Heliyon. 2024 Mar 7;10(6):e27567. doi: 10.1016/j.heliyon.2024.e27567. eCollection 2024 Mar 30.

ABSTRACT

BACKGROUND: When the first known US case of COVID-19 (Coronavirus Disease 2019) was reported in early 2020, little was known about the impact of this novel virus on the cystic fibrosis community. As the majority of individuals with CF have chronic lung disease, this population was initially considered to be at high risk for severe disease as infection with a multitude of viruses has proven to cause pulmonary exacerbation. SARS-CoV-2 virus has proven challenging to study given the multiple disease manifestations, range of severity, and wave-like phenomenon that varies geographically. People with CF who become infected with COVID-19 can be asymptomatic or have symptoms ranging from mild cough and congestion to full respiratory failure, similar to the manifestations seen in non-CF individuals. By studying the seroprevalence, clinical course, and antibody durability due to COVID-19 and vaccinations, we will be better equipped to provide appropriate and informed care to people with CF.

METHODS: Between July 2020 and April 2021 we enrolled 123 people with CF (pwCF) who receive care at the MN CF Center. We monitored their serology every 6 months for SARS-CoV-2 immunoglobulins (nucleocapsid and spike IgG) for evidence of natural and induced immunity. Medication use, pulmonary function, exacerbation history, and hospitalizations were extracted via electronic medical record (EMR).

RESULTS: 84% (101/120) of enrolled participants were vaccinated against SARS-CoV-2 during the study. Eighty three percent of the cohort showed evidence of either natural or induced "immunity." The average duration of antibody from induced immunity in participants was 6.1 months and from natural immunity was 7.4 months with an overall average duration of antibody of 6.8 months. Earliest antibody detected was 12 days after a single dose of the BNT162b2 vaccine and antibody was detectable across a span of 13 months. Eleven percent of vaccinated individuals did not have measurable IgG. 36% of non-responders (NRs) were solid organ transplant patients on chronic immunosuppressive therapy. Only 3 people within this cohort were hospitalized due to COVID pneumonia and all three survived.

CONCLUSION: To our knowledge, this is the first report on the seroprevalence and longevity of SARS-CoV-2 IgG to 1 year in adults with CF after the widespread availability of SARS-CoV-2 vaccinations. These data show that pwCF respond to the COVID vaccination and produce long-lasting antibodies similar to the general population.

PMID:38501003 | PMC:PMC10945179 | DOI:10.1016/j.heliyon.2024.e27567

ERJ Open Res. 2024 Mar 18;10(2):00715-2023. doi: 10.1183/23120541.00715-2023. eCollection 2024 Mar.

ABSTRACT

INTRODUCTION: Non-cystic fibrosis bronchiectasis is a disease which is increasing in incidence and prevalence worldwide. The incidence of the disease is frequently estimated using databases that rely on International Classification of Diseases, ninth and tenth revisions, clinical modification (ICD-9-CM/ICD-10-CM) discharge diagnoses. Code accuracy has proved to be a major issue for other diagnoses using ICD codes. This study aims to investigate the accuracy of the ICD codes for the diagnosis of non-cystic fibrosis bronchiectasis.

METHODS: This is a retrospective diagnostic accuracy study which compares the radiologist's diagnosis of bronchiectasis with the ICD code reflection of that diagnosis at discharge.

RESULTS: Sensitivities were 34% (same for both ICD-9-CM and ICD-10-CM windows) and specificities ranged from 69% for the ICD-9-CM window to 81% for ICD-10-CM window.

CONCLUSION: We observed that ICD codes are an insufficient method to identify patients with a radiologist diagnosis of bronchiectasis.

PMID:38500799 | PMC:PMC10945379 | DOI:10.1183/23120541.00715-2023

ERJ Open Res. 2024 Mar 18;10(2):00713-2023. doi: 10.1183/23120541.00713-2023. eCollection 2024 Mar.

ABSTRACT

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

PMID:38500794 | PMC:PMC10945380 | DOI:10.1183/23120541.00713-2023

Am J Respir Crit Care Med. 2024 Mar 18. doi: 10.1164/rccm.202402-0388ED. Online ahead of print.

NO ABSTRACT

PMID:38498854 | DOI:10.1164/rccm.202402-0388ED

Rhinology. 2024 Mar 18. doi: 10.4193/Rhin23.057. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic sinus surgery (ESS) is an established surgical option for cystic fibrosis (CF) patients with chronic rhinosinusitis that is refractory to conventional medical management. Objective and subjective evidence of benefit of ESS in this cohort of patients is currently conflicting in the literature.

METHODOLOGY: A single center retrospective study was undertaken of all CF patients (transplanted and non-transplanted) over the age of 16 who underwent an ESS over a six-year period from 2015 to 2021. Patients on triple-therapy CFTR modulators were excluded. Data was collected on demographics, clinical management, and outcome measures. The objective outcome measures were lung function (%predicted FEV1), pulmonary exacerbations (total number of days of IV antibiotics- both ambulatory and in hospital). The subjective outcome measure was SNOT-22 scores preand 6 months post-operatively. A minimally clinical important difference (MCID) in SNOT-22 scores of 9 points was used.

RESULTS: 55 patients were included in our study, with a median age of 31 and 53% females. Median Lund-Mackay scores for the cohort was 13 (3- 24). There was a significant improvement in lung function at 1-year post-surgery, and a significant MCID reduction in SNOT-22 scores at 6 months post-surgery across the cohort. Sub-group analysis revealed a sustained MCID reduction in SNOT-22 scores in both lung-transplanted and native lung groups, and in patients with primary ESS or previous ESS. However, there was no post-operative pulmonary function improvement in lung transplanted patients and patients with previous ESS. There was no impact on the rate of pulmonary exacerbations across the cohort. 2 patients in the cohort died secondary to pulmonary disease.

CONCLUSIONS: There was a demonstrated clinical and symptomatic benefit of ESS in CF patients in this study. Stricter guidelines for indications for ESS need to be established with regards to CF patients who will undergo ESS in the future.

PMID:38497762 | DOI:10.4193/Rhin23.057

Rhinology. 2024 Mar 18. doi: 10.4193/Rhin23.331. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is a highly prevalent airway disease worldwide. Whereas eosinophilic CRS with nasal polyps (eCRSwNP) represents its most severe phenotype, pathogenic mechanisms remain poorly understood despite a wide spectrum of in vitro and in vivo experimental models. A mouse model of experimental ovalbumin (OVA)-induced airway allergy with coadministration of Staphylococcus aureus enterotoxin B (SEB) has been widely used to study eosinophilic eCRSwNP. This study revisits the features of this model and its suitability for studying eCRS.

METHODOLOGY: We implemented the most used eCRSwNP mouse model based on OVA+SEB intranasal challenges. Readouts including inflammatory features by (immuno)histology of the sinonasal epithelium (NP formation, eosinophils, epithelial and basement membrane thickness, fibrosis, goblet cells, Charcot-Leyden crystals (CLC)-like, tight junctions) and IgE production by enzyme-linked immunosorbent assay (ELISA), were compared to features of the corresponding human disease.

RESULTS: The OVA+SEB model induced eosinophilic inflammation of upper and lower airways, with epithelial and basement membrane thickening, goblet cell hyperplasia and subepithelial fibrosis in the sinuses, along increased IgE production. Except local IgE in nasal lavage (NL), which was only increased in OVA+SEB group, all other features did not differ between OVA and OVA+SEB groups. Macro- or microscopic NP were not detected.

CONCLUSIONS: With the notable exception of local IgE production, the addition of SEB did not induce additional inflammatory or structural change in the sinuses from mice exposed to and challenged with OVA. This model might represent a model for severe upper airway allergy rather than a specific model of human eCRSwNP.

PMID:38497676 | DOI:10.4193/Rhin23.331

bioRxiv [Preprint]. 2024 Mar 10:2024.03.10.584330. doi: 10.1101/2024.03.10.584330.

ABSTRACT

Despite great progress in the field, chronic Pseudomonas aeruginosa ( Pa ) infections remain a major cause of morbidity and mortality in patients with cystic fibrosis, necessitating treatment with inhaled antibiotics. Pf phage is a filamentous bacteriophage produced by Pa that has been reported to act as a structural element in Pa biofilms. Pf presence has been associated with resistance to antibiotics and poor outcomes in cystic fibrosis, though the underlying mechanisms are unclear. Here, we have investigated how Pf phages and sputum biopolymers impede antibiotic diffusion using human sputum samples and fluorescent recovery after photobleaching. We demonstrate that tobramycin interacts with Pf phages and sputum polymers through electrostatic interactions. We also developed a set of mathematical models to analyze the complex observations. Our analysis suggests that Pf phages in sputum reduce the diffusion of charged antibiotics due to a greater binding constant associated with organized liquid crystalline structures formed between Pf phages and sputum polymers. This study provides insights into antibiotic tolerance mechanisms in chronic Pa infections and may offer potential strategies for novel therapeutic approaches.

TEASER: Pf phages and sputum polymers reduce antibiotic diffusion via electrostatic interactions and liquid crystal formation.

PMID:38496625 | PMC:PMC10942440 | DOI:10.1101/2024.03.10.584330

bioRxiv [Preprint]. 2024 Mar 4:2024.03.01.582742. doi: 10.1101/2024.03.01.582742.

ABSTRACT

BACKGROUND: Cystic Fibrosis causing mutations in the gene CFTR , reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis.

METHODS: A novel small molecule potentiator (SK-POT1), previously identified in CFTR binding studies, was tested for its activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement.

RESULTS: We showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures.

CONCLUSION: Together, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.

PMID:38496440 | PMC:PMC10942391 | DOI:10.1101/2024.03.01.582742

Ann Pancreat Cancer. 2023 Nov;6(10). doi: 10.21037/apc-23-13. Epub 2023 Nov 20.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is highly metastatic. Our prior studies have demonstrated the critical role of axon guidance pathway genes in PDAC and the connection between neuronal development and the tumor microenvironment. A recent study newly identified 20 neuronal development genes [disks large homolog 2 (DLG2), neuron-glial-related cell adhesion molecule (NRCAM), neurexin3 (NRXN3), mitogen-activated protein kinase 10 (MAPK10), platelet-derived growth factor D (PDGFD), protein kinase C epsilon (PRKCE), potassium calcium-activated channel subfamily M alpha 1 (KCNMA1), polycystic kidney and hepatic disease 1 (PKHD1), neural cell adhesion molecule 1 (NCAM1), neuregulin-1 (NRG1), zinc finger protein 667 (ZNF667), cystic fibrosis transmembrane conductance regulator (CFTR), acyl-CoA medium-chain synthetase-3 (ACSM3), complement 6 (C6), protein tyrosine phosphatase receptor type M (PTPRM), hypoxia-inducible factor 1 alpha (HIF1A), adenylyl cyclase 5 (ADCY5), adherens junctions-associated protein 1 (AJAP1), neurobeachin (NBEA), sodium voltage-gated channel alpha subunit 9 (SCN9A)] that are associated with perineural invasion and poor prognosis of PDAC. The relationship between genetic alterations in these 20 genes and tumor immune microenvironment (TME) has not previously been investigated.

METHODS: We hence applied the sequential multiplex immunohistochemistry results of biopsy specimens from 63 PDAC patients to investigate this relationship.

RESULTS: We found that, except for PTPRM and NBEA, genetic alterations involving these 20 genes are associated with significant changes in the densities of major immune cell subtypes. Except for AJAP1, the copy number loss involving this panel of neuronal development genes is significantly associated with changes in immune cell infiltrates. In contrast, the copy number gain in fewer genes, including NRXN3, ZNF667, ACSM3, C6, ADCY5, SCN9A, and PRKCE, is significantly associated with changes in immune cell infiltrates.

CONCLUSIONS: Our study suggested that neuronal development genes play a role in modulating TME in a pancreatic cancer setting.

PMID:38495381 | PMC:PMC10942730 | DOI:10.21037/apc-23-13

J Cyst Fibros. 2024 Mar 16:S1569-1993(24)00038-9. doi: 10.1016/j.jcf.2024.03.010. Online ahead of print.

ABSTRACT

Therapeutic drug monitoring (TDM) of elexacaftor, tezacaftor, ivacaftor (ETI) could be a useful tool to increase efficacy and decrease the risk of adverse effects in people with Cystic Fibrosis (pwCF). It is however unclear whether drug exposure should be monitored by assessment of trough (Cmin) levels or determination of the area under the curve (AUC). Hence, in this study the correlation between measured Cmin concentration and AUC was evaluated. Serial plasma samples, including Cmin, were drawn after administration of ETI in order to calculate the AUC and assess the correlation between the two parameters. A linear correlation between Cmin and AUC0-24h was found, with Pearson's r correlation coefficients of 0.963, 0.908 and 0.860 for elexacaftor, tezacaftor and ivacaftor, respectively. Exposure of ETI may be monitored by assessment of Cmin levels.

PMID:38494378 | DOI:10.1016/j.jcf.2024.03.010

Nutr Clin Pract. 2024 Mar 16. doi: 10.1002/ncp.11142. Online ahead of print.

ABSTRACT

BACKGROUND: Approximately 85% of patients with cystic fibrosis (CF) have exocrine pancreatic insufficiency (EPI) with 10% requiring supplemental nighttime enteral tube feedings. Administration of pancreatic enzyme replacement therapy (PERT) with nighttime feedings is fraught with challenges. RELiZORB (Alcresta Therapeutics, Inc), an in-line lipase cartridge, delivers PERT continuously with enteral feedings. Outcomes related to the use of this in-line lipase cartridge are lesser known. This project evaluated anthropometrics related to in-line lipase cartridge use among pediatric patients with CF already receiving oral PERT therapy prior to nighttime enteral feedings.

METHODS: Retrospective chart review was performed on 29 patients with CF and EPI receiving supplemental tube feedings and utilizing in-line lipase cartridge for a continuous 12 month period between 2015 and 2019. Anthropometrics were evaluated 12 months before and after initiation of in-line lipase cartridge.

RESULTS: Compared with mean height z score at 6-months pre-in-line lipase cartridge, mean height z score at 6-months post-in-line-lipase cartridge (adjusted mean difference [AMD] = 0.2540; 95% CI = [0.0487, 0.4592]; P = 0.0153) and mean height z score at 12-months post-in-line lipase cartridge (AMD = 0.2684; 95% CI = [0.0203, 0.5166]; P = 0.0340) were significantly higher. Mean weight z score at 12-months post-in-line-lipase-cartridge neared statistical significance compared with 6-months pre-in-line lipase cartridge (AMD = 0.2816; 95% CI = [-0.0003, 0.5634]; P = 0.0502) when excluding seven patients with advanced lung disease (forced expiratory volume in the first second of expiration of 40%). Weight-for-length or body mass index did not significantly differ compared with pre-in-line lipase cartridge.

CONCLUSION: Use of in-line lipase cartridge with enteral feeds improved anthropometrics, especially height, in pediatric patients with CF.

PMID:38493301 | DOI:10.1002/ncp.11142

Pancreatology. 2024 Mar 10:S1424-3903(24)00066-8. doi: 10.1016/j.pan.2024.03.005. Online ahead of print.

ABSTRACT

BACKGROUND: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants.

METHODS: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI).

RESULTS: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function.

CONCLUSIONS: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.

PMID:38493004 | DOI:10.1016/j.pan.2024.03.005

J Cyst Fibros. 2024 Mar 14:S1569-1993(24)00030-4. doi: 10.1016/j.jcf.2024.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Iron deficiency (ID) is a common extrapulmonary manifestation in cystic fibrosis (CF). CF transmembrane conductance regulator (CFTR) modulator therapies, particularly highly-effective modulator therapy (HEMT), have drastically improved health status in a majority of people with CF. We hypothesize that CFTR modulator use is associated with improved markers of ID.

METHODS: In a multicenter retrospective cohort study across 4 United States CF centers 2012-2022, the association between modulator therapies and ID laboratory outcomes was estimated using multivariable linear mixed effects models overall and by key subgroups. Summary statistics describe the prevalence and trends of ID, defined a priori as transferrin saturation (TSAT) <20 % or serum iron <60 μg/dL (<10.7 μmol/L).

RESULTS: A total of 568 patients with 2571 person-years of follow-up were included in analyses. Compared to off modulator therapy, HEMT was associated with +8.4 % TSAT (95 % confidence interval [CI], +6.3-10.6 %; p < 0.0001) and +34.4 μg/dL serum iron (95 % CI, +26.7-42.1 μg/dL; p < 0.0001) overall; +5.4 % TSAT (95 % CI, +2.8-8.0 %; p = 0.0001) and +22.1 μg/dL serum iron (95 % CI, +13.5-30.8 μg/dL; p < 0.0001) in females; and +11.4 % TSAT (95 % CI, +7.9-14.8 %; p < 0.0001) and +46.0 μg/dL serum iron (95 % CI, +33.3-58.8 μg/dL; p < 0.0001) in males. Ferritin was not different in those taking modulator therapy relative to off modulator therapy. Hemoglobin was overall higher with use of modulator therapy. The prevalence of ID was high throughout the study period (32.8 % in those treated with HEMT).

CONCLUSIONS: ID remains a prevalent comorbidity in CF, despite availability of HEMT. Modulator use, particularly of HEMT, is associated with improved markers for ID (TSAT, serum iron) and anemia (hemoglobin).

PMID:38490920 | DOI:10.1016/j.jcf.2024.03.002

J Pediatr Nurs. 2024 Mar 14;77:96-105. doi: 10.1016/j.pedn.2024.03.011. Online ahead of print.

ABSTRACT

PURPOSE: The present study evaluates the effects of the application of Self-Care Deficit Nursing Theory (SCDNT) on the self-care knowledge and skills in adolescents with Cystic Fibrosis.

DESIGN AND METHODS: This randomized controlled study included 30 adolescents who were equally divided into the intervention and control groups. The data were collected by using the Sociodemographic Data Form and the Self-Care Knowledge and Skills Evaluation Forms for Adolescents with Cystic Fibrosis. A total of seven home visits were conducted with the adolescents in the intervention group, during which individualized care plans were applied based on the Self-Care Deficit Nursing Theory. The self-care needs of the adolescents in the control group were identified based on data collected during two home visits conducted at the onset of the study and after 4.5 months.

RESULTS: As a result of the application of nursing interventions based on the SCDNT, a statistically significant increase was noted in the self-care knowledge and skills of the adolescents in the intervention group (p < 0.05). Additionally, after the interventions based on SCDNT, the need of adolescents for nursing interventions decreased significantly over time in all adolescents in the intervention group (p < 0.05).

CONCLUSIONS: The application of nursing interventions based on the SCDNT was effective in enhancing the self-care knowledge and skills of adolescents with Cystic Fibrosis.

PRACTICE IMPLICATIONS: Nurses can benefit from Orem's Self-Care Deficit Nursing Theory in the design and application of the individualized care of adolescents with Cystic Fibrosis to improve their self-care practices.

PMID:38490107 | DOI:10.1016/j.pedn.2024.03.011

EBioMedicine. 2024 Mar 14;102:105058. doi: 10.1016/j.ebiom.2024.105058. Online ahead of print.

ABSTRACT

BACKGROUND: In male mice, a circadian rhythm in myogenic reactivity influences the extent of brain injury following subarachnoid haemorrhage (SAH). We hypothesized that female mice have a different cerebrovascular phenotype and consequently, a distinct SAH-induced injury phenotype.

METHODS: SAH was modelled by pre-chiasmatic blood injection. Olfactory cerebral resistance arteries were functionally assessed by pressure myography; these functional assessments were related to brain histology and neurobehavioral assessments. Cystic fibrosis transmembrane conductance regulator (CFTR) expression was assessed by PCR and Western blot. We compared non-ovariectomized and ovariectomized mice.

FINDINGS: Cerebrovascular myogenic reactivity is not rhythmic in females and no diurnal differences in SAH-induced injury are observed; ovariectomy does not unmask a rhythmic phenotype for any endpoint. CFTR expression is rhythmic, with similar expression levels compared to male mice. CFTR inhibition studies, however, indicate that CFTR activity is lower in female arteries. Pharmacologically increasing CFTR expression in vivo (3 mg/kg lumacaftor for 2 days) reduces myogenic tone at Zeitgeber time 11, but not Zeitgeber time 23. Myogenic tone is not markedly augmented following SAH in female mice and lumacaftor loses its ability to reduce myogenic tone; nevertheless, lumacaftor confers at least some injury benefit in females with SAH.

INTERPRETATION: Female mice possess a distinct cerebrovascular phenotype compared to males, putatively due to functional differences in CFTR regulation. This sex difference eliminates the CFTR-dependent cerebrovascular effects of SAH and may alter the therapeutic efficacy of lumacaftor compared to males.

FUNDING: Brain Aneurysm Foundation, Heart and Stroke Foundation and Ted Rogers Centre for Heart Research.

PMID:38490104 | DOI:10.1016/j.ebiom.2024.105058

J Antimicrob Chemother. 2024 Mar 15:dkae069. doi: 10.1093/jac/dkae069. Online ahead of print.

NO ABSTRACT

PMID:38489535 | DOI:10.1093/jac/dkae069

Pediatr Allergy Immunol. 2024 Mar;35(3):e14109. doi: 10.1111/pai.14109.

NO ABSTRACT

PMID:38488437 | DOI:10.1111/pai.14109

Rev Med Liege. 2024 Mar;79(3):175-180.

ABSTRACT

It is estimated that in highly medicalised countries, median life expectancy for most newborns with cystic fibrosis now exceeds 70 years, approaching that of the general population. However, socio-economic disparities between countries continue to have a devastating impact on the prognosis of patients in Eastern Europe, Africa, India and South America. In Morocco, very limited genetic data suggest that the prevalence of this disease is at least of the same order as in Belgium. But as it is not really recognised by the national health system, patients are denied access even to symptomatic treatment. As a result, their outcome is tragic, similar to what it was 60 years ago in the most medicalised countries. A pilot project for a first paediatric reference centre in Casablanca is currently being set up. If properly resourced, this project can only be a success and should be the first step on the road towards cystic fibrosis care in this country. In a very humble way, several Belgian stakeholders are trying to support this project.

PMID:38487912

Ital J Pediatr. 2024 Mar 14;50(1):51. doi: 10.1186/s13052-024-01607-y.

ABSTRACT

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms' exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered.

PMID:38486305 | DOI:10.1186/s13052-024-01607-y

J Health Psychol. 2024 Mar 14:13591053241235095. doi: 10.1177/13591053241235095. Online ahead of print.

ABSTRACT

The purpose of the study was to assess the psychometric properties of the parent-report version of the Sibling Perception Questionnaire (SPQ) in well-siblings. Participants were 200 caregivers of healthy children ages 9-17 years who had a sibling (ages 0-18 years) diagnosed with cancer, diabetes, cystic fibrosis, epilepsy, spina bifida, or congenital heart disease. The SPQ had acceptable internal consistency reliability for the total score (α = 0.83) and displayed acceptable convergent validity as evidenced by medium to large positive correlations with the Strengths and Difficulties Questionnaire and Pediatric Quality of Life Inventory 4.0 (r's ranged from 0.39 to 0.56). The original four-factor model displayed a poor model fit (CFI = 0.6, RMSEA = 0.11, TLI = 0.55, SRMR = 0.14) in comparison to a revised, 14-item four-factor model (CFI = 0.92, RMSEA = 0.07, TLI = 0.90, SRMR = 0.06). The shortened, 14-item parent-report version of the SPQ largely demonstrated good psychometric properties and has the potential to reduce the burden of caregivers filling out the measure.

PMID:38485711 | DOI:10.1177/13591053241235095