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As curative therapies for pediatric AML remain elusive, identifying potential new treatment targets is vital. We assessed the cell surface expression of CD74, also known as the MHC-II invariant chain, by multidimensional flow cytometry in 973 patients enrolled in the Children's Oncology Group AAML1031 clinical trial. 38% of pediatric AML patients expressed CD74 at any level and a comparison to normal hematopoietic cells revealed a subset with increased expression relative to normal myeloid progenitor cells. Pediatric AML patients expressing high intensity CD74 typically had an immature immunophenotype and an increased frequency of lymphoid antigen expression. Increased CD74 expression was associated with older patients with lower WBC and peripheral blood blast counts, and was enriched for t(8;21), trisomy 8, and CEBPA mutations. Overall, high CD74 expression was associated with low-risk status, however 26% of patients were allocated to high-risk protocol status and 5-year event free survival was 53%, indicating that a significant number of high expressing patients had poor outcomes. In vitro pre-clinical studies indicate that anti-CD74 therapy demonstrates efficacy against AML cells but has little impact on normal CD34+ cells. Together, we demonstrate that CD74 is expressed on a subset of pediatric AMLs at increased levels compared to normal hematopoietic cells and is a promising target for therapy in expressing patients. Given that nearly half of patients expressing CD74 at high levels experience an adverse event within 5 years, and the availability of CD74 targeting drugs, this represents a promising line of therapy worthy of additional investigation.
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BACKGROUND: After settling in the United States (US), immigrants often accumulate obesity and cardiovascular risk factors. As mood is often associated with health behaviors in the US population, mood may be an important mediating factor in immigrant populations. METHODS: The Healthy Immigrant Community (HIC) study, set in southeast Minnesota, enrolled 475 adult participants in a weight loss intervention designed to reduce cardiovascular risk. Baseline questionnaires assessed mood, nutrition, physical activity, self-efficacy for healthy eating and physical activity, social support, and cohesion. A single-item mood rating of poor or fair was considered "negative", while ratings of good, very good, or excellent were considered "positive". RESULTS: Hispanic/Latino (n = 268) and Somali (n = 181) adults enrolled in HIC completed baseline measures and were included in this analysis. Participants endorsing negative mood compared to positive mood had lower healthy eating scores (p = 0.02), lower physical activity levels (p = 0.03), lower confidence in eating a healthy diet (p = 0.001), and felt less of a sense of belonging to their community (p = 0.01). Those endorsing negative mood reported receiving less social support to eat healthy (p = < 0.001) and be physically active (p = 0.01). They also accessed community resources for healthy eating (p = 0.001) and physical activity (p = < 0.01) less frequently than participants endorsing positive mood. CONCLUSIONS: On self-report, negative mood was associated with less healthy nutrition, lower confidence in eating healthy, sedentary lifestyle, and perceived lack of belonging to the community. Integrating mood management and self-efficacy strategies may enhance the effectiveness of lifestyle interventions to reduce obesity and cardiovascular risk among immigrants who report negative mood. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT05136339; April 23, 2022.
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Afecto , Enfermedades Cardiovasculares , Emigrantes e Inmigrantes , Ejercicio Físico , Factores de Riesgo de Enfermedad Cardiaca , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/psicología , Enfermedades Cardiovasculares/etnología , Emigrantes e Inmigrantes/psicología , Emigrantes e Inmigrantes/estadística & datos numéricos , Ejercicio Físico/psicología , Conductas Relacionadas con la Salud , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Minnesota , Autoeficacia , Apoyo Social , Somalia/etnología , Encuestas y CuestionariosRESUMEN
In this work, the effect of microwave-assisted acid treatments on the morphological and crystallochemical characteristics of chrysotile fibers is investigated. A low concentration of nitric acid (0.2 N) is used to remove Mg2+-species located in the octahedral sheet of its structure, thereby causing a crystallo-chemical change forming a skeleton of non-crystalline amorphous silica. This skeleton maintains an elongated morphology but characterized by rounded -not sharp-edges and porous surfaces whose physical resistance under stress is reduced when compared with the initial fibers of chrysotile, favoring a lower pathogenicity of the fibers. Thus, microwave-assisted acid treatment rise as a low-cost, fast and effective option in avoiding the dangerousness associated with asbestos waste management.
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Asbestos Serpentinas , Microondas , Ácido Nítrico , Asbestos Serpentinas/química , Ácido Nítrico/química , Administración de Residuos/métodos , Difracción de Rayos X , Microscopía Electrónica de RastreoRESUMEN
Biallelic CEBPA mutations are associated with favorable outcomes in acute myeloid leukemia (AML). We evaluated the clinical and biologic implications of CEBPA-basic leucine zipper (CEBPA-bZip) mutations in children and young adults with newly diagnosed AML. CEBPA-bZip mutation status was determined in 2958 patients with AML enrolled on Children's Oncology Group trials (NCT00003790, NCT0007174, NCT00372593, NCT01379181). Next-generation sequencing (NGS) was performed in 1863 patients (107 with CEBPA mutations) to characterize the co-occurring mutations. CEBPA mutational status was correlated with disease characteristics and clinical outcomes. CEBPA-bZip mutations were identified in 160 (5.4%) of 2958 patients, with 132 (82.5%) harboring a second CEBPA mutation (CEBPA-double-mutated [CEBPA-dm]) and 28 (17.5%) had a single CEBPA-bZip only mutation. The clinical and laboratory features of the 2 CEBPA cohorts were very similar. Patients with CEBPA-dm and CEBPA-bZip experienced identical event-free survival (EFS) of 64% and similar overall survival (OS) of 81% and 89%, respectively (P = .259); this compared favorably to EFS of 46% and OS of 61% in patients with CEBPA-wild-type (CEBPA-WT) (both P < .001). Transcriptome analysis demonstrated similar expression profiles for patients with CEBPA-bZip and CEBPA-dm. Comprehensive NGS of patients with CEBPA mutations identified co-occurring CSF3R mutations in 13.1% of patients and GATA2 mutations in 21.5% of patients. Patients with dual CEBPA and CSF3R mutations had an EFS of 17% vs 63% for patients with CEBPA-mutant or CSF3R-WT (P < .001) with a corresponding relapse rate (RR) of 83% vs 22%, respectively (P < .001); GATA2 co-occurrence did not have an impact on outcome. CEBPA-bZip domain mutations are associated with favorable clinical outcomes, regardless of monoallelic or biallelic status. Co-occurring CSF3R and CEBPA mutations are associated with a high RR that nullifies the favorable prognostic impact of CEBPA mutations.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Proteínas Potenciadoras de Unión a CCAAT/genética , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/diagnóstico , Masculino , Mutación , Pronóstico , Transcriptoma , Adulto JovenRESUMEN
NUP98 fusions comprise a family of rare recurrent alterations in AML, associated with adverse outcomes. In order to define the underlying biology and clinical implications of this family of fusions, we performed comprehensive transcriptome, epigenome, and immunophenotypic profiling of 2,235 children and young adults with AML and identified 160 NUP98 rearrangements (7.2%), including 108 NUP98-NSD1 (4.8%), 32 NUP98-KDM5A (1.4%) and 20 NUP98-X cases (0.9%) with 13 different fusion partners. Fusion partners defined disease characteristics and biology; patients with NUP98-NSD1 or NUP98-KDM5A had distinct immunophenotypic, transcriptomic, and epigenomic profiles. Unlike the two most prevalent NUP98 fusions, NUP98-X variants are typically not cryptic. Furthermore, NUP98-X cases are associated with WT1 mutations, and have epigenomic profiles that resemble either NUP98-NSD1 or NUP98-KDM5A. Cooperating FLT3-ITD and WT1 mutations define NUP98-NSD1, and chromosome 13 aberrations are highly enriched in NUP98-KDM5A. Importantly, we demonstrate that NUP98 fusions portend dismal overall survival, with the noteworthy exception of patients bearing abnormal chromosome 13 (clinicaltrials gov. Identifiers: NCT00002798, NCT00070174, NCT00372593, NCT01371981).
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Leucemia Mieloide Aguda , Niño , Adulto Joven , Humanos , Leucemia Mieloide Aguda/genética , Mutación , Proteínas de Complejo Poro Nuclear/genética , Perfilación de la Expresión Génica , Proteína 2 de Unión a Retinoblastoma/genéticaRESUMEN
Primary effusion lymphoma (PEL), Kaposi's sarcoma (KS), and multicentric Castleman's disease (MCD) is an uncommon group of diseases included in the same spectrum with related characteristics. The coexistence of all of them in the same individual is a rare occurrence. We present the case of a 25-year-old patient diagnosed with human immunodeficiency virus (HIV) and the development of all these related pathologies. Despite the use of intensive treatment according to the latest recommendations, the evolution was unfavorable. This case reflects the need for new therapies and research in this field.
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Infecciones por VIH , Herpesvirus Humano 8 , Linfoma de Efusión Primaria , Sarcoma de Kaposi , Humanos , Adulto , Sarcoma de Kaposi/complicaciones , Sarcoma de Kaposi/patología , Linfoma de Efusión Primaria/complicaciones , Linfoma de Efusión Primaria/diagnóstico , Infecciones por VIH/complicacionesRESUMEN
Human immunodeficiency virus (HIV) infection is known to be associated with the development of Hodgkin's lymphoma (HL). Exclusive extranodal bone marrow involvement is less common. Co-infection by other viruses, such as the Epstein-Barr virus (EBV), increases the incidence of a frequent complication denominated by hemophagocytic lymphohistocytosis (HLH). We present the case of a 50-year-old patient with the above clinical spectrum who develops several serious complications during treatment.
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Infecciones por Virus de Epstein-Barr , Infecciones por VIH , Enfermedad de Hodgkin , Linfohistiocitosis Hemofagocítica , Humanos , Persona de Mediana Edad , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Enfermedad de Hodgkin/complicaciones , Herpesvirus Humano 4 , Infecciones por VIH/complicaciones , Médula Ósea/patologíaRESUMEN
BACKGROUND AND PURPOSE: Progressive lacunar syndromes (PLS) occur in up to 20-30% of patients with lacunar strokes, increasing the risk of long term dependency. Our aim is to develop a predictive score to identify patients at high risk of presenting PLS. METHODS: We derived a risk score for PLS in a cohort of consecutive patients (n=187) presenting with one of the five classic lacunar syndromes (LS) and absence of vascular occlusion, perfusion deficit or symptomatic stenosis. A risk score was developed using the coefficients from the logistic regression model, and receiver operating characteristic (ROC) analysis was conducted to assess the prognostic value of the risk score. Sensitivity, specificity and accuracy were estimated for each total point score. RESULTS: Out of 187 patients included in our sample, 52 (27.8%) presented PLS. Previous history of diabetes mellitus (1 point), diastolic blood pressure at admission (2 points), clinical deficits consistent with a pure motor syndrome (1 point) and asymptomatic intracranial atheromatosis or stenosis in non-symptomatic territory (1 point) were independent predictors for PLS. The estimated area under the ROC curve for this model was 0.77 (95% CI,0.68 - 0.84). CONCLUSION: This score could be a useful tool in routine clinical practice to predict the occurrence of PLS, allowing the identification of those patients with LS who are at high risk of long term dependency due to early neurological worsening, and who would benefit the most from an intensive treatment.
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Accidente Vascular Cerebral Lacunar , Estudios de Cohortes , Constricción Patológica , Humanos , Pronóstico , Factores de Riesgo , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/etiologíaRESUMEN
The aim of this study was to establish the therapeutic relevance of the CD33D2 isoform by developing novel antibodies targeting the IgC domain of CD33. Two novel IgC-targeting antibodies, HL2541 and 5C11-2, were developed, and CD33 isoforms were assessed using multiple assays in cells overexpressing either CD33FL or CD33D2 isoforms, unmodified acute myeloid leukemia (AML) cell lines and primary AML specimens representing different genotypes for the CD33 splicing single nucleotide polymorphism. CD33D2 was recognized on cells overexpressing CD33D2 and unmodified AML cell lines; however, minimal/no cell surface detection of CD33D2 was observed in primary AML specimens. Both isoforms were detected intracellularly using novel antibodies. Minimal cell surface expression of CD33D2 on primary AML/progenitor cells warrants further studies on anti-CD33D2 immunotherapeutics.
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Anticuerpos Monoclonales/inmunología , Lectina 3 Similar a Ig de Unión al Ácido Siálico/inmunología , Lectina 3 Similar a Ig de Unión al Ácido Siálico/metabolismo , Adolescente , Animales , Anticuerpos Monoclonales/uso terapéutico , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Línea Celular Tumoral , Niño , Preescolar , Femenino , Genotipo , Humanos , Dominios de Inmunoglobulinas/inmunología , Lactante , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Ratones , Isoformas de Proteínas , Lectina 3 Similar a Ig de Unión al Ácido Siálico/química , Lectina 3 Similar a Ig de Unión al Ácido Siálico/genéticaRESUMEN
Healthcare professionals in endoscopy units have a possible risk of SARS-CoV-2 infection by different routes: inhalation of airborne droplets, aerosols, conjunctival contact and faecal-oral transmission. OBJECTIVE: To describe the detection of SARS-CoV-2 in a series of patients scheduled for digestive endoscopy at the Hospital Santa Caterina. Salt. (Girona). METHODS: Descriptive study of a series of cases of patients scheduled for endoscopy during the month of May 2020, when endoscopic activity was resumed after the peak of the pandemic, following SCD, SEED, AEG and ESGE recommendations. We examined nasopharyngeal samples 48-72 hours before the appointment, by RT-PCR, in all patients. RNA extraction was performed using the kits: Qiagen®-adapted, BiosSprint®96-DNA-Blood-Kit (384). For amplification-detection of SARS-CoV-2, methods recommended by the WHO and the CDC were followed. RESULTS: 110 asymptomatic patients without close contact with a positive case in the previous 14 days were scheduled; 105 (96.4%) were negative and five (4.5%) were positive. Two patients developed respiratory symptoms after diagnosis (presymptomatic) and three remained asymptomatic. Allfive5 patients were autochthonous cases with no history of travel or residence in another city or country associated with high prevalence of infection. Four cases were women aged 60-81 years. The N gene was detected in all cases. CONCLUSIONS: A high prevalence of SARS-CoV-2 infection was detected in patients scheduled for digestive endoscopy. Given the risk of transmission to professionals, we consider it advisable to perform SARS-CoV-2 RT-PCR 48-72 hours before the examination in situations of high incidence in the population.
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COVID-19/epidemiología , Endoscopía del Sistema Digestivo/estadística & datos numéricos , Pandemias , Anciano , Anciano de 80 o más Años , COVID-19/diagnóstico , COVID-19/transmisión , Prueba de Ácido Nucleico para COVID-19/estadística & datos numéricos , Femenino , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Masculino , Persona de Mediana Edad , Prevalencia , SARS-CoV-2 , España/epidemiologíaRESUMEN
Background and Purpose- Stroke Risk Analysis (SRA) comprises an algorithm for automated analysis of ECG monitoring, enabling the detection of paroxysmal atrial fibrillation (pxAF) and identifying patterns indicating a high risk of atrial fibrillation (R_AF). We compared Holter-enabled continuous ECG monitoring in combination with SRA (hSRA) with standard continuous ECG monitoring for pxAF detection in patients with acute ischemic stroke. Also, we sought to identify whether the detection of R_AF patterns during the first cycle (first 2 hours) of hSRA recording was associated with the detection of pxAF during the Stroke Unit stay. Methods- We enrolled 524 consecutive patients admitted in the Stroke Unit with acute ischemic stroke or transient ischemic attack with neither history of AF nor AF at admission into a prospective multicentric observational analytic clinical study with intrapatient comparison, who received both continuous ECG monitoring as well as hSRA up to 7 days. Investigators were blinded to hSRA results unless pxAF was detected on SRA. Results- Of the 524 consecutive acute stroke patients (median age, 70.0 years; 60% male; acute ischemic stroke 93%, transient ischemic attack 7%), 462 were eligible and included in the study. Among 462 patients with hSRA available for 66 hours, AF was documented by hSRA in 79 patients (17.1%). From this group, 45 AF cases (9.7%) were confirmed after review by an independent and blinded cardiologist. continuous ECG monitoring detected 21 AF cases (4.3%; P<0.0001). hSRA detected R_AF patterns in 92 patients. 35 out of the 92 R_AF patients showed an episode of AF during the Stroke Unit stay. Predictive values of R_AF patterns within the first cycle of hSRA were: sensitivity 71%, specificity 86%, positive predictive value 38%, and negative predictive value 96%. Conclusions- Automated analysis using SRA technology strongly improves pxAF detection in acute ischemic stroke patients compared with continuous ECG monitoring. The predictive value of a R_AF pattern, as detected by hSRA during the first few hours after admission, deserves further investigation.
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Fibrilación Atrial/fisiopatología , Electrocardiografía , Ataque Isquémico Transitorio/fisiopatología , Accidente Cerebrovascular/fisiopatología , Anciano , Fibrilación Atrial/complicaciones , Fibrilación Atrial/terapia , Femenino , Humanos , Ataque Isquémico Transitorio/etiología , Ataque Isquémico Transitorio/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapiaRESUMEN
Identification and quantification of maturing hematopoietic cell populations in flow cytometry data sets is a complex and sometimes irreproducible step in data analysis. Supervised machine learning algorithms present promise to automatically classify cells into populations, reducing subjective bias in data analysis. We describe the use of support vector machines (SVMs), a supervised algorithm, to reproducibly identify two distinctly different populations of normal hematopoietic cells, mature lymphocytes and uncommitted progenitor cells, in the challenging setting of pediatric bone marrow specimens obtained 1 month after chemotherapy. Four-color flow cytometry data were collected on a FACS Calibur for 77 randomly selected postchemotherapy pediatric patients enrolled on the Children's Oncology Group clinical trial AAML1031. These patients demonstrated no evidence of detectable residual disease and were divided into training (n = 27) and testing (n = 50) cohorts. SVMs were trained to identify mature lymphocytes and uncommitted progenitor cells in the training cohort before independent evaluation of prediction efficiency in the testing cohort. Both SVMs demonstrated high predictive performance (lymphocyte SVM: sensitivity >0.99, specificity >0.99; uncommitted progenitor cell SVM: sensitivity = 0.94, specificity >0.99) and closely mirrored manual cell classifications by two expert-analysts. SVMs present an efficient, automated methodology for identifying normal cell populations even in stressed bone marrows, replicating the performance of an expert while reducing the intrinsic bias of gating procedures between multiple analysts. © 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.
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Algoritmos , Perfilación de la Expresión Génica/métodos , Células Madre Hematopoyéticas/clasificación , Máquina de Vectores de Soporte , Adolescente , Niño , Femenino , Citometría de Flujo/métodos , Células Madre Hematopoyéticas/citología , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Reconocimiento de Normas Patrones Automatizadas/métodos , Sensibilidad y EspecificidadAsunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/fisiopatología , Heparina de Bajo-Peso-Molecular/farmacocinética , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/fisiopatología , Eliminación Renal/fisiología , COVID-19 , Infecciones por Coronavirus/epidemiología , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiologíaRESUMEN
Early response to induction chemotherapy is a predictor of outcome in acute myeloid leukemia (AML). We determined the prevalence and significance of postinduction residual disease (RD) by multidimensional flow cytometry (MDF) in children treated on Children's Oncology Group AML protocol AAML03P1. Postinduction marrow specimens at the end of induction (EOI) 1 or 2 or at the end of therapy from 249 patients were prospectively evaluated by MDF for RD, and presence of RD was correlated with disease characteristics and clinical outcome. Of the 188 patients in morphologic complete remission at EOI1, 46 (24%) had MDF-detectable disease. Those with and without RD at the EOI1 had a 3-year relapse risk of 60% and 29%, respectively (P < .001); the corresponding relapse-free survival was 30% and 65% (P < .001). Presence of RD at the EOI2 and end of therapy was similarly predictive of poor outcome. RD was detected in 28% of standard-risk patients in complete remission and was highly associated with poor relapse-free survival (P = .008). In a multivariate analysis, including cytogenetic and molecular risk factors, RD was an independent predictor of relapse (P < .001). MDF identifies patients at risk of relapse and poor outcome and can be incorporated into clinical trials for risk-based therapy allocation. This study was registered at www.clinicaltrials.gov as NCT00070174.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citometría de Flujo/métodos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Neoplasia Residual/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/prevención & control , Masculino , Prevalencia , Pronóstico , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Some patients with severe asthma may benefit from treatment with biologics, but evidence has been mostly collected from randomized controlled trials (RCTs), in which patients' characteristics are different from those encountered in asthma patients in the real-world setting. The aim of this study was to describe the clinical features of complete responders versus non-complete responders to long-term treatment with biologics in patients with severe asthma attended in routine daily practice. METHODS: Data of a cohort of 90 patients with severe asthma who were treated with biologics (omalizumab, benralizumab, and mepolizumab) for at least 12 months and were followed up to March 2022. Data recorded included clinical characteristics and effectiveness of treatment (exacerbation, Asthma Control Test [ACT] score, lung function, use of maintenance oral corticosteroids [mOCS]), FeNO, and blood eosinophils at baseline, at 12 months, and at the end of follow-up. Complete response is considered if, in addition to not presenting exacerbations or the use of mOCS, the ACT score was >20 and, the FEV1 >80% predicted. RESULTS: An improvement in all asthma control parameters was observed after 12 months of treatment and a mean follow-up of 55 months. After 12 months of treatment 27.2% of patients met the criteria of complete response and this percentage even increased to 35.3% at the end of follow-up. Long-term complete response was associated to better lung function with mepolizumab and omalizumab treatment and to less previous exacerbations in the benralizumab group. The main cause of not achieving a complete response was the persistence of an airflow obstructive pattern. CONCLUSIONS: This study shows that omalizumab, benralizumab, and mepolizumab improved the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs in the long term follow-up. Airflow obstruction, however, was a predictor of a non-complete response to biologics.
Treatment with anti-IgE and anti-IL-5 biologics significantly improved clinical outcomes in severe asthma patients.The rate of complete responders of 27.2% at 12 months even increased to 35.3% at the end of a mean follow-up of 55 months.The persistence of an airflow obstructive pattern was the main cause of the failure to achieve complete response.
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Antiasmáticos , Anticuerpos Monoclonales Humanizados , Asma , Productos Biológicos , Humanos , Omalizumab/uso terapéutico , Antiasmáticos/uso terapéutico , Antiasmáticos/efectos adversos , Asma/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Corticoesteroides/uso terapéuticoRESUMEN
T-cell lymphoblastic lymphoma is an uncommon lymphoid neoplasm in adults, although more frequent in children and teenagers, that often affects the mediastinum and bone marrow, requiring intensive chemotherapy protocols. Its prognosis is poor if a cure is not achieved with first-line treatments. We present a case report of a 19-year-old man diagnosed with this type of lymphoma due to significant respiratory distress and a mediastinal mass. He received treatment according to the hyper-CVAD regimen, with a complete metabolic response. However, seven months later a new mediastinal growth was observed, leading to salvage treatment with a combination of nelarabine and daratumumab. We observed not only refractoriness, but also leukemization, which prompted consideration of hematopoietic stem cell transplantation. Based on this case, we conducted a review of pharmacological treatment options for refractory or relapsed lymphoblastic lymphoma, as well as the role of radiotherapy in managing mediastinal disease. This case report highlights the limited evidence available regarding later-line treatments, with unusual reports regarding employing our combination of daratumumab and nelarabine, and emphasizes the importance of achieving cures in the first line of treatment.
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Background: Immigrants to the United States, on average, accumulate cardiovascular risk after resettlement, including obesity. There is a need to co-create interventions to address these disparities, and mood may be an important mediating factor. Methods: The Healthy Immigrant Community (HIC) study, set in southeast Minnesota, enrolled 475 adult participants in a weight loss intervention to reduce cardiovascular risk. Baseline questionnaires assessed mood, nutrition, physical activity, self-efficacy for healthy eating and physical activity, social support, and cohesion. A single-item mood rating of poor or fair was considered "negative", while ratings of good, very good, or excellent were considered "positive". Results: A total of 449 HIC participants (268 Hispanic/Latino and 181 Somali) with complete baseline measures and were included in this analysis. Participants endorsing negative mood compared to those endorsing positive mood had lower scores for healthy eating (p = 0.02) and physical activity levels (p = 0.03), lower confidence in eating a healthy diet (p = 0.001), and felt less of a sense of belonging to their community (p = 0.01). Those endorsing negative mood also reported receiving less social support from their family and friends to eat healthy (p = < 0.001) and be physically active (p = 0.01), and less often accessed community resources for healthy eating (p = 0.001) and physical activity (p = < 0.01) compared to participants reporting positive mood. Conclusions: Negative mood was associated with less healthy nutrition, lower confidence in eating healthy, sedentary lifestyle, and perceived lack of belonging to the community. Integrating mood management and self-efficacy strategies may enhance the effectiveness of lifestyle interventions among immigrants who report negative mood. ClinicalTrialsgov registration: NCT05136339; April 23, 2022.
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Identifying biomarkers linked to pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) is crucial for early detection, treatment, and prevention. Methods: Association analyses of 10 serological biomarkers involved in cell signalling (IFN-γ, IL-6, IL-8, IL-10), oxidative stress (superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, total glutathione (GSH), malondialdehyde (MDA) levels), and intestinal permeability proteins (zonulin, I-FABP2) were conducted across PDAC (n = 12), CP (n = 21) and control subjects (n = 23). A Mendelian randomisation (MR) approach was used to assess causality of the identified significant associations in two large genetic cohorts (FinnGen and UK Biobank). Results: Observational results showed a downregulation of SOD and GPx antioxidant enzyme activities in PDAC and CP patients, respectively, and higher MDA levels in CP patients. Logistic regression models revealed significant associations between CP and SOD activity (OR = 0.21, 95% CI [0.05, 0.89], per SD), GPx activity (OR = 0.28, 95% CI [0.10, 0.79], per SD), and MDA levels (OR = 2.05, 95% CI [1.36, 3.08], per SD). MR analyses, however, did not support causality. Conclusions: These findings would not support oxidative stress-related biomarkers as potential targets for pancreatic diseases prevention. Yet, further research is encouraged to assess their viability as non-invasive tools for early diagnosis, particularly in pre-diagnostic CP populations.
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OBJECTIVES: To determine the intention to use physical restraint (PR) and the relationship with sociodemographic and professional variables of the Paediatric Intensive Care Unit (PICU) nurses. RESEARCH METHODOLOGY/DESIGN AND SETTING: A multicentre and correlational study was carried out from October 2021 to December 2023 in five paediatric intensive care units from five maternal and child hospitals in Spain. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire was provided. Moreover, sociodemographic and employment variables were registered. RESULTS: A total of 230 paediatric nurses participated in the study. A total of 87.7 % were females with an average age of 35.5 ± 9.7 years and working experience of 10.5 ± 8.4 years. The mean scores obtained were 21.1 ± 3.8 for attitude, 13.1 ± 5.0 for subjective norms, 14.4 ± 4.3 for perceived behavioural control and 28.0 ± 6.0 for intention. The nurses apply more physical restraint to anxious patients, with scarce analgesics and sedation, those affected with pharmacological withdrawal symptoms and those with a high risk of accidental removal of vital support devices or fall from bed. The sex (p = 0.007) and type of employment contract (p = 0.01) are the variables that are significantly correlated with the intention to use of PR. CONCLUSION: The paediatric nurses analysed had a moderate attitude, social pressure and perceived behavioural control towards the use of PR. IMPLICATIONS FOR CLINICAL PRACTICE: It is important to know the factors that influence the intention to use physical restraint in order to standardise safe practice for critically ill paediatric and to ensure that patients' rights are respected by obtaining informed consent and assessing the prescription, continuation and removal of physical restraint.
Asunto(s)
Unidades de Cuidado Intensivo Pediátrico , Intención , Restricción Física , Humanos , Femenino , Masculino , Restricción Física/estadística & datos numéricos , Restricción Física/métodos , Restricción Física/psicología , Unidades de Cuidado Intensivo Pediátrico/organización & administración , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Estudios Transversales , Encuestas y Cuestionarios , España , Adulto , Persona de Mediana Edad , Actitud del Personal de SaludRESUMEN
OBJECTIVE: To calculate the prevalence of physical restraint (PR) use in Spanish PICUs and (2) to analyze the correlation between the prevalence of PR use and the sociodemographic, clinical variables of the patients and the PICU structural and organizational variables. METHODS: We conducted a multicenter prevalence study from January 2022 to January 2023 in Spanish PICUs. The method of data collection was by direct observation, review of the patient's medical history, and asking the professionals involved in the patient's care. Three weekly 24-hour prevalence observations (morning, afternoon, and night) were conducted for 6 months. RESULTS: A total of 336 patients were included in the study, obtaining an overall crude prevalence of PR use of 16 % (95 %CI: 15 %-17.7 %). Pediatric patients with respiratory pathology received the highest number of hours of PR, with significant differences observed when comparing respiratory cases with post-surgical cases. Statistical significance was also observed when comparing the mean scores of hours of PR according to admission diagnosis (p = 0.01), with respiratory patients being the ones who were restrained the longest (24 h [20-24]) and infectious patients the least (15 h [14-20]). Patients who receive PR upon admission remain in this situation for more hours (24 h [15-24] and in the PICUs that specifically recorded PR application, fewer hours of PR occurred (20 h [4-24]). CONCLUSIONS: The use of PR is still present in the PICUs analyzed, with a crude prevalence of 16%. Factors such as the reason for admission, the use of respiratory support, and the reason for application of PR were linked to the hours of use of PR. IMPLICATIONS FOR CLINICAL PRACTICE: Knowing the prevalence of PR use will make professionals aware that it is still necessary to implement policies that avoid its use to prevent the side effects they have in pediatric patients.