Use of High-Flow Cannula in Pediatric Patients With Respiratory Failure: A Prospective Cohort Study in Three High-Altitude Hospitals

BACKGROUND AND AIMS: Acute respiratory failure (ARF) is a common cause of morbimortality, and a frequent reason for admission to the pediatric intensive care unit (PICU). It requires a high-flow oxygen device as treatment. Our aim is to determine the frequency and main indications for the use of high-flow nasal cannula (HFNC), and the prevalence of HFNC failure and its main causes, in three hospitals. METHODS: It is a multicenter prospective cohort study, developed in three hospitals in Bogota. Eligible patients were children older than 1 month and younger than 18 years who presented ARF and required management with an HFNC. The study was carried out between April 2020 and December 2021. The follow-up was carried out at 1, 6, and 48 h after starting the management. RESULTS: Of 685 patients included in the study, 296 developed ARF. The prevalence of patients with ARF who required management with HFNC was 48%. The frequency of the pathologies that cause the ARF was: Bronchiolitis was the most frequent pathology (34.5%), followed by asthmatic crisis (15.5%) and pneumonia (12.7%). The average time of use of HFNC was 81.6 h. Regarding treatment failure with HFNC, 15 patients presented torpid evolution and required invasive mechanical ventilation, with a prevalence of therapeutic failure of the HFNC of 10.6%. CONCLUSION: The use of HFNC is more frequent in patients with bronchiolitis, in children under 2 years of age and in males, which is in line with what has been reported in the literature. In addition, the failure rate of HFNC is low (10.6%), and it may be useful in other pathologies besides bronchiolitis, such as asthma, pneumonia, among others. It opens the possibility to continue evaluating the role of HFNC in pediatric pathology in new studies

Use of High-Flow Cannula in Pediatric Patients with Respiratory Failure: A Prospective Cohort Study in Three High-Altitude Hospitals

BACKGROUND AND AIMS: Acute respiratory failure (ARF) is a common cause of morbimortality, and a frequent reason for admission to the pediatric intensive care unit (PICU). It requires a high-flow oxygen device as treatment. Our aim is to determine the frequency and main indications for the use of high-flow nasal cannula (HFNC), and the prevalence of HFNC failure and its main causes, in three hospitals. METHODS: It is a multicenter prospective cohort study, developed in three hospitals in Bogota. Eligible patients were children older than 1 month and younger than 18 years who presented ARF and required management with an HFNC. The study was carried out between April 2020 and December 2021. The follow-up was carried out at 1, 6, and 48 h after starting the management. RESULTS: Of 685 patients included in the study, 296 developed ARF. The prevalence of patients with ARF who required management with HFNC was 48%. The frequency of the pathologies that cause the ARF was: Bronchiolitis was the most frequent pathology (34.5%), followed by asthmatic crisis (15.5%) and pneumonia (12.7%). The average time of use of HFNC was 81.6 h. Regarding treatment failure with HFNC, 15 patients presented torpid evolution and required invasive mechanical ventilation, with a prevalence of therapeutic failure of the HFNC of 10.6%. CONCLUSION: The use of HFNC is more frequent in patients with bronchiolitis, in children under 2 years of age and in males, which is in line with what has been reported in the literature. In addition, the failure rate of HFNC is low (10.6%), and it may be useful in other pathologies besides bronchiolitis, such as asthma, pneumonia, among others. It opens the possibility to continue evaluating the role of HFNC in pediatric pathology in new studies

Burden of Respiratory Failure in Pediatric Patients: Analysis of a Prospective Multicenter Cohort in Bogotá, Colombia

BACKGROUND AND AIMS: The approach to the burden of disease is a demographic, economic, and a health problem, which requires the design and application of specific measures of cost of the disease, such as disability-adjusted life years (DALYs), to establish better public health policies in the pediatric population. The aim of this study is to approach the burden of disease in children with acute respiratory failure (ARF) through the calculation of DALYs. METHODS: This study was conducted in the framework of a prospective, multicenter cohort in Bogotá, Colombia. Inclusion criteria were all pediatric patients admitted to the emergency department, hospitalization, and intensive care unit with respiratory distress; eligible patients were all those who developed ARF between April 2020 and December 2021. They were followed-up during hospitalization, at 30 and 60 days after admission. The Infant/Toddler Quality of Life Questionnaire and KIDSCREEN quality of life scales were applied for follow-up according to the age group. The results were used to calculate DALYs. RESULTS: Six hundred and eighty-five eligible patients, 296 (43.08%) developed ARF, of these 22 (6.08%) patients died (mortality rate = 7.43%). The total DALYs was 277.164 years. For younger than 9 years, the DALYs were 302.64 years, while for older than 10 years were 40.49 years. CONCLUSION: ARF is one of the main causes of preventable mortality in pediatrics, its progression to respiratory failure is a highly prevalent condition in pediatric age, a condition that has a great impact on mortality, morbidity, and disability in our patients

Temas Socio-Jurídicos. Volumen 27 No. 57 Diciembre de 2009

Temas Socio-jurídicos en su edición número 57, prosigue con su tarea iniciada hace más de cinco lustros, de divulgar la producción académica de los investigadores y profesores de la Facultad de Derecho de la Universidad Autónoma de Bucaramanga.Socio-legal Issues in its 57th edition, continues with its task begun more than five decades ago, to disseminate the academic production of researchers and professors of the Faculty of Law of the Autonomous University of Bucaramanga

Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients

A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had <1% probability of having prodromal PD; 100 between 1 and 10%, 26 siblings between 10 and 80%, one fulfilled the criteria for prodromal PD. According to the current analysis, we cannot confirm the increased risk of PD siblings for prodromal PD. Siblings showed a heterogeneous distribution of prodromal PD markers and probability. Additional parameters, including strong disease markers, should be investigated to verify if these results depend on validity and sensitivity of prodromal PD criteria, or if siblings’ risk is not elevated

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery