Impact of High-Flow Nasal Cannula Use in Subjects With COVID-19 ARDS at High Altitudes: Clinical Presentation and Prognostic Factors.

BACKGROUND: High-flow nasal cannula (HFNC) reduces the need for intubation in adult subject with acute respiratory failure. Changes in hypobaric hypoxemia have not been studied for subject with an HFNC in ICUs at altitudes > 2,600 m above sea level. In this study, we investigated the efficacy of HFNC treatment in subjects with COVID-19 at high altitudes. We hypothesized that progressive hypoxemia and the increase in breathing frequency associated with COVID-19 in high altitudes affect the success of HFNC therapy and may also influence the performance of the traditionally used predictors of success and failure. METHODS: This was a prospective cohort study of subjects >18 y with a confirmed diagnosis of COVID-19-induced ARDS requiring HFNC who were admitted to the ICU. Subjects were followed up during the 28 d of HFNC treatment or until failure. RESULTS: One hundred and eight subjects were enrolled. At admission to the ICU, FIO2 delivery between 0.5-0.8 (odds ratio 0.38 [95% CI 0.17-0.84]) was associated with a better response to HFNC therapy than oxygen delivery on admission between 0.8-1.0 (odds ratio 3.58 [95% CI 1.56-8.22]). This relationship continued during follow-ups at 2, 6, 12, and 24 h, with a progressive increase in the risk of failure (odds ratio 24 h 13.99 [95% CI 4.32-45.26]). A new cutoff for the ratio of oxygen saturation (ROX) index (ROX ≥ 4.88) after 24 h of HFNC administration was demonstrated to be the best predictor of success (odds ratio 11.0 [95% CI 3.3-47.0]). CONCLUSIONS: High-altitude subjects treated with HFNC for COVID-19 showed a high risk of respiratory failure and progressive hypoxemia when FIO2 requirements were > 0.8 after 24 h of treatment. In these subjects, personalized management should include continuous monitoring of individual clinical conditions (such as oxygenation indices, with cutoffs adapted to those corresponding to high-altitude cities).

Hallazgos histopatológicos pulmonares en COVID-19. Experiencia de autopsias mínimamente invasivas / Pulmonary histopathological findings in Covid-19 patients: based on minimally invasive autopsies

Introducción: la COVID-19 es causada por el virus SARS-CoV-2. La presentación clínica varía desde pacientes asintomáticos hasta manifestaciones severas. Durante la pandemia se han realizado autopsias que han permitido reconocer los cambios en diferentes órganos, siendo el pulmón el más afectado. El objetivo del presente estudio es informar nuestra experiencia en cuanto a los hallazgos histopatológicos pulmonares, mediante el sistema de autopsia mínimamente invasiva. Metodología: se tomaron muestras a 8 pacientes fallecidos por COVID-19 en la unidad de cuidado intensivo (UCI) confirmado por PCR en el Hospital de San José, Bogotá, Colombia, en la primera hora después de la muerte. Los tejidos fueron analizados por dos patólogos en forma independiente. Resultados: se observó en todos daño alveolar difuso (DAD) en fases exudativa, proliferativa o ambas, además de bronconeumonía y neumonitis intersticial. Discusión: el pulmón es el principal órgano afectado por el SARS-CoV-2 y el hallazgo histopatológico más frecuente es el DAD en fases exudativa y mixta. También se han descrito alteraciones en diferentes sistemas. Conclusiones: el hallazgo histopatológico pulmonar más frecuente es el DAD en diferentes estadios. Se considera que la autopsia mínimamente invasiva es de gran utilidad en escenarios donde la convencional se encuentra limitada, pues no presenta grandes restricciones y permite obtener tejidos viables.

Introduction: COVID-19 is caused by the SARS-CoV-2 virus. Its clinical presentation varies from asymptomatic patients to severe manifestations. During the pandemic, autopsies have allowed the recognition of changes in different organs, with the lung being the main affected organ. The aim of this study is reporting our experience derived from pulmonary histopathological findings, based on the minimally invasive autopsy method. Methodology: samples were taken in the immediate postmortem (one hour) period from 8 patients who died with PCR-confirmed COVID-19, in the intensive care unit (ICU) of Hospital de San José, Bogotá, Colombia. Tissue specimens were analyzed independently by two pathologists. Results: all specimens exhibited, diffuse alveolar damage (DAD) in exudative or proliferative phases, or both, in addition to bronchopneumonia and interstitial pneumonitis. Discussion: the lung is the main organ affected by SARS-CoV-2 and the most frequent histopathologic finding is exudative phase or various phases DAD. Alterations in different systems have also been described. Conclusions: the most frequent histopathological finding is DAD in any of its phases. Minimally invasive autopsy is considered a very useful alternative when conventional autopsy cannot be performed, since it does not have major restrictions and allows collecting viable samples.

Oral immunotherapy tolerizes mice to enzyme replacement therapy for Morquio A syndrome.

Immune response to therapeutic enzymes poses a detriment to patient safety and treatment outcome. Enzyme replacement therapy (ERT) is a standard therapeutic option for some types of mucopolysaccharidoses, including Morquio A syndrome caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. Current protocols tolerize patients using cytotoxic immunosuppressives, which can cause adverse effects. Here we show development of tolerance in Morquio A mice via oral delivery of peptide or GALNS for 10 days prior to ERT. Our results show that using an immunodominant peptide (I10) or the complete GALNS enzyme to orally induce tolerance to GALNS prior to ERT resulted in several improvements to ERT in mice: (a) decreased splenocyte proliferation after in vitro GALNS stimulation, (b) modulation of the cytokine secretion profile, (c) decrease in GALNS-specific IgG or IgE in plasma, (d) decreased GAG storage in liver, and (e) fewer circulating immune complexes in plasma. This model could be extrapolated to other lysosomal storage disorders in which immune response hinders ERT.

Efecto de un plan educativo en la capacidad de agencia de autocuidado del paciente con hipertensión arterial en una institución de segundo nivel / Effect of an Educational Plan on the Self-care Management Capacity of Hypertensive Patients at a Second-tier Institution / Efeito de um programa educativo na capacidade de agência de autocuidado do paciente com hipertensão arterial em uma instituição segundo nível

Objetivo: el propósito de este estudio fue determinar el efecto de un plan educativo en la capacidad de agencia de autocuidado del paciente hipertenso en una institución de segundo nivel. Materiales y métodos: se realizó un estudio de intervención pre y postest, con la participación de 83 pacientes con diagnóstico de hipertensión arterial, a quienes se les aplicó el instrumento "Evaluación de la capacidad de agencia de autocuidado en el paciente hipertenso" al inicio del estudio y tres meses posteriores a la implementación del plan educativo. Resultados: el plan educativo mejoró tanto la capacidad de agencia de autocuidado global como sus rangos, encontrando significancia estadística con un valor de probabilidad menor de 0,002 y de 0,0001 respectivamente. Conclusiones: las intervenciones educativas estructuradas a partir de la identificación de las necesidades individuales de información, en conjunto con el empoderamiento del individuo y el seguimiento por parte del profesional de enfermería, permiten alcanzar conductas permanentes de autocuidado que facilitan el autoconocimiento, la modificación del comportamiento así como la adquisición de conocimientos y habilidades.

Objective: The purpose of this study was to determine the effect of an educational plan on the capacity of hypertensive patients at a second-tier institution to manage self-care. Materials and methods: A pre -and post-intervention test was conducted with the participation of 83 patients who had been diagnosed with hypertension. An instrument entitled "Assessment of Self-care Management Capacity among Hypertensive Patients" was applied to this group at the beginning of the study and three months after implementation of the educational plan. Results: The educational plan improved self-care management capacity overall and in the different ranges, showing a statistical significance with a probability value under 0.002 and 0.0001, respectively. Conclusions: Structured educational interventions based on identified individual needs, coupled with individual empowerment and monitoring done by nursing professionals, made it possible to achieve permanent behavior with respect to self-care, facilitating self-knowledge and changes in behavior patterns, in addition to the acquisition of skills and know-how.

Objetivo: o propósito deste artigo foi determinar o efeito de um programa educativo na capacidade de agência de autocuidado do paciente hipertenso em uma instituição de segundo nível. Materiais e métodos: realizou-se um estudo de intervenção pré e pós-teste, com a participação de 83 pacientes com diagnóstico de hipertensão arterial, aos quais se aplicou o instrumento "Avaliação da capacidade de agência de autocuidado no paciente hipertenso" ao início do estudo e três meses posteriores à implementação do programa educativo. Resultados: o programa educativo melhorou tanto a capacidade de agência de autocuidado global quanto suas faixas, constatando significância estatística com um valor de probabilidade menor de 0,002 e de 0,0001, respectivamente. Conclusões: as intervenções educativas estruturadas a partir da identificação das necessidades individuais de informação, em conjunto com o empoderamento do indivíduo e o seguimento por parte do profissional de enfermagem, permitem atingir condutas permanentes de autocuidado que facilitam o autoconhe-cimento, a modificação do comportamento, bem como a aquisição de conhecimentos e habilidades.

Identificación auxotípica de cepas de Pseudomonas aeruginosa aisladas de pacientes con fibrosis quística o VIH/SIDA / Auxotypic identification of Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis or HIV/AIDS

Objetivo: Identificar la presencia del fenotipo auxotrofo en cepas de P. aeruginosa aisladas de pacientes con fibrosis quística o con VIH/SIDA. Métodos: Se realizó un estudio observacional descriptivo longitudinal utilizando la metodolog¡a de Barth y Pitt. En la determinación de la auxotrofía se realizó la siembra de la dilución 1:100 de cada cepa en un medio nutricionalmente completo agar Pseudomonas P (King A) y en un medio incompleto Agar Medio Mínimo y para la determinación del requerimiento específico en las auxotrofas se utilizaron 22 soluciones madre de aminoácidos en su forma L. Resultados: Se identificaron 20 cepas auxotrofas, once procedentes de pacientes VIH/SIDA y nueve de pacientes con fibrosis quística. Todos los aislamientos nutricionalmente dependientes proced¡an de muestras de esputo. El aminoácido simple de mayor requerimiento fue la metionina (7 de 20 aislamientos auxotrofos) seguido de arginina, lisina y glutamina. Conclusiones: Estos resultados sugieren que la P. aeruginosa auxotrofa coloniza a los pacientes VIH/SIDA durante el curso de la infección pulmonar al igual que en los pacientes con fibrosis quística. Confirmamos la auxotrofía como un fenotipo exclusivo de infecciones respiratorias.

Objective: To identify the presence of auxotrophic phenotype in strains of P. aeruginosa isolated from patients with cystic fibrosis or HIV/AIDS. Methods: We conducted a longitudinal descriptive study using the methodology of Barth and Pitt. For determination of auxotrophy, a seeding of a 1:100 dilution of each strain was made on nutritionally complete medium P Pseudomonas agar (King A) and in the incomplete medium minimal medium agar. For determining the specific requirement of auxotrophs, 22 amino acids solutions in their L-form were used. Results: We identified 20 auxotrophic strains, eleven from HIV/AIDS patients and nine frompatients with cystic fibrosis. All isolates that were nutritionally dependent came from sputum samples. The amino acid with the highest requirement was methionine (7 of 20 auxotrophs isolates) followed by arginine, lysine and glutamine. Conclusions: These results suggest that auxotrophic P. aeruginosa colonizes HIV/AIDS patients during the course of pulmonary infection, as in patients with cystic fibrosis. Auxotrophy was confirmed as a unique phenotype of respiratory infections.

Self-care agency capacity in Patients with diagnostic of high blood pressure in a second level institution / Capacidad de agencia de autocuidadoen el paciente con hipertensión arterial en una institución de segundo nivel / Capacidade de agencia de autocuidado no paciente com hipertensão arterial em uma instituição de segundo nível

El objetivo de este estudio fue determinar la capacidad de agencia de autocuidado en245 pacientes hipertensos que asistieron a una institución de segundo nivel de atenciónen el 2010, mediante el desarrollo de un estudio descriptivo de tipo transversalcon la aplicación del instrumento Evaluación de la capacidad de agencia de autocuidadoen el paciente hipertenso. Se encontró que el 81,22 % (n = 199) y el 8,16 % (n = 20)de los pacientes presentaron una capacidad de agencia de autocuidado media y bajarespectivamente, y tan solo el 10,61 % (n = 26) de los pacientes presentó una capacidadde agencia de autocuidado alta. Ello indicaría que aunque el paciente con hipertensiónarterial posee algunas habilidades que le permiten discernir acerca de los factores quedebe controlar para promover su salud y su cuidado, son insuficientes para lograr unaadecuada adherencia al tratamiento, ya que para alcanzar un compromiso y participaciónen este, es necesario que existan conductas permanentes de autocuidado quefaciliten el autoconocimiento, el empoderamiento del individuo y el desarrollo de lacapacidad de tomar decisiones sobre su salud. La percepción del paciente de su estadode salud es fundamental para el desarrollo de las capacidades de autocuidado; por esoes fundamental que el profesional de enfermería intervenga de acuerdo con las capacidadesdel individuo, para autocuidarse promoviendo apoyo educativo que le permita alpaciente modificar su comportamiento, adquirir conocimiento y habilidad...

The objective of this study was to determine the self-care ability on 245 hypertensivepatients who attended to a secondary level institution in 2010. This was done by developinga descriptive cross-sectional study with the application of the “Assessmentself-care ability instrument in hypertensive patients” (Evaluación de la capacidad deagencia de autocuidado en el paciente hipertenso). We found that 81.22% (n = 199) and8.16% (n = 20) of the patients presented a medium and low Self-care ability respectively,and only the 10.61% (n = 26) of the patients presented a high self-care ability.This would indicate that, although the patient with hypertension has some abilitiesthat let him/her discern about the factors that he/she should control to promote hishealth and health care, they are insufficient to achieve an adequate adherence to thetreatment. In order to have their commitment and participation, it is necessary to havepermanent self care behaviors to facilitate the self-awareness, the empowerment of theindividual and the development of the capacity to make decisions about their health.The patient's perception of his health is critical to the development of the self careabilities, so it is essential that the nurse intervene in accordance with the individual'scapacities to self-care, by promoting educational support to allow the patient to modifyhis behavior, acquiring knowledge and skill...

O objetivo deste estudo foi determinar a capacidade de agencia de autocuidado em245 pacientes hipertensos que compareceram a uma instituição de segundo nível deatenção em 2010, mediante o desenvolvimento de um estudo descritivo de tipo transversalcom a aplicação do instrumento Avaliação da capacidade de agencia de autocuidadono paciente hipertenso. Encontrou-se que 81,22 % (n = 199) e 8,16 % (n = 20)dos pacientes apresentaram uma capacidade de agencia de autocuidado média e baixarespectivamente, e somente 10,61 % (n = 26) dos pacientes apresentou uma capacidadede agencia de autocuidado alta. Isso indicaria que, o paciente com hipertensãoarterial possui algumas habilidades que lhe permitem discernir sobre os fatores quedeve controlar para promover sua saúde e seu cuidado, são insuficientes para conseguiruma adequada aderência ao tratamento, já que para alcançar um compromisso eparticipação neste, é preciso que existam condutas permanentes de autocuidado quefacilitem o autoconhecimento, o empoderamento do indivíduo e o desenvolvimento dacapacidade de tomar decisões sobre sua saúde. A percepção do paciente de seu estadode saúde é fundamental para o desenvolvimento das capacidades de autocuidado; porisso é fundamental que o profissional de enfermagem intervenha de acordo com as capacidadesdo indivíduo, para autocuidar-se promovendo apoio educativo que permitaao paciente modificar seu comportamento, adquirir conhecimento e habilidade...

Long circulating enzyme replacement therapy rescues bone pathology in mucopolysaccharidosis VII murine model.

Mucopolysaccharidosis (MPS) type VII is a lysosomal storage disease caused by deficiency of the lysosomal enzyme ß-glucuronidase (GUS), leading to accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) effectively clears GAG storage in the viscera. Recent studies showed that a chemically modified form of GUS (PerT-GUS), which escaped clearance by mannose 6-phosphate and mannose receptors and showed prolonged circulation, reduced CNS storage more effectively than native GUS. Clearance of storage in bone has been limited due to the avascularity of the growth plate. To evaluate the effectiveness of long-circulating PerT-GUS in reducing the skeletal pathology, we treated MPS VII mice for 12 weeks beginning at 5 weeks of age with PerT-GUS or native GUS and used micro-CT, radiographs, and quantitative histopathological analysis for assessment of bones. Micro-CT findings showed PerT-GUS treated mice had a significantly lower BMD. Histopathological analysis also showed reduced storage material and a more organized growth plate in PerT-GUS treated mice compared with native GUS treated mice. Long term treatment with PerT-GUS from birth up to 57 weeks also significantly improved bone lesions demonstrated by micro-CT, radiographs and quantitative histopathological assay. In conclusion, long-circulating PerT-GUS provides a significant impact to rescue of bone lesions and CNS involvement.

Anti-inflammatory properties from isolated compounds of Cyclolepis genistoides.

CONTEXT: Cyclolepis genistoides D. Don (Asteraceae) is an Argentinean endemic shrub, known by the vernacular name "palo azul" or "matorro negro". It is widely used in folk medicine as a diuretic, an antirheumatic, and an antispasmodic agent. OBJECTIVE: The aim of this work was to describe the activity of two isolated compounds of C. genistoides, oleanolic acid (1) and deacylcynaropicrin (2), using the carrageenan-induced paw edema method in mice. MATERIALS AND METHODS: Aerial parts of C. genistoides were dried, powdered, and extracted with petroleum ether, ethyl acetate, dichloromethane, and methanol for 48 h. The fractions obtained from the ethyl acetate extract yielded oleanolic acid, while deacylcynaropicrin was obtained according to Abdei-Mogib et al. Structures were elucidated by ¹H-NMR and ¹³C-NMR. The products were administered intraperitoneally at doses of 40, 75, and 100 mg/kg. RESULTS AND DISCUSSION: Compound 1 exhibited significant activity during the first 7 h of the inflammatory phase (at 1, 3, 5, and 7 h), exercising its inhibitory action on inflammation mediated by histamine, prostaglandins, serotonin, and kinins, while compound 2 showed a significant inhibition at 3 and 5 h contributing to this effect, acting in the intermediate phase. CONCLUSIONS: According to the results of this work, the intraperitoneal administration of oleanolic acid and deacylcynaropicrin isolated from the aerial parts of C. genistoides produced a significant inhibition of carrageenan-induced inflammation at doses of 75 and 100 mg/kg. These results give support to the use of this plant as an anti-inflammatory in traditional medicine.

Development of a sandwich enzyme linked immunosorbent assay (ELISA) for the quantification of iduronate-2-sulfate sulfatase.

Iduronate-2-sulfate sulfatase (IDS; EC 3.1.6.13) is an enzyme that belongs to human sulfatases. IDS deficiency causes the Hunter syndrome or mucopolysaccharidosis type II (MPS II; OMIM 309900). We have been developing an expression system for human recombinant IDS (hrIDS) in Pichia pastoris, therefore a method was required for its detection during production and purification processes, which could be used also to measure the enzyme in human fluids. In this study, an immunoquantification assay for human and recombinant IDS was developed with the combination of two antibodies. Rabbit IgG and chicken IgY were used as IDS capture and detection antibodies, respectively. Chicken IgY antibodies were developed against specific amino acid sequences present in IDS but absent in other human sulfatases. hrIDS produced in P. pastoris, commercial hrIDS, and normal human plasma samples were used as antigens and immunoquantification results were compared to enzyme activity. The technique was linear over the range 8 to 500 ng mL(-1) using commercial hrIDS. The concentration range detected for IDS in normal human plasma was 14.43 to 287.88 ng mL(-1). The hrIDS was detected in P. pastoris cultures even when the enzyme was inactive, which is convenient for monitoring the production of recombinant proteins. These results show that chicken site-specific antibodies provide a good alternative, as a substitute of monoclonal antibodies, for the detection of human proteins. This is the first report on the development of an ELISA system to detect and quantify IDS with IgY antibodies.

[Computational prediction of the tertiary structure of the human iduronate 2-sulfate sulfatase]. / Predicción computacional de la estructura terciaria de la iduronato 2-sulfato sulfatasa humana.

INTRODUCTION: Hunter syndrome (MC KUSIK 309900) or mucopolysacharidosis type II is due to the deficiency of the enzyme iduronate 2 sulfate sulfatase (E.C. 3.1.6.13). This enzyme has not been crystallized, and therefore the experimental structures are not available. OBJECTIVES: A computational three-dimensional model was proposed for the iduronate 2 sulfate sulfatase enzyme. MATERIALS AND METHODS: A computational analysis of this enzyme used the following free internet software programs: Comput pI/MW, JaMBW Chapter 3.1.7, SWISS-MODEL, Geno3d, ProSup. Energy minimization was done with Discover 3 and Insight II version 2004. RESULTS: A three-dimensional conformational model was proposed. The model showed 33.3% of helix structure, 7.2% beta sheet, and 59.5% random coil. RMS values (Root Mean Square) (0.78 and 0.86A) were found when compared with other enzymes of the same family. The model presented 5 exposed N-glycosylation potential sites and an entry to the pocket that contains the amino acids of the active site. A high correlation was found between the type of mutations and the severity of the phenotype in twenty patients analyzed. CONCLUSION: The RMS values, as well as the high correlation between the type of mutation and the phenotype, indicated that the model predicts some aspects of the enzymes biological behavior.

[Production of polyclonal antibodies to protein iduronate-2-sulphate sulphatase (IDS) and development of a detection system for human recombinant IDS]. / Producción de anticuerpos policlonales IgG contra la proteina iduronato-2-sulfato sulfatasa y desarrollo de un sistema de detección para IDS humana recombinante.

INTRODUCTION: Hunter syndrome is a lysosomal disorder characterized by iduronate 2-sulphate sulphatase (IDS) genetic deficiency. Although MPS type II (Hunter) has no cure, enzyme replacement therapy (ERT) and gene therapy are potential new approaches to treatment. OBJECTIVE: The Institute for the Study of Innate Errors of Metabolism is currently developing a sulphatase expression system through human recombinant IDS (hrIDS) in Pichia pastoris and Escherichia coli. MATERIAL AND METHODS: A monitoring method for IDS was developed by production of polyclonal antibodies from rabbit against human IDS. Two New Zealand white rabbits were immunized with commercial IDS. These antibodies were used in a dot-blot method for detection and partial quantification of human recombinant IDS. P. pastoris and E. coli fermentation crude extracts were processed to determine IDS presence. RESULTS: The antibodies were demonstrably IDS specific, without cross reaction with crude extract contaminant proteins. CONCLUSION: Therefore, these antibodies can be used to establish an ELISA sandwich system as a method for detecting and quantifying a protein of interest. The antibodies can also be employed in an affinity chromatography step during the IDS purification process.

Producción de anticuerpos policlonales IgG contra la proteína iduronato-2-sulfato sulfatasa y desarrollo de un sistema de detección para IDS humana recombinante / Production of polyclonal antibodies to protein iduronate-2-sulphate sulphatase (IDS) and development of a detection system for human recombinant IDS

Introducción. La enfermedad de Hunter es un trastorno lisosómico caracterizado por la deficiencia de la enzima iduronato-2-sulfato sulfatasa (IDS) (EC 3.1.6.13). Esta enfermedad, al igual que muchos trastornos metabólicos, son patologías intratables mediante la terapéutica convencional; sin embargo, existe la posibilidad de ser tratada alternativamente mediante terapia génica o terapia de reemplazo enzimático. Objetivo. El Instituto de Errores Innatos del Metabolismo (IEIM) ha desarrollado un sistema de expresión de sulfatasas para producir IDS humana recombinante (IDShr) en Escherichia coli y Pichia pastoris,con resultados favorables. El objetivo principal de este trabajo fue desarrollar un sistema de detección de IDS humana recombinante. Materiales y métodos. Para el efecto, se inmunizaron con IDS comercial de TKT (Cambridge, MA) dos conejos de raza Nueva Zelanda blanca y los anticuerpos purificados a partir del suero se utilizaron en el desarrollo de una técnica semicuantitativa por dot-blot. Diferentes muestras de extractos crudos de fermentaciones con P. pastoris y E. coli se procesaron con el fin de poder determinar la presencia de la enzima. Resultados. Se demostró que los anticuerpos eran específicos en el reconocimiento de la IDS sin presentar reactividad cruzada con proteínas contaminantes de los extractos crudos. Conclusión. Por consiguiente, los anticuerpos se podrán usar en el desarrollo de una técnica ELISA tipo sandwich como método de detección y cuantificación de la enzima y en procesos de purificación de la misma mediante cromatografía de afinidad