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OBJECTIVE: We created a finite element model to predict the probability of dissection based on imaging-derived aortic stiffness and investigated the link between stiffness and wall tensile stress using our model. METHODS: Transthoracic echocardiogram measurements were used to calculate aortic diameter change over the cardiac cycle. Aortic stiffness index was subsequently calculated based on diameter change and blood pressure. A series of logistic models were developed to predict the binary outcome of aortic dissection using 1 or more series of predictor parameters such as aortic stiffness index or patient characteristics. Finite element analysis was performed on a subset of diameter-matched patients exhibiting patient-specific material properties. RESULTS: Transthoracic echocardiogram scans of patients with type A aortic dissection (n = 22) exhibited elevated baseline aortic stiffness index when compared with aneurysmal patients' scans with tricuspid aortic valve (n = 83, P < .001) and bicuspid aortic valve (n = 80, P < .001). Aortic stiffness index proved an excellent discriminator for a future dissection event (area under the curve, 0.9337, odds ratio, 2.896). From the parametric finite element study, we found a correlation between peak longitudinal wall tensile stress and stiffness index (ρ = .6268, P < .001, n = 28 pooled). CONCLUSIONS: Noninvasive transthoracic echocardiogram-derived aortic stiffness measurements may serve as an impactful metric toward predicting aortic dissection or quantifying dissection risk. A correlation between longitudinal stress and stiffness establishes an evidence-based link between a noninvasive stiffness parameter and stress state of the aorta with clinically apparent dissection events.
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RESUMEN Objetivo: Explorar el esquema terapéutico y factores asociados a mortalidad en pacientes con un cuadro severo de COVID-19 atendidos en el Hospital Nacional Alberto Sabogal Sologuren en 2020. Materiales y métodos: Estudio observacional, analítico de caso-control y prospectivo. Fueron incluidos los pacientes que ingresaron al hospital con un cuadro severo de COVID-19 entre junio a septiembre de 2020 y fueron clasificados en dos grupos: el grupo caso (61 pacientes fallecidos) y el grupo control (60 sobrevivientes que recibieron el alta hospitalaria). Los datos fueron analizados en el software estadístico Stata(R) y se realizó análisis bivariado y multivariado con regresión logística, nivel de confianza del 95 %. Resultados: En pacientes con cuadro severo de COVID-19, la edad mayor de 60 años está asociada a la mortalidad (p=0,035; OR=2,21 IC: [1,05-4,63]). Los esquemas terapéuticos fueron variados, los participantes que recibieron metilprednisolona a dosis altas tuvieron mayor probabilidad de morir en comparación a los que recibieron otros corticoides (p=0,001; OR ajustado=5,18 IC: [1,94-13,83]). El tratamiento con azitromicina por más de cinco días incrementa la probabilidad de fallecer en comparación a los que la tomaron por menos días (p=0,000; OR ajustado=7,14 IC: [2,22-22,99]). El modelo multivariado tenía una probabilidad predictiva de mortalidad de 73,06 % para los pacientes con cuadro severo de COVID-19. Conclusiones: Los esquemas terapéuticos que incluyen administración de metilprednisolona a dosis altas y azitromicina por más de 5 días incrementan la probabilidad de fallecer en los pacientes con una presentación severa de COVID-19. Además, la edad mayor a 60 años estuvo asociada a la mortalidad en los pacientes analizados en el estudio.
ABSTRACT Objective: To explore the therapeutic regimen and factors associated with mortality in patients with severe COVID-19 infection treated at the Hospital Nacional Alberto Sabogal Sologuren in 2020. Materials and methods: An observational, case-control, analytical and prospective study conducted in patients with severe COVID-19 infection at hospital admission between June and September 2020. The study population was classified into two groups: case group (61 deceased patients) and control group (60 discharged patients). Data were analyzed using Stata statistical software. Bivariate and multivariate logistic regression analyses were performed with a 95 % confidence level. Results: As for patients with severe COVID-19 infection, ages older than 60 years are associated with mortality (p = 0.035; OR = 2.21; CI: [1.05 - 4.63]). Different therapeutic regimens were included in the research: patients who received high-dose methylprednisolone had more probability of dying compared to those who received other corticosteroids (p = 0.001; adjusted OR = 5.18; CI: [1.94 - 13.83]). Patients who were treated with azithromycin for more than five days had more probability of dying compared to those that took it for fewer days (p = 0.000; adjusted OR = 7.14; CI: [2.22 - 22.99]). The multivariate model showed a 73.06 % predictive probability of mortality for patients with severe COVID-19 infection. Conclusions: The therapeutic regimens that include the administration of high-dose methylprednisolone and azithromycin for more than five days increase the probability of dying in patients with severe COVID-19 infection. Furthermore, ages over 60 years were associated with mortality in the patients who participated in the study.
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OBJECTIVE: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours. STUDY DESIGN: Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age. RESULTS: Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively. CONCLUSIONS: MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia-ischemia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00614744.
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Discapacidades del Desarrollo/diagnóstico por imagen , Hipoxia-Isquemia Encefálica/terapia , Imagen por Resonancia Magnética , Discapacidades del Desarrollo/etiología , Femenino , Humanos , Hipotermia Inducida/efectos adversos , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Lactante , Recién Nacido , Recien Nacido Prematuro , Masculino , Valor Predictivo de las Pruebas , Índice de Severidad de la EnfermedadRESUMEN
In this study, we identify and describe the risk factors and symptoms that are suggestive of sexually transmitted infections (STIs) in rural Mayan villages of Guatemala. We used the World Health Organization's syndromic guidelines for diagnosis and management of STIs to design questionnaires and to identify STI symptoms among indigenous Mayans who presented to mobile clinics in villages served by Guatemala Village Health (GVH). Symptoms that include abdominal pain or pain on urination, genital discharge, itching and sores were highest among younger participants. Lack of male participation in sexual health matters constitutes an important determinant of risk of exposure.
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Población Rural/estadística & datos numéricos , Salud Sexual , Enfermedades de Transmisión Sexual/epidemiología , Adolescente , Adulto , Estudios Transversales , Femenino , Guatemala/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To assess the frequency of gastrostomy tube (GT) placement in extremely low birth weight (ELBW) infants, associated comorbidities, and long-term outcomes. STUDY DESIGN: Analysis of ELBW infants from 25 centers enrolled in the National Institute of Child Health and Human Development Neonatal Research Network's Generic Database and Follow-up Registry from 2006 to 2012. Frequency of GT placement before 18-22 months, demographic and medical factors associated with GT placement, and associated long-term outcomes at 18-22 months of corrected age were described. Associations between GT placement and neonatal morbidities and long-term outcomes were assessed with logistic regression after adjustment for center and common co-variables. RESULTS: Of the 4549 ELBW infants included in these analyses, 333 (7.3%) underwent GT placement; 76% had the GT placed postdischarge. Of infants with GTs, 11% had birth weights small for gestational age, 77% had bronchopulmonary dysplasia, and 29% severe intraventricular hemorrhage or periventricular leukomalacia. At follow-up, 56% of infants with a GT had weight <10th percentile, 61% had neurodevelopmental impairment (NDI), and 55% had chronic breathing problems. After adjustment, small for gestational age, bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, poor growth, and NDI were associated with GT placement. Thirty-two percent of infants with GTs placed were taking full oral feeds at follow-up. CONCLUSIONS: GT placement is common in ELBW infants, particularly among those with severe neonatal morbidities. GT placement in this population was associated with poor growth, NDI, and chronic respiratory and feeding problems at follow-up. The frequency of GT placement postneonatal discharge indicates the need for close nutritional follow-up of ELBW infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063.
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Nutrición Enteral/estadística & datos numéricos , Gastrostomía/estadística & datos numéricos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Enfermedades del Prematuro/terapia , Pautas de la Práctica en Medicina/estadística & datos numéricos , Desarrollo Infantil , Comorbilidad , Bases de Datos Factuales , Nutrición Enteral/métodos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/epidemiología , Masculino , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Acinetobacter calcoaceticus-A. baumannii (Acb) complex and Stenotrophomonas maltophilia represent frequent causes of hospital-acquired infections. We evaluated the frequency and resistance rates of Acb complex and S. maltophilia isolates from medical centers enrolled in the SENTRY Program. METHODS: A total of 13 752 Acb complex and 6467 S. maltophilia isolates were forwarded to a monitoring laboratory by 259 participating sites from the Asia-Pacific region, Latin America, Europe, and North America between 1997 and 2016. Confirmation of species identification and antimicrobial susceptibility testing were performed using conventional methods and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry and the broth microdilution method, respectively. Antimicrobial susceptibility results were interpreted by CLSI and EUCAST 2018 criteria. RESULTS: Acb complex and S. maltophilia were most frequently isolated from patients hospitalized with pneumonia (42.9% and 55.8%, respectively) and bloodstream infections (37.3% and 33.8%, respectively). Colistin and minocycline were the most active agents against Acb complex (colistin MIC50/90, ≤0.5/2 mg/L; 95.9% susceptible) and S. maltophilia (minocycline MIC50/90, ≤1/2 mg/L; 99.5% susceptible) isolates, respectively. Important temporal decreases in susceptibility rates among Acb complex isolates were observed for all antimicrobial agents in all regions. Rates of extensively drug-resistant Acb complex rates were highest in Europe (66.4%), followed by Latin America (61.5%), Asia-Pacific (56.9%), and North America (38.8%). Among S. maltophilia isolates, overall trimethoprim-sulfamethoxazole (TMP-SMX) susceptibility rates decreased from 97.2% in 2001-2004 to 95.7% in 2013-2016, but varied according to the geographic region. CONCLUSIONS: We observed important reductions of susceptibility rates to all antimicrobial agents among Acb complex isolates obtained from all geographic regions. In contrast, resistance rates to TMP-SMX among S. maltophilia isolates remained low and relatively stable during the study period.
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BACKGROUND: Therapeutic hypothermia reduces the risk of death, or moderate to severe neurodevelopmental impairment (NDI) in term infants with hypoxic-ischemic encephalopathy (HIE). Reports of its safety and efficacy in preterm infants are scarce. OBJECTIVE: Report short and long-term outcomes of preterm infants with HIE who received therapeutic hypothermia. METHODS: A retrospective cohort analysis of all preterm infants <36â¯weeks' gestation with HIE who received whole body hypothermia in a single center from January 2007 to April 2015. The primary outcome was death or moderate to severe NDI defined by moderate or severe cerebral palsy, severe hearing or visual impairment, or cognitive scoreâ¯<â¯85 on the Bayley Scales of Infant Development III (BSID III) at 18-24â¯months' adjusted age. RESULTS: 30 infants with a median gestational age and birthweight of 35â¯weeks' (range; 33-35) and 2575â¯g (1850-4840) and a median first postnatal blood pH of 6.81 (6.58-7.14). Complications included coagulopathy (50%), early clinical seizures (43.3%), arterial hypotension (40%), persistent metabolic acidosis (37%) and thrombocytopenia (20%). Four infants died before or soon after discharge (18.2%). Eighteen surviving infants (69.2%) had follow up data; 7 of them had moderate to severe NDI (38.9%). Cognitive, motor and language mean composite BSID III scores were 84 (54-110), 83 (46-118), and 78 (46-112). Death or moderate to severe NDI occurred in 11/22 (50%) infants with known outcomes. CONCLUSION: Large randomized trials on efficacy and safety are needed in this highly vulnerable population as the incidence of complications and the combined outcome of death and NDI is concerning.
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Asfixia Neonatal/terapia , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica/terapia , Asfixia Neonatal/complicaciones , Peso al Nacer/fisiología , Discapacidades del Desarrollo/etiología , Femenino , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Recién Nacido , Recien Nacido Prematuro , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
El lenguaje médico en español está plagado de vicios que le restan credibilidad al mensaje científico. Entre ellos, sobresalen los extranjerismos innecesarios. Principalmente traducciones erróneas del inglés, aunque no solamente de este idioma, conocidas como 'palabras traidoras' o 'falsos amigos', es decir, palabras de ortografía muy similar o idéntica en inglés y español, pero con significados diferentes en ambos idiomas. Así, el objetivo del presente artículo está dirigido a revisar un grupo de estas palabras con el interés de estimular a los profesionales de las ciencias médicas para el uso adecuado del idioma español en las ciencias médicas(AU)
Medical language in Spanish is plagued of bad habits that subtract credibility to the scientific message. Among them are outstanding unnecessary foreign expressions, mainly erroneous translations from English, although not only from this language, known as 'treacherous words' or 'false friends'; that is to say, words of very similar or identical spelling in English and Spanish, but with different meanings in both languages. Thus, the objective of the present article is aimed to revise a group of these words, with the interest of stimulating the professionals of the medical sciences for the appropriate use of the Spanish language in the field(AU)
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Humanos , Lenguaje , Traducción , Pruebas de Asociación de PalabrasRESUMEN
El lenguaje médico en español está plagado de vicios que le restan credibilidad al mensaje científico. Entre ellos, sobresalen los extranjerismos innecesarios. Principalmente traducciones erróneas del inglés, aunque no solamente de este idioma, conocidas como 'palabras traidoras' o 'falsos amigos', es decir, palabras de ortografía muy similar o idéntica en inglés y español, pero con significados diferentes en ambos idiomas. Así, el objetivo del presente artículo está dirigido a revisar un grupo de estas palabras con el interés de estimular a los profesionales de las ciencias médicas para el uso adecuado del idioma español en las ciencias médicas(AU)
Medical language in Spanish is plagued of bad habits that subtract credibility to the scientific message. Among them are outstanding unnecessary foreign expressions, mainly erroneous translations from English, although not only from this language, known as 'treacherous words' or 'false friends'; that is to say, words of very similar or identical spelling in English and Spanish, but with different meanings in both languages. Thus, the objective of the present article is aimed to revise a group of these words, with the interest of stimulating the professionals of the medical sciences for the appropriate use of the Spanish language in the field(AU)
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Humanos , Lenguaje , Traducción , Pruebas de Asociación de PalabrasRESUMEN
OBJECTIVES: To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates. STUDY DESIGN: This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network's Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 240/7 to 276/7 weeks' gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation. RESULTS: Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/ bronchopulmonary dysplasia (OR 3.27). CONCLUSIONS: Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00233324.
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Extubación Traqueal/métodos , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Extubación Traqueal/efectos adversos , Femenino , Humanos , Recien Nacido Extremadamente Prematuro , Recién Nacido , Recien Nacido Prematuro , Masculino , Morbilidad , Síndrome de Dificultad Respiratoria del Recién Nacido/mortalidad , Insuficiencia del TratamientoRESUMEN
KEY POINTS: Long-chain acyl-CoA synthetase 6 (ACSL6) mRNA is present in human and rat skeletal muscle, and is modulated by nutritional status: exercise and fasting decrease ACSL6 mRNA, whereas acute lipid ingestion increase its expression. ACSL6 genic inhibition in rat primary myotubes decreased lipid accumulation, as well as activated the higher mitochondrial oxidative capacity programme and fatty acid oxidation through the AMPK/PGC1-α pathway. ACSL6 overexpression in human primary myotubes increased phospholipid species and decreased oxidative metabolism. ABSTRACT: Long-chain acyl-CoA synthetases (ACSL 1 to 6) are key enzymes regulating the partitioning of acyl-CoA species toward different metabolic fates such as lipid synthesis or ß-oxidation. Despite our understanding of ecotopic lipid accumulation in skeletal muscle being associated with metabolic diseases such as obesity and type II diabetes, the role of specific ACSL isoforms in lipid synthesis remains unclear. In the present study, we describe for the first time the presence of ACSL6 mRNA in human skeletal muscle and the role that ACSL6 plays in lipid synthesis in both rodent and human skeletal muscle. ACSL6 mRNA was observed to be up-regulated by acute high-fat meal ingestion in both rodents and humans. In rats, we also demonstrated that fasting and chronic aerobic training negatively modulated the ACSL6 mRNA and other genes of lipid synthesis. Similar results were obtained following ACSL6 knockdown in rat myotubes, which was associated with a decreased accumulation of TAGs and lipid droplets. Under the same knockdown condition, we further demonstrate an increase in fatty acid content, p-AMPK, mitochondrial content, mitochondrial respiratory rates and palmitate oxidation. These results were associated with increased PGC-1α, UCP2 and UCP3 mRNA and decreased reactive oxygen species production. In human myotubes, ACSL6 overexpression reduced palmitate oxidation and PGC-1α mRNA. In conclusion, ACSL6 drives acyl-CoA toward lipid synthesis and its downregulation improves mitochondrial biogenesis, respiratory capacity and lipid oxidation. These outcomes are associated with the activation of the AMPK/PGC1-α pathway.
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Coenzima A Ligasas/metabolismo , Metabolismo de los Lípidos/fisiología , Mitocondrias Musculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Animales , Células Cultivadas , Citrato (si)-Sintasa/metabolismo , Coenzima A Ligasas/genética , Dieta Alta en Grasa , Ácidos Grasos/metabolismo , Femenino , Humanos , Masculino , Obesidad/metabolismo , Oxidación-Reducción , Consumo de Oxígeno , ARN Mensajero/metabolismo , Ratas WistarRESUMEN
En la Universidad de la Amazonia, en Florencia, Caquetá - Colombia, se llevó a cabo la descripción anatómica detallada del espécimen adulto de la especie Bradypus variegatus, a través de la cual se abordan aspectos clave de la osamenta, correspondientes al esqueleto apendicular, conformado por los huesos del miembro torácico (escápula, húmero, radio, ulna, carpos, metacarpos y falanges) y pelviano (pelvis, sacro, fémur, rótula, tibia, peroné, tarso, metatarso y falanges). Asimismo, se describe el esqueleto axial que corresponde a la línea media del esqueleto, formando el eje del cuerpo a través de los huesos del cráneo, columna vertebral, costillas y esternón. La descripción se desarrolló teniendo en cuenta metodologías previas y considerando datos de descripciones anteriores llevadas a cabo por otros autores, en algunas estructuras. Los resultados se consideran un precepto en el conocimiento del área quirúrgica como pieza fundamental en el desarrollo de la veterinaria en especies de fauna silvestre.
At the University of Amazonia, in Florencia, Caqueta - Colombia, a detailed osteological description of adult specimen of the species brown-throated sloth developed or Bradypus variegatus, through which key skeleton aspects are addressed, for the skeleton apendicular, comprising the forelimb bones (scapula, humerus, radius, ulna, carpal bones, metacarpals and phalanges) and pelvic (pelvis, sacrum, femur, patella, tibia, fibula, tarsus, metatarsus and phalanges). Also, the axial skeleton corresponding to the middle line of the skeleton, forming the body axis through the skull bones, spine, ribs and sternum described. The description was developed considering previous methodologies and data considering previous descriptions carried out by other authors in some structures. The results are considered a precept knowledge of the surgical area as a cornerstone in the development of veterinary species of wildlife.
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OBJECTIVE: To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns. STUDY DESIGN: We evaluated blood spots collected from 943 infants born at ≤1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days). Median cytokine levels for infants with BPD were compared with the IQR of results among infants with NLD. RESULTS: The distribution of enrolled infants by group was as follows: 69 (NLD), 73 (respiratory distress syndrome), 381 (classic BPD), and 160 (atypical BPD). The remaining 260 infants could not be classified because of missing data (104) or not fitting a predefined pattern (156). Median levels of 3 cytokines (elevated interleukin [IL]-8, matrix metalloproteinase-9; decreased granulocyte macrophage colony-stimulating factor) fell outside the IQR for at least 2 time points in both infants with atypical and classic BPD. Profiles of 7 cytokines (IL-6, IL-10, IL-18, macrophage inflammatory protein-1α, C-reactive protein, brain-derived neurotrophic factor, regulated on activation, normal T cell expressed and secreted) differed between infants with classic and atypical BPD. CONCLUSIONS: Blood cytokine profiles may differ between infants developing classic and atypical BPD. These dissimilarities suggest the possibility that differing mechanisms could explain the varied patterns of pathophysiology of lung disease in extremely premature infants.
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Displasia Broncopulmonar/sangre , Citocinas/sangre , Síndrome de Dificultad Respiratoria del Recién Nacido/sangre , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recién Nacido , Recien Nacido Prematuro , Masculino , Terapia por Inhalación de Oxígeno , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatologíaRESUMEN
Baseline methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with nosocomial and community-acquired pneumonia collected during Phase 3 trials for ceftobiprole were characterized. Eighty-four unique isolates from patients enrolled in Europe (50.0%), Asia-Western Pacific region (APAC; 20.2%), North America (19.0%), Latin America (8.3%), and South Africa (2.4%) were included. Antimicrobial susceptibility testing was performed by broth microdilution and isolates screened for Panton-Valentine leukocidin. SCCmec and agr types were determined. Strains were subjected to pulsed-field gel electrophoresis and spa typing. Clonal complexes (CCs) were assigned based on spa and/or multilocus sequence typing. Most isolates were CC5-MRSA-I/II/IV (44.0%; 37/84), followed by CC8-MRSA-IV (22.6%; 19/84) and CC239-MRSA-III (21.4%; 18/84). Other MRSA formed seven clonal clusters. Isolates from North America were associated with USA100, while those from South America belonged to the Cordobes/Chilean CC. A greater clonal diversity was observed in Europe; however, each country had CC5, CC8, or CC239 as prevalent lineages. Isolates from APAC were CC5-MRSA-II (47.1%; 8/17) or CC239-MRSA-III (47.1%; 8/17). Isolates carrying SCCmec I and III had ceftobiprole MIC50 values of 2 µg/ml, while those isolates with SCCmec II and IV had MIC50 values of 1 µg/ml. Ceftobiprole inhibited 96% and 100.0% of the isolates at ≤ 2 and ≤ 4 µg/ml, respectively. These isolates represented common circulating MRSA clones. Ceftobiprole demonstrated in vitro activity with a slight variation of minimum inhibitory concentrations (MICs) according to SCCmec or clonal type.
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Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Neumonía/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Asia , Toxinas Bacterianas/genética , Ensayos Clínicos Fase III como Asunto , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Europa (Continente) , Exotoxinas/genética , Genotipo , Humanos , Leucocidinas/genética , Pruebas de Sensibilidad Microbiana/métodos , Tipificación de Secuencias Multilocus/métodos , América del Norte , Neumonía/microbiología , Sudáfrica , América del Sur , Infecciones Estafilocócicas/microbiologíaRESUMEN
A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active againstStaphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at <1mg/L and all isolates at <2mg/L (MIC5090, 0.25/2mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC50/90 values were at <0.015/<0.015mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. Susceptibility to ceftriaxone was at 88.4% (CLSI non-meningitis interpretive criteria) and 73.9% (CLSI meningitis interpretive criteria) for all S. pneumoniae. Ceftriaxone susceptibility was only at 33.3% (CLSI non-meningitis interpretive criteria) and 0.0% (CLSI meningitis interpretive criteria) for penicillin-intermediate (penicillin MIC, 4mg/L) strains. AllHaemophilus influenzae (29.4% β-lactamase-positive) isolates were susceptible to ceftaroline, amoxicillin-clavulanate, ceftriaxone, and levofloxacin. For the Latin American region, the ESBL-phenotype rate was 37.6% for Escherichia coli and 53.3% for Klebsiella pneumoniae. Ceftaroline was not active against ESBL-phenotype strains but was active against >90.0% of the non-ESBL-phenotype. The spectrum of activity of ceftaroline against pathogens from Latin America indicates that it merits further study for its potential use in the Latin American region.
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Humanos , Antibacterianos/farmacología , Cefalosporinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , América Latina , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Vigilancia en Salud PúblicaRESUMEN
UNLABELLED: There are currently no U.S. Food and Drug Administration (FDA)-approved vaccines or therapeutics to prevent or treat Argentine hemorrhagic fever (AHF). The causative agent of AHF is Junin virus (JUNV); a New World arenavirus classified as a National Institute of Allergy and Infectious Disease/Centers for Disease Control and Prevention category A priority pathogen. The PTAP late (L) domain motif within JUNV Z protein facilitates virion egress and transmission by recruiting host Tsg101 and other ESCRT complex proteins to promote scission of the virus particle from the plasma membrane. Here, we describe a novel compound (compound 0013) that blocks the JUNV Z-Tsg101 interaction and inhibits budding of virus-like particles (VLPs) driven by ectopic expression of the Z protein and live-attenuated JUNV Candid-1 strain in cell culture. Since inhibition of the PTAP-Tsg101 interaction inhibits JUNV egress, compound 0013 serves as a prototype therapeutic that could reduce virus dissemination and disease progression in infected individuals. Moreover, since PTAP l-domain-mediated Tsg101 recruitment is utilized by other RNA virus pathogens (e.g., Ebola virus and HIV-1), PTAP inhibitors such as compound 0013 have the potential to function as potent broad-spectrum, host-oriented antiviral drugs. IMPORTANCE: There are currently no FDA-approved vaccines or therapeutics to prevent or treat Argentine hemorrhagic fever (AHF). The causative agent of AHF is Junin virus (JUNV); a New World arenavirus classified as an NIAID/CDC category A priority pathogen. Here, we describe a prototype therapeutic that blocks budding of JUNV and has the potential to function as a broad-spectrum antiviral drug.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Interacciones Huésped-Patógeno , Virus Junin/inmunología , Virus Junin/fisiología , Factores de Transcripción/metabolismo , Proteínas Virales/metabolismo , Liberación del Virus , Animales , Línea Celular , Humanos , Unión ProteicaRESUMEN
A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active against Staphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at ≤ 1 mg/L and all isolates at ≤ 2 mg/L (MIC5090, 0.25/2mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC50/90 values were at ≤ 0.015/≤ 0.015 mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. Susceptibility to ceftriaxone was at 88.4% (CLSI non-meningitis interpretive criteria) and 73.9% (CLSI meningitis interpretive criteria) for all S. pneumoniae. Ceftriaxone susceptibility was only at 33.3% (CLSI non-meningitis interpretive criteria) and 0.0% (CLSI meningitis interpretive criteria) for penicillin-intermediate (penicillin MIC, 4 mg/L) strains. All Haemophilus influenzae (29.4% ß-lactamase-positive) isolates were susceptible to ceftaroline, amoxicillin-clavulanate, ceftriaxone, and levofloxacin. For the Latin American region, the ESBL-phenotype rate was 37.6% for Escherichia coli and 53.3% for Klebsiella pneumoniae. Ceftaroline was not active against ESBL-phenotype strains but was active against >90.0% of the non-ESBL-phenotype. The spectrum of activity of ceftaroline against pathogens from Latin America indicates that it merits further study for its potential use in the Latin American region.
Asunto(s)
Antibacterianos/farmacología , Cefalosporinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , América Latina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Vigilancia en Salud Pública , CeftarolinaRESUMEN
OBJECTIVE: To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. RESULTS: Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85. CONCLUSIONS: Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Hipoxia-Isquemia Encefálica/cirugía , Preescolar , Terapia Combinada , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/etiología , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/mortalidad , Hipoxia-Isquemia Encefálica/terapia , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/mortalidad , Enfermedades del Prematuro/cirugía , Enfermedades del Prematuro/terapia , Masculino , Proyectos Piloto , Índice de Severidad de la Enfermedad , Trasplante Autólogo/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: To establish a resistance (R) surveillance program monitoring antimicrobial susceptibility patterns in Latin America (LATAM; Argentina [ARG], Brazil [BRA], Chile, Colombia [CBA], Costa Rica, Ecuador [ECU], Guatemala [GUA], Mexico [MEX], Panama [PAN], Peru, and Venezuela [VEN]). METHODS: In 2011, 4979 organisms were collected from 11 nations (20 laboratories) for susceptibility testing in a central laboratory design. Antimicrobials were tested by CLSI methods and results interpreted by CLSI and EUCAST breakpoints. Most common Gram-positive (Staphylococcus aureus [SA, 921], other staphylococci [CoNS; 299], enterococci [218], Streptococcus pneumoniae [SPN; 182], β-haemolytic streptococci [115]) and Gram-negative (E. coli [EC; 644], Klebsiella spp. [KSP; 517], Enterobacters [272], Pseudomonas aeruginosa [PSA; 586], Acinetobacters [ACB; 494]) pathogens were analyzed against linezolid (LZD), vancomycin (VAN), tigecycline (TIG), colistin (COL), cefoperazone/sulbactam (C/S), and amikacin (AMK). RESULTS: MRSA rates varied from 29% (CBA, BRA) to 79% (Peru); but LZD (MIC90, 2 mg/L), TIG (MIC90, 0.12mg/L) and VAN (MIC90, 1mg/L) covered all strains. Enterococci showed a 14% VRE rate, highest in BRA and MEX; all inhibited by TIG and daptomycin, but not LZD (three non-susceptible with G2576T mutations or cfr). Penicillin-R among SPN and viridans streptococci was 51.6 and 41.1%, respectively. LZD overall R against Gram-positives was 0.3%. High ESBL rates were observed in EC (54-71%) and KSP (>50%) from GUA, MEX and Peru, and six nations, respectively. Carbapenem-R in KSP was 9%, highest rates associated with KPC in BRA, CBA, ECU, PAN and VEN; also a NDM-1 in KSP from CBA. AMK, TIG, C/S and carbapenems were the broadest-spectrum agents tested against Enterobacteriaceae. Only COL inhibited >90% of PSA; COL and TIG (<2 mg/L) covered >85% of ACB. CONCLUSIONS: LATAM nations demonstrated variable levels of antimicrobial R especially among Enterobacteriaceae (β-lactamase-mediated), PSA and ACB. MRSA (48%), VRE (14%) and multidrug-R SPN were also regional therapeutic challenges.
Asunto(s)
Humanos , Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Vigilancia de la Población , Bacterias Gramnegativas/clasificación , Bacterias Grampositivas/clasificación , América Latina , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVE: To establish a resistance (R) surveillance program monitoring antimicrobial susceptibility patterns in Latin America (LATAM; Argentina [ARG], Brazil [BRA], Chile, Colombia [CBA], Costa Rica, Ecuador [ECU], Guatemala [GUA], Mexico [MEX], Panama [PAN], Peru, and Venezuela [VEN]). METHODS: In 2011, 4979 organisms were collected from 11 nations (20 laboratories) for susceptibility testing in a central laboratory design. Antimicrobials were tested by CLSI methods and results interpreted by CLSI and EUCAST breakpoints. Most common Gram-positive (Staphylococcus aureus [SA, 921], other staphylococci [CoNS; 299], enterococci [218], Streptococcus pneumoniae [SPN; 182], ß-haemolytic streptococci [115]) and Gram-negative (E. coli [EC; 644], Klebsiella spp. [KSP; 517], Enterobacters [272], Pseudomonas aeruginosa [PSA; 586], Acinetobacters [ACB; 494]) pathogens were analyzed against linezolid (LZD), vancomycin (VAN), tigecycline (TIG), colistin (COL), cefoperazone/sulbactam (C/S), and amikacin (AMK). RESULTS: MRSA rates varied from 29% (CBA, BRA) to 79% (Peru); but LZD (MIC90, 2mg/L), TIG (MIC90, 0.12mg/L) and VAN (MIC90, 1mg/L) covered all strains. Enterococci showed a 14% VRE rate, highest in BRA and MEX; all inhibited by TIG and daptomycin, but not LZD (three non-susceptible with G2576T mutations or cfr). Penicillin-R among SPN and viridans streptococci was 51.6 and 41.1%, respectively. LZD overall R against Gram-positives was 0.3%. High ESBL rates were observed in EC (54-71%) and KSP (≥50%) from GUA, MEX and Peru, and six nations, respectively. Carbapenem-R in KSP was 9%, highest rates associated with KPC in BRA, CBA, ECU, PAN and VEN; also a NDM-1 in KSP from CBA. AMK, TIG, C/S and carbapenems were the broadest-spectrum agents tested against Enterobacteriaceae. Only COL inhibited >90% of PSA; COL and TIG (≤2mg/L) covered ≥85% of ACB. CONCLUSIONS: LATAM nations demonstrated variable levels of antimicrobial R especially among Enterobacteriaceae (ß-lactamase-mediated), PSA and ACB. MRSA (48%), VRE (14%) and multidrug-R SPN were also regional therapeutic challenges.