Horm Res Paediatr. 2023 Apr 11. doi: 10.1159/000530571. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis transmembrane receptor (CFTR) modulators are increasingly used in children and young people with Cystic Fibrosis (CF). Data in adults show there may be an impact on glycaemic control in those with CF related diabetes (CFRD). Paediatric data are rare. Case series/presentation: Children aged > 12 years with CFRD, who were eligible for Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) were commenced on treatment. Glucose monitoring via the Libre freestyle system was commenced prior to, immediately after and several months after commencing ELX/TEZ/IVA. Glycaemic control, shown by time in range (3 - 10 mmol/L), percentage of time spent hypoglycaemic (<3mmol/L) and percentage of time spent hyperglycaemic (>10mmol/L) on Insulin doses were recorded. Following ELX/TEZ/IVA, four of seven children stopped insulin, two required substantially reduced doses of insulin, one showed no response. Glycaemic control remained similar on lower doses or no insulin. Hypoglycaemia was detected in those not requiring insulin.

DISCUSSION/CONCLUSION: ELX/TEZ/IVA has a positive impact on glycaemic control and insulin requirements in children with CFRD. Close monitoring is required when commencing treatment. Children with CFRD need counselling regarding possible reductions in insulin requirement and re-education regarding symptoms, signs and management of hypoglycaemia.

PMID:37040724 | DOI:10.1159/000530571

Lung Cancer. 2023 Mar 31;179:107184. doi: 10.1016/j.lungcan.2023.107184. Online ahead of print.

ABSTRACT

INTRODUCTION: Checkpoint-inhibitor pneumonitis (CIP) represents a major immune-related adverse event (irAE) in patients with lung cancer. We aimed for the clinical characterization, diagnostics, risk factors, treatment and outcome in a large cohort of patients from everyday clinical practice.

PATIENTS AND METHODS: For this retrospective analysis, 1,376 patients having received checkpoint inhibitors (CPI) in any line of therapy from June 2015 until February 2020 from three large-volume lung cancer centers in Berlin, Germany were included and analyzed.

RESULTS: With a median follow-up of 35 months, all-grade, high-grade (CTCAE ≥ 3) and fatal CIP were observed in 83 (6.0%), 37 (2.7%) and 12 (0.9%) patients, respectively, with a median onset 4 months after initiation of CPI therapy. The most common radiologic patterns were organizing pneumonia (OP) and non-specific interstitial pneumonia (NSIP) (37% and 31%). All except 7 patients with G1-2 CIP interrupted treatment. Corticosteroids were administered to 74 patients with a median starting dose of 0.75 mg/kg. After complete restitution (n = 67), re-exposure to CPI (n = 14) led to additional irAE in 43% of the cases. Thoracic radiotherapy targeting the lung was the only independent risk factor for CIP (odds ratio 2.8, p < 0.001) and pretherapeutic diffusing capacity for carbon monoxide inversely correlated with CIP severity. Compared with patients without CIP and non-CIP irAE, CIP was associated with impaired overall survival (hazard ratios 1.23, p = 0.24 and 2.01, p = 0.005).

CONCLUSIONS: High-grade CIP accounts for almost half of all CIP cases in an allcomer lung cancer population. A continuous vigilance, rapid diagnostics and adequate treatment are key to prevent disease progression associated with impaired survival.

PMID:37040677 | DOI:10.1016/j.lungcan.2023.107184

Proc Natl Acad Sci U S A. 2023 Apr 18;120(16):e2217557120. doi: 10.1073/pnas.2217557120. Epub 2023 Apr 11.

ABSTRACT

Oxygen is a vital molecule involved in regulating development, homeostasis, and disease. The oxygen levels in tissue vary from 1 to 14% with deviations from homeostasis impacting regulation of various physiological processes. In this work, we developed an approach to encapsulate enzymes at high loading capacity, which precisely controls the oxygen content in cell culture. Here, a single microcapsule is able to locally perturb the oxygen balance, and varying the concentration and distribution of matrix-embedded microcapsules provides spatiotemporal control. We demonstrate attenuation of hypoxia signaling in populations of stem cells, cancer cells, endothelial cells, cancer spheroids, and intestinal organoids. Varying capsule placement, media formulation, and timing of replenishment yields tunable oxygen gradients, with concurrent spatial growth and morphogenesis in a single well. Capsule containing hydrogel films applied to chick chorioallantoic membranes encourages neovascularization, providing scope for topical treatments or hydrogel wound dressings. This platform can be used in a variety of formats, including deposition in hydrogels, as granular solids for 3D bioprinting, and as injectable biomaterials. Overall, this platform's simplicity and flexibility will prove useful for fundamental studies of oxygen-mediated processes in virtually any in vitro or in vivo format, with scope for inclusion in biomedical materials for treating injury or disease.

PMID:37040415 | DOI:10.1073/pnas.2217557120

mBio. 2023 Apr 11:e0047223. doi: 10.1128/mbio.00472-23. Online ahead of print.

ABSTRACT

Pf is a filamentous bacteriophage integrated in the chromosome of most clinical isolates of Pseudomonas aeruginosa. Under stress conditions, mutations occurring in the Pf genome result in the emergence of superinfective variants of Pf (SI-Pf) that are capable of circumventing phage immunity; therefore, SI-Pf can even infect Pf-lysogenized P. aeruginosa. Here, we identified specific mutations located between the repressor and the excisionase genes of Pf4 phage in the P. aeruginosa PAO1 strain that resulted in the emergence of SI-Pf. Based on these findings, we genetically engineered an SI-Pf (eSI-Pf) and tested it as a phage therapy tool for the treatment of life-threatening burn wound infections caused by PAO1. In validation experiments, eSI-Pf was able to infect PAO1 grown in a lawn as well as biofilms formed in vitro on polystyrene. eSI-Pf also infected PAO1 present in burned skin wounds on mice but was not capable of maintaining a sustained reduction in bacterial burden beyond 24 h. Despite not lowering bacterial burden in burned skin tissue, eSI-Pf treatment completely abolished the capability of P. aeruginosa to disseminate from the burn site to internal organs. Over the course of 10 days, this resulted in bacterial clearance and survival of all treated mice. We subsequently determined that eSI-Pf induced a small-colony variant of P. aeruginosa that was unable to disseminate systemically. This attenuated phenotype was due to profound changes in virulence determinant production and altered physiology. Our results suggest that eSI-Pf has potential as a phage therapy against highly recalcitrant antimicrobial-resistant P. aeruginosa infections of burn wounds. IMPORTANCE Pseudomonas aeruginosa is a major cause of burn-related infections. It is also the most likely bacterial infection to advance to sepsis and result in burn-linked death. Frequently, P. aeruginosa strains isolated from burn patients display a multidrug-resistant phenotype necessitating the development of new therapeutic strategies and prophylactic treatments. In this context, phage therapy using lytic phages has demonstrated exciting potential in the control P. aeruginosa infection. However, lytic phages can present a set of drawbacks during phage therapy, including the induction of bacterial resistance and limited bacteria-phage interactions in vivo. Here, we propose an alternative approach to interfere with P. aeruginosa pathogenesis in a burn infection model, i.e., by using an engineered superinfective filamentous phage. Our study demonstrates that treatment with the engineered Pf phage can prevent sepsis and death in a burn mouse model.

PMID:37039641 | DOI:10.1128/mbio.00472-23

Am J Physiol Lung Cell Mol Physiol. 2023 Apr 11. doi: 10.1152/ajplung.00382.2022. Online ahead of print.

ABSTRACT

Multiciliated cell loss is a hallmark of airway epithelial remodeling in chronic inflammatory airway diseases including cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease. It disrupts mucociliary clearance, which fuels disease progression. Effective clearance requires an optimal proportion of multiciliated and secretory cells. This is controlled by Notch signaling such that between two adjacent cells the one that activates Notch becomes a secretory cell and the one that avoids Notch activation becomes a multiciliated cell. Consequently, blocking Notch by a small molecule inhibitor of the gamma-secretase enzyme that cleaves the Notch receptor for signal activation directs differentiation towards the multiciliated lineage. Thus, gamma-secretase inhibitor (GSI) treatment may alleviate multiciliated cell loss in lung disease. Here we demonstrate therapeutic restoration of multiciliated cells by the GSI LY450139 (semagacestat). LY450139 increased multiciliated cell numbers in a dose-dependent manner in healthy primary human nasal epithelial cells (HNECs) during differentiation and in mature cultures, but not when applied during early epithelialization of progenitors. LY450139 did not impact stem cell proliferation. Basal and apical administration were equally effective. In healthy adult mice, LY450139 increased multiciliated cell numbers without detectible toxicity. LY450139 also increased multiciliated cells and decreased excess mucus secretory cells in CF HNECs and IL-13 remodeled healthy HNECs. LY450139 normalized multiciliated cell numbers in CF HNECs without interfering with the activity of CFTR modulator compounds. In sum, we demonstrate that GSI administration is a promising therapeutic to restore multiciliated cells and potentially improve epithelial function in a wide range of chronic lung diseases.

PMID:37039381 | DOI:10.1152/ajplung.00382.2022

BMC Pediatr. 2023 Apr 11;23(1):166. doi: 10.1186/s12887-023-03982-7.

ABSTRACT

BACKGROUND: This case report describes a cystic fibrosis case after 7 years of a presumed diagnosis of celiac disease without confirming laboratory tests and biopsies. Both cystic fibrosis and celiac disease cause malnutrition, malabsorption, and failure to thrive. Also, the occurrence of cystic fibrosis in celiac disease patients is higher than in the normal population. Therefore, the differentiation between the two diseases might be challenging. This article highlights the reason for the confusion between cystic fibrosis and celiac disease and emphasizes the importance of not skipping the necessary investigations no matter how difficult it is to perform them.

CASE PRESENTATION: This report details the case history of a patient presumed to have celiac disease for 7 years without confirming investigations. He developed multiple respiratory infections and weight loss throughout the 7 years but was only diagnosed with cystic fibrosis after hospitalization for gradual abdominal distension and productive cough. Chest CT showed atelectasis in the right upper lobe, tree-in-bud sign on both sides, and right periumbilical mass with several enlargements in the mediastinal nodes. Ascites paracentesis revealed a high SAAG gradient and low-protein fluid. The sweat chloride test resulted in a chloride level of 90 mEq/L, which confirmed the cystic fibrosis diagnosis. Subsequent genetic testing revealed the rare G85E mutation.

CONCLUSION: This report highlights the potential for diagnostic confusion between cystic fibrosis and celiac disease. Also, it reminds physicians about the importance of taking a detailed medical history and performing the essential investigations no matter how difficult it is to do them. Finally, it emphasizes the need to verify the patient's previous medical history in case there is no official documentation of his case. This should be considered particularly in rural areas in low-income countries where the possibility of medical malpractice should not be forgotten.

PMID:37038158 | DOI:10.1186/s12887-023-03982-7

J Cyst Fibros. 2023 Apr 8:S1569-1993(23)00080-2. doi: 10.1016/j.jcf.2023.03.016. Online ahead of print.

ABSTRACT

BACKGROUND: A collaboration between the University of Michigan (U of M) Cystic Fibrosis Center (CFC) and Marmara University (MU) CFC was initiated to improve the health status of people with cystic fibrosis (pwCF) at MU through implementing Quality Improvement (QI) initiatives. The main aim was to improve lung function in children with FEV1pp <80. The secondary aim was to assess the changes in health related quality of life.

METHODS: Included in the project were pwCF who received cystic fibrosis (CF) care at the MU CFC and were 6-18 years of age with an FEV1pp <80. Flow charts were created and a standardized CF care algorithm was implemented. Weekly case review were done to develop individualized treatment plans. Appropriate intervention was applied and patient data were assessed at baseline, 3, 6, 9 and 12 months. The Cystic Fibrosis Revised Questionnaire (CFQ-R) was completed.

RESULTS: 55 pwCF were included (mean age:11.8 ± 3.3 years). Mean FEV1pp (SD) at baseline, 6 and 12 month was 63.7 (14.6), 66.9 (16.6), 70.4 (19.2), respectively, with a relative increase of 5.0% in 6 months (p:0.002) and 10.5% in 12 months compared to baseline (p<0.001). Physical functioning, eating problems and respiratory symptoms domains of the CFQ-R questionnaire were improved at the end of the one year for 6-13 (p = 0.024, p = 0.009, p = 0.002) and 13-18 year olds (p = 0.013, p = 0.002, p = 0.038).

CONCLUSION: There was significant improvement in pwCF with FEV1<80%pp after implementing this QI project. The processes and assessments used can be adopted by other low-middle income countries to improve similar measures.

PMID:37037703 | DOI:10.1016/j.jcf.2023.03.016

Respir Med Res. 2023 Mar 5;83:101006. doi: 10.1016/j.resmer.2023.101006. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive health condition caused by gene mutations causing quantitative and or qualitative defect in the cystic-fibrosis transmembrane conductance regulator (CFTR) protein. CFTR defects lead to abnormal ion transport affecting multiple body systems. In CF thick secretions accumulate causing impairment in the pancreas, whole airways, gut and reproductive organs.

CFTR MODULATORS AND PREGNANCY: CFTR modulators have improved the quantity and quality of life of CF patients. There is limited literature on CFTR modulator use in pregnancy and its impact on foetal health. A recent case report described a child with CF being born with pancreatic sufficiency following in-utero CFTR modulator exposure. We review the potential impact of in-utero exposure to CFTR modulators, focusing on pancreatic function and future fertility of unborn individuals with CF.

CONCLUSION: CFTR modulator exposure in-utero is a new concept, therefore the consequences on foetal health remain uncertain. Foetal exposure to modulators could prevent pancreatic damage and infertility.

PMID:37037055 | DOI:10.1016/j.resmer.2023.101006

Respir Med Res. 2023 Feb 1;83:100998. doi: 10.1016/j.resmer.2023.100998. Online ahead of print.

NO ABSTRACT

PMID:37037054 | DOI:10.1016/j.resmer.2023.100998

Pediatr Pulmonol. 2023 Apr 10. doi: 10.1002/ppul.26412. Online ahead of print.

ABSTRACT

INTRODUCTION: Reports of neuropsychiatric symptoms proximal to cystic fibrosis transmembrane conductance regulator (CFTR) modulator initiation are emerging, but their prevalence and management remain poorly characterized.

METHODS: Retrospective chart review was used to categorize symptom trajectories of all adults at a single CF Center who initiated elexacaftor/tezacaftor/ivacaftor (ETI) before March 2022 and subsequently had ≥1 outpatient visit with the consulting CF psychiatrist. For those who developed neuropsychiatric symptoms probably related to ETI and modified treatment in response, the strategy resulting in greatest improvement with acceptable physical course and tolerability was identified. Ratings were made by a psychiatrist not involved in clinical care.

RESULTS: Of 148 adults initiating ETI, 31 were psychiatrically evaluated, 16 of whom developed new/worsening and unexpected neuropsychiatric symptoms probably related to ETI, including neurocognitive (word finding, brain fog, memory, attention/concentration), insomnia, depression, anxiety, fatigue/low energy, mania/hypomania, other distress. This group had higher maximum lifetime Generalized Anxiety Disorder-7 scores (14.42 ± 0.96; p = 0.05) than those with improved, unchanged, or worsening/possibly related symptoms (N = 15; 9.9 ± 1.82). Treatment strategies resulting in much/very much improvement included pharmacologic interventions, psychotherapy, and dose reduction/discontinuing ETI.

CONCLUSIONS: Although many people initiating ETI experience improved physical and mental health and quality of life, a subset report worsening neurocognition, mood, and anxiety. As novel therapies are developed, ascertaining and evaluating neuropsychiatric symptoms in clinical and research settings is advisable. Larger studies are needed to characterize prevalence, course, and risk factors (e.g., age, gender, clinical status, pharmacokinetics/pharmacogenomics, drug-drug interactions) for neuropsychiatric adverse events related to CFTR modulators and guide effective management.

PMID:37036050 | DOI:10.1002/ppul.26412

Liver Int. 2023 Apr 10. doi: 10.1111/liv.15572. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Early identification of risk factors for the development of severe fibrosis in children with cystic fibrosis-related liver disease (CFLD) is crucial as promising therapies emerge.

METHODS: This multi-center cohort study of children with a priori defined CFLD from 1999 to 2016, was designed to evaluate the clinical utility of CF-specific characteristics and liver biomarkers assessed years prior to liver biopsy-proven CFLD to predict risk of developing severe fibrosis (F3-4) over time. Fibrosis was staged by Metavir classification.

RESULTS: The overall study cohort of 42 patients (F0-2 (n = 22) and F3-4 (n = 20)) was 57% male (n = 24) with median age of 7.6 years at baseline visit versus 10.3 years at biopsy. Median FEV1 % predicted was lower in F3-4 participants at baseline versus F0-2 (59% vs. 85%; p = .002), while baseline FIB-4, APRI and GGT were higher in F3-4. Median splits for FIB-4 (≥.13), APRI (≥.36), GPR (≥.09), GGT (≥25.5), and FEV1 % (<64%) were associated with more rapid progression to F3-4 (p < .01 for all). Using a combination of change/year in FIB-4, APRI, and GPR to predict F3-4, the AUROC was .81 (95% CI, .66, .96; p < .0001). For up to 5.8 years prior, thresholds for GPR were met 6.5-fold more rapidly, and those for APRI and FIB-4 were met 2.5-fold more rapidly, in those who progressed to F3-4 than those that did not.

CONCLUSIONS: This study suggests mild-moderate pulmonary dysfunction and higher liver biomarker indices at baseline may be associated with faster progression of CFLD.

PMID:37035868 | DOI:10.1111/liv.15572

Adv Redox Res. 2023 Apr;7:100065. doi: 10.1016/j.arres.2023.100065. Epub 2023 Feb 18.

ABSTRACT

Cadmium (Cd) is a toxic environmental metal that interacts with selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We sought to identify whether an antagonistic relationship existed between Se and Cd burdens and determine whether this relationship may associate with metabolic variation within human lungs. We performed metabolomics of 31 human lungs, including 25 with end-stage lung disease due to idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive lung disease (COPD)/emphysema and other causes, and 6 non-diseased lungs. Results showed pathway associations with Cd including amino acid, lipid and energy-related pathways. Metabolic pathways varying with Se had considerable overlap with these pathways. Hierarchical cluster analysis (HCA) of individuals according to metabolites associated with Cd showed partial separation of disease types, with COPD/emphysema in the cluster with highest Cd, and non-diseased lungs in the cluster with the lowest Cd. When compared to HCA of metabolites associated with Se, the results showed that the cluster containing COPD/emphysema had the lowest Se, and the non-diseased lungs had the highest Se. A greater number of pathway associations occurred for Cd to Se ratio than either Cd or Se alone, indicating that metabolic patterns were more dependent on Cd to Se ratio than on either alone. Network analysis of interactions of Cd and Se showed network centrality was associated with pathways linked to polyunsaturated fatty acids involved in inflammatory signaling. Overall, the data show that metabolic pathway responses in human lung vary with Cd and Se in a pattern suggesting that Se is antagonistic to Cd toxicity in humans.

PMID:37034445 | PMC:PMC10078579 | DOI:10.1016/j.arres.2023.100065

Front Pediatr. 2023 Mar 24;11:1112881. doi: 10.3389/fped.2023.1112881. eCollection 2023.

ABSTRACT

INTRODUCTION: Chronic health effects following acute COVID-19 are increasingly observed as the pandemic continues and are grouped under long COVID. Although the acute course of the COVID disease is often milder, long COVID also affects children and adolescents. As the symptoms present in Long-COVID often seem to be non-specific and not limited to organ systems, clarification of the causes and the creation of a meaningful, efficient and targeted diagnostic algorithm is urgently needed.

METHODS: Therefore, in this prospective observational study, we examined 30 children with long COVID using lung ultrasound and compared the results with those of 15 lung-healthy children.

RESULTS: In our study, no significant difference was found between the two groups in the morphological criteria of lung ultrasound of the pleura or pleural lung structures. There was no significant correlation between the lung ultrasound findings and clinical Data.

DISCUSSION: Our findings are congruent with the current, albeit sparse, data. It is possible that the causes of persistent thoracic symptoms in long COVID might be more likely to be present in functional examinations, but not morphologically imageable. Nonspecific symptoms do not appear to be due to changes in the lung parenchyma. In conclusion, lung ultrasound alone and without baseline in acute disease is not suitable as a standard in the follow-up of long COVID patients. Further investigations on the morphological and functional changes in patient with long COVID is needed.

PMID:37033176 | PMC:PMC10080098 | DOI:10.3389/fped.2023.1112881

J Cyst Fibros. 2023 Apr 7:S1569-1993(23)00083-8. doi: 10.1016/j.jcf.2023.03.019. Online ahead of print.

ABSTRACT

BACKGROUND: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD).

METHODS: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD.

RESULTS: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years.

CONCLUSIONS: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD.

CLINICAL TRIAL REGISTRATION: Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF: NCT 01,144,507 (observational study, no consort checklist).

PMID:37032248 | DOI:10.1016/j.jcf.2023.03.019

Chest. 2023 Apr;163(4):e194-e195. doi: 10.1016/j.chest.2023.01.006.

NO ABSTRACT

PMID:37031994 | DOI:10.1016/j.chest.2023.01.006

Chest. 2023 Apr;163(4):e193-e194. doi: 10.1016/j.chest.2022.11.046.

NO ABSTRACT

PMID:37031993 | DOI:10.1016/j.chest.2022.11.046

J Pediatr. 2023 Apr 6:113411. doi: 10.1016/j.jpeds.2023.113411. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the association between race/ethnicity, poverty, and mental health in youth with chronic conditions.

STUDY DESIGN: A cross-sectional comparative study was performed using the records of a tertiary care center from 2011-2015.

INCLUSION CRITERIA: children aged 4-17 years with >1 hospitalization/ED visit.

EXCLUSION CRITERIA: those with arrhythmias or treatment with clonidine/benzodiazepines.

PRIMARY OUTCOME VARIABLE: diagnosis or medication for anxiety, depression, or attention deficit hyperactivity disorder (ADHD). Primary predictor variable: diagnosis of cystic fibrosis (CF), sickle cell disease (SCD), and congenital heart disease (CHD).

RESULTS: 112,313 patients were identified, 0.2% with CF, 0.4% with SCD, and 1.0% with CHD. Patients with CF had the highest prevalence (23%) and odds (OR 4.21, 95% CI 3.07-5.77) of anxiety or depression, while patients with SCD had the lowest prevalence (7%) and odds (OR 1.54, 95% CI 1.11-2.14). Those with CHD had a prevalence of up to 17%, with 3-4 times higher odds of anxiety or depression (OR 3.70, 95% CI 2.98-4.61). All non-White participants were less likely to be diagnosed/treated for anxiety or depression and ADHD. While poverty increased the probability of anxiety or depression in patients with CHD, this was not seen in CF or SCD.

CONCLUSIONS: Children with CF, SCD, and CHD are at increased risk of anxiety or depression; however non-White patients are likely being under-diagnosed/treated. Increased screening and recognition in minority children are needed to reduce disparities in mental health outcomes.

PMID:37030612 | DOI:10.1016/j.jpeds.2023.113411

Respir Med. 2023 Apr 6:107237. doi: 10.1016/j.rmed.2023.107237. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy have resulted in longer life expectancies, yet pulmonary exacerbations remain a leading cause of morbidity. Intravenous antibiotics is the mainstay treatment, however achieving adequate concentrations remains challenging. The effect of therapeutic drug monitoring (TDM) of beta-lactams on exacerbations and lung function has not been studied.

METHODS: Patient demographics, antibiotic regimens, forced expiratory volume 1 second (FEV1), and exacerbation history was obtained from 32 patients with cystic fibrosis admitted for exacerbations. All patients were colonized with Pseudomonas aeruginosa, received CFTR therapy for at least one year, and had 3-month interval follow ups. Plasma concentrations, FEV1, and exacerbation history was obtained before and after therapeutic drug monitoring. This included peak and trough plasma concentrations of piperacillin-tazobactam and cefepime using liquid chromatography with mass spectrometry. T-test and Mann-Whitney U test were used to compare medians/means of FEV1 and pulmonary exacerbations pre and post-TDM as well as free trough-to-minimum inhibitory concentration ratio (fCmin/MIC) ≥1 and ≥ 4.

RESULTS: TDM was associated with decreased exacerbations/year from 1.91 to 1.31 (p = 0.04) and among the cohort with >/ = 2 exacerbations per year, there was a longer exacerbation free interval after TDM (196.2 vs 103.7 days, p = 0.02). The decline in FEV1% predicted after therapeutic drug monitoring to the first exacerbation was -4.9 compared to -9.7 prior (p = 0.03).

CONCLUSIONS: TDM for cystic fibrosis pulmonary exacerbations results in decreased pulmonary exacerbations, longer intervals to pulmonary exacerbation, and lower decline in FEV1% predicted.

PMID:37030586 | DOI:10.1016/j.rmed.2023.107237

Diabetes Metab. 2023 Apr 6:101444. doi: 10.1016/j.diabet.2023.101444. Online ahead of print.

ABSTRACT

The increase in life expectancy of patients with cystic fibrosis has come with new comorbidities, particularly diabetes. The gradual development of glucose tolerance abnormalities means that 30 to 40% of adults will be diabetic. Cystic fibrosis-related diabetes is a major challenge in the care of these patients because it is a morbidity and mortality factor at all stages of the disease. Early glucose tolerance abnormalities observed from childhood, before the stage of diabetes, are also associated with a poor pulmonary and nutritional outcome. The long asymptomatic period justifies systematic screening with an annual oral glucose tolerance test from the age of 10 years. However, this strategy does not take into account the new clinical profiles of patients with cystic fibrosis, recent pathophysiological knowledge of glucose tolerance abnormalities, and the emergence of new diagnostic tools in diabetology. In this paper, we summarise the challenges of screening in the current context of new patient profiles - patients who are pregnant, have transplants, or are being treated with fibrosis conductance transmembrane regulator modulators - and put forward an inventory of the various screening methods for cystic fibrosis-related diabetes, including their applications, limitations and practical implications.

PMID:37030530 | DOI:10.1016/j.diabet.2023.101444

Lancet Psychiatry. 2023 Apr 5:S2215-0366(23)00115-3. doi: 10.1016/S2215-0366(23)00115-3. Online ahead of print.

NO ABSTRACT

PMID:37030311 | DOI:10.1016/S2215-0366(23)00115-3