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1.
Gene ; 766: 145119, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32946928

RESUMEN

BACKGROUND: Cervical cancer is the fourth most commonly diagnosed cancer in women worldwide. The metastasis and invasion of this type of cancer are closely related to the tumor microenvironment. Immune cells and stromal cells dominate the tumor microenvironment in cervical cancer. Therefore, we should further investigate the complex interplay between the tumor progression with immune cells or stromal cells. METHODS: We downloaded the gene expression profiles and clinical data of 307 patients with cervical cancers based on the TCGA database. Subsequently, the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm was used to calculate the scores of stromal cells and immune cells in order to uncover differential expressed genes, and we analyzed the correlation between their scores and patient survival. Then the Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) deconvolution algorithm was applied to quantify the fraction and infiltration of 22 types of immune cells in cervical cancer. Moreover, we also used R language packs and network tools to analyze GO term, gene enrichment pathway, and protein-protein relationship to trace down genes related to inflammation and immune regulation. RESULTS: The gene expression profiles and corresponding clinical data of 307 patients were obtained from TCGA database. The results showed that the scores were statistically significant between the high immunescore group and the low immunescore group. And the low immunescore group had shorter survival period than the high scores group (P = 0.035). Among the 22 types of immune cells, only T cells and mast cells were significantly related to the survival rate of cervical cancer patients. Moreover, PPI network analysis revealed that CCR5 and CXCL9, -10, -11/CXCR3 axis might be a new target for cervical cancer treatment. Finally, Kaplan-Meier survival curves found outnine representative genes significantly related to survival rate including BTNL8, CCR7, CD1E, CD6, CD27, CD79A, GRAP2, SP1B, LY9. CONCLUSIONS: These genes can be used as markers for the prognosis and diagnosis of cervical cancer and also might be used as treatment targets.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/genética , Transcriptoma/genética , Microambiente Tumoral/genética , Neoplasias del Cuello Uterino/genética , Adulto , Biomarcadores de Tumor/genética , Manejo de Datos , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Mapas de Interacción de Proteínas/genética , Células del Estroma/patología , Neoplasias del Cuello Uterino/patología , Adulto Joven
2.
Gene ; 764: 145105, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32882333

RESUMEN

Sarcoma (SARC) represents a group of highly histological and molecular heterogeneous rare malignant tumors with poor prognosis. There are few proposed classifiers for predicting patient's outcome. The Cancer Proteome Atlas (TPCA) and The Cancer Genome Atlas (TCGA) databases provide multi-omics datasets that enable a comprehensive investigation for this disease. The proteomic expression profile of SARC patients along with the clinical information was downloaded. 55 proteins were found to be associated with overall survival (OS) of patients using univariate Cox regression analysis. We developed a prognostic risk signature that comprises seven proteins (AMPKALPHA, CHK1, S6, ARID1A, RBM15, ACETYLATUBULINLYS40, and MSH6) with robust predictive performance using multivariate Cox stepwise regression analysis. Additionally, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters. Patients in high-risk group also have worse progression free intervals (PFI) than that of patients in low-risk group, but not for disease free intervals (DFI). The signature was validated using transcriptomic profile of SARC patients from TCGA. Potential mechanisms between high- and low-risk groups were identified using differentially expressed genes (DEGs) analysis. These DEGs were primarily enriched in RAS and MPAK signaling pathways. The signature protein molecules are candidate biomarkers for SARC, and the analysis of computational biology in tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinctly immune landscapes of high- and low-risk patients. Together, we constructed a prognostic signature for predicting outcomes for SARC integrating proteomic and transcriptomic profiles, this might have value in guiding clinical practice.


Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/inmunología , Pruebas Genéticas/métodos , Sarcoma/mortalidad , Microambiente Tumoral/inmunología , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/genética , Antígeno CTLA-4/inmunología , Conjuntos de Datos como Asunto , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunología , Supervivencia sin Progresión , Mapeo de Interacción de Proteínas , Proteómica , Curva ROC , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Sarcoma/inmunología , Transcriptoma/genética , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética
3.
Tumour Biol ; 42(11): 1010428320971404, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33169632

RESUMEN

Ovarian cancer is the most lethal of gynecological cancers with 5-year survival rate of ca. 45%. The most common histologic subtype is high-grade serous carcinoma, which typically is presented with advanced stage and development of chemoresistance. Therefore, new treatment options, including immunotherapies, are needed. Understanding the features of the immune cell populations in the tumor microenvironment is essential for developing personalized treatments and finding predictive biomarkers. Digital image analysis may enhance the accuracy and reliability of immune cell infiltration assessment in the tumor microenvironment. The aim of this study was to characterize tumor microenvironment in a retrospective cohort of high-grade serous carcinoma samples with whole-slide imaging and digital image analysis. Formalin-fixed paraffin-embedded high-grade serous carcinoma tumor tissue samples (n = 67) were analyzed for six immunohistochemical stainings: CD4, CD8, FoxP3, granzyme B, CD68, and CD163. The stained sample slides were scanned into a digital format and assessed using QuPath 0.1.2 and ImageJ software. Staining patterns were associated with clinicopathological data. The higher numbers of intraepithelial CD8+, CD163+, and granzyme B+ immune cells were associated with survival benefit when analyzed individually, while high levels of both CD8+ and granzyme B+ tumor-infiltrating lymphocytes were an independent prognostic factor in the Cox multivariate regression analysis (median progression-free survival; hazard ratio = 0.287, p = 0.002). Specimens taken after administration of neoadjuvant chemotherapy presented with lower FoxP3+ tumor-infiltrating lymphocyte density (Fisher's exact test, p = 0.013). However, none of the studied immunomarkers was associated with overall survival or clinical factors. Tumors having high amount of both intraepithelial CD8+ and granzyme B+ tumor-infiltrating lymphocytes showed better progression-free survival, possibly reflecting an activated immune state in the tumor microenvironment. The combined positivity of CD8 and granzyme B warrants further investigation with respect to predicting response to immune therapy. Neoadjuvant chemotherapy may have an effect on the tumor microenvironment and therefore on the response to immuno-oncologic or chemotherapy treatments.


Asunto(s)
Antígenos CD8/sangre , Carcinoma Epitelial de Ovario/sangre , Granzimas/sangre , Linfocitos Infiltrantes de Tumor/metabolismo , Adulto , Anciano , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Antígenos CD4/sangre , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/epidemiología , Carcinoma Epitelial de Ovario/patología , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Factores de Transcripción Forkhead/sangre , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/patología , Persona de Mediana Edad , Receptores de Superficie Celular/sangre , Microambiente Tumoral/efectos de los fármacos
4.
Biomedica ; 40(Supl. 2): 116-130, 2020 10 30.
Artículo en Inglés, Español | MEDLINE | ID: mdl-33152195

RESUMEN

Introduction: Infection with the new SARS-Cov-2 coronavirus is a worldwide public health emergency; its diagnosis is based on molecular tests, while its prognosis depends on the patient's history and on some paraclinical tests. In Colombia, forecasts are not yet counted. Objective: To assess the factors associated with the development of severe disease in hospitalized patients diagnosed with SARS-CoV-2 infection, as well as the prognostic factors for the outcome of mortality. Materials and methods: We conducted an ambispective cohort study in hospitalized patients at the Fundación Cadioinfantil from March to June, 2020. Results: Of the 104 patients analyzed, 31.7% (n=33) had a severe presentation and 9.6% (n=10) had a mortality outcome. For mortality, the most important prognostic factor was the development of severe disease followed by age over 60 years and malnutrition. For the development of the severe disease, prognostic factors were a history of hemodialysis (HR=135), diabetes (HR=4.4), and an increased level of lactate dehydrogenase (LDH) (HR=1,004), while the lymphocyte count over 1,064 was a protective factor (HR=0.9). In the classification of patients, the National Early Warning Score (NEWS2) score in the high and low-risk categories corresponded to the best performance. There was no difference between the treatments administered. Conclusions: The most important prognostic factors for mortality were being over 60 years of age, hypertension, diabetes, and cirrhosis, while for the development of severe disease they were chronic kidney disease with hemodialysis, NEWS2 with high risk at admission, increased levels of LDH and C reactive protein (CRP), and leukocytosis.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/mortalidad , Pandemias , Neumonía Viral/mortalidad , Adulto , Anciano , Antígenos de Grupos Sanguíneos , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Colombia/epidemiología , Comorbilidad , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/terapia , Diabetes Mellitus/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Pacientes Internos/estadística & datos numéricos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neumonía Viral/sangre , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Insuficiencia Renal Crónica/epidemiología , Síndrome de Dificultad Respiratoria del Adulto/etiología , Síndrome de Dificultad Respiratoria del Adulto/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Fumar/epidemiología
5.
BMC Infect Dis ; 20(1): 810, 2020 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-33158426

RESUMEN

PURPOSE: The purpose of this study was to explore the clinical features, risk factors, and outcomes of mixed Candida albicans/bacterial bloodstream infections (mixed-CA/B-BSIs) compared with monomicrobial Candida albicans bloodstream infection (mono-CA-BSI) in adult patients in China. METHODS: All hospitalized adults with Candida albicans bloodstream infection (CA-BSI) were recruited for this retrospective observational study from January 1, 2013, to December 31, 2018. RESULTS: Of the 117 patients with CA-BSI, 24 patients (20.5%) had mixed-CA/B-BSIs. The most common copathogens were coagulase-negative Staphylococcus (CNS) (24.0%), followed by Klebsiella pneumoniae (20.0%) and Staphylococcus aureus (16.0%). In the multivariable analysis, a prior ICU stay > 2 days (adjusted odds ratio [OR], 7.445; 95% confidence interval [CI], 1.152-48.132) was an independent risk factor for mixed-CA/B-BSIs. Compared with patients with mono-CA-BSI, patients with mixed-CA/B-BSIs had a prolonged length of mechanical ventilation [17.5 (4.5, 34.8) vs. 3.0 (0.0, 24.5), p = 0.019] and prolonged length of ICU stay [22.0 (14.3, 42.2) vs. 8.0 (0.0, 31.5), p = 0.010]; however, mortality was not significantly different. CONCLUSIONS: There was a high rate of mixed-CA/B-BSIs cases among CA-BSI cases, and CNS was the predominant coexisting species. A prior ICU stay > 2 days was an independent risk factor for mixed -CA/B-BSIs. Although there was no difference in mortality, the outcomes of patients with mixed -CA/B-BSIs, including prolonged length of mechanical ventilation and prolonged length of ICU stay, were worse than those with mono-CA-BSI; this deserves further attention from clinicians.


Asunto(s)
Bacteriemia/complicaciones , Candida albicans/aislamiento & purificación , Candidiasis/complicaciones , Infecciones por Klebsiella/complicaciones , Klebsiella pneumoniae/aislamiento & purificación , Infecciones Estafilocócicas/complicaciones , Staphylococcus aureus/aislamiento & purificación , Anciano , Bacteriemia/microbiología , Bacteriemia/mortalidad , Candidiasis/microbiología , Candidiasis/mortalidad , China/epidemiología , Infección Hospitalaria/microbiología , Femenino , Humanos , Estimación de Kaplan-Meier , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/mortalidad , Masculino , Persona de Mediana Edad , Respiración Artificial/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad
6.
PLoS One ; 15(11): e0242045, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33166991

RESUMEN

Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. However, the information on the risk factors associated with the mortality of COVID-19 and of their prognostic potential is limited. In this retrospective study, the clinical characteristics, treatment and outcome data were collected and analyzed from 676 COVID-19 patients stratified into 140 non-survivors and 536 survivors. We found that the levels of Dimerized plasmin fragment D (D-dimer), C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in non-survivals on admission (non-survivors vs. survivors: D-Dimer ≥ 0.5 mg/L, 83.2% vs. 44.9%, P<0.01; CRP ≥10 mg/L, 50.4% vs. 6.0%, P<0.01; LDH ≥ 250 U/L, 73.8% vs. 20.1%, P<0.01; PCT ≥ 0.5 ng/ml, 27.7% vs. 1.8%, P<0.01). Moreover, dynamic tracking showed D-dimer kept increasing in non-survivors, while CRP, LDH and PCT remained relatively stable after admission. D-dimer has the highest C-index to predict in-hospital mortality, and patients with D-dimer levels ≥0.5 mg/L had a higher incidence of mortality (Hazard Ratio: 4.39, P<0.01). Our study suggested D-dimer could be a potent marker to predict the mortality of COVID-19, which may be helpful for the management of patients.


Asunto(s)
Infecciones por Coronavirus/mortalidad , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Neumonía Viral/mortalidad , Adulto , Anciano , Betacoronavirus/aislamiento & purificación , Proteína C-Reactiva/análisis , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Femenino , Humanos , Estimación de Kaplan-Meier , L-Lactato Deshidrogenasa/análisis , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología , Neumonía Viral/virología , Polipéptido alfa Relacionado con Calcitonina/análisis , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo
7.
DNA Cell Biol ; 39(11): 2028-2039, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33147069

RESUMEN

Hepatocellular carcinoma (HCC) with metastasis indicates worse prognosis for patients. However, the current methods are insufficient to accurately predict HCC metastasis at early stage. Based on the expression profiles of three Gene Expression Omnibus datasets, the differentially expressed genes associated with HCC metastasis were screened by online analytical tool GEO2R and weighted gene co-expression network analysis. Second, a risk score model including 27-mRNA was established by univariate Cox regression analyses, time-dependent ROC curves and least absolute shrinkage and selection operator Cox regression analysis. Then, we validated the model in cohort The Cancer Genome Atlas-liver hepatocellular carcinoma and analyzed the functions and key signaling pathways of the genes associated with the risk score model. According to the risk score model, patients were divided into two subgroups (high risk and low risk groups). The metastasis rate between two subgroups was significantly different in training cohort (p < 0.0001, hazard ratio [HR]: 10.3, confidence interval [95% CI]: 6.827-15.55) and external validation cohort (p = 0.0008, HR: 1.768, 95% CI: 1.267-2.467). Multivariable analysis showed that the risk score model was superior to and independent of other clinical factors (such as tumor stage, tumor size, and other parameters) in predicting early HCC metastasis. Moreover, the risk score model could predict the overall survival of patients with HCC. Finally, most of 27-mRNA were enriched in exosome and membrane bounded organelle, and these were involved in transportation and metabolic biological process. Protein-protein interaction network analysis showed most of these genes might be key genes affecting the progression of HCC. In addition, 3 genes of 27-mRNA were also differentially expressed in peripheral blood mononuclear cell. In conclusion, by using two combined methods and a broader of HCC datasets, our study provided reliable and superior predictive model for HCC metastases, which will facilitate individual medical management for these high metastatic risk HCC patients.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , ARN Mensajero/genética , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/patología , Biología Computacional , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Estimación de Kaplan-Meier , Hígado/metabolismo , Neoplasias Hepáticas/patología , Masculino , Metástasis de la Neoplasia/genética , Pronóstico , Modelos de Riesgos Proporcionales , Mapas de Interacción de Proteínas/genética , Transcriptoma
8.
N Engl J Med ; 383(17): 1645-1656, 2020 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-33026741

RESUMEN

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Interferon beta-1b/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Administración Oral , Adulto , Anciano , Infecciones por Coronavirus/mortalidad , Método Doble Ciego , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Hospitalización , Humanos , Inyecciones Subcutáneas , Interferon beta-1b/efectos adversos , Estimación de Kaplan-Meier , Lopinavir/efectos adversos , Masculino , Persona de Mediana Edad , Ritonavir/efectos adversos , Estadísticas no Paramétricas , Tiempo de Tratamiento
9.
PLoS One ; 15(10): e0237365, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33075076

RESUMEN

BACKGROUND: Urinary tract infections caused by extended-spectrum beta-lactamase producing Enterobacterales (ESBL-EB) are a problem increasing in our clinical practice. OBJECTIVES: The aim of this study was to evaluate the clinical outcome in patients who received short (≤ 7 days) versus long courses (>7 days) of antimicrobial therapy for complicated ESBL-EB urinary tract infections. METHODS: This is a retrospective and observational study. Positive urine cultures for ESBL-EB in our hospital between March 2015 and July 2017 were identified. Patients with complicated urinary tract infection were included. Differences between treatment groups (7 days or less vs more than 7 days) were analyzed according to baseline characteristics and severity of clinical presentation. Primary outcome was all cause 30-day mortality. Secondary outcome was a combined item of all cause mortality and reinfection by the same enterobacteria at 30 days. RESULTS: 273 urine cultures were positive for ESBL-EB during the study period. 75 episodes were included, 40 in the long treatment group and 35 in the short treatment group. Mean treatment duration in short and long treatment groups was 6,1 and 13,8 days respectively. Mortality at 30 days was 5,7% in the short treatment group and 5% in the long treatment group without significant differences (P = 0,8). Mortality or reinfection by the same ESBL-EB at 30 days was 8,6% in the short treatment group and 10% in the long treatment group, without significant differences (P = 0,8). CONCLUSIONS: Short courses of antimicrobial treatment seems to be effective as treatment of complicated urinary tract infections by ESBL-EB.


Asunto(s)
Antibacterianos/administración & dosificación , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Anciano , Anciano de 80 o más Años , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Duración de la Terapia , Enterobacteriaceae/efectos de los fármacos , Infecciones por Enterobacteriaceae/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España/epidemiología , Infecciones Urinarias/mortalidad , Resistencia betalactámica
10.
PLoS One ; 15(10): e0238795, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33001991

RESUMEN

Hypomethylating agents are a classical frontline low-intensity therapy for older patients with acute myeloid leukemia. Recently, TP53 gene mutations have been described as a potential predictive biomarker of better outcome in patients treated with a ten-day decitabine regimen., However, functional characteristics of TP53 mutant are heterogeneous, as reflected in multiple functional TP53 classifications and their impact in patients treated with azacitidine is less clear. We analyzed the therapeutic course and outcome of 279 patients treated with azacitidine between 2007 and 2016, prospectively enrolled in our regional healthcare network. By screening 224 of them, we detected TP53 mutations in 55 patients (24.6%), including 53 patients (96.4%) harboring high-risk cytogenetics. The identification of any TP53 mutation was associated with worse overall survival but not with response to azacitidine in the whole cohort and in the subgroup of patients with adverse karyotype. Stratification of patients according to three recent validated functional classifications did not allow the identification of TP53 mutated patients who could benefit from azacitidine. Systematic TP53 mutant classification will deserve further exploration in the setting of patients treated with conventional therapy and in the emerging field of therapies targeting TP53 pathway.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Genes p53 , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Mutación , Proteína p53 Supresora de Tumor/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Femenino , Francia/epidemiología , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sistema de Registros
11.
PLoS One ; 15(10): e0238782, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33021973

RESUMEN

In 2015, UN member states committed to eliminate female genital mutilation (FGM) by 2030 as part of the Sustainable Development Agenda. To reach this goal, interventions need to be targeted and guided by the best available evidence. To date, however, estimates of the number of girls and women affected by FGM and their trends over time and geographic space have been limited by the availability, specificity and quality of population-level data. We present new estimates based on all publicly available nationally representative surveys collected since the 1990s that contain both information on FGM status and on the age at which FGM occurred. Using survival analysis, we generate estimates of FGM risk by single year of age for all countries with available data, and for rural and urban areas separately. The likelihood of experiencing FGM has decreased at the global level, but progress has been starkly uneven between countries. The available data indicate no progress in reducing FGM risk in Gambia, Guinea-Bissau, Mali and Guinea. In addition, rural and urban areas have diverged over the last two decades, with FGM declining more rapidly in urban areas. We describe limitations in the availability and quality of data on FGM occurrence and age-at-FGM. Based on current trends, the SDG goal of eliminating FGM by 2030 is out of reach, and the pace at which the practice is being abandoned would need to accelerate to eliminate FGM by 2030. The heterogeneity in trends between countries and rural vs urban areas offers an opportunity to contrast countries where FGM is in rapid decline and explore potential policy lessons and programmatic implications for countries where the practice of FGM appears to remain entrenched.


Asunto(s)
Circuncisión Femenina , Adolescente , Adulto , Niño , Preescolar , Circuncisión Femenina/legislación & jurisprudencia , Circuncisión Femenina/estadística & datos numéricos , Circuncisión Femenina/tendencias , Estudios de Cohortes , Estudios Transversales , Femenino , Salud Global/legislación & jurisprudencia , Salud Global/estadística & datos numéricos , Salud Global/tendencias , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estudios Retrospectivos , Salud Rural , Encuestas y Cuestionarios , Naciones Unidas , Salud Urbana , Salud de la Mujer/legislación & jurisprudencia , Salud de la Mujer/estadística & datos numéricos , Salud de la Mujer/tendencias , Adulto Joven
12.
JAMA ; 324(16): 1629-1639, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-33095849

RESUMEN

Importance: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. Objective: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. Design, Setting, and Participants: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. Interventions: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. Main Outcomes and Measures: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. Results: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002). Conclusions and Relevance: Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02669589.


Asunto(s)
Lesión Renal Aguda/terapia , Anticoagulantes/administración & dosificación , Ácido Cítrico/administración & dosificación , Terapia de Reemplazo Renal Continuo/instrumentación , Heparina/administración & dosificación , Lesión Renal Aguda/sangre , Lesión Renal Aguda/mortalidad , Anciano , Anticoagulantes/efectos adversos , Calcio/sangre , Ácido Cítrico/efectos adversos , Terapia de Reemplazo Renal Continuo/mortalidad , Enfermedad Crítica , Terminación Anticipada de los Ensayos Clínicos , Femenino , Filtración/instrumentación , Alemania , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Heparina/efectos adversos , Humanos , Infecciones/epidemiología , Estimación de Kaplan-Meier , Masculino , Tiempo de Tromboplastina Parcial , Modelos de Riesgos Proporcionales , Factores de Tiempo
13.
JAMA ; 324(16): 1620-1628, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-33107945

RESUMEN

Importance: Catheter ablation of persistent atrial fibrillation (AF) has limited success. Procedural strategies beyond pulmonary vein isolation have failed to consistently improve results. The vein of Marshall contains innervation and AF triggers that can be ablated by retrograde ethanol infusion. Objective: To determine whether vein of Marshall ethanol infusion could improve ablation results in persistent AF when added to catheter ablation. Design, Setting, and Participants: The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial was an investigator-initiated, National Institutes of Health-funded, randomized, single-blinded trial conducted in 12 centers in the United States. Patients (N = 350) with persistent AF referred for first ablation were enrolled from October 2013 through June 2018. Follow-up concluded in June 2019. Interventions: Patients were randomly assigned to catheter ablation alone (n = 158) or catheter ablation combined with vein of Marshall ethanol infusion (n = 185) in a 1:1.15 ratio to accommodate for 15% technical vein of Marshall ethanol infusion failures. Main Outcomes and Measures: The primary outcome was freedom from AF or atrial tachycardia for longer than 30 seconds after a single procedure, without antiarrhythmic drugs, at both 6 and 12 months. Outcome assessment was blinded to randomization treatment. There were 12 secondary outcomes, including AF burden, freedom from AF after multiple procedures, perimitral block, and others. Results: Of the 343 randomized patients (mean [SD] age, 66.5 [9.7] years; 261 men), 316 (92.1%) completed the trial. Vein of Marshall ethanol was successfully delivered in 155 of 185 patients. At 6 and 12 months, the proportion of patients with freedom from AF/atrial tachycardia after a single procedure was 49.2% (91/185) in the catheter ablation combined with vein of Marshall ethanol infusion group compared with 38% (60/158) in the catheter ablation alone group (difference, 11.2% [95% CI, 0.8%-21.7%]; P = .04). Of the 12 secondary outcomes, 9 were not significantly different, but AF burden (zero burden in 78.3% vs 67.9%; difference, 10.4% [95% CI, 2.9%-17.9%]; P = .01), freedom from AF after multiple procedures (65.2% vs 53.8%; difference, 11.4% [95% CI, 0.6%-22.2%]; P = .04), and success achieving perimitral block (80.6% vs 51.3%; difference, 29.3% [95% CI, 19.3%-39.3%]; P < .001) were significantly improved in vein of Marshall-treated patients. Adverse events were similar between groups. Conclusions and Relevance: Among patients with persistent AF, addition of vein of Marshall ethanol infusion to catheter ablation, compared with catheter ablation alone, increased the likelihood of remaining free of AF or atrial tachycardia at 6 and 12 months. Further research is needed to assess longer-term efficacy. Trial Registration: ClinicalTrials.gov Identifier: NCT01898221.


Asunto(s)
Fibrilación Atrial/terapia , Ablación por Catéter/métodos , Etanol/administración & dosificación , Vena Cava Superior , Anciano , Terapia Combinada/métodos , Femenino , Humanos , Infusiones Intravenosas/efectos adversos , Infusiones Intravenosas/métodos , Estimación de Kaplan-Meier , Masculino , Método Simple Ciego , Taquicardia/terapia , Resultado del Tratamiento , Vena Cava Superior/embriología , Vena Cava Superior/inervación
14.
Medicine (Baltimore) ; 99(43): e22893, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33120837

RESUMEN

Radical cystectomy is considered the standard treatment for patients with muscle-invasive bladder tumors and has high postoperative complication rates among urological surgeries. High-risk patients, defined as those ≥45 years of age with history of coronary artery disease, stroke, or peripheral artery disease or those ≥65 years of age, can have a higher incidence of cardiac complications. Therefore, we evaluated the incidence, risk factors, and outcomes of myocardial injury after non-cardiac surgery (MINS) in high-risk patients who underwent radical cystectomy.This retrospective observational study analyzed 248 high-risk patients who underwent radical cystectomy. MINS was defined as serum troponin I concentration ≥0.04 mg/L within postoperative 3 days. The risk factors for MINS were evaluated by multivariate logistic regression analysis. Postoperative outcomes were evaluated. The 1-year survival after radical cystectomy was also compared between patients who developed MINS (MINS group) and those who did not (non-MINS group) by Kaplan-Meier analysis.MINS occurred in 35 patients (14.1%). Multivariate logistic regression analysis showed that early diastolic transmitral filling velocity (E)/early diastolic septal mitral annular velocity (E') ratio (odds ratio = 1.102, 95% confidence interval [1.009-1.203], P = .031) and large volume blood transfusion (odds ratio = 2.745, 95% confidence interval [1.131-6.664], P = .026) were significantly associated with MINS in high-risk patients who underwent radical cystectomy. Major adverse cardiac events and 1-year mortality were significantly higher in the MINS group than in the non-MINS group (17.1% vs 6.1%, P = .035; 28.6% vs 12.7%, P = .021, respectively). Kaplan-Meier analysis showed significantly lower 1-year survival in the MINS group than in the non-MINS group (P = .010).MINS occurred in 14.1% of patients. High E/E' ratio and large volume blood transfusion were risk factors for MINS in high-risk patients who underwent radical cystectomy. Postoperative major adverse cardiac events and 1-year mortality were significantly higher in the MINS group than in the non-MINS group. Preoperative evaluation of risk factors for MINS may provide useful information to detect cardiovascular complications after radical cystectomy in high-risk patients.


Asunto(s)
Cistectomía/efectos adversos , Isquemia Miocárdica/etiología , Troponina I/sangre , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea/estadística & datos numéricos , Estudios de Casos y Controles , Cistectomía/mortalidad , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/metabolismo , Estadificación de Neoplasias/métodos , Complicaciones Posoperatorias/epidemiología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/patología
15.
Sci Rep ; 10(1): 17524, 2020 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-33067568

RESUMEN

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case-control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival.


Asunto(s)
Infecciones por Coronavirus/patología , Neumonía Viral/patología , Anciano , Betacoronavirus/aislamiento & purificación , Estudios de Casos y Controles , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Mortalidad Hospitalaria , Humanos , Interleucina-6/metabolismo , Estimación de Kaplan-Meier , Modelos Logísticos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Puntuaciones en la Disfunción de Órganos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Neumonía Viral/virología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad
16.
Medicine (Baltimore) ; 99(40): e22292, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019404

RESUMEN

This study aims to assess the survival status of patients with Primary gallbladder cancer (PGC) and analyze the prognosis factors to facilitate the exploration of the prevention and therapeutic strategies of PGC.Data from 2433 PGC patients collected from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The SEER*Stat, SPSS 23.0 and GraphPad Prism 8 were used for statistical analyses. Kaplan Meier analysis was performed for the survival curve, log-rank test analyses were used to compare the survival rate difference and Cox regression analyses were performed to determine the prognosis factors.A total of 2433 PGC cases were reported from 2010 to 2015. The median age was 64.2 ±â€Š10.4 years old and the percentages of the white patients were 73.7% (1794/2433). The percentage of patients who received surgery treatment was 82.1% (1998/2433). The overall median survival time of all patients was 19 months and the 5-year survival rate was 28.8%. The 5-year survival rate of PGC patients in pN2 stage dropped to 0% and the 5-year survival rate for PGC patients with distant metastasis was only 2.7%. Age, tumor size, grade, pT stage, pM stage were risk factors for prognosis, surgery or not and radiation or not were protective factors for prognosis.Survival analysis of PGC patients based on the SEER database have provided an opportunity for understanding PGC prognosis and the basis for the exploration of viable PGC prevention and therapeutic strategies.


Asunto(s)
Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/patología , Anciano , Femenino , Neoplasias de la Vesícula Biliar/terapia , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Programa de VERF , Factores Socioeconómicos , Carga Tumoral
17.
Mediators Inflamm ; 2020: 3764515, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33061826

RESUMEN

This study aimed at determining the relationship between baseline cystatin C levels and coronavirus disease 2019 (COVID-19) and investigating the potential prognostic value of serum cystatin C in adult patients with COVID-19. 481 patients with COVID-19 were consecutively included in this study from January 2, 2020, and followed up to April 15, 2020. All clinical and laboratory data of COVID-19 patients with definite outcomes were reviewed. For every measure, COVID-19 patients were grouped into quartiles according to the baseline levels of serum cystatin C. The highest cystatin C level was significantly related to more severe inflammatory conditions, worse organ dysfunction, and worse outcomes among patients with COVID-19 (P values < 0.05). In the adjusted logistic regression analyses, the highest cystatin C level and ln-transformed cystatin C levels were independently associated with the risks of developing critically ill COVID-19 and all-cause death either in overall patients or in patients without chronic kidney disease (P values < 0.05). As a potential inflammatory marker, increasing baseline levels of serum cystatin C might independently predict adverse outcomes for COVID-19 patients. Serum cystatin C could be routinely monitored during hospitalization, which showed clinical importance in prognosticating for adult patients with COVID-19.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/sangre , Cistatina C/sangre , Pandemias , Neumonía Viral/sangre , Adulto , Anciano , Biomarcadores/sangre , China/epidemiología , Estudios de Cohortes , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Enfermedad Crítica , Femenino , Humanos , Mediadores de Inflamación/sangre , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Dinámicas no Lineales , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
18.
Clin Mol Hepatol ; 26(4): 562-576, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33053932

RESUMEN

BACKGROUND/AIMS: Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved.
. METHODS: A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed.
. RESULTS: Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P<0.05). The overall survival rate was significantly lower in patients with liver cirrhosis than in those without liver cirrhosis (log-rank test, P=0.003). Along with old age and diabetes, the presence of liver cirrhosis was found to be an independent predictor of severe disease (odds ratio, 4.52; 95% confidence interval [CI], 1.20-17.02;P=0.026) and death (hazard ratio, 2.86; 95% CI, 1.04-9.30; P=0.042) in COVID-19 patients.
. CONCLUSION: This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.


Asunto(s)
Infecciones por Coronavirus/patología , Hepatopatías/patología , Neumonía Viral/patología , Factores de Edad , Anciano , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Femenino , Humanos , Oxigenación Hiperbárica , Unidades de Cuidados Intensivos , Estimación de Kaplan-Meier , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Cirrosis Hepática/patología , Hepatopatías/complicaciones , Hepatopatías/mortalidad , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/terapia , Neumonía Viral/virología , Pronóstico , República de Corea , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del Tratamiento
19.
Medicine (Baltimore) ; 99(44): e22968, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-33126369

RESUMEN

Heterogeneous associations exist between alcohol consumption and the initial presentation of cardiovascular diseases (CVDs). Studies regarding the association between abdominal aortic aneurysms (AAAs) and alcohol consumption are still limited and controversial. We hypothesize that patients with alcohol-related diseases are susceptible to AAA formation due to the presence of overlapping epidemiological factors and molecular mechanisms. We aimed to use a nationwide population-based retrospective cohort study to evaluate the association between alcohol-related diseases and AAA.The data were extracted from the National Health Insurance Research Database (NHIRD) in Taiwan. The study outcome assessed was the cumulative incidence of AAA in patients with alcohol-related diseases during a 14-year follow-up period.Our study included 22,878 patients who had alcohol-related diseases; these patients with alcohol-related diseases had a significantly higher cumulative risk of developing AAA 5 years after the index date than did the 91,512 patients without alcohol-related diseases. Patients with alcohol-related diseases also exhibited a significantly increased incidence of AAA compared with the incidence among patients without alcohol-related diseases, according to Cox regression analysis and Fine & Gray's competing risk model (adjusted hazard ratio = 2.379, 95% confidence interval = 1.653 -3.424, P < .001). In addition, male gender, older age, and chronic kidney disease were also associated with an increased risk of developing AAA. An interaction model showed that males with alcohol-related diseases had a 10.4-fold higher risk of AAA than did females without alcohol-related diseases.We observed an association between alcohol-related diseases and AAA even after adjusting for several comorbidities and medications in a nationwide population database.


Asunto(s)
Trastornos Relacionados con Alcohol/complicaciones , Aneurisma de la Aorta Abdominal/etiología , Estudios de Casos y Controles , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales
20.
BMC Infect Dis ; 20(1): 756, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-33059622

RESUMEN

BACKGROUND: Infection with the Human Immunodeficiency Virus (HIV) dramatically increases the risk of developing active tuberculosis (TB). Several studies have indicated that co-infection with TB increases the risk of HIV progression and death. Sub-Saharan Africa bears the brunt of these dual epidemics, with about 2.4 million HIV-infected people living with TB. The main objective of our study was to assess whether the pre-HAART CD4+ T-lymphocyte counts and percentages could serve as biomarkers for post-HAART treatment immune-recovery in HIV-positive children with and without TB co-infection. METHODS: The data analyzed in this retrospective study were collected from a cohort of 305 HIV-infected children being treated with HAART. A Lehmann family of ROC curves were used to assess the diagnostic performance of pre- HAART treatment CD4+ T-lymphocyte count and percentage as biomarkers for post-HAART immune recovery. The Kaplan-Meier estimator was used to compare differences in post-HAART recovery times between patients with and without TB co-infection. RESULTS: We found that the diagnostic performance of both pre-HARRT treatment CD4+ T-lymphocyte count and percentage was comparable and achieved accuracies as high as 74%. Furthermore, the predictive capability of pre-HAART CD4+ T-lymphocyte count and percentage were slightly better in TB-negative patients. Our analyses also indicate that TB-negative patients have a shorter recovery time compared to the TB-positive patients. CONCLUSIONS: Pre-HAART CD4+ T-lymphocyte count and percentage are stronger predictors of immune recovery in TB-negative pediatric patients, suggesting that TB co-infection complicates the treatment of HIV in this cohort. These findings suggest that the detection and treatment of TB is essential for the effectiveness of HAART in HIV-infected pediatric patients.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Coinfección , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Tuberculosis/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA , Biomarcadores/análisis , Linfocitos T CD4-Positivos/virología , Niño , Preescolar , Femenino , Ghana , Infecciones por VIH/microbiología , Infecciones por VIH/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Curva ROC , Estudios Retrospectivos , Resultado del Tratamiento , Tuberculosis/virología
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