RESUMEN
OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3⯱â¯14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8⯱â¯14.2 years vs 54.5⯱â¯13.9 years, pâ¯<â¯.001). Familial PCCs were more frequently associated with MEN2A (nâ¯=â¯8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3â¯cm (3-6â¯cm); 27.7% of the patients had tumors ≥6â¯cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4â¯cm [2.4-5.0â¯cm] vs 5.6â¯cm [4.0-7.0â¯cm], pâ¯<â¯.001). Scintigraphy by ¹²³I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , 3-Yodobencilguanidina , Adolescente , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/terapia , Antagonistas Adrenérgicos alfa/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Catecolaminas/orina , Conversión a Cirugía Abierta/estadística & datos numéricos , Doxazosina/uso terapéutico , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Metanefrina/orina , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/complicaciones , Neoplasias Pancreáticas/genética , Fenoxibenzamina/uso terapéutico , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/genética , Feocromocitoma/patología , Feocromocitoma/terapia , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Tiempo , Carga Tumoral , Adulto JovenRESUMEN
Objetivo Analizar las características clínicas y analíticas, las pruebas diagnósticas, los tratamientos y los resultados del feocromocitoma (FCC). Diseño y métodos Estudio multicéntrico retrospectivo en pacientes con FCC tratados quirúrgicamente y seguidos en 3 hospitales terciarios de referencia españoles. Resultados Se analizó a un total de 106 pacientes (61 [57,5%] mujeres, edad media 52,3 ± 14,8 años). En el diagnóstico, el FCC fue sintomático en el 62% de los casos y esporádico en el 83%. Los pacientes con FCC familiar eran significativamente más jóvenes que aquellos que presentaban la enfermedad esporádica (40,8 ± 14,2 años vs. 54,5 ± 13,9 años, p < 0,001). El FCC familiar se asociaba con mayor frecuencia a la MEN2A (n = 8). Los niveles de metanefrinas en orina de 24h se relacionaron positivamente con el tamaño del tumor. El diámetro tumoral máximo fue 4,3cm (3-6cm); el 27,8% de los pacientes tenían tumores ≥ 6cm. Los FCC incidentales eran significativamente más pequeños que los FCC sintomáticos (3,4cm [2,4-5,0cm] vs. 5,6cm [4,0-7,0cm], p < 0,001). La gammagrafía con 123I-metaiodobencilguanidina mostró una alta sensibilidad (81,9%). En el 93,6% de los casos se usó el bloqueo alfa preoperatorio con fenoxibenzamina y con doxazosina en los demás casos. En 2/3 de los pacientes se empleó la cirugía laparoscópica, con una baja tasa de conversión (1,9%) a cirugía abierta. Aproximadamente en el 20% de los pacientes aparecieron complicaciones perioperatorias, principalmente crisis hipertensivas (9,4%). La enfermedad recurrente apareció en el 10% de los casos y el FCC maligno fue raro (6,3%). Conclusiones Los FCC tratados quirúrgicamente en España suelen ser tumores grandes, sintomáticos y esporádicos diagnosticados alrededor de la sexta década de vida. El FCC hereditario está generalmente asociado con MEN2A. La cirugía laparoscópica es el tipo principal de técnica quirúrgica utilizada y la prevalencia del FCC metastásico es baja (AU)
Objective To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). Design and methods A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. Results A total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs. 54.5 ± 13.9 years, p<.001). Familial PCCs were more frequently associated with MEN2A (n=8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3cm (3-6cm); 27.7% of the patients had tumors ≥6cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4cm [2.4-5.0cm] vs. 5.6cm [4.0-7.0cm], p<.001). Scintigraphy by 123I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). Conclusion PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/terapia , Feocromocitoma/diagnóstico , Feocromocitoma/terapia , Estudios Retrospectivos , Estudios de SeguimientoAsunto(s)
Betacoronavirus , Infecciones por Coronavirus/terapia , Posicionamiento del Paciente , Neumonía Viral/terapia , Posición Prona/fisiología , Terapia Respiratoria/métodos , Vibración/uso terapéutico , COVID-19 , Infecciones por Coronavirus/complicaciones , Enfermedad Crítica , Humanos , Terapia por Inhalación de Oxígeno/métodos , Pandemias , Presión Parcial , Neumonía Viral/complicaciones , Respiración Artificial , Terapia Respiratoria/instrumentación , SARS-CoV-2 , Esputo , Posición Supina/fisiologíaRESUMEN
OBJECTIVE: Nowadays, the algorithms for the study of hydronephrosis in children include voiding cystourethrogram (VCUG) and diuretic renogram (DR) in all patients. Both are invasive, distressing, and associated with radiation risk. However, basic renal function tests (bRFTs) are not included. This study was designed to determine whether bRFTs may help avoid VCUG and/or DR in some children. METHODS: Retrospective review of hydronephrosis (≥20 mm renal pelvis) patient records over one year (n = 38) (pyeloureteral stenosis (PUS) n = 12; high-grade vesicoureteral reflux (VUR) n = 8; non-obstructive hydronephrosis (NOH) n = 18. Data from the three protocolized bRFTs (maximum urine osmolality after DDAVP (UOsm), albumin/creatinine ratio (Alb/Cr), and NAG/creatinine ratio (NAG/Cr), together with VCUG and DR, were analyzed. RESULTS: 38 hydronephrosis patients (pyeloureteral stenosis (PUS) n = 12; high grade vesicoureteral reflux (VUR) n = 8; non-obstructive hydronephrosis (NOH) n = 18. UOsm was decreased in 100% of VUR patients, 75% of PUS patients, and 16.7% of NOH patients. Alb/Cr ratio was increased in 62.5% of VUR patients, 8.3% of PUS patients, and 11.1% of NOH patients. NAG/Cr ratio was increased in 42.8% of VUR patients, 25% of PUS patients, and 6.7% of NOH patients. UOsm was decreased in most patients who required surgery (100% of VUR patients and 74% of PUS patients), but only in 11.1% of patients who did not (NOH group). CONCLUSIONS: These results suggest that bRFTs may be useful in delaying or avoiding VCUG in some hydronephrosis cases. UOsm is the most sensitive test. No child with (high grade) VUR had a normal UOsm. VCUG could have been avoided in 43% of our patients -with a normal UOsm- without missing any high grade VUR.
OBJETIVO: Actualmente, los algoritmos para estudiar hidronefrosis en niños, incluyen realizar cistografía miccional (CUMS) y renograma diurético (RD) a todos. Ambos son invasivos, molestos, y con riesgo de radiación. Contrariamente, las pruebas básicas de función renal (PFRb), no están incluidas. Este estudio se realizó para saber si las PFRb, pueden ayudarnos a evitar alguna CUMS y/o RD. METODOS: Análisis retrospectivo de todas las historias de niños con hidronefrosis (pelvis renal ≥20 mm) atendidos durante un año (n=38), [estenosis pieloureteral (EPU) n = 12; reflujo vesicoureteral (RVU) de alto grado n = 8; hidronefrosis no obstructiva (HNO) n = 18]. Analizamos las tres PFRb protocolizadas [osmolalidad urinaria máxima tras DDAVP (UOsm), albúmina/creatinina (Alb/Cr) y NAG/creatinina (NAG/Cr)], junto con CUMS y RD. RESULTADOS: UOsm estaba disminuida en 100% RVU, 75% EPU, 16,7% HNO. Alb/Cr estaba aumentado en 62,5% RVU, 8,3% EPU, 11,1% HNO. NAG/Cr estaba aumentado en 42,8% RVU, 25% EPU, 6,7% HNO. En relación a la necesidad de cirugía, UOsm estaba disminuida en la mayoría de pacientes intervenidos (100% con RVU y 74% con EPU), mientras solo en el 11% de pacientes sin cirugía (HNO). CONCLUSION: Estos resultados sugieren que las PFRb pueden ser útiles para retrasar o evitar CUMS en algunos niños con hidronefrosis. La UOsm es la PFRb más sensible. Ningún niño con RVU (de alto grado) mostró una UOsm normal. Se podrían haber evitado CUMS en el 43% de nuestros pacientes, con UOsm normal, sin haber perdido ningún diagnóstico de VUR (de alto grado).
Asunto(s)
Hidronefrosis/diagnóstico , Pruebas de Función Renal/métodos , Obstrucción Ureteral/complicaciones , Reflujo Vesicoureteral/complicaciones , Adolescente , Algoritmos , Niño , Preescolar , Femenino , Humanos , Hidronefrosis/etiología , Hidronefrosis/terapia , Lactante , Recién Nacido , Masculino , Renografía por Radioisótopo , Estudios Retrospectivos , Urografía , Adulto JovenRESUMEN
OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs. 54.5 ± 13.9 years, p<.001). Familial PCCs were more frequently associated with MEN2A (n=8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3cm (3-6cm); 27.7% of the patients had tumors ≥6cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4cm [2.4-5.0cm] vs. 5.6cm [4.0-7.0cm], p<.001). Scintigraphy by 123I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.
RESUMEN
OBJETIVO: Actualmente, los algoritmos para estudiar hidronefrosis en niños incluyen realizar cistografía miccional (CUMS) y renograma diurético (RD) a todos. Ambos son invasivos, molestos y con riesgo de radiación. Contrariamente, las pruebas básicas de función renal (PFRb) no están incluidas. Este estudio se realizó para saber si las PFRb pueden ayudarnos a evitar alguna CUMS y/o RD. MÉTODOS: Análisis retrospectivo de todas las historias de niños con hidronefrosis (pelvis renal ≥ 20 mm) atendidos durante un año (n = 38), [estenosis pieloureteral (EPU) n = 12; reflujo vesicoureteral (RVU) de alto grado n = 8; hidronefrosis no obstructiva (HNO) n = 18]. Analizamos las tres PFRb protocolizadas [osmolalidad urinaria máxima tras DDAVP (UOsm), albúmina/creatinina (Alb/Cr) y NAG/creatinina (NAG/Cr)], junto con CUMS y RD. RESULTADOS: UOsm estaba disminuida en 100% RVU, 75% EPU, 16,7% HNO. Alb/Cr estaba aumentado en 62,5% RVU, 8,3% EPU, 11,1% HNO. NAG/Cr estaba aumentado en 42,8% RVU, 25% EPU, 6,7% HNO. En relación a la necesidad de cirugía, UOsm estaba disminuida en la mayoría de pacientes intervenidos (100% con RVU y 74% con EPU), mientras solo en el 11% de pacientes sin cirugía (HNO). CONCLUSIÓN: Estos resultados sugieren que las PFRb pueden ser útiles para retrasar o evitar CUMS en algunos niños con hidronefrosis. La UOsm es la PFRb más sensible. Ningún niño con RVU (de alto grado) mostró una UOsm normal. Se podrían haber evitado CUMS en el 43% de nuestros pacientes, con UOsm normal, sin haber perdido ningún diagnóstico de VUR (de alto grado)
OBJECTIVE: Nowadays, the algorithms for the study of hydronephrosis in children include voiding cystourethrogram (VCUG) and diuretic renogram (DR) in all patients. Both are invasive, distressing, and associated with radiation risk. However, basic renal function tests (bRFTs) are not included. This study was designed to determine whether bRFTs may help avoid VCUG and/or DR in some children. METHODS: Retrospective review of hydronephrosis (≥ 20 mm renal pelvis) patient records over one year (n = 38) (pyeloureteral stenosis (PUS) n = 12; high-grade vesicoureteral reflux (VUR) n = 8; non-obstructive hydronephrosis (NOH) n = 18. Data from the three protocolized bRFTs (maximum urine osmolality after DDAVP (UOsm), albumin/creatinine ratio (Alb/Cr), and NAG/creatinine ratio (NAG/Cr), together with VCUG and DR, were analyzed. RESULTS: 38 hydronephrosis patients (pyeloureteral stenosis (PUS) n = 12; high grade vesicoureteral reflux (VUR) n = 8; non-obstructive hydronephrosis (NOH) n = 18. UOsm was decreased in 100% of VUR patients, 75% of PUS patients, and 16.7% of NOH patients. Alb/Cr ratio was increased in 62.5% of VUR patients, 8.3% of PUS patients, and 11.1% of NOH patients. NAG/Cr ratio was increased in 42.8% of VUR patients, 25% of PUS patients, and 6.7% of NOH patients. UOsm was decreased in most patients who required surgery (100% of VUR patients and 74% of PUS patients), but only in 11.1% of patients who did not (NOH group). CONCLUSIONS: These results suggest that bRFTs may be useful in delaying or avoiding VCUG in some hydronephrosis cases. UOsm is the most sensitive test. No child with (high grade) VUR had a normal UOsm. VCUG could have been avoided in 43% of our patients with a normal UOsm-without missing any high grade VUR
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Hidronefrosis/diagnóstico por imagen , Hidronefrosis/cirugía , Algoritmos , Cistografía , Renografía por Radioisótopo , Estudios Retrospectivos , Pelvis Renal/diagnóstico por imagen , Pelvis Renal/patología , Albuminuria/diagnóstico , Reflujo Vesicoureteral/diagnóstico , Oportunidad Relativa , Técnicas de Laboratorio ClínicoRESUMEN
BACKGROUND: Cancer-specific survival for patients with clinical stage I (CSI) germ cell testicular cancer (GCTC) is outstanding after inguinal orchidectomy regardless the treatment utilized. This study evaluated whether active surveillance (AS) of such patients yielded similar health outcomes to other therapeutic strategies such as adjuvant chemotherapy, radiotherapy or primary retroperitoneal lymphadenectomy as described in the literature. PATIENTS AND METHODS: Patients with CSI GCTC were screened between January 2012 and December 2016. Patients had previously undergone inguinal orchidectomy as the primary treatment and chosen AS as their preferred management strategy after receiving information about all available strategies. RESULTS: Out of 91 patients screened, 82 patients selected AS as their preferred management strategy. Relapse rate in the overall population was 20% (95% CI 12-30) and median time to relapse was 11.5 months (range 1.0-35.0). In patients with seminomatous tumors, relapse rate decreased to 13% and median time to relapse was 13 months; whereas in patients with non-seminomatous tumors, relapse rate was 33% (IA) or 29% (IB) and median time to relapse was 12 months in stage IA and 4.5 months in stage IB patients. All relapses were rescued with three or four cycles of chemotherapy and two also required a retroperitoneal lymphadenectomy. All patients are currently alive and free of disease. CONCLUSIONS: The clinical outcomes of patients with CSI GCTC managed by AS in this series were excellent. This strategy limited the administration of active treatments specifically to the minority of patients who relapsed without compromising performance.
Asunto(s)
Imagen Multimodal/métodos , Neoplasias de Células Germinales y Embrionarias/prevención & control , Orquiectomía/mortalidad , Vigilancia de la Población , Neoplasias Testiculares/prevención & control , Espera Vigilante/estadística & datos numéricos , Adolescente , Adulto , Anciano , Manejo de la Enfermedad , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/cirugía , Espera Vigilante/normas , Adulto JovenRESUMEN
OBJECTIVES: The aim of this case-control study was to carry out an oral health assessment on a group of Alzheimer's patients and to establish a hypothesis regarding the implication of the characteristics of the disease and the treatment of oral health. MATERIALS AND METHODS: A total of 70 Alzheimer's patients, residents at the Alzheimer Center Reina Sofia Foundation (Madrid, Spain) and at the Alzheimer State Reference Center (Salamanca, Spain), and 36 controls (companions/acquaintances), were studied by oral examination and saliva sampling. The oral health indices DMFT/DMFS, CPI, the prosthetic condition, oral hygiene, saliva volume, and pH, as well as the specific microbiological parameters governing the risk of developing caries were assessed. RESULTS: Alzheimer's patients exhibited, as compared to the control group, (1) fewer teeth (10.9 ± 10.5 vs 23.7 ± 6.5), (2) fewer obturations (2.2 ± 3.4 vs 6.6 ± 5.6), (3) fewer periodontally healthy sextants (0.1 ± 0.4 vs 1.4 ± 2.2), (4) worse oral hygiene (43.1 vs 72.2% brushed), (5) greater use of removable prostheses (47.8 vs 8.4%), (6) higher incidence of candida infection (11.8 vs 0.0%) and cheilitis (15.9 vs 0.0%), (7) lower salivary flow (0.6 ± 0.6 vs 1.1 ± 0.6), and (8) lower buffering capacity (46 vs 80%). CONCLUSIONS: After taking into account the influence of age, Alzheimer's patients had worse oral health (caries and periodontal disease), more mucosal lesions (cheilitis and candidiasis), and worse saliva quantity and quality. CLINICAL RELEVANCE: Clinicians should be aware of the implications of Alzheimer's disease in oral health, in order to stablish the effective preventive measures and the optimal treatment plan.
Asunto(s)
Enfermedad de Alzheimer/complicaciones , Evaluación Geriátrica , Salud Bucal , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , EspañaRESUMEN
BACKGROUND: Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. Fas cell surface death receptor and mammalian target of rapamycin pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients. PATIENTS AND METHODS: A multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or progressing after standard chemotherapy and unsuitable for metastasectomy received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of gemcitabine administration, and the day before. The main end point was 4-month progression-free survival rate (PFSR), with the assumption that rates higher than 40% would be considered as an active regimen. Translational research aimed to correlate biomarkers with the clinical outcome. RESULTS: Thirty-five patients were enrolled and received at least one cycle. PFSR at 4 months was 44%, and after central radiologic assessment, 2 partial responses and 14 stabilizations (48.5%) were reported from 33 assessable patients. The most frequent grade 3-4 adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and fatigue (15%); however, only three patients had febrile neutropenia. Positive protein expression of RRM1 significantly correlated with worse PFS and overall survival, while positivity of P-ERK1/2 was correlated with significant better overall survival. CONCLUSION: Gemcitabine plus sirolimus exhibits satisfactory antitumor activity and safety in this osteosarcoma population, exceeding the prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with clinical outcome encourages further prospective investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/patología , Niño , Preescolar , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteosarcoma/patología , Recurrencia , Sirolimus/administración & dosificación , Sirolimus/efectos adversos , Adulto Joven , GemcitabinaRESUMEN
Current frontline therapies have improved overall survival in acute promyelocytic leukemia (APL) patients to exceptional rates; however, relapse is still a problem among high-risk and old patients. Therefore, the development of better and safer therapies continues to be a goal in the treatment of this disease. In the present work, we examined three different pathways that hinder cell death in the APL cell line NB4, shedding light on the mechanisms that underlie resistance to apoptosis in these cells and that might help provide them with a proliferative advantage. We found that the proteasome inhibitor MG-132 specifically induces in NB4 cells an Nrf2-mediated antioxidant response which counteracts mitochondria-dependent apoptosis induced by the lipophilic cation dequalinium. More importantly, we also demonstrated that high basal autophagy levels and the gain-of-function of mutant p53 are intrinsic mechanisms of resistance to apoptosis in this cell line. According to our results, the pharmacological inhibition of autophagy and p53 mutants are useful tools to explore resistance to apoptosis in APL and other types of cancer and could be the bases of new therapeutic approaches that improve the efficiency and allow dose reduction of the current treatments.
Asunto(s)
Apoptosis/genética , Resistencia a Antineoplásicos/genética , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Decualinio/administración & dosificación , Decualinio/farmacología , Relación Dosis-Respuesta a Droga , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leupeptinas/administración & dosificación , Leupeptinas/farmacología , Transporte de Proteínas/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Abstract: Rosenberg's self-esteem scale has been extensively used in all areas of psychology to assess global self-esteem (Rosenberg, 1965, 1979). Its construct validity, and specifically its factor structure, has almost from the beginning been under debate. More than four decades after its creation the cumulated evidence points that the scale measures a single trait (self-esteem) but confounded by a method factor associated to negatively worded items. The aim of the study is to examine the measurement invariance of the RSES by gender and test potential gender differences at the latent (trait and method) variable level, while controlling for method effects, in a sample of Spanish students. A series of completely a priori structural models were specified, with a standard invariance routine implemented for male and female samples. The results lead to several conclusions. Conclusions: a) the scale seem gender invariant for both trait and method factors; b) there were small but significant differences between males and females in self-esteem, differences that favored male respondents; and c) there were statistically non-significant differences between men and women in the method factor's latent means.
Resumen: La Escala de Autoestima de Rosenberg (EAR) ha sido utilizada extensamente en todas las áreas de la Psicología para evaluar la autoestima (Rosenberg, 1965, 1979). Su validez de constructo, y particularmente su estructura factorial, ha estado en debate casi desde que fue construida. Más de cuatro décadas después de su creación, la evidencia acumulada señala que la escala evalúa un solo rasgo (autoestima), aunque se confunde con un método factorial asociado de manera negative con reactivos verbales. El objetivo de este estudio fue evaluar la estabilidad de la medición de la EAR entre sexos y poner a prueba potenciales diferencias entre los mismos en un nivel latente de la variable (rasgo y estado), controlando efectos de método, en una muestra de estudiantes españoles. Se especificaron una serie de modelos estructurales a priori, con rutinas implementadas de invarianza estándar para muestras de hombres y mujeres. Los resultados llevan a diferentes conclusiones: a) La escala parece ser invariable ante el sexo tanto para factores de rasgo como de estado; b) existieron diferencias pequeñas, pero significativas, entre hombres y mujeres en autoestima, favoreciendo ligeramente a los hombres; y, c) no existieron diferencias estadísticamente significativas entre hombres y mujeres en las medias de la variable latente del factor.
RESUMEN
OBJECTIVE: The variety and extent of impairments occurring after traumatic brain injury vary according to the nature and severity of the lesions. In order to better understand their interactions and long-term outcome, we have studied and compared the cognitive and neurobehavioral profile one year post onset of patients with and without traumatic brain injury in a cohort of motor vehicle accident victims. METHOD: The study population is composed of 207 seriously injured persons from the ESPARR cohort. This cohort, which has been followed up in time, consists in 1168 motor vehicle accident victims (aged 16 years or more) with injuries with all degrees of severity. Inclusion criteria were: living in Rhone county, victim of a traffic accident having involved at least one wheel-conducted vehicle and having occurred in Rhone county, alive at the time of arrival in hospital and having presented in one of the different ER facilities of the county. The cohort's representativeness regarding social and geographic criteria and the specificities of the accidents were ensured by the specific targeting of recruitment. Deficits and impairments were assessed one year after the accident using the Neurobehavioral Rating Scale - Revised and the Trail-Making Test. Within our seriously injured group, based on the Glasgow Score, the presence of neurological deficits, aggravation of neurological condition in the first 72hours and/or abnormal cerebral imaging, we identified three categories: (i) moderate/severe traumatic brain injury (n=48), (ii) mild traumatic brain injury (n=89), and (iii) severely injured but without traumatic brain injury (n=70). RESULTS: The most frequently observed symptoms were anxiety, irritability, memory and attention impairments, depressive mood and emotional lability. While depressive mood and irritability were observed with similar frequency in all three groups, memory and attention impairments, anxiety and reduced initiative were more specific to traumatic brain injury whereas executive disorders were associated with moderate/severe traumatic brain injury. DISCUSSION-CONCLUSION: The presence and the initial severity of a traumatic brain injury condition the nature and frequency of residual effects after one year. Some impairments such as irritability, which is generally associated with traumatic brain injury, do not appear to be specific to this population, nor does depressive mood. Substantial interactions between cognitive, affective and neurobehavioral disorders have been highlighted.
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Lesiones Encefálicas/psicología , Trastornos del Conocimiento/etiología , Escala de Coma de Glasgow , Accidentes de Tránsito , Adolescente , Adulto , Síntomas Afectivos/etiología , Ansiedad/etiología , Atención , Depresión/etiología , Femenino , Estudios de Seguimiento , Humanos , Genio Irritable , Masculino , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Adulto JovenRESUMEN
No disponible
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Humanos , Pruebas de Función Renal/métodos , Urinálisis/métodos , Toma de Muestras de Orina/métodos , Pruebas Diagnósticas de Rutina/métodos , Tasa de Filtración Glomerular , Creatinina/orinaRESUMEN
Mitochondria play central roles in diverse physiological and pathological conditions associated with cell survival and death. Delocalized lipophilic cations, such as dequalinium (DQA), are accumulated in cancer cells attracted by the highly negative mitochondrial transmembrane potential of these cells. DQA showed a potent anticancer activity in cells from different malignancies. Here, we report the effect of DQA on PC-3 prostate cancer cells. Incubation with DQA at concentrations between 1.5 and 100 microM from 24 to 48 h decreases cell viability. The decrease in cell viability together with a loss of mitochondrial transmembrane potential induced an increase in reactive oxygen species production and cell death via caspase-3 dependent apoptotic pathway. QA was shown to cause moderate to strong cell death in a time and concentration dependent manner, causing a most advantageous effect at a concentration of 10 microM applied for a long 48 h time period, which might be a consequence of the kinetics of intracellular DQA accumulation in mitochondria, but also of the mechanisms of DQA-induced cell death. This data shows DQA as a promising agent against the human prostate cancer PC-3 cell line, activating the caspase-3 dependent apoptotic pathway. This fact might be beneficial for possible future applications in cancer therapy.
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Antineoplásicos/farmacología , Decualinio/farmacología , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Estrés Oxidativo , Neoplasias de la Próstata/metabolismo , Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Mitocondrias/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
La craneotomía en el paciente consciente (CPC) permite valorar los cambios neurológicos durante la obtención de mapas neurológicos en la cirugía de la epilepsia, la localización de los electrodos durante la cirugía de estimulación cerebral profunda y la extirpación tumoral en áreas elocuentes del cerebro. La CPC consciente es útil para realizar cirugía radical, minimizando el daño en las zonas funcionales del cerebro. El anestesiólogo debe asegurar un adecuado bienestar al paciente, una óptima analgesia y garantizar su colaboración. Se debe realizar una adecuada selección conjunta de los posibles candidatos con todos los profesionales implicados en el caso. El conocimiento de las distintas fases de esta forma de craneotomía, la coordinación y comunicación entre los especialistas, el dominio de la farmacología y de las técnicas anestésicas específicas, junto con la capacidad de comunicación psicoemocional con el paciente, son los determinantes del éxito del procedimiento, que debe someterse, además, a la cultura de seguridad. El objetivo de esta revisión es describir el tratamiento anestésico integral, las consideraciones neurofisiológicas y las complicaciones intraoperatorias de la CPC(AU)
Craniotomy in the conscious patient (CPC) enables the neurological changes to be assessed during the mapping in epilepsy surgery, the location of the electrodes during deep brain stimulation surgery, and tumor resection in eloquent areas of the brain. CPC is a useful technique for radical surgery in order to minimize the damage to the functional areas of the brain. The anesthesiologist must ensure, adequate patient comfort, analgesia and ensure optimal collaboration. The appropriate selection of potential candidates for CPC should be made jointly with all professionals involved in the case. Knowledge of the different phases of CPC, coordination and communication among specialists, the right management of the pharmacology, and anesthetic techniques specific to CPC, along with the ability of psycho-emotional communication with the patient, determine the success of the procedure to be performed in the culture of patient safety. The aim of this review was to describe the anesthetic management, comprehensive considerations, and intraoperative neurophysiological tests for CPC(AU)
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Humanos , Masculino , Femenino , Craneotomía/métodos , Electrodos/tendencias , Electrodos , Analgesia/instrumentación , Analgesia/métodos , Analgesia , Neurofisiología/métodos , Neurofisiología/organización & administración , Complicaciones Intraoperatorias/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Epilepsia/cirugía , Atención al Paciente/métodos , Complicaciones Intraoperatorias/fisiopatología , Complicaciones Intraoperatorias/rehabilitaciónRESUMEN
Craniotomy in the conscious patient (CPC) enables the neurological changes to be assessed during the mapping in epilepsy surgery, the location of the electrodes during deep brain stimulation surgery, and tumor resection in eloquent areas of the brain. CPC is a useful technique for radical surgery in order to minimize the damage to the functional areas of the brain. The anesthesiologist must ensure, adequate patient comfort, analgesia and ensure optimal collaboration. The appropriate selection of potential candidates for CPC should be made jointly with all professionals involved in the case. Knowledge of the different phases of CPC, coordination and communication among specialists, the right management of the pharmacology, and anesthetic techniques specific to CPC, along with the ability of psycho-emotional communication with the patient, determine the success of the procedure to be performed in the culture of patient safety. The aim of this review was to describe the anesthetic management, comprehensive considerations, and intraoperative neurophysiological tests for CPC.
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Anestesia Local , Sedación Consciente , Craneotomía , Craneotomía/efectos adversos , Humanos , Monitoreo IntraoperatorioRESUMEN
Satisfaction with life is of particular interest in the study of old age well-being because it has arisen as an important component of old age. A considerable amount of research has been done to explain life satisfaction in the elderly, and there is growing empirical evidence on best predictors of life satisfaction. This research evaluates the predictive power of some aging process variables, on Angolan elderly people's life satisfaction, while including perceived health into the model. Data for this research come from a cross-sectional survey of elderly people living in the capital of Angola, Luanda. A total of 1003 Angolan elderly were surveyed on socio-demographic information, perceived health, active engagement, generativity, and life satisfaction. A Multiple Indicators Multiple Causes model was built to test variables' predictive power on life satisfaction. The estimated theoretical model fitted the data well. The main predictors were those related to active engagement with others. Perceived health also had a significant and positive effect on life satisfaction. Several processes together may predict life satisfaction in the elderly population of Angola, and the variance accounted for it is large enough to be considered relevant. The key factor associated to life satisfaction seems to be active engagement with others.
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Envejecimiento/psicología , Población Negra/psicología , Satisfacción Personal , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Angola , Estudios Transversales , Análisis Factorial , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Percepción , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
La recomendación de invertir ítems al medir constructos psicológicos mediante escalas ha estado presente casi desde siempre en la práctica psicométrica. Pese a esto, esta estrategia parece interferir en el examen de la estructura latente de las escalas, tal y como se ha demostrado en diversas investigaciones. Este trabajo pretende aportar evidencia empírica que permita clarificar el efecto de la formulación invertida de los ítems, utilizando dos versiones de la Escala de Autoestima de Rosenberg (1965), una en su formato original con ítems positivos e invertidos y otra transformada de modo que todos los ítems sean positivos, para comprobar si se mantienen o desaparecen los efectos de método encontrados en la literatura asociados a los ítems invertidos. Para ello, se ha contado con una muestra incidental de 390 estudiantes de instituto y universidad de la ciudad de Valencia. Se han llevado a cabo diversos modelos de ecuaciones estructurales (incluyendo CTCM) alternativos, comparando los índices de ajuste de éstos. A partir de los resultados, se obtienen dos puntos relevantes de información: por una parte, se observa de nuevo un efecto de método asociado a los ítems invertidos; por otra, se observa como estos ítems, cuando son formulados en positivo, no presentan tal efecto, de manera que la Escala de Autoestima de Rosenberg presenta una estructura de un solo factor: el factor de autoestima. Las implicaciones de estos resultados se recogen en las conclusiones y discusión(AU)
Negatively worded items have been long used in the measurement of psychological constructs, since almost the beginning of the psychometric practice. However, this strategy interferes in the examination of the scales latent structures, as it has been shown in several studies. This paper aims to provide new evidence on this topic, in order to clarify the negatively worded items effect, by using two versions of the Rosenberg Self-Esteem Scale (1965), one in its original form, with positive and negatively worded items, and the other one in a transformed version, in which all the items are positive, in order to test if, in this latest version, the method effect associated to negatively worded items still remains. The sample was composed by 390 high-school and university students from Valencia, Spain. Several alternative (including CTCM) structural equation models have been tested, and their fit indices are compared. Results offer empiric evidence on the method effect associated to negatively worded items. This effect disappears when items are worded in a positive way and, thus, Rosenberg Self-Esteem Scale structure is composed by just one factor: the self-esteem factor. Implications of these results are pointed out in the discussion(AU)