Cystic Fibrosis
The modified shuttle test as a predictor of risk for hospitalization in youths with cystic fibrosis: A two-year follow-up study: Modified shuttle test as a predictor of hospitalization.
The modified shuttle test as a predictor of risk for hospitalization in youths with cystic fibrosis: A two-year follow-up study: Modified shuttle test as a predictor of hospitalization.
J Cyst Fibros. 2021 Jan 07;:
Authors: Donadio MVF, Vendrusculo FM, Campos NE, Becker NA, de Almeida IS, Queiroz KCV, Leite LR, Aquino ES
Abstract
BACKGROUND: Patients with cystic fibrosis (CF) present exercise intolerance and episodes of pulmonary exacerbations. This study aimed to evaluate the association of the distance covered on the modified shuttle test (MST), as well as other clinical variables (anthropometry, chronic colonization by Pseudomonas aeruginosa, lung function), with the risk of hospitalization for pulmonary exacerbation.
METHODS: Cohort study including CF patients older than 6 years, from two specialized CF centers. All patients underwent a MST and a lung function test at the time of inclusion. Demographic, anthropometric and clinical data were collected. Free time until the first hospitalization, total days of hospitalization and use of antibiotics during the two years of follow-up were recorded.
RESULTS: Sixty-seven patients with a mean (SD) age of 12.4 (5.2) years and forced expiratory volume in the first second (FEV1) of 78.7% (22.4) were included. The mean distance covered (m) in the MST was 775.6 (255.7) (73.4 ± 19.5% of predicted). The distance achieved (MST) was considered as the main independent variable to predict the risk of hospitalization (Cox HR 0.97, p = 0.029). Patients who walked a distance of less than 80% of predicted in the MST showed an increase of 3.9 (95%CI 1.0-15.3) in the relative risk for hospitalization and significantly higher total number of days of hospitalization (p = 0.022).
CONCLUSION: There is an association between the distance covered in the MST and the risk of hospitalization in youths with CF. Patients with reduced exercise capacity presented a 3.9 times increase in the relative risk for hospitalization due to pulmonary exacerbation.
PMID: 33422453 [PubMed - as supplied by publisher]
Tackling the COVID-19 "cytokine storm" with microRNA mimics directly targeting the 3'UTR of pro-inflammatory mRNAs.
Tackling the COVID-19 "cytokine storm" with microRNA mimics directly targeting the 3'UTR of pro-inflammatory mRNAs.
Med Hypotheses. 2020 Nov 25;:110415
Authors: Gasparello J, Finotti A, Gambari R
Abstract
COVID-19 is characterized by two major clinical phases, the SARS-CoV-2 infection of target cells and tissues, and a deep inflammatory state, known as "cytokine storm", caused by activation of pro-inflammatory genes, such as NF-kB, STAT-3, IL-6, IL-8, IL-1ß. Among possible anti-inflammatory agents, the "microRNA targeting" should be carefully considered, since it is well known that microRNAs are deeply involved in the expression of cytokines, chemokines and growth factors. The working general hypothesis is that targeting the microRNA network might be important for the development of therapeutic approaches to counteract the COVID-19 induction of inflammatory response. This hypothesis is based on several publications demonstrating the use of miRNA mimics for inhibitory effects on the production of proteins characterizing the COVID-19 "cytokine storm".
PMID: 33422363 [PubMed - as supplied by publisher]
Introducing the Adult Cystic Fibrosis Series: An Exciting Time of Change, But New Challenges Lie Ahead.
Introducing the Adult Cystic Fibrosis Series: An Exciting Time of Change, But New Challenges Lie Ahead.
Chest. 2021 Jan;159(1):3-4
Authors: Simmonds NJ
PMID: 33422202 [PubMed - as supplied by publisher]
Looking beyond pulmonary disease in COVID-19: A lesson from patients with cystic fibrosis.
Looking beyond pulmonary disease in COVID-19: A lesson from patients with cystic fibrosis.
Med Hypotheses. 2021 Jan 04;147:110481
Authors: Manti S, Parisi GF, Papale M, Mulè E, Aloisio D, Rotolo N, Leonardi S
Abstract
Coronavirus disease 2019 (COVID-19) caused more than 52.775.271 million confirmed cases, 1.293.106 deaths, globally, and afflicted 208 countries, areas, or territories; and almost three months have passed since the World Health Organisation (WHO) declared COVID-19 as a pandemic. Despite the dramatic and global impact of the Coronavirus, the knowledge about the SARS-CoV-2 infection has been improved remarkably. Herein, we provided the rationale for SARS-CoV-2 infection as endothelial dysfunction rather than respiratory disease. Accordingly, we strongly invited the researchers to look beyond pulmonary injury and shift their attention from respiratory disease to endothelial disorder. This strategy could be particularly relevant to identifying therapeutic weapons stabilizing the endothelium rather than the lungs.
PMID: 33421691 [PubMed - as supplied by publisher]
Implementation of microbiota analysis in clinical trials for cystic fibrosis lung infection: Experience from the OligoG phase 2b clinical trials.
Implementation of microbiota analysis in clinical trials for cystic fibrosis lung infection: Experience from the OligoG phase 2b clinical trials.
J Microbiol Methods. 2021 Jan 06;:106133
Authors: Weiser R, Rye PD, Mahenthiralingam E
Abstract
Culture-independent microbiota analysis is widely used in research and being increasingly used in translational studies. However, methods for standardisation and application of these analyses in clinical trials are limited. Here we report the microbiota analysis that accompanied two Phase 2b clinical trials of the novel, non-antibiotic therapy OligoG CF-5/20 for cystic fibrosis (CF) lung infection. Standardised protocols (DNA extraction, PCR, qPCR and 16S rRNA gene sequencing analysis) were developed for application to the Pseudomonas aeruginosa (NCT02157922) and Burkholderia cepacia complex (NCT02453789) clinical trials involving 45 and 13 adult trial participants, respectively. Microbiota analysis identified that paired sputum samples from an individual participant, taken within 2 h of each other, had reproducible bacterial diversity profiles. Although culture microbiology had identified patients as either colonised by P. aeruginosa or B. cepacia complex species at recruitment, microbiota analysis revealed patient lung infection communities were not always dominated by these key CF pathogens. Microbiota profiles were patient-specific and remained stable over the course of both clinical trials (6 sampling points over the course of 140 days). Within the Burkholderia trial, participants were infected with B. cenocepacia (n = 4), B. multivorans (n = 6), or an undetermined species (n = 3). Colonisation with either B. cenocepacia or B. multivorans influenced the overall bacterial community structure in sputum. Overall, we have shown that sputum microbiota in adults with CF is stable over a 2-h time-frame, suggesting collection of a single sample on a collection day is sufficient to capture the microbiota diversity. Despite the uniform pathogen culture-positivity status at recruitment, trial participants were highly heterogeneous in their lung microbiota. Understanding the microbiota profiles of individuals with CF ahead of future clinical trials would be beneficial in the context of patient stratification and trial design.
PMID: 33421446 [PubMed - as supplied by publisher]
Effect of Expiratory Muscle Training on Peak Cough Flow in Children and Adolescents with Cystic Fibrosis: A Randomized Controlled Trial.
Effect of Expiratory Muscle Training on Peak Cough Flow in Children and Adolescents with Cystic Fibrosis: A Randomized Controlled Trial.
Pediatr Pulmonol. 2021 Jan 09;:
Authors: Emirza C, Aslan GK, Kilinc AA, Cokugras H
Abstract
BACKGROUND: Cough is an important defense and airway clearance mechanism for removing thick and viscous secretions in cystic fibrosis (CF). The primary aim of this study was to investigate the effect of expiratory muscle training (EMT) on peak cough flow (PCF) and secondly on respiratory muscle functions, functional exercise capacity, and quality of life (QoL) in CF.
METHODS: Thirty patients were randomized as training and sham groups. Both groups were trained with the EMT protocol, which involved twice per day for at least five days per week for six weeks. The training intensity in the training group was 30% of the maximal expiratory pressure (MEP). In the sham group, it remained at the lowest pressure (5cmH2 O). The primary outcome was PCF. The secondary outcomes were MEP, maximal inspiratory pressure (MIP), spirometric measures, six-minute walking distance (6MWD), and QoL (Cystic Fibrosis Questionnaire-Revised).
RESULTS: Twenty-eight patients completed the study. Changes in PCF (p=0.041) and MEP (p=0.003) were higher in the training group than the sham group. Also, treatment burden (p=0.008), digestive symptoms (p=0.019), and vitality (p=0.042) in QoL were more improved in the training group. MIP (p=0.028) and 6MWD (p=0.035) changed significantly only in the training group. Spirometric measurements did not change (p>0.05).
CONCLUSIONS: The results of the study show that EMT could improve PCF, MEP, treatment burden, digestive symptoms, and vitality domains of QoL in patients with CF. Moreover, MIP and functional exercise capacity improved in the training group with EMT.
CLINICALTRIALS NUMBER: NCT03873688. This article is protected by copyright. All rights reserved.
PMID: 33421333 [PubMed - as supplied by publisher]
MicroRNA-1246 regulates proliferation, invasion, and differentiation in human vascular smooth muscle cells by targeting cystic fibrosis transmembrane conductance regulator (CFTR).
MicroRNA-1246 regulates proliferation, invasion, and differentiation in human vascular smooth muscle cells by targeting cystic fibrosis transmembrane conductance regulator (CFTR).
Pflugers Arch. 2021 Jan 08;:
Authors: Pan D, Liu G, Li B, Jiang J, Chen W, Li W, Zhang L, Hu Y, Xie S, Yang H
Abstract
MicroRNA (miRNA) plays a key role in the proliferation and invasion of vascular smooth muscle cells (VSMCs). However, the role and underlying mechanism of miRNAs in VSMCs are not fully understood. Therefore, this study was designed to investigate the role and mechanism of microRNA-1246 (miR-1246) in VSMCs. VSMCs were cultured, and the proliferation of VSMCs was stimulated by platelet-derived growth factor (PDGF-BB) or 15% fetal bovine serum (FBS). The quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression levels of miR-1246 and cystic fibrosis transmembrane conductance regulator (CFTR) in VSMCs. The CCK-8 assay and transwell assay were used to detect the proliferation and invasion of VSMCs. Target gene prediction and screening and luciferase reporter assays were used to verify downstream target genes of miR-1246. Western blotting was used to detect the protein expression levels of PCNA, α-SMA, SM-MHC, Collagen-1, and Cyclin D1 in VSMCs. PDGF-BB and FBS treatment induced VSMCs proliferation and the upregulation of miR-1246 expression. Overexpression of miR-1246 promoted VSMCs proliferation, invasion, and differentiation towards synthetic phenotype, while knockdown of miR-1246 had opposite effects. In addition, CFTR was found to be a direct target for miR-1246, and miR-1246 inhibited the expression of CFTR. Moreover, overexpression of CFTR inhibited VSMC proliferation and synthetic differentiation, while overexpression of miR-1246 partly abolished the effects of CFTR overexpression on VSMCs proliferation and differentiation. Our data suggest that MiR-1246 promotes VSMC proliferation, invasion, and differentiation to synthetic phenotype by regulating CFTR. MiR-1246 may be a potential therapeutic target for atherosclerosis.
PMID: 33420548 [PubMed - as supplied by publisher]
Childhood acute respiratory illnesses: will normal inadequate services be resumed?
Childhood acute respiratory illnesses: will normal inadequate services be resumed?
Arch Dis Child. 2021 Jan 08;:
Authors: Nagakumar P, Bush A, Gupta A
PMID: 33419729 [PubMed - as supplied by publisher]
Therapeutic Potential of Antimicrobial Peptides in Polymicrobial Biofilm-Associated Infections.
Therapeutic Potential of Antimicrobial Peptides in Polymicrobial Biofilm-Associated Infections.
Int J Mol Sci. 2021 Jan 06;22(2):
Authors: Batoni G, Maisetta G, Esin S
Abstract
It is widely recognized that many chronic infections of the human body have a polymicrobial etiology. These include diabetic foot ulcer infections, lung infections in cystic fibrosis patients, periodontitis, otitis, urinary tract infections and even a proportion of systemic infections. The treatment of mixed infections poses serious challenges in the clinic. First, polymicrobial communities of microorganisms often organize themselves as biofilms that are notoriously recalcitrant to antimicrobial therapy and clearance by the host immune system. Secondly, a plethora of interactions among community members may affect the expression of virulence factors and the susceptibility to antimicrobials of individual species in the community. Therefore, new strategies able to target multiple pathogens in mixed populations need to be urgently developed and evaluated. In this regard, antimicrobial or host defense peptides (AMPs) deserve particular attention as they are endowed with many favorable features that may serve to this end. The aim of the present review is to offer a comprehensive and updated overview of studies addressing the therapeutic potential of AMPs in mixed infections, highlighting the opportunities offered by this class of antimicrobials in the fight against polymicrobial infections, but also the limits that may arise in their use for this type of application.
PMID: 33418930 [PubMed - as supplied by publisher]
A dyadic approach to the delineation of diagnostic entities in clinical genomics.
A dyadic approach to the delineation of diagnostic entities in clinical genomics.
Am J Hum Genet. 2021 Jan 07;108(1):8-15
Authors: Biesecker LG, Adam MP, Alkuraya FS, Amemiya AR, Bamshad MJ, Beck AE, Bennett JT, Bird LM, Carey JC, Chung B, Clark RD, Cox TC, Curry C, Dinulos MBP, Dobyns WB, Giampietro PF, Girisha KM, Glass IA, Graham JM, Gripp KW, Haldeman-Englert CR, Hall BD, Innes AM, Kalish JM, Keppler-Noreuil KM, Kosaki K, Kozel BA, Mirzaa GM, Mulvihill JJ, Nowaczyk MJM, Pagon RA, Retterer K, Rope AF, Sanchez-Lara PA, Seaver LH, Shieh JT, Slavotinek AM, Sobering AK, Stevens CA, Stevenson DA, Tan TY, Tan WH, Tsai AC, Weaver DD, Williams MS, Zackai E, Zarate YA
Abstract
The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as "GENE-related phenotype descriptor" (e.g., "CFTR-related cystic fibrosis"). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.
PMID: 33417889 [PubMed - as supplied by publisher]
Ataluren and aminoglycosides stimulate read-through of nonsense codons by orthogonal mechanisms.
Ataluren and aminoglycosides stimulate read-through of nonsense codons by orthogonal mechanisms.
Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):
Authors: Ng MY, Li H, Ghelfi MD, Goldman YE, Cooperman BS
Abstract
During protein synthesis, nonsense mutations, resulting in premature stop codons (PSCs), produce truncated, inactive protein products. Such defective gene products give rise to many diseases, including cystic fibrosis, Duchenne muscular dystrophy (DMD), and some cancers. Small molecule nonsense suppressors, known as TRIDs (translational read-through-inducing drugs), stimulate stop codon read-through. The best characterized TRIDs are ataluren, which has been approved by the European Medicines Agency for the treatment of DMD, and G418, a structurally dissimilar aminoglycoside. Previously [1], we applied a highly purified in vitro eukaryotic translation system to demonstrate that both aminoglycosides like G418 and more hydrophobic molecules like ataluren stimulate read-through by direct interaction with the cell's protein synthesis machinery. Our results suggested that they might do so by different mechanisms. Here, we pursue this suggestion through a more-detailed investigation of ataluren and G418 effects on read-through. We find that ataluren stimulation of read-through derives exclusively from its ability to inhibit release factor activity. In contrast, G418 increases functional near-cognate tRNA mispairing with a PSC, resulting from binding to its tight site on the ribosome, with little if any effect on release factor activity. The low toxicity of ataluren suggests that development of new TRIDs exclusively directed toward inhibiting termination should be a priority in combatting PSC diseases. Our results also provide rate measurements of some of the elementary steps during the eukaryotic translation elongation cycle, allowing us to determine how these rates are modified when cognate tRNA is replaced by near-cognate tRNA ± TRIDs.
PMID: 33414181 [PubMed - in process]
Significant functional differences in differentiated Conditionally Reprogrammed (CRC)- and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells.
Significant functional differences in differentiated Conditionally Reprogrammed (CRC)- and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells.
J Cyst Fibros. 2021 Jan 04;:
Authors: Awatade NT, Wong SL, Capraro A, Pandzic E, Slapetova I, Zhong L, Turgutoglu N, Fawcett LK, Whan RM, Jaffe A, Waters SA
Abstract
BACKGROUND: Patient-derived airway cells differentiated at Air Liquid Interface (ALI) are valuable models for Cystic fibrosis (CF) precision therapy. Different culture expansion methods have been established to extend expansion capacity of airway basal cells, while retaining functional airway epithelium physiology. Considerable variation in response to CFTR modulators is observed in cultures even within the same CFTR genotype and despite the use of similar ALI culture techniques. We aimed to address culture expansion method impact on differentiation.
METHODS: Nasal epithelial brushings from 14 individuals (CF=9; non-CF=5) were collected, then equally divided and expanded under conditional reprogramming culture (CRC) and feeder-serum-free "dual-SMAD inhibition" (SMADi) methods. Expanded cells from each culture were differentiated with proprietary PneumaCult™-ALI media. Morphology (Immunofluorescence), global proteomics (LC-MS/MS) and function (barrier integrity, cilia motility, and ion transport) were compared in CRCALI and SMADiALI under basal and CFTR corrector treated (VX-809) conditions.
RESULTS: No significant difference in the structural morphology or baseline global proteomics profile were observed. Barrier integrity and cilia motility were significantly different, despite no difference in cell junction morphology or cilia abundance. Epithelial Sodium Channels and Calcium-activated Chloride Channel activity did not differ but CFTR mediated chloride currents were significantly reduced in SMADiALI compare to their CRCALI counterparts.
CONCLUSION: Alteration of cellular physiological function in vitro were more prominent than structural and differentiation potential in airway ALI. Since initial expansion culture conditions significantly influence CFTR activity, this could lead to false conclusions if data from different labs are compared against each other without specific reference ranges.
PMID: 33414087 [PubMed - as supplied by publisher]
Clinico-microbiological profile of Burkholderia cepacia keratitis: a case series.
Clinico-microbiological profile of Burkholderia cepacia keratitis: a case series.
Ann Clin Microbiol Antimicrob. 2021 Jan 07;20(1):6
Authors: Ho MC, Kang EY, Yeh LK, Ma DHK, Lin HC, Tan HY, Chen HC, Hsiao CH
Abstract
BACKGROUND: Burkholderia cepacia, an opportunistic pathogen mainly affecting patients with cystic fibrosis or immunocompromised, has rarely been documented as a cause of corneal infection. The clinical and microbiological profiles of B. cepacia keratitis are reported herein.
METHODS: We retrospectively reviewed the medical record of 17 patients with culture-proven B. cepacia keratitis, treated between 2000 and 2019 at Chang Gung Memorial Hospital, Taiwan. Our data included predisposing factors, clinical presentations, treatments, and visual outcomes of B. cepacia keratitis as well as the drug susceptibility of the causative agent.
RESULTS: The most common predisposing factor for B. cepacia keratitis was preexisting ocular disease (seven, 41.2%), particularly herpetic keratitis (five). Polymicrobial infection was detected in seven (41.2%) eyes. All B. cepacia isolates were susceptible to ceftazidime. Main medical treatments included levofloxacin or ceftazidime. Surgical treatment was required in five (29.4%) patients. Only four (23.5%) patients exhibited final visual acuity better than 20/200.
CONCLUSIONS: B. cepacia keratitis primarily affects patients with preexisting ocular disease, particularly herpetic keratitis, and responds well to ceftazidime or fluoroquinolones. However, the visual outcomes are generally poor.
PMID: 33413453 [PubMed - in process]
CRISPR/Cas9 Gene Editing Therapies for Cystic Fibrosis.
CRISPR/Cas9 Gene Editing Therapies for Cystic Fibrosis.
Expert Opin Biol Ther. 2021 Jan 08;:
Authors: Graham C, Hart S
Abstract
INTRODUCTION: Cystic fibrosis (CF) is a life-limiting genetic disorder affecting approximately 70,000 people worldwide. Current burden of treatment is high. While the latest pharmaceutical innovation has benefitted many, patients with certain genotypes remain excluded. Gene editing has the potential to correct the underlying cause of disease for all patients, representing a permanent cure. Areas covered: Various DNA editing-based strategies for treatment are currently being developed. Different strategies are called for based upon location of mutations (intronic vs. exonic), delivery mechanism of editing machinery, and cell type being targeted. Furthermore, the unique physiology of the CF lung presents a variety of barriers to delivery of CRISPR-Cas9 machinery. Expert opinion: The most significant obstacle to the use of CRISPR-Cas9 in vivo is the fact that the most clinically relevant and accessible CF tissue, the airway epithelium, is made up of non-dividing cells where precise editing via homology-directed repair (HDR) does not occur; rather, potentially deleterious imprecise editing via non-homologous end joining (NHEJ) dominates. Future research should focus on the development of either more precise NHEJ-based approaches, access to airway basal cells, editing approaches that do not involve introducing genomic double strand breaks, and strategies with ex vivo edited cells.
PMID: 33412935 [PubMed - as supplied by publisher]
Impaired cholesterol metabolism in the mouse model of cystic fibrosis. A preliminary study.
Impaired cholesterol metabolism in the mouse model of cystic fibrosis. A preliminary study.
PLoS One. 2021;16(1):e0245302
Authors: Amato F, Castaldo A, Castaldo G, Cernera G, Corso G, Ferrari E, Gelzo M, Monzani R, Villella VR, Raia V
Abstract
This study aims to investigate cholesterol metabolism in a mouse model with cystic fibrosis (CF) by the comparison of affected homozygous versus wild type (WT) mice. In particular, we evaluated the effects of a diet enriched with cholesterol in both mice groups in comparison with the normal diet. To this purpose, beyond serum and liver cholesterol, we analyzed serum phytosterols as indirect markers of intestinal absorption of cholesterol, liver lathosterol as indirect marker of de novo cholesterol synthesis, liver cholestanol (a catabolite of bile salts synthesis) and the liver mRNA levels of LDL receptor (LDLR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR), acyl CoA:cholesterol acyl transferase 2 (ACAT2), cytochrome P450 7A1 (CYP7A1) and tumor necrosis factor alpha (TNFα). CF mice showed lower intestinal absorption and higher liver synthesis of cholesterol than WT mice. In WT mice, the cholesterol supplementation inhibits the synthesis of liver cholesterol and enhances its catabolism, while in CF mice we did not observe a reduction of LDLR and HMG-CoAR expression (probably due to an altered feed-back), causing an increase of intracellular cholesterol. In addition, we observed a further increase (5-fold) in TNFα mRNA levels. This preliminary study suggests that in CF mice there is a vicious circle in which the altered synthesis/secretion of bile salts may reduce the digestion/absorption of cholesterol. As a result, the liver increases the biosynthesis of cholesterol that accumulates in the cells, triggering inflammation and further compromising the metabolism of bile salts.
PMID: 33412572 [PubMed - as supplied by publisher]
Factors associated to functional recovery of left vocal fold motion impairment at two-years-old age in very preterm infants.
Factors associated to functional recovery of left vocal fold motion impairment at two-years-old age in very preterm infants.
Int J Pediatr Otorhinolaryngol. 2021 Jan 02;142:110612
Authors: Garcia-Marcos PW, Pastor-Costa P, Mondejar-Lopez P, Sanchez-Solis M, Garcia-Marcos L, Diaz-Manzano JA
Abstract
OBJECTIVE: To describe a cohort of neonates with left vocal fold motion impairment (LVFMI) and the factors associated to it in the neonatal period; procedures required during LVFMI treatment; and clinical outcomes at the age of 2-years. An additional objective was to study those factors which are likely to be most associated to functional recovery of LVFMI at this age.
METHODS: A cohort of patients born in a tertiary care hospital with a diagnosis of left VFMI was included. Factors registered were: gender; clinical presentation at the time of examination; diagnosis of other laryngeal defects associated; data related to their neonatal period (gestational age, congenital heart defects corrective surgery required, neurologic disease, bronchopulmonary dysplasia, non-invasive ventilation required, invasive ventilation required, and tracheostomy required); treatment applied for LVFMI (tracheostomy and/or laryngeal surgery); need of language and hearing therapy; and outcomes considered by the pediatric otolaryngologist at the 2 years-old follow-up visit.
RESULTS: A total of 56 patients with LVFMI diagnosis were included. Only 10 patients (17.9%) showed functional recovery from LVFMI at the age of 2 years. We found significant negative association between this recovery and language and hearing therapy (p = 0.03), which was also associated to psychomotor retardation (p < 0.001). Multivariate analysis produced similar results, being language and hearing therapy the only significant factor associated to a worse outcome (OR = 4.77 [CI95% 1.14; 20.08] p = 0.03).
CONCLUSION: Psychomotor development retardation is negatively associated to functional recovery of full speech in a preterm infant's population with LVFMI diagnosis, regardless of other factors related to LVFMI etiology and severity.
PMID: 33412342 [PubMed - as supplied by publisher]
Positive expiratory pressure (PEP) therapy. What pressures do we achieve in young children with cystic fibrosis? A single-centre study.
Positive expiratory pressure (PEP) therapy. What pressures do we achieve in young children with cystic fibrosis? A single-centre study.
BMJ Paediatr Open. 2020;4(1):e000792
Authors: Kiernan N, Johnstone B, Anderson P, Stewart R
Abstract
This study was a clinical review of infant positive expiratory pressure (PEP) therapy in young children with cystic fibrosis (CF). The aim of this study was to determine whether pressures of 10-20 cm H2O PEP therapy (recommended by the CF trust) are being achieved with routine airway clearance therapy. This took place at the Royal Hospital for Children, Glasgow a specialist UK CF centre. Values were obtained from 21 young children. Pressures above 10 cm H2O during tidal volume breathing were not achieved within our cohort. Further investigation is required to determine efficacy of lower pressures in PEP therapy with young children.
PMID: 33409382 [PubMed]
Tribulations and (clinical) trials in cystic fibrosis.
Tribulations and (clinical) trials in cystic fibrosis.
J Cyst Fibros. 2021 Jan 03;:
Authors: Cagnina RE, Sawicki GS
PMID: 33408059 [PubMed - as supplied by publisher]
Cystic fibrosis in Tuscany: evolution of newborn screening strategies over time to the present.
Cystic fibrosis in Tuscany: evolution of newborn screening strategies over time to the present.
Ital J Pediatr. 2021 Jan 06;47(1):2
Authors: Botti M, Terlizzi V, Francalanci M, Dolce D, Cavicchi MC, Neri AS, Galici V, Mergni G, Zavataro L, Centrone C, Festini F, Taccetti G
Abstract
BACKGROUND: Cystic fibrosis (CF) is a life-threatening disease affecting about 1:3000 newborns in Caucasian populations. The introduction of newborn screening for cystic fibrosis (CF NBS) has improved the clinical outcomes of individuals with CF through early diagnosis and early treatment. NBS strategies have been implemented over time. CF NBS was introduced extensively in 1984 in Tuscany, a region with 3.7 million people, characterized by a high allelic heterogeneity of CFTR gene.
AIM AND METHODS: The aim of the study is to present the results from 34 years (1984-2018) of CF NBS, retrospectively evaluating the sensitivity, specificity and predictive values of the tests. In particular, we studied the impact of the introduction of DNA molecular analysis in NBS in a region with high allelic heterogeneity, such as Tuscany.
RESULTS: Over these 34 years, 919,520 neonates were screened, using four different NBS strategies. From 1984 to 1991, CF NBS was performed by the determination of albumin on dried meconium (sensitivity 68.75%; specificity 99.82%). Subsequently, the analysis of immunoreactive trypsinogen on a blood spot was adopted as CF NBS protocol (sensitivity 83.33%; specificity 99.77%). From 1992 to 2010, this strategy was associated with lactase meconium dosage: IRT1/IRT2 + LACT protocol (sensitivity 87.50%; specificity 99.82%). From 2011, when the existing algorithm was integrated by analysis of CF causing variants of the CFTR gene (IRT1/IRT2 + LACT + IRT1/DNA protocol), a substantial improvement in sensitivity was seen (senisitivity 96.15%; specificity 99.75%). Other improved parameters with DNA analysis in the NBS programme, compared with the previous method, were the diagnosis time (52 days vs. 38 days) and the recall rate (0.58 to 0.38%).
CONCLUSION: The inclusion of DNA analysis in the NBS was a fundamental step in improving sensitivity, even in a region with high allelic variability.
PMID: 33407736 [PubMed - in process]
Response to Comment on Jaworska, J. et al. Consensus on the Application of Lung Ultrasound in Pneumonia and Bronchiolitis in Children. Diagnostics 2020, 10, 935.
Response to Comment on Jaworska, J. et al. Consensus on the Application of Lung Ultrasound in Pneumonia and Bronchiolitis in Children. Diagnostics 2020, 10, 935.
Diagnostics (Basel). 2021 Jan 04;11(1):
Authors: Komorowska-Piotrowska A, Jaworska J, Pomiećko A, Wiśniewski J, Woźniak M, Littwin B, Kryger M, Kwaśniewicz P, Szczyrski J, Kulińska-Szukalska K, Buda N, Doniec Z, Kosiak W
Abstract
Thank you for the opportunity to respond to the issues raised by Nenna et al [...].
PMID: 33406637 [PubMed]