introduction and objectives: Patients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy. Methods: Electrographic assessments were performed at baseline and immediately after standing in 36 LQTS patients (6 LQT1 [17%], 20 LQT2 [56%], 3 LQT7 [8%], 7 unidentified-genotype patients [19%]) and 41 controls. The corrected QT interval (QTc) was measured at baseline (QTcsupine) and immediately after standing (QTcstanding); the QTc change from baseline (ΔQTc) was calculated as QTcstanding - QTcsupine. The test was repeated in 26 patients receiving beta-blocker therapy. Results: Both QTcstanding and ΔQTc were significantly higher in the LQTS group than in controls (QTcstanding, 528 ± 46 ms vs 420 ± 15 ms, P < .0001; ΔQTc, 78 ± 40 ms vs 8 ± 13 ms, P < .0001). No significant differences were noted between LQT1 and LQT2 patients. Typical ST-T wave patterns appeared after standing in LQTS patients. Receiver operating characteristic curves of QTcstanding and ΔQTc showed a significant increase in diagnostic value compared with the QTcsupine (area under the curve for both, 0.99 vs 0.85; P < .001). Beta-blockers attenuated the response to standing in LQTS patients (QTcstanding, 440 ± 32 ms, P < .0001; ΔQTc, 14 ± 16 ms, P < .0001). Conclusions: Evaluation of the QTc after the simple maneuver of standing shows a high diagnostic performance and could be important for monitoring the effects of beta-blocker therapy in LQTS patients (AU)


Assuntos
Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Frequência Cardíaca , Protocolos Clínicos , Estudos de Coortes , Eletrocardiografia , Postura , 28599
7.
Farm. hosp ; 41(5): 611-617, sept.-oct. 2017. tab
Artigo em Inglês | IBECS | ID: ibc-166598

RESUMO

Objective: To assess the toxicity of a standardized triple intrathecal chemotherapy in onco- hematological adult patients and to establish risk factors of toxicity. Method: Observational and prospective study of standardized triple intrathecal chemotherapy administrations in onco-hematologic adult patients for 18 months. Results: There were some adverse events in 39.3% of the 56 administrations registered. 96.7% of the events were grade 1-2 and only 1 event was grade 3. The lower age of the patient and the greater difference between the administered drug volume and cerebrospinal fluid removed volume were shown as risk factors for toxicity. Conclusions: The administration of standardized triple intrathecal chemotherapy was related to a low frequency of toxicity and most of adverse events were mild-moderate. The detection of adverse effects was significantly greater in young adults and in those administrations where the difference between cerebrospinal fluid remove volume and the administered drug was greater (AU)


Objetivo: Evaluar la toxicidad asociada a la administración de quimioterapia triple intratecal estandarizada en pacientes onco-hematológicos adultos e identificar los factores de riesgo asociados. Método: Estudio observacional y prospectivo de las administraciones de quimioterapia triple intratecal estandarizada administradas a pacientes onco-hematológicos adultos durante 18 meses. Resultados: Se registró algún evento adverso en el 39,3% de las 56 administraciones registradas. El 96,7% de los eventos fueron grado 1-2 y solo 1 evento fue grado 3. La menor edad del paciente y la mayor diferencia entre el volumen administrado y el líquido cefalorraquídeo extraído se mostraron como factores de riesgo de toxicidad. Conclusiones: La administración de quimioterapia triple intratecal estandarizada estuvo relacionada con una baja frecuencia de toxicidad y la mayoría de los eventos adversos fueron de gravedad leve-moderada. La detección de efectos adversos fue significativamente mayor en adultos jóvenes y en aquellas administraciones en las que la diferencia entre el volumen de líquido cefalorraquídeo extraído y de fármaco administrado fue mayor (AU)


Assuntos
Humanos , Adulto , Neoplasias Hematológicas/tratamento farmacológico , Antineoplásicos/toxicidade , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Injeções Espinhais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Fatores de Risco , Estudos Prospectivos
8.
Farm Hosp ; 41(5): 611-617, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28847250

RESUMO

OBJECTIVE: To assess the toxicity of a standardized triple intrathecal chemotherapy in onco- hematological adult patients and to establish risk factors of toxicity. METHOD: Observational and prospective study of standardized triple intrathecal chemotherapy administrations in onco-hematologic adult patients for 18 months. RESULTS: There were some adverse events in 39.3% of the 56 administrations registered. 96.7% of the events were grade 1-2 and only 1 event was grade 3. The lower age of the patient and the greater difference between the administered drug volume and cerebrospinal fluid removed volume were shown as risk factors for toxicity. CONCLUSIONS: The administration of standardized triple intrathecal chemotherapy was related to a low frequency of toxicity and most of adverse events were mild-moderate. The detection of adverse effects was significantly greater in young adults and in those administrations where the difference between cerebrospinal fluid remove volume and the administered drug was greater.


Objetivo: Evaluar la toxicidad asociada a la administración de quimioterapia triple intratecal estandarizada en pacientes onco-hematológicos adultos e identificar los factores de riesgo asociados.Método: Estudio observacional y prospectivo de las administraciones de quimioterapia triple intratecal estandarizada administradas a pacientes onco-hematológicos adultos durante 18 meses.Resultados: Se registró algún evento adverso en el 39,3% de las 56 administraciones registradas. El 96,7% de los eventos fueron grado 1-2 y solo 1 evento fue grado 3. La menor edad del paciente y la mayor diferencia entre el volumen administrado y el líquido cefalorraquídeo extraído se mostraron como factores de riesgo de toxicidad.Conclusiones: La administración de quimioterapia triple intratecal estandarizada estuvo relacionada con una baja frecuencia de toxicidad y la mayoría de los eventos adversos fueron de gravedad leve-moderada. La detección de efectos adversos fue significativamente mayor en adultos jóvenes y en aquellas administraciones en las que la diferencia entre el volumen de líquido cefalorraquídeo extraído y de fármaco administrado fue mayor.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Feminino , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/uso terapêutico , Injeções Espinhais , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
9.
Rev Esp Cardiol (Engl Ed) ; 70(11): 907-914, 2017 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28233664

RESUMO

INTRODUCTION AND OBJECTIVES: Patients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy. METHODS: Electrographic assessments were performed at baseline and immediately after standing in 36 LQTS patients (6 LQT1 [17%], 20 LQT2 [56%], 3 LQT7 [8%], 7 unidentified-genotype patients [19%]) and 41 controls. The corrected QT interval (QTc) was measured at baseline (QTcsupine) and immediately after standing (QTcstanding); the QTc change from baseline (ΔQTc) was calculated as QTcstanding - QTcsupine. The test was repeated in 26 patients receiving beta-blocker therapy. RESULTS: Both QTcstanding and ΔQTc were significantly higher in the LQTS group than in controls (QTcstanding, 528 ± 46ms vs 420 ± 15ms, P < .0001; ΔQTc, 78 ± 40ms vs 8 ± 13ms, P < .0001). No significant differences were noted between LQT1 and LQT2 patients. Typical ST-T wave patterns appeared after standing in LQTS patients. Receiver operating characteristic curves of QTcstanding and ΔQTc showed a significant increase in diagnostic value compared with the QTcsupine (area under the curve for both, 0.99 vs 0.85; P < .001). Beta-blockers attenuated the response to standing in LQTS patients (QTcstanding, 440 ± 32ms, P < .0001; ΔQTc, 14 ± 16ms, P < .0001). CONCLUSIONS: Evaluation of the QTc after the simple maneuver of standing shows a high diagnostic performance and could be important for monitoring the effects of beta-blocker therapy in LQTS patients.


Assuntos
Teste de Esforço/métodos , Síndrome do QT Longo/diagnóstico , Antagonistas Adrenérgicos beta , Adulto , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/fisiopatologia , Masculino , Testes Imediatos , Postura , Curva ROC
10.
Oncoimmunology ; 5(4): e1093721, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27141379

RESUMO

Missing self recognition makes cancer sensitive to natural killer cell (NKc) reactivity. However, this model disregards the NKc licensing effect, which highly increases NKc reactivity through interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) with their cognate HLA-I ligands. The influence of iKIR/HLA-ligand (HLA-C1/C2) licensing interactions on the susceptibility to and progression of plasma cell (PC) dyscrasias was evaluated in 164 Caucasian patients and 286 controls. Compared to controls, myeloma accumulates KIR2DL1-L2+L3- genotypes (2.8% vs. 13.2%, p < 0.01, OR = 5.29) and less diverse peripheral repertoires of NKc clones. Less diverse and weaker-affinity repertoires of iKIR2D/HLA-C licensing interactions increased myeloma susceptibility. Thus, the complete absence of conventional iKIR2D/HLA-C licensing interactions (KIR2DL1-L2+L3-/C2C2, 2.56% vs. 0.35%; p < 0.05; OR = 15.014), single-KIR2DL3+/C1+ (20.51% vs. 10.84%; p < 0.05; OR = 2.795) and single-KIR2DL2+/C1+ (12.82% vs. 4.9%; p < 0.01; OR = 5.18) interactions were over-represented in myeloma, compared to controls. Additionally, KIR2DL1-L2+L3- (20% vs. 83%, p < 0.00001) as well as KIR3DL1- (23% vs. 82%, p < 0.00001) genotypes had a dramatic negative impact on the 3-y progression-free survival (PFS), particularly in patients with low-tumor burden. Remarkably, myeloma-PCs, compared to K562 and other hematological cancers, showed substantial over-expression of HLA-I ("increasing-self" instead of missing-self), including HLA-C, and mild expression of ligands for NKc activating receptors (aRec) CD112, CD155, ULBP-1 and MICA/B, which apparently renders myeloma-PCs susceptible to lysis mainly by licensed NKc. KIR2DL1-L2+L3-/C2C2 patients (with no conventional iKIR2D/HLA-C licensing interactions) lyse K562 but barely lyse myeloma-PCs (4% vs. 15%; p < 0.05, compared to controls). These results support a model where immunosurveillance of no-missing-self cancers, e.g., myeloma, mainly depends on NKc licensing.

12.
Hematol Oncol ; 34(2): 108-114, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25491088

RESUMO

Multiple myeloma (MM) is a hematologic neoplasm characterized by plasma tumor cell proliferation in the bone marrow. It's a rare malignancy before a 40-year-old and it is extremely uncommon during pregnancy. We report the case of a 37-year-old woman with a newly diagnosed IgG λ MM (Durie-Salmon stage IIIA, International Staging System II and good prognosis cytogenetic) at the 27th week of her pregnancy. Our management during pregnancy, the delivery, and initiation of anti-myeloma treatment with bortezomib, lenalidomide, and dexamethasone are published. There are a few reviews reporting the most common features and management of MM during pregnancy. We perform a comprehensive review of all 32 cases reported between 1965 and 2014 in which a MM was diagnosed during pregnancy including score, cytogenetic results, labor characteristics, and response to therapy. About 53% of pregnant women did not start treatment before partum. Cesarean section was the most common form of delivery (82%). About 88% of newborns were healthy, although most of them were premature (73%). Management of a MM diagnosed during pregnancy should be based on the presence of myeloma-related organ damage to secure survival of the mother without fetal adverse effects related to treatment. Serial fetal ultrasound may be helpful in order to avoid complications. The cesarean section may be preferred depending on maternal and fetus prognosis. Whole-body diffusion-weighted imaging minimal response could be an appropriate technique to discard plasmacytomas during pregnancy in critical situations such as the appearance of symptoms of spinal cord compression. Therapeutic choices should be agreed with the pregnant after a thorough discussion of the prognostic factors of the disease and the potential risk for the fetus and the patient. While awaiting partum, dexamethasone is a non-toxic treatment. Triple therapy including a proteasome inhibitor should be started quickly after delivery. Copyright © 2014 John Wiley & Sons, Ltd.

13.
Rev. esp. cardiol. (Ed. impr.) ; 68(10): 861-868, oct. 2015. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-143223

RESUMO

Introducción y objetivos: El síndrome de QT largo es una canalopatía hereditaria que se asocia a síncope y muerte súbita. La heterogeneidad fenotípica de esta enfermedad hace que el estudio genético sea fundamental para detectar a los sujetos con síndrome de QT largo oculto. En este trabajo se exponen las características de una familia con 13 portadores de la mutación missense KCNH2-H562R que afecta a la región del poro del canal HERG. Métodos: Se describió la mutación KCNH2-H562R en un varón de 65 años con intervalo QTc prolongado que presentó un episodio de torsade de pointes. Posteriormente, se identificaron 13 portadores de la mutación en la familia. Se realizó evaluación clínica, electrocardiograma y ecocardiograma a los portadores (edad, 48 ± 26 años; el 46% varones). Resultados: El QTc medio en los portadores fue de 493 ± 42 ms (3 [23%] mostraron QTc normal); 6 (46%) tuvieron síntomas (4, síncope; 1, muerte súbita; 1, muerte súbita resucitada [probando]). Durante el tratamiento con bloqueadores beta, 11 (92%) de los 12 portadores permanecieron asintomáticos a los 5 años de seguimiento (1 paciente requirió simpatectomía cardiaca izquierda). El acortamiento del QTc con bloqueadores beta fue de 50 ± 37 ms. Hubo 1 muerte súbita en un paciente que rechazó tratamiento con bloqueadores beta. Conclusiones: El estudio familiar es fundamental en la interpretación de los resultados de los tests genéticos en la actualidad. Este artículo describe el fenotipo variable y heterogéneo de una amplia familia portadora de la mutación KCNH2-H562R y destaca el papel del estudio genético en la identificación de los individuos en riesgo que se beneficiarían del tratamiento con bloqueadores beta (AU)


Introduction and objectives: Long QT syndrome is an inherited ion channelopathy that leads to syncope and sudden death. Because of the heterogeneous phenotype of this disease, genetic testing is fundamental to detect individuals with concealed long QT syndrome. In this study, we determined the features of a family with 13 carriers of the KCNH2-H562R missense mutation, which affects the pore region of the HERG channel. Methods: We identified the KCNH2-H562R mutation in a 65-year-old man with a prolonged QTc interval who had experienced an episode of torsade de pointes. Subsequently, a total of 13 mutation carriers were identified in the family. Carriers (age 48 [26] years; 46% males) underwent clinical evaluation, electrocardiography and echocardiography. Results: The mean (standard deviation) QTc in carriers was 493 (42) ms (3 [23%] showed normal QTc); 6 (46%) had symptoms (4, syncope; 1, sudden death; 1, aborted sudden death [proband]). While under treatment with beta-blockers, 11 of 12 carriers (92%) remained asymptomatic at 5 years of follow-up (1 patient required left cardiac sympathectomy). The QTc shortening with beta-blockers was 50 (37) ms. There was 1 sudden death in a patient who refused treatment. Conclusions: Family study is essential in the interpretation of a genetic testing result. This article describes the heterogeneous and variable phenotype of a large family with the KCNH2-H562R mutation and highlights the role of genetic study for the appropriate identification of at-risk individuals who would benefit from treatment (AU)


Assuntos
Idoso , Humanos , Masculino , Torsades de Pointes/genética , Síndrome do QT Longo/genética , Morte Súbita Cardíaca/epidemiologia , Técnicas Genéticas , /métodos , Eletrocardiografia , Ecocardiografia , Fenótipo , Bisoprolol/uso terapêutico , Claritromicina , Hipopotassemia/complicações
14.
Rev Esp Cardiol (Engl Ed) ; 68(10): 861-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25819988

RESUMO

INTRODUCTION AND OBJECTIVES: Long QT syndrome is an inherited ion channelopathy that leads to syncope and sudden death. Because of the heterogeneous phenotype of this disease, genetic testing is fundamental to detect individuals with concealed long QT syndrome. In this study, we determined the features of a family with 13 carriers of the KCNH2-H562R missense mutation, which affects the pore region of the HERG channel. METHODS: We identified the KCNH2-H562R mutation in a 65-year-old man with a prolonged QTc interval who had experienced an episode of torsade de pointes. Subsequently, a total of 13 mutation carriers were identified in the family. Carriers (age 48 [26] years; 46% males) underwent clinical evaluation, electrocardiography and echocardiography. RESULTS: The mean (standard deviation) QTc in carriers was 493 (42) ms (3 [23%] showed normal QTc); 6 (46%) had symptoms (4, syncope; 1, sudden death; 1, aborted sudden death [proband]). While under treatment with beta-blockers, 11 of 12 carriers (92%) remained asymptomatic at 5 years of follow-up (1 patient required left cardiac sympathectomy). The QTc shortening with beta-blockers was 50 (37) ms. There was 1 sudden death in a patient who refused treatment. CONCLUSIONS: Family study is essential in the interpretation of a genetic testing result. This article describes the heterogeneous and variable phenotype of a large family with the KCNH2-H562R mutation and highlights the role of genetic study for the appropriate identification of at-risk individuals who would benefit from treatment.


Assuntos
DNA/genética , Canal de Potássio ERG1/genética , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Síndrome do QT Longo/genética , Mutação , Linhagem , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Análise Mutacional de DNA , Canal de Potássio ERG1/metabolismo , Feminino , Testes Genéticos , Heterozigoto , Humanos , Síndrome do QT Longo/fisiopatologia , Masculino , Fenótipo , Adulto Jovem
15.
FEM (Ed. impr.) ; 17(3): 143-149, sept. 2014. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-130964

RESUMO

Introducción: Los recientes cambios socioeconómicos pueden modificar las características de los residentes que se incorporen a la formación sanitaria especializada (FSE), por lo que es oportuno, como punto de partida, estudiar algunas de sus particularidades en estos últimos años, incluida la incidencia de la denominada 'recirculación' dentro de la FSE. Sujetos y métodos: Se analizaron los datos demográficos, número obtenido en la convocatoria y otras características de todos los médicos internos residentes (MIR) que accedieron al Hospital Universitario Virgen de la Arrixaca (Murcia) durante el periodo 2009-2012. El estudio de la recirculación se limitó a los MIR ingresados en 2011 y 2012. Resultados: De los 226 MIR, 55% de sexo femenino, 73% de nacionalidad española, edad mediana de 25 años (rango intercuartílico: 25-28), la elección más frecuente es una especialidad clínica, y la mediana del número de acceso MIR, de 2.413 (rango intercuartílico: 1.305-3.425). El número de acceso es mejor en los varones que en las mujeres y en especialidades quirúrgicas respecto a médicas. La proporción de mujeres y de MIR de nacionalidad no española no ha cambiado significativamente durante los cuatro años. La recirculación se evidenció en el 17,1% (9,9% por segunda especialización y 7,2% por cambio de especialidad o con titulación fuera de la FSE antes de su conclusión). Conclusiones: Nuestros MIR en un hospital de tercer nivel son mujeres en mayor proporción. Un mejor número de acceso al examen MIR se asocia a varones y especialidades quirúrgicas. La tasa de recirculación en el periodo 2011-2012 no es desdeñable, predominando la reespecialización


Introduction: Recent economic and social changes may result in changes in the profile of our Residents currently admitted to postgraduate medical training (PMT) programs. Therefore, it seemed appropriate to study the current profile of trainees and proportion of residents retraining within our PMT programs to know the extent of these changes. Subjects and methods. We analyzed the demographic, examination score and other trainee data of 226 residents admitted to PMT programs in a tertiary hospital (Hospital Universitario Virgen de la Arrixaca, Murcia) during the 2009-2012 period. The study of retraining was limited to years 2011 and 2012. Results: Among 226 residents, females accounted for 55%, median age was 25 years (interquartile range: 25-28), they more frequently chose a clinical specialty, their median score in the national examination was 2,413 (interquartile range: 1,305-3,425) and there was no change in the proportion of foreign residents during the study. Male gender and the option for a surgical specialty were associated with a better examination score. Retraining accounted for 17.1% of our residents: 9.9% entered the PMT system to carry out a second specialty and 7.2 % after a previously unfinished specialty. Conclusions: The residents' profile in a tertiary hospital has remained unchanged during the last four years apart from a higher proportion of females. A higher score in the PTM examination was associated with male gender and the option for a surgical specialty. The proportion of foreign trainees did not change. The retraining rate among our residents was not negligible and was mostly due to respecialization


Assuntos
Humanos , Medicina Interna , /organização & administração , Internato e Residência , Educação Médica/tendências , Descrição de Cargo , Especialização/tendências
16.
Hematol Rep ; 4(3): e17, 2012 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-23087806

RESUMO

A case of pure red cell aplasia in a simultaneous kidney-pancreas transplant recipient on immunosuppressive therapy is reported here. The patient presented with anemia unresponsive to erythropoietin treatment. Bone marrow cytomorphology was highly suggestive of parvovirus pure red cell aplasia, which was confirmed with serology and polymerase chain reaction positive for parvovirus B19 DNA in peripheral blood. After the administration of intravenous immunoglobulin the anemia improved with a rising number of the reticulocytes.

17.
Transfusion ; 52(11): 2382-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22404870

RESUMO

BACKGROUND: Products cryopreserved with dimethyl sulfoxide (DMSO) in stem cell transplant (SCT) often cause many adverse effects during their infusion (major cardiovascular events, dyspnea … even death). These are especially frequent in pediatric patients. We tested if a fully automated and closed wash procedure (Sepax S-100, Biosafe) allowed us to maintain the absolute CD34+ cell number, cell viability, and engraftment potential, decreasing the untoward reactions. STUDY DESIGN AND METHODS: Forty-six washes of DMSO cryopreserved peripheral blood hematopoietic progenitor (HP) apheresis were studied. Blood aliquots were taken both after thawing and after washing to assess the total nucleated and CD34+ cell counts, as well as cell viability. The washed products were infused in 26 autologous SCTs (ASCTs). Results were compared with the 53 previous SCTs performed without DMSO removal. RESULTS: After washing there were no significant differences between the pre- and postwashing CD34+ cell counts (p=0.08) or viability (p=0.68). No significant differences were observed between washed and nonwashed infusions in relation to the day of the neutrophil (p=0.46) and platelet (p=0.26) engraftment. One adverse event, abdominal pain, occurred during the washed cells infusions. When compared with the 14 untoward reactions that took place during the nonwashed HP infusions, significance was reached (p=0.00043). CONCLUSIONS: The automatic method described is effective in terms of CD34+ cell recovery and viability in ASCT. Moreover, Sepax decreased significantly the untoward reactions during the infusion.


Assuntos
Preservação de Sangue/efeitos adversos , Crioprotetores/isolamento & purificação , Dimetil Sulfóxido/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/normas , Doença de Hodgkin/terapia , Adulto , Idoso , Remoção de Componentes Sanguíneos , Preservação de Sangue/métodos , Transfusão de Sangue Autóloga , Sobrevivência Celular/efeitos dos fármacos , Criança , Pré-Escolar , Crioprotetores/efeitos adversos , Dimetil Sulfóxido/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia
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