J Allergy Clin Immunol Pract. 2021 Jun 11:S2213-2198(21)00654-1. doi: 10.1016/j.jaip.2021.05.028. Online ahead of print.

NO ABSTRACT

PMID:34126272 | DOI:10.1016/j.jaip.2021.05.028

Actas Dermosifiliogr. 2021 Jun 11:S0001-7310(21)00209-X. doi: 10.1016/j.ad.2021.05.016. Online ahead of print.

ABSTRACT

{0>La Queratodermia Acuagénica (QA) es una afectación dermatológica adquirida poco frecuente que se caracteriza por la aparición de edema y pápulas blanquecinas-translúcidas desencadenado por la inmersión o contacto con agua.<}100{>Aquagenic keratoderma is an uncommon acquired dermatosis characterized by edema and whitish-translucent papules triggered by immersion or contact with water.<0} {0>Se han descrito casos asociados a fármacos, hiperhidrosis y a fibrosis quística.<}100{>Cases have been described in association with certain medications, hyperhidrosis, and cystic fibrosis.<0} {0>Los objetivos del estudio son evaluar la efectividad de los distintos tratamientos existentes para la QA.<}0{>The aim of this review is to evaluate the effectiveness of different treatments for aquagenic keratoderma.<0} {0>Realizamos una revisión de la literatura existente al respecto hasta el momento, incluyendo series de casos y reportes de caso.<}94{>We reviewed the literature and analyzed treatments for aquagenic keratoderma described in case series and reports.<0} {0>El tratamiento de la QA es efectivo en las formas asociadas a hiperhidrosis.<}100{>Aquagenic keratoderma associated with hyperhidrosis can be treated effectively.<0} {0>La iontoforesis de agua del grifo, la simpatectomía torácica endoscópica, las inyecciones de toxina botulínica y la oxibutinina son efectivas en las formas refractarias.<}100{>Tap water iontophoresis, endoscopic thoracic sympathectomy, botulinum toxin injections, and oxybutynin are effective against refractory forms.<0} {0>La aplicación tópica de ácido salicílico o sales de aluminio es efectiva pero resulta poco eficaz como tratamiento de mantenimiento.<}0{>Topical salicylic acid and aluminum salts are effective, but of little value as maintenance therapy.<0} {0>Probablemente la mejor alternativa para el tratamiento de la QA sea la Oxibutinina 5mg/día v.o.<}100{>Oral oxybutynin 5 mg/d is probably the best option for treating aquagenic keratoderma.<0} {0>Se ha observado que los efectos fisiopatológicos de los antiinflamatorios no esteroideos en la QA podrían justificar el uso de las prostaglandinas como un tratamiento dirigido de la enfermedad.<}100{>The reported pathophysiological effects of nonsteroidal anti-inflammatory drugs in this setting suggest that the use of prostaglandins might be justified.<0} {0>Se necesitan estudios adicionales para fortalecer estas deducciones y abordar las incertidumbres restantes.<}100{>Additional studies are needed to investigate these hypotheses and resolve other questions.<0}.

PMID:34126071 | DOI:10.1016/j.ad.2021.05.016

J Vis Exp. 2021 May 26;(171). doi: 10.3791/62468.

ABSTRACT

The Ussing chamber technique was first invented by the Danish scientist Hans Ussing in 1951 to study the transcellular transport of sodium across frog skin. Since then, this technique has been applied to many different tissues to study the physiological parameters of transport across membranes. The Ussing chamber method is preferable to other methods because native tissue can be used, making it more applicable to what is happening in vivo. However, because native tissue is used, throughput is low, time is limited, and tissue preparation requires skill and training. These chambers have been used to study specific transporter proteins in various tissues, understand disease pathophysiology such as in Cystic Fibrosis, study drug transport and uptake, and especially contributed to the understanding of nutrient transport in the intestine. Given the whole epithelial transport process of a tissue, not only transepithelial pathways, but also paracellular pathways are important. Tight junctions are a key determinant of tissue specific paracellular permeability across the intestine. In this article, the Ussing chamber technique will be used to assess paracellular permselectivity of ions by measuring transepithelial conductance and dilution potentials.

PMID:34125105 | DOI:10.3791/62468

Cureus. 2021 May 10;13(5):e14945. doi: 10.7759/cureus.14945.

ABSTRACT

Candida blankii is an emerging pathogenic fungus, first identified in 1968 as a new species. In the past five years, it has been identified in cystic fibrosis patient's airways and as fungemia in immunocompromised patients (post lung transplant and preterm neonates). It has been postulated to be a possible opportunistic pathogen based on the published case reports. We report a case of C. blankii fungemia with possible endocarditis in an immunocompetent individual. To our knowledge, this is also the first case of C. blankii bloodstream infection reported in an adult patient (age > 18 years). The C. blanki i isolate from our patient had high minimum inhibitory concentrations (MICs) to azoles similar to the published reports. There is a dearth of literature guiding the treatment of this organism, given the variable susceptibility pattern and lack of data. Here, we describe successful treatment of possible C. blanki i endocarditis with a combination of polyene and echinocandin antifungal agents.

PMID:34123642 | PMC:PMC8189539 | DOI:10.7759/cureus.14945

Front Microbiol. 2021 May 28;12:670202. doi: 10.3389/fmicb.2021.670202. eCollection 2021.

ABSTRACT

Pseudomonas aeruginosa is one of the most common opportunistic pathogens, which causes severe nosocomial infections because of its well-known multidrug-resistance and hypervirulence. It is critical to curate routinely the epidemic P. aeruginosa clones encountered in the clinic. The aim of the present study was to investigate the connection between virulence factors and antimicrobial resistance profiles in epidemic clones. Herein, we found that ST463 (O4), ST1212 (O11), and ST244 (O5) were prevalent in 30 isolates derived from non-cystic fibrosis patients, based on multilocus sequence type (MLST) and serotype analysis. All isolates were multidrug-resistant (MDR) and each was resistance to at least three classes of antibiotics in antimicrobial susceptibility tests, which was consistent with the presence of the abundant resistance genes, such as bla OXA-50, bla PAO, aph(3'), catB7, fosA, crpP, and bla KPC-2. Notably, all bla KPC-2 genes were located between ISKpn6-like and ISKpn8-like mobile genetic elements. In addition, classical exotoxins encoded by exoU, exoS, and pldA were present in 43.44% (13/40), 83.33% (25/30), and 70% (21/30) of the isolates, respectively. The expression of phz operons encoding the typical toxin, pyocyanin, was observed in 60% of isolates (18/30) and was quantified using triple quadrupole liquid chromatograph mass (LC/MS) assays. Interestingly, compared with other MLST types, all ST463 isolates harbored exoU, exoS and pldA, and produced pyocyanin ranging from 0.2 to 3.2 μg/mL. Finally, we evaluated the potential toxicity of these isolates using hemolysis tests and Galleria mellonella larvae infection models. The results showed that ST463 isolates were more virulent than other isolates. In conclusion, pyocyanin-producing ST463 P. aeruginosa, carrying diverse virulence genes, is a potential high-risk clone.

PMID:34122384 | PMC:PMC8193091 | DOI:10.3389/fmicb.2021.670202

Clin Radiol. 2021 Jun 10:S0009-9260(21)00273-7. doi: 10.1016/j.crad.2021.05.015. Online ahead of print.

ABSTRACT

Lung magnetic resonance imaging (MRI) is considered to be challenging, because the low proton density of the tissue, fast signal decay, and respiratory artefacts hamper adequate image quality. MRI of the lungs and thorax is increasingly used in the paediatric population, because it is a radiation-free alternative to chest CT. Recently, ultrashort echo-time (UTE) sequences have been introduced into clinical MRI protocols, in order to improve the contrast-to-noise ratio due to reduced susceptibility artefacts and to depict structural alterations comparable to CT. The purpose of this review is to provide an overview of various clinical conditions and pathologies in the paediatric chest depicted by an UTE sequence, the so-called three-dimensional (3D) Cones sequence, in comparison with conventional MRI sequences. Besides describing typical features of cystic fibrosis, we present UTE application in other more or less common paediatric lung pathologies, for instance, interstitial pneumopathies, pulmonary infections, and congenital pulmonary malformations.

PMID:34120734 | DOI:10.1016/j.crad.2021.05.015

Curr Opin Gastroenterol. 2021 Jun 11. doi: 10.1097/MOG.0000000000000764. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Approximately 20-30% of children who experience one episode of acute pancreatitis will have at least one additional episode. For some children, pancreatitis recurs multiple times and in a few years is followed by the diagnosis of chronic pancreatitis. Identifying risk factors for recurrent episodes and disease progression is critical to developing therapeutic interventions.

RECENT FINDINGS: Obesity is driving an increase in biliary stone disease and severe acute pancreatitis. Recurrent acute pancreatitis (RAP) may lead to the development of diabetes through autoimmune mechanisms. Cystic fibrosis or CFTR-related disorders may present as RAP and CFTR modulator therapy can increase or decrease the risk of acute pancreatitis in these populations. Children with Crohn disease have a three-fold risk of acute pancreatitis over the general population while children with ulcerative colitis are at increased risk for pediatric autoimmune pancreatitis, a disorder that may be distinct from autoimmune pancreatitis described in adults. Obstructive jaundice in the absence of identified mechanical factors may be a presenting sign of pediatric autoimmune pancreatitis.

SUMMARY: Pediatric RAP is a painful condition that leads to gland destruction and functional insufficiency. Risk factors are being clarified but preventive treatments remain elusive.

PMID:34120130 | DOI:10.1097/MOG.0000000000000764

Int J Antimicrob Agents. 2021 Jun 8:106372. doi: 10.1016/j.ijantimicag.2021.106372. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a disease caused by mutations in the CF transmembrane conductance regulator. The resulting chloride and bicarbonate imbalance produces a thick static lung mucus. This mucus is not easily expelled from the lungs, and so can be colonised by bacteria, leading to biofilm formation. CF lung infection with Burkholderia cepacia complex (BCC), especially the subspecies B. cenocepacia, results in higher morbidity and mortality. Patients infected with BCC can rapidly progress to "cepacia syndrome", a fatal necrotising pneumonia. We aimed to identify whether a combination therapy (CT) of selected antioxidants and antibiotics significantly disrupts B. cenocepacia biofilms and determine the optimum CT level for treatment. Using controlled in vitro spectrophotometry, colony forming unit and microscopy assays, three antioxidants: (N-acetylcysteine (NAC), glutathione and vitamin C) and three antibiotics: (ciprofloxacin, ceftazidime and tobramycin) were screened and assessed for their ability to disrupt the early and mature biofilms of six B. cenocepacia CF isolates. A combination of NAC and ciprofloxacin produced a statistically significant biofilm disruption in all strains tested, with growth inhibition (>5-8 log10) observed when exposed to 4890- or 8150 μg/mL NAC in combination with 32- or 64 μg/mL ciprofloxacin. NAC-mediated biofilm disruption may be aided by the acidic pH of NAC at higher concentrations. Our study demonstrated that NAC is an effective disruptor that reduces the necessity for high concentrations of antibiotic. Further research will focus on the host toxicity and efficacy in ex vivo CF models.

PMID:34116184 | DOI:10.1016/j.ijantimicag.2021.106372

J Pediatr (Rio J). 2021 Jun 8:S0021-7557(21)00078-4. doi: 10.1016/j.jped.2021.02.009. Online ahead of print.

ABSTRACT

OBJECTIVE: In this present study, the authors evaluated the predictive factors for adverse maternal-fetal outcomes in pregnancies of women with cystic fibrosis (CF). Patients were followed up by a referral center for adults in southern Brazil.

METHODS: This is a retrospective cohort study that used data from electronic medical records regarding pregnancies of women diagnosed with CF.

RESULTS: The study included 39 pregnancies related to 20 different women. The main adverse outcomes were high prevalence rates of premature birth (38.5%) and maternal respiratory exacerbation (84.6%). Lower body mass index (BMI) values (< 20.8) and younger ages of CF diagnosis increased the risk of premature birth. The presence of methicillin-resistant and absence of methicillin-sensitive Staphylococcus aureus, as well as a younger age of diagnosis, increased the risk of maternal respiratory exacerbation during pregnancy.

CONCLUSIONS: Conception in women with CF is often associated with maternal and fetal complications. Continuous monitoring by a multidisciplinary team should emphasize appropriate nutritional status, investigation of bacterial colonization, and immediate attention to respiratory exacerbations.

PMID:34115976 | DOI:10.1016/j.jped.2021.02.009

J Cell Sci. 2021 Jun 11:jcs.256313. doi: 10.1242/jcs.256313. Online ahead of print.

ABSTRACT

Membrane voltage (Vm) plays a critical role in the regulation of several cellular behaviors, including proliferation, apoptosis, and phenotypic plasticity. Many of these same behaviors are affected by the stiffness of the underlying extracellular matrix, but the connections between Vm and the mechanical properties of the microenvironment are unclear. Here, we investigated the relationship between matrix stiffness and Vm by culturing mammary epithelial cells on synthetic substrata, the stiffnesses of which mimicked those of the normal mammary gland and breast tumors. Although proliferation is associated with depolarization, we surprisingly observed that cells are hyperpolarized when cultured on stiff substrata, a microenvironmental condition that enhances proliferation. Accordingly, we found that Vm becomes depolarized as stiffness decreases, in a manner dependent on intracellular calcium. Furthermore, inhibiting calcium-gated chloride currents abolishes the effects of substratum stiffness on Vm. Specifically, we uncovered a role for cystic fibrosis transmembrane conductance regulator (CFTR) in the regulation of Vm by substratum stiffness. Together, these results suggest a novel role for CFTR and membrane voltage in the response of mammary epithelial cells to their mechanical microenvironment.

PMID:34114636 | DOI:10.1242/jcs.256313

J Cyst Fibros. 2021 Jun 7:S1569-1993(21)00122-3. doi: 10.1016/j.jcf.2021.04.012. Online ahead of print.

ABSTRACT

BACKGROUND: In Cystic Fibrosis (CF) airways, the dehydrated, thick mucus promotes the establishment of persistent polymicrobial infections and drives chronic airways inflammation. This also predisposes the airways to further infections, the vicious, self-perpetuating cycle causing lung damage and progressive lung function decline. The airways are a poly-microbial environment, containing both aerobic and anaerobic bacterial species. Pseudomonas aeruginosa (P. aeruginosa) infections contribute to the excessive inflammatory response in CF, but the role of anaerobic Prevotella spp., frequently found in CF airways, is not known.

MATERIALS: We assessed innate immune signalling in CF airway epithelial cells in response to clinical strains of P. histicola, P. nigresens and P. aeruginosa. CFBE41o- cells were infected with P. aeruginosa (MOI 100, 2h) followed by infection with P. histicola or P. nigrescens (MOI 100, 2h). Cells were incubated under anaerobic conditions for the duration of the experiments.

RESULTS: Our study shows that P. histicola and P. nigresens can reduce the growth of P. aeruginosa and dampen the inflammatory response in airway epithelial cells. We specifically illustrate that the presence of the investigated Prevotella spp. reduces Toll-like-receptor (TLR)-4, MAPK, NF-κB(p65) signalling and cytokine release (Interleukin (IL)-6, IL-8) in mixed infections.

CONCLUSION: Our work, for the first time, strongly indicates a relationship between P. aeruginosa and anaerobic Prevotella spp.. The observed modified NF-κB and MAPK signalling indicates some mechanisms underlying this interaction that could offer a novel therapeutic approach to combat chronic P. aeruginosa infection in people with CF.

PMID:34112603 | DOI:10.1016/j.jcf.2021.04.012

ERJ Open Res. 2021 Jun 7;7(2):00062-2021. doi: 10.1183/23120541.00062-2021. eCollection 2021 Apr.

ABSTRACT

BACKGROUND: Impaired mucus clearance and airway mucus plugging have been shown to occur in moderate-severe asthma, especially during acute exacerbations. In cystic fibrosis, where airway mucus is dehydrated, it has been shown that inhaled hypertonic saline (HS) produces both acute and sustained enhancement of mucociliary clearance (MCC). The current study was designed to assess the acute and sustained effect of inhaled 7% HS on MCC in adult asthma.

METHODS: Well-controlled, moderate-severe female asthmatic patients (n=8) were screened with a single test dose of albuterol (four puffs by metered-dose inhaler) followed by HS (7% sodium chloride, 4 mL using PARI LC Star nebuliser). Spirometry was measured pre-treatment and 5 and 30 min post-treatment for safety. MCC was measured using γ-scintigraphy on three separate visits: at baseline, during inhalation and 4 h after a single dose of HS.

RESULTS: MCC was acutely enhanced during HS treatment; mean±sd clearance over 60 min of dynamic imaging (Ave60Clr) was 8.9±7.9% (baseline) versus 23.4±7.6% (acute HS) (p<0.005). However, this enhancement was not maintained over a 4-h period where post-HS treatment Ave60Clr was 9.3±8.2%. In this small cohort we found no decrements in lung function up to 30 min post-treatment (forced expiratory volume in 1 s 97.4±10.0% predicted pre-treatment and 98.9±10.7% predicted 30 min post-treatment).

CONCLUSION: While MCC was rapidly enhanced during 7% HS treatment there was no effect on MCC at 4 h post-treatment. While these findings may not support aerosolised HS use for maintenance therapy, they do suggest a benefit of treating acute exacerbations in patients with moderate-severe asthma.

PMID:34109248 | PMC:PMC8184161 | DOI:10.1183/23120541.00062-2021

J Cyst Fibros. 2021 May;20(3):525-532. doi: 10.1016/j.jcf.2020.09.012. Epub 2020 Oct 21.

ABSTRACT

BACKGROUND: Little is known about long-term bone mineral density (BMD) changes and fractures in lung transplant recipients with cystic fibrosis (CF). We examined femur and lumbar spine (LS) BMD changes in men and women with CF up to 10 years post-transplant and documented post-transplant fracture prevalence.

METHODS: Retrospective study of individuals who had undergone a lung transplant (2000-2015) and had a pre-transplant and at least one BMD measurement after transplant. Vertebral fractures were assessed on chest computed tomography scans and other fractures abstracted from medical records.

RESULTS: The cohort consisted of 131 individuals; 53% males, median age: 28 years [interquartile range: 24-35] and 31% having pre-transplant low bone mass. Most recipients were given bisphosphonates after transplant with proportion reaching 94% at 10 years. Up to 10 years post-transplant, men experienced positive or little change in LS BMD, indicating minimal loss from pre-transplant values. In contrast, women displayed negative changes in BMD up to 5 years post-transplant before recovering pre-transplant BMD values by 10 years. Similar patterns were observed at the femur BMD where men demonstrated a lower bone loss and faster recovery towards pre-transplant values than women. After transplant, 88% of recipients maintained their pre-transplant bone status, 3% experienced an improvement, mostly progressing from low bone mass to normal status whereas 9% had a deterioration of their pre-transplant bone status. Twenty-seven recipients suffered fractures in the post-transplant period.

CONCLUSIONS: These findings underline that lung recipients with CF remain at risk of skeletal fragility despite prompt initiation of post-transplant anti-osteoporosis therapy.

PMID:34108100 | DOI:10.1016/j.jcf.2020.09.012

Cell Rep. 2021 Jun 8;35(10):109217. doi: 10.1016/j.celrep.2021.109217.

ABSTRACT

The ubiquitous ribosome-associated complex (RAC) is a chaperone that spans ribosomes, making contacts near both the polypeptide exit tunnel and the decoding center, a position prime for sensing and coordinating translation and folding. Loss of RAC is known to result in growth defects and sensitization to translational and osmotic stresses. However, the physiological substrates of RAC and the mechanism(s) by which RAC is involved in responding to specific stresses in higher eukaryotes remain obscure. The data presented here uncover an essential function of mammalian RAC in the unfolded protein response (UPR). Knockdown of RAC sensitizes mammalian cells to endoplasmic reticulum (ER) stress and selectively interferes with IRE1 branch activation. Higher-order oligomerization of the inositol-requiring enzyme 1α (IRE1α) kinase/endoribonuclease depends upon RAC. These results reveal a surveillance function for RAC in the UPR, as follows: modulating IRE1α clustering as required for endonuclease activation and splicing of the substrate Xbp1 mRNA.

PMID:34107246 | DOI:10.1016/j.celrep.2021.109217

Nucleic Acids Res. 2021 Jun 9:gkab488. doi: 10.1093/nar/gkab488. Online ahead of print.

ABSTRACT

Pulmonary diseases offer many targets for oligonucleotide therapeutics. However, effective delivery of oligonucleotides to the lung is challenging. For example, splicing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) affect a significant cohort of Cystic Fibrosis (CF) patients. These individuals could potentially benefit from treatment with splice switching oligonucleotides (SSOs) that can modulate splicing of CFTR and restore its activity. However, previous studies in cell culture used oligonucleotide transfection methods that cannot be safely translated in vivo. In this report, we demonstrate effective correction of a splicing mutation in the lung of a mouse model using SSOs. Moreover, we also demonstrate effective correction of a CFTR splicing mutation in a pre-clinical CF patient-derived cell model. We utilized a highly effective delivery strategy for oligonucleotides by combining peptide-morpholino (PPMO) SSOs with small molecules termed OECs. PPMOs distribute broadly into the lung and other tissues while OECs potentiate the effects of oligonucleotides by releasing them from endosomal entrapment. The combined PPMO plus OEC approach proved to be effective both in CF patient cells and in vivo in the mouse lung and thus may offer a path to the development of novel therapeutics for splicing mutations in CF and other lung diseases.

PMID:34107015 | DOI:10.1093/nar/gkab488

Br J Radiol. 2021 Jun 9:20210207. doi: 10.1259/bjr.20210207. Online ahead of print.

ABSTRACT

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique - hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe - a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.

PMID:34106792 | DOI:10.1259/bjr.20210207

Biol Reprod. 2021 Jun 8:ioab113. doi: 10.1093/biolre/ioab113. Online ahead of print.

ABSTRACT

The epididymis is composed of a pseudostratified epithelium comprised of various cell types. Studies have shown that rat basal cells share common properties with adult stem cells and begin to differentiate in vitro in response to fibroblast growth factor and 5α-dihydrotestosterone. The characterization of rat basal cells is therefore necessary to fully understand the role of these cells. The objectives of this study were to assess the ability of single basal cells to develop organoids and to assess their ability to self-renew and differentiate in vitro. We isolated basal cells from the rat epididymis and established 3-dimensional cell cultures from the basal and non-basal cell fractions. Organoids were formed by single adult epididymal basal cells. Organoids were dissociated into single basal cells which were able to reform new organoids, and were maintained over 10 generations. Long-term culture of organoids revealed that these cells could differentiated into cells expressing the principal cell markers aquaporin 9 and cystic fibrosis transmembrane conductance regulator. Electron microscopy demonstrated that organoids were comprised of several polarized cell types displaying microvilli and the ability to form tight junctions. Additionally, organoids could be formed by basal cells from either the proximal or distal region of the epididymis, and are able to secrete clusterin, a protein implicated in the maturation of spermatozoa. These data indicate that rat basal cells can be used to derive epididymal organoids, and further supports that notion that these may represent a stem cell population in the epididymis.

PMID:34104939 | DOI:10.1093/biolre/ioab113

BMJ Paediatr Open. 2021 May 21;5(1):e001055. doi: 10.1136/bmjpo-2021-001055. eCollection 2021.

ABSTRACT

OBJECTIVE: As parents majorly impact their child's well-being, and as fatigue is a highly prevalent threat to the well-being of children with a chronic disease, we aimed to explore the association between parental factors and fatigue in children with a chronic disease.

DESIGN: Cross-sectional study.

SETTING: Two Dutch children's hospitals.

POPULATION: Children 2-18 years of age with either an autoimmune disease, cystic fibrosis or post-cancer treatment, and one of their parents.

MAIN OUTCOME MEASURES: Paediatric fatigue was measured using the PedsQL Multidimensional Fatigue Scale. Parental factors included parental pain, fatigue and physical symptoms, parental distress, catastrophising thoughts about their child's pain and family empowerment. Multiple linear regressions were used to study associations with paediatric fatigue. A multivariable regression model was used to assess the effect of the different parental factors on paediatric fatigue. All analyses were adjusted for the age and sex of the child.

RESULTS: 204 families participated (mean age 11.0±4.3 and 43.5±6.3 years for children and parents, respectively; 69% participation rate). More parental pain, fatigue and physical symptoms, and more parental distress and pain catastrophising were associated with more paediatric fatigue. More parental empowerment was associated with less paediatric fatigue on both subscales. In the multivariable model, only paediatric age remained significantly associated with fatigue. In a separate multivariable model for children 8-18 years old, more parental distress (β=-1.9, 95% CI -3.7 to -0.1) was also significantly associated with more paediatric fatigue.

CONCLUSIONS: In a population of children with a chronic disease, parental factors, both physical and psychosocial, were associated with paediatric fatigue. Our study provides evidence that more family empowerment is associated with less paediatric fatigue. This exploratory study adds to our knowledge of associated factors with fatigue in paediatric chronic disease, providing starting points for targeted interventions.

PMID:34104803 | PMC:PMC8144042 | DOI:10.1136/bmjpo-2021-001055

J Oral Microbiol. 2021 May 17;13(1):1897328. doi: 10.1080/20002297.2021.1897328.

ABSTRACT

Introduction: Cystic fibrosis (CF) is an autosomal genetic disease, associated with the production of excessively thick mucosa and with life-threatening chronic lung infections. The microbiota of the oral cavity can act as a reservoir or as a barrier for infectious microorganisms that can colonize the lungs. However, the specific composition of the oral microbiome in CF is poorly understood.Methods: In collaboration with CF associations in Spain, we collected oral rinse samples from 31 CF persons (age range 7-47) and matched controls, and then performed 16S rRNA metabarcoding and high-throughput sequencing, combined with culture and proteomics-based identification of fungi to survey the bacterial and fungal oral microbiome.Results: We found that CF is associated with less diverse oral microbiomes, which were characterized by higher prevalence of Candida albicans and differential abundances of a number of bacterial taxa that have implications in both the connection to lung infections in CF, as well as potential oral health concerns, particularly periodontitis and dental caries.Conclusion: Overall, our study provides a first global snapshot of the oral microbiome in CF. Future studies are required to establish the relationships between the composition of the oral and lung microbiomes in CF.

PMID:34104346 | PMC:PMC8143623 | DOI:10.1080/20002297.2021.1897328

Eur J Hosp Pharm. 2021 Jun 8:ejhpharm-2020-002676. doi: 10.1136/ejhpharm-2020-002676. Online ahead of print.

ABSTRACT

OBJECTIVES: Cystic fibrosis is a devastating life-limiting genetic condition characterised by a progressive decline in lung function, respiratory infections and premature death. Tezacaftor-ivacaftor is a combined cystic fibrosis transmembrane conductance regulator (CFTR) modulator that targets the underlying cause of the disease. This study aimed to assess the impact of tezacaftor-ivacaftor use in routine clinical practice for adults with cystic fibrosis.

METHODS: A retrospective observational longitudinal cohort study design was applied to examine the clinical effect of tezacaftor-ivacaftor in routine practice in the West of Scotland Adult Cystic Fibrosis Unit. Adults receiving tezacaftor-ivacaftor for at least 4 weeks were included in this medicine use evaluation.A standardised data form was used to collect patient-level data: demographics, genotype, complications of cystic fibrosis, medicine access process. Fifty-two weeks pre and post tezacaftor-ivacaftor initiation data: lung function, body mass index (BMI), days spent in hospital, days receiving antibiotic treatment for respiratory exacerbations. Anonymised data were collated and analysed using SPSS V.26.

RESULTS: Of 121 potential patients, 45 received treatment with tezacaftor-ivacaftor; median age 30 years (range 17-64) at initiation, 56% were male, 76% were deemed to be homozygote and 41 patients continued treatment for at least 52 weeks. There was no significant change in % predicted FEV1; median difference 0 (IQR -3 to 6). There was a significant improvement in BMI, mean 0.6 kg/m2 (95% CI 0.2 to 1.0), as well as a median 4 (IQR -17 to 0) day reduction in days in hospital and 21 (IQR -42 to 0) day reduction in days receiving antibiotics.

CONCLUSIONS: The use of tezacaftor-ivacaftor in routine practice for people with cystic fibrosis was associated with improvements in weight, as well as reducing the number of days people needed to spend in hospital and receive antibiotics.

PMID:34103394 | DOI:10.1136/ejhpharm-2020-002676