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Chemotherapy remains a primary treatment for younger AML patients, though many relapse. Data from our group have shown that highly phosphorylated S6 in blasts may predict response to sirolimus given with chemotherapy. We report the results of a phase I study of this combination in newly diagnosed AML and the pharmacodynamic analysis of pS6 before and after treatment. Subjects received sirolimus (12 mg on day 1, 4 mg daily, days 2-10), then idarubicin and cytarabine (days 4-10). Response was assessed at hematologic recovery or by day 42 using a modified IWG criteria. Fifty-five patients received sirolimus. Toxicity was similar to published 7 + 3 data, and 53% had high-, 27% intermediate-, and 20% favorable-risk disease. Forty-four percent of the high-risk patients entered into CR/CRp. Seventy-nine percent of the intermediate-risk subjects had a CR/CRp. All favorable-risk patients had a CR by day 42; 9/11 remained alive and in remission with a median follow-up of 660 days. Additionally, 41/55 patients had adequate samples for pharmacodynamic analysis. All patients demonstrated activation of S6 prior to therapy, in contrast to 67% seen in previous studies of relapsed AML. mTORC1 inhibition was observed in 66% of patients without enrichment among patients who achieved remission. We conclude that sirolimus and 7 + 3 is a well-tolerated and safe regimen. mTORC1 appears to be activated in almost all patients at diagnosis of AML. Inhibition of mTORC1 did not differ based on response, suggesting that AML cells may have redundant signaling pathways that regulate chemosensitivity in the presence of mTORC1 inhibition.
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Contemporary, prospective data regarding the impact of granulocyte-colony stimulating factor (G-CSF) on outcomes after autologous hematopoietic stem cell transplantation (Auto-HSCT) in an era when stem cell grafts are more qualitatively robust are limited. Recent retrospective analyses have not supported a beneficial effect of post-transplantation G-CSF use on major outcomes after Auto-HSCT leading to strategies to delay or eliminate the use of G-CSF altogether in this context. To test the hypothesis that the infusion of consistently higher doses of stem cells (defined as ≥4 × 106/kg) in Auto-HSCT will obviate the need for post-transplantation G-CSF. If so, the impact of withholding G-CSF will be noninferior to the use of G-CSF in terms of length of stay (LOS). The specific objectives were to conduct a prospective, randomized clinical trial primarily examining the impact of post-transplantation G-CSF on LOS, and secondarily on engraftment, infectious complications, antibiotic usage, and incidence of engraftment syndrome after Auto-HSCT in patients receiving versus not receiving G-CSF after Auto-HSCT. Patients with multiple myeloma or non-Hodgkin lymphoma (NHL) who underwent Pegfilgrastim plus Plerixafor-primed stem cell collection followed by Auto-HSCT were randomized to the G-CSF group (receive G-CSF starting at day 3 after Auto-HSCT) or the no G-CSF group (G-CSF withheld after Auto-HSCT). Seventy patients per arm were planned to demonstrate the primary endpoint of noninferiority in LOS between the G-CSF and the no G-CSF groups. Patient outcomes in the two groups were followed up and compared after Auto-HSCT, and an interim analysis for futility was planned when accrual reached 50%.The primary finding of this study was that despite only a 2-day longer median absolute neutrophil count (ANC) recovery in the no G-CSF arm (median 11 versus 13 days; P = .001), LOS was 4 days longer in patients not treated with G-CSF (median 11 days versus 15 days; P = .001). G-CSF use was associated with more robust incremental daily increases in ANC once recovered (P = .001), fewer days of febrile neutropenia (P = .001), and fewer days on antibiotics (P = .001), potentially contributing to this disproportionate finding. Inferiority in LOS in the no G-CSF group was demonstrated on the interim analysis, and the study was closed at the half-way point. There were no significant group differences in platelet recovery, documented infections, hospital readmissions, or overall survival at 1 year. Engraftment syndrome occurred in 54.3% of patients and was not related to G-CSF use. These results suggest that the increased LOS associated with the omission of G-CSF is largely due to concerns regarding the potential for infection in patients without a stable, recovered ANC in a hospital setting. Engraftment syndrome represented a significant source of febrile neutropenia further contributing to patient safety concerns and requires strategies to decrease its incidence. Infectious complications and death were not affected by the omission of G-CSF supporting a carefully monitored outpatient approach to Auto-HSCT in which white blood cell growth factor is eliminated or given as needed for documented infection. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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Neutropenia Febril , Compuestos Heterocíclicos , Humanos , Trasplante Autólogo , Movilización de Célula Madre Hematopoyética/métodos , Estudios Retrospectivos , Estudios Prospectivos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neutropenia Febril/tratamiento farmacológicoRESUMEN
The most common cause of stroke in children with sickle cell anemia is infarction due to ischemia. In adults, however, stroke is most commonly hemorrhagic in nature. Other causes of stroke in patients with sickle cell disease are very rare. In this short communication, we describe a woman with sickle cell anemia responsive to hydroxyurea (HU) therapy who had primary stroke due to paradoxical embolization caused by a large atrial septal defect. Successful management of the stroke included surgical closure of the defect with trans-esophageal echocardiographic guidance. To the best of our knowledge, this is the first patient with sickle cell anemia and stroke due to congenital heart disease who did not require open heart surgery for successful management.
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Anemia de Células Falciformes/fisiopatología , Isquemia Encefálica/etiología , Defectos del Tabique Interatrial/complicaciones , Accidente Cerebrovascular/etiología , Adulto , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Ecocardiografía Transesofágica , Femenino , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/cirugía , Humanos , Hidroxiurea/uso terapéutico , Philadelphia , Resultado del TratamientoRESUMEN
UNLABELLED: Hispanic children and those from low-socioeconomic status are predisposed to unhealthy eating habits and obesity. AIM: to implement an individualized, face-to-face, parent supported, and school-partnership dietetic intervention to promote healthy eating habits and decrease body mass index. Prospective school year dietetic intervention of 101 obese, Hispanic, low-socioeconomic school-age children representative of Monterrey, Mexico, consisted of anthropometrics, dietetic assessment, energy-restriction tailor-made daily menus, and parental education every three weeks. Student's t-test was used for means comparison. A significant decrease was found in body mass index percentile (96.43 ± 3.32 to 93.42 ± 8.12/P = 0.00) and energy intake/day of -755.7 kcal/day (P = 0.00). Among other energy dense foods with significant decline in servings/day and servings/week were processed meats (3.13 ± 1.43 to 2.19 ± 1.04/P = 0.00 and 5.60 ± 1.75 to 4.37 ± 2.10/P = 0.00, resp.), saturated fat (1.47 ± 1.08 to 0.78 ± 0.79/P = 0.00 and 2.19 ± 2.18 to 1.1 ± 1.36/P = 0.00), sweetened beverages (2.79 ± 1.99 to 1.42 ± 1.21 and 6.21 ± 1.72 to 3.89 ± 2.80/P = 0.00), and desserts and refined-grain bakery (1.99 ± 1.54 to 1.32 ± 1.59 and 2.85 ± 2.54 to 1.57 ± 2.20/P = 0.00). There was a significant increase in servings/day and servings/week of water (2.98 ± 2.02 to 4.91 ± 2.37 and 6.62 ± 2.03 to 6.87 ± 0.91/P = 0.00, resp.) and nutrient dense foods such as fruits (1.31 ± 0.89 to 1.66 ± 0.96 and 3.34 ± 2.24 to 4.28 ± 2.43/P = 0.00) and fish and poultry (3.76 ± 2.15 to 4.54 ± 2.25/P = 0.00). This intervention created healthy eating habits and decreased body mass index in a high risk population. TRIAL REGISTRATION NUMBER: NCT01925976.
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Restricción Calórica , Dieta con Restricción de Grasas , Conducta Alimentaria , Obesidad/dietoterapia , Pobreza , Niño , Femenino , Humanos , Masculino , México/epidemiología , Obesidad/epidemiología , Obesidad/etnología , Instituciones AcadémicasRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome (MetS); Hispanics being particularly predisposed. Alanine aminotransferase (ALT) is considered a marker of NAFLD. The aim of this study was to determine the prevalence and associations between ALT elevations and MetS in normal-weight, overweight and obese Mexican children and adolescents, since data in Mexico is scarce. Body mass index (BMI), waist circumference (WC), percentage body fat, blood pressure, glucose, lipid profiles, ALT and aspartate aminotransferase (AST) were measured in 236, 6-12yo normal-weight, overweight and obese Mexicans from eight public schools. The results showed that elevated ALT (>40 IU/L) was found in 17.7% of the obese and overweight population, with no gender difference. The prevalence of elevated ALT increased linearly across BMI categories (p = 0.001), from 0.0% for the normal-weight group (95%CI 0.0-8.0) to 22.4% for the obese one (95%CI 16.2-30.2). AST/ALT ratio <1 also increased linearly, as did the prevalence of MetS (p = 0.001), from 0.0% for the normal-weight group to 40.3% for the obese one. The prevalence of MetS was strongly associated with elevated ALT (p = 0.002), 50% in the elevated ALT group (95%CI 34.1-65.9) and 24.1% in the normal ALT one (95%CI 18.1-31.3). There was also a strong association between MetS and an AST/ALT ratio <1. WC was the best predictor of elevated ALT (AOR = 7.13). Pearson correlation showed that MetS components were significantly correlated with elevated ALT. Therefore elevated ALT levels were highly prevalent and strongly associated with MetS in Mexican children, it should be screened in overweight and obese children.
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Adiposidad , Alanina Transaminasa/sangre , Índice de Masa Corporal , Hígado Graso/sangre , Hígado/enzimología , Síndrome Metabólico/sangre , Obesidad/metabolismo , Niño , Hígado Graso/enzimología , Hígado Graso/etiología , Femenino , Hispánicos o Latinos , Humanos , Resistencia a la Insulina , Masculino , Síndrome Metabólico/complicaciones , México , Enfermedad del Hígado Graso no Alcohólico , Obesidad/sangre , Obesidad/complicaciones , Sobrepeso , Circunferencia de la CinturaRESUMEN
BACKGROUND: Clinical features of pandemic H1N1 have been derived from lab-confirmed, hospitalized, or critically ill subjects. This report describes the clinical features of H1N1 and their prevalence from non-confirmed subjects according to seroprevalence status in México. The objective was to determine the prevalence of these clinical features from non-confirmed cases of pandemic H1N1 and to compare them according to seroprevalence status in northern Monterrey, México, during 2009, and to identify the predictive signs and symptoms; there have been no prior serologic studies in México. METHODS: During November-December 2009, 2,222 volunteers, ages 6-99 years, were categorized into 3 symptomatic groups: influenza-like illness, respiratory illness, and non-respiratory illness. Antibodies against influenza A/H1N1/2009 were determined by a virus-free enzyme-linked immunosorbent assay (ELISA) method. Demographics and clinical presentation were assessed through face-to-face questionnaire, and the association with seroprevalence status was determined and compared. RESULTS: Overall seroprevalence was 39%. Of the seropositive subjects, 67% were symptomatic and 33% were asymptomatic. Seventy-one percent of seropositive symptomatic subjects reported respiratory illness, 17% reported non-respiratory symptoms, and 12% reported influenza-like illness. The most common symptoms were rhinorrhea/nasal congestion (93%) and headache (83%). No significant difference was found between the symptom profiles of the seropositive group, compared to the seronegative one, nor of the median duration of symptoms. The seropositive group had a significantly elevated proportion of influenza-like illness (12%), compared to the seronegative group (8%). The proportion of subjects who took days off and who sought medical attention was significantly higher in the seropositive group. No single symptom was associated as a predictor of seropositiveness. CONCLUSIONS: One third of the seropositive subjects were asymptomatic, and few had an influenza-like illness. No difference was found in the symptom profiles of the seropositive and seronegative groups. No single symptom predicted seropositiveness. Large scale population studies are needed, especially in México, to characterize clinical syndromes.
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Infecciones Asintomáticas/epidemiología , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artralgia/epidemiología , Artralgia/virología , Niño , Femenino , Cefalea/epidemiología , Cefalea/virología , Humanos , Gripe Humana/fisiopatología , Gripe Humana/virología , Masculino , México/epidemiología , Persona de Mediana Edad , Dolor Musculoesquelético/epidemiología , Dolor Musculoesquelético/virología , Obstrucción Nasal/epidemiología , Obstrucción Nasal/virología , Aceptación de la Atención de Salud/estadística & datos numéricos , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/virología , Estudios Seroepidemiológicos , Ausencia por Enfermedad/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Los autores consideran de vital importancia, la problemática maternoinfantil, en el país y debido ha ésto, han diseñado un programa de salud maternoinfantil para la población nacional del Sector Carapita, Parroquia Antímano de Caracas