Heliyon. 2025 May 16;11(10):e43353. doi: 10.1016/j.heliyon.2025.e43353. eCollection 2025 May.

ABSTRACT

[This corrects the article DOI: 10.1016/j.heliyon.2024.e25241.].

PMID:40535871 | PMC:PMC12169290 | DOI:10.1016/j.heliyon.2025.e43353

Am J Transl Res. 2025 May 15;17(5):3813-3823. doi: 10.62347/ENOM2926. eCollection 2025.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive monogenic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in impaired CFTR protein function. Predominantly affecting Caucasians, CF involves multiple organ systems, including the lungs, pancreas, liver, gastrointestinal tract, and reproductive system. In contrast, CF remains rare among Asian populations, particularly within the Chinese demographic. Reported cases in China predominantly feature heterozygous CFTR mutations, with no confirmed instances of homozygous mutations. A 15-year-old male presented with a 6-year history of recurrent cough and purulent yellow-green sputum production, without hemoptysis. Whole exome sequencing identified a homozygous CFTR mutation, NM_000492.4:c.2290C>T (p.Arg764*), confirming the diagnosis of CF complicated by pulmonary infection. The patient received intravenous cefoperazone/sulbactam (2.25 g every 12 hours) and moxifloxacin (400 mg once daily). Symptomatic improvement was achieved after 2 weeks, and azithromycin was prescribed (three times weekly) upon discharge. This case highlights the importance of considering CFTR gene mutations in patients with prolonged respiratory symptoms (recurrent cough and sputum production) and imaging findings indicative of pulmonary CF. Whole exome sequencing is recommended to determine the genetic etiology in such cases and guide targeted management.

PMID:40535643 | PMC:PMC12170377 | DOI:10.62347/ENOM2926

J Pediatr Pharmacol Ther. 2025 Jun;30(3):332-339. doi: 10.5863/JPPT-24-00061. Epub 2025 Jun 9.

ABSTRACT

OBJECTIVE: The purpose of this study was to characterize reported usage, dosage regimens, and monitoring practices of inhaled tobramycin in health systems with neonatal intensive care units (NICUs), pediatric intensive care units (PICUs), and cardiovascular intensive care units (CICUs) from the members of the Pediatric Pharmacy Association (PPA). The primary objective was to identify the number of respondents who use an inhaled tobramycin protocol. The secondary objectives included the main indications, dosage regimens, monitoring parameters used, and administration details for inhaled tobramycin.

METHODS: A cross-sectional questionnaire was distributed to PPA members from March 28-May 22, 2023. Descriptive statistics were employed.

RESULTS: The questionnaire was completed by respondents at 79 institutions; respondents at 61 institutions used inhaled tobramycin in PICUs (n = 45; 73.8%), NICUs (n = 36; 59.0%), and CICUs (n = 14; 23.0%). Most respondents (n = 73; 92.4%) in the 61 institutions that use inhaled tobramycin did not have an established protocol. The most common tobramycin product used was a tobramycin nebulization solution, and the most common indication was ventilator-associated tracheitis. Respondents noted the most common dosage regimen was 40 to 80 mg every 8 to 12 hours or 150 mg every 12 hours, regardless of patient age. Most respondents were unaware of the nebulizer used and the location of the nebulizer within the ventilator circuit. Additionally, the respondents noted that their intensive care units do not routinely check tobramycin serum concentrations.

CONCLUSION: Most respondents did not have a standardized inhaled tobramycin protocol. There are variations in the dosage regimen, administration, and monitoring practices in critically ill children receiving inhaled tobramycin. Pediatric clinical pharmacists should work with interprofessional teams, including respiratory therapists and providers, to standardize the use of inhaled antibiotics.

PMID:40534942 | PMC:PMC12172681 | DOI:10.5863/JPPT-24-00061

Mol Ther. 2025 Jun 17:S1525-0016(25)00472-1. doi: 10.1016/j.ymthe.2025.06.021. Online ahead of print.

ABSTRACT

Cystic Fibrosis (CF) is a severe genetic disorder caused by loss-of-function mutations in the CFTR gene. Gene editing approaches have the potential to correct such mutations. This systematic review outlines the mechanisms of the main CRISPR-based technologies, and, through cross-study comparisons, analyzes twenty-seven research articles that applied these technologies to target CF-causing variants. We report and discuss the strategy design, target cell selection, editing efficiency, prevalence of editing byproducts and levels of CFTR functional restoration achieved in each work, with the aim of providing technical insights for further exploration of CRISPR-based gene editing approaches. Our findings show that the F508del and W1282X mutations were the most extensively studied CF-causing variants, though over fifteen mutations were targeted overall. The majority of works under review explored the use of homology-directed repair (HDR) or base editing, with a growing number reporting efficient prime editing. Some studies tackled multiple individual mutations, compared different editors, or tested strategies across various models, while others focused on approaches that rescue CFTR function without directly correcting a mutation. Several works also proposed strategies that could address multiple variants with a single approach, while others highlighted technical difficulties in editing certain regions of the CFTR gene. This cross-study comparison also emphasizes the need for standardized reporting of editing efficiency and functional rescue, and stresses the importance of further single-cell RNA sequencing and in-vivo studies to reach clinically-relevant conclusions. However, as gene editing techniques continue to evolve, and with over sixty ongoing CRISPR-based clinical trials, there is growing optimism for meaningful advancements in CF gene-editing therapeutics.

PMID:40534129 | DOI:10.1016/j.ymthe.2025.06.021

Nutr Clin Pract. 2025 Jun 18. doi: 10.1002/ncp.11332. Online ahead of print.

ABSTRACT

Cystic fibrosis transmembrane regulator (CFTR)-directed therapies, such as modulators, have transformed the medical management of people with CF, resulting in better lung function, weight, and body mass index in recent years. With improved nutrition status in people on CFTR modulators, the emphasis on a high-energy, high-fat diet (the legacy CF diet) is declining, with an increased focus on a healthy diet. The increased survival and median predicted age of people with CF have created a need for more attention to metabolic diseases, including hypertension, dyslipidemia, and cardiovascular diseases. The effects of modulators on extrapulmonary manifestations associated with CF, such as CF-related diabetes, CF hepatobiliary involvement, gastrointestinal tract disorders, and pancreatic manifestations, are currently unknown. Approximately 95% of people with CF qualify for treatment with a CFTR modulator. This review discusses the basics of CFTR gene mutations and changes in nutrition status related to treatment with CFTR modulators.

PMID:40533897 | DOI:10.1002/ncp.11332

JAMA Psychiatry. 2025 Jun 18:e251246. doi: 10.1001/jamapsychiatry.2025.1246. Online ahead of print.

ABSTRACT

IMPORTANCE: Psychiatric diagnoses are not defined by neurobiological measures hindering the development of therapies targeting mechanisms underlying mental illness. Research confined to diagnostic boundaries yields heterogeneous biological results, whereas transdiagnostic studies often investigate individual symptoms in isolation.

OBJECTIVE: To develop a framework that groups clinical symptoms compatible with ICD-10 and DSM-5 according to their covariation and shared brain mechanisms.

DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study was conducted in 2 samples, the population-based Reinforcement-Related Behaviour in Normal Brain Function and Psychopathology (IMAGEN) cohort (longitudinal assessments at 14, 19, and 23 years; study duration from March 2010 to the present) and the cross-diagnostic Brain Network Based Stratification of Mental Illness (STRATIFY)/Earlier Detection and Stratification of Eating Disorders and Comorbid Mental Illnesses (ESTRA) samples (study duration from October 2016 to September 2023). The samples are from 8 clinical research hospitals in Germany, the UK, France, and Ireland. For the population-based IMAGEN study, 794 of 1253 23-year-old participants had complete assessments including complete clinical assessments and neuroimaging data across all time points. For the cross-diagnostic STRATIFY/ESTRA samples, 209 of 485 participants aged 18 to 26 years had complete clinical and neuroimaging data. The sample included healthy control individuals and patients with alcohol use disorder, major depressive disorder, anorexia nervosa, and bulimia nervosa.

EXPOSURES: Sparse generalized canonical correlation analysis was used to integrate diverse data from clinical symptoms and 7 brain imaging modalities.

MAIN OUTCOMES AND MEASURES: The prediction of symptom features was the main outcome. The model was developed in the training set from the IMAGEN Study at age 23 years (70%), then applied in the remaining holdout test sample (30%), the independent STRATIFY/ESTRA patient sample, and longitudinally in the IMAGEN set.

RESULTS: In total, 1003 participants were included (425 male and 578 female; mean [SD] age, 22.1 [1.5] years). The reassembly of existing ICD-10 and DSM-5 symptoms revealed 6 cross-diagnostic psychopathology scores. They were consistently associated with multimodal neuroimaging components: excitability and impulsivity (training set: r, 0.26; 95% CI, 0.18-0.33; test set: r, 0.22; 95% CI, 0.10-0.35; STRATIFY/ESTRA set: r, 0.19; 95% CI, 0.07-0.31), depressive mood and distress (training: r, 0.30; 95% CI, 0.20-0.38; test: r, 0.22; 95% CI, 0.09-0.35; STRATIFY/ESTRA: r, 0.19; 95% CI, 0.04-0.33), emotional and behavioral dysregulation (training: r, 0.40; 95% CI, 0.31-0.48; test: r, 0.17; 95% CI, 0.14-0.36; STRATIFY/ESTRA: r, 0.19; 95% CI, 0.06-0.30), stress pathology (training: r, 0.32; 95% CI, 0.19-0.43; test: r, 0.14; 95% CI, 0.05-0.23; STRATIFY/ESTRA: r, 0.12; 95% CI, 0.01-0.22), eating pathology (training: r, 0.34; 95% CI, 0.25-0.42; test: r, 0.26; 95% CI, 0.15-0.37; STRATIFY/ESTRA: r, 0.15; 95% CI, 0.12-0.34), and social fear and avoidance symptoms (training: r, 0.31; 95% CI, 0.25-0.42; test: r, 0.18; 95% CI, 0.15-0.35; STRATIFY/ESTRA: r, 0.12; 95% CI, 0.12-0.33).

CONCLUSION AND RELEVANCE: In this study, the identification of symptom groups of mental illness robustly defined by precisely characterized brain mechanisms enabled the characterization of dimensions of psychopathology based on quantifiable neurobiological measures.

PMID:40531512 | PMC:PMC12177734 | DOI:10.1001/jamapsychiatry.2025.1246

Eur Respir Rev. 2025 Jun 18;34(176):250002. doi: 10.1183/16000617.0002-2025. Print 2025 Apr.

ABSTRACT

Primary ciliary dyskinesia (PCD) is a heterogeneous multiorgan genetic disease characterised by motile cilia impairment that primarily affects the respiratory system. Multiple breath washout (MBW) is an emerging pulmonary function test. Its main outcome, the lung clearance index (LCI), is a valuable sensitive measure in obstructive lung disease, especially in cystic fibrosis. The potential value of MBW as a monitoring tool for patients with PCD is not well known. This systematic review summarises all articles published by the end of 2022 reporting MBW data in patients with PCD and compares MBW parameters to spirometry and chest imaging findings. We searched PubMed, Embase and Scopus for original studies with MBW measurements in patients with PCD. 14 studies were included in the analysis with a total number of 398 patients. The mean/median LCI ranged from 7.98 to 11.8, whereas mean/median forced expiratory volume in 1 s (FEV1) z-score ranged from -1.98 to -0.5. The LCI was abnormally increased in all studies, whereas only two studies had abnormally decreased FEV1 The LCI also had a stronger correlation with chest computed tomography and magnetic resonance imaging results, compared to FEV1 In conclusion, this review shows that the LCI is abnormally high in PCD from the preschool age up to adulthood. MBW appears to be more sensitive than spirometry in identifying pulmonary function impairment at the early stages of disease. These findings support the use of the LCI in daily clinical practice and provide evidence of using it as an outcome measure in upcoming clinical trials for patients with PCD.

PMID:40533103 | DOI:10.1183/16000617.0002-2025

J Bras Pneumol. 2025 Jun 13;51(2):e20250143. doi: 10.36416/1806-3756/e20250143.

NO ABSTRACT

PMID:40531743 | DOI:10.36416/1806-3756/e20250143

J Bras Pneumol. 2025 Jun 13;51(2):e20240416. doi: 10.36416/1806-3756/e20240416. eCollection 2025.

ABSTRACT

OBJECTIVE: Depression and anxiety have been documented in people with cystic fibrosis (CF), jeopardizing treatment adherence. To date, no studies have assessed the prevalence of psychosocial issues in adolescents with CF in Brazil. We sought to assess the prevalence of depression and anxiety in adolescents with CF in Brazil, as well as the impact of depression and anxiety on treatment adherence.

METHODS: This was a multicenter, prospective, observational, longitudinal study conducted between 2017 and 2019 at 14 CF referral centers in Brazil. We used standardized tools such as the nine-item Patient Health Questionnaire (for depression), the seven-item Generalized Anxiety Disorder scale (for anxiety), and the eight-item Morisky Medication Adherence Scale (for treatment adherence) in order to collect data on 218 CF patients at two different time points.

RESULTS: The prevalence of depression was 19.1% at time point 1 and 15.4% at time point 2. The prevalence of anxiety was 19.1% at time point 1 and 18.0% at time point 2. Depression and anxiety were significantly higher in female patients and lower in those who underwent home physiotherapy or had psychological support. Significant correlations were found between depression and anxiety at both time points, the associations being strongest at time point 1 (r = 0.68; p < 0.001). Most (66.7%) of the study participants reported low adherence to treatment, and the remainder reported either average adherence (in 28%) or high adherence (in 5.3%). Depression and anxiety showed inverse correlations with treatment adherence.

CONCLUSIONS: The prevalence of depression and anxiety in adolescents with CF in Brazil appears to be similar to that reported in other countries, being higher in females and lower in those undergoing home physiotherapy or receiving psychological care. Depression and anxiety appear to correlate with lower treatment adherence. Treating psychosocial issues may effectively improve rates of treatment adherence in adolescents with CF.

PMID:40531733 | DOI:10.36416/1806-3756/e20240416

J Bras Pneumol. 2025 Jun 13;51(2):e20240406. doi: 10.36416/1806-3756/e20240406. eCollection 2025.

ABSTRACT

OBJECTIVE: To evaluate the impact of the elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination on the small airways in adults with cystic fibrosis (CF), a genetic disorder that primarily affects the respiratory system, leading to progressive lung disease. In CF, the small airways play a critical role, contributing to chronic symptoms such as cough, sputum production, and dyspnea.

METHODS: This was a single-center, retrospective observational study of adults with CF treated with ELX/TEZ/IVA for 12 months. We compared the patients who were homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene with those who were heterozygous for that mutation, in terms of lung function outcomes (FEV1, FEF25-75%, and the RV/TLC ratio) and the extent of non-homogeneous ground-glass opacity. Among the patients within the cohort, the same parameters were evaluated separately in those who had advanced lung disease and in those who had previously undergone CFTR modulator therapy.

RESULTS: There was a significant post-treatment improvement in lung function, with a median increase of 0.42 L/s in the FEF25-75% (p < 0.001) and a 5% reduction in the mean RV/TLC ratio (p < 0.001). There was a trend toward a higher improvement the F508del homozygous patients. A significant reduction in non-homogeneous ground-glass opacity was observed in 79.5% of the patients. Among the patients with advanced lung disease, there were notable post-treatment improvements in all of the parameters assessed.

CONCLUSIONS: Our results highlight the positive impact that ELX/TEZ/IVA treatment can have on small airway function in patients with CF, with potential benefits even for those with advanced lung disease. Further research is needed in order to evaluate the long-term effects of this treatment and its relationship with patient-reported outcomes.

PMID:40531731 | DOI:10.36416/1806-3756/e20240406

CVIR Endovasc. 2025 Jun 18;8(1):51. doi: 10.1186/s42155-025-00551-0.

ABSTRACT

BACKGROUND: Bronchial artery embolisation (BAE) is considered the most effective non-surgical technique for management of moderate-massive haemoptysis. Associated risks include neurological compromise such as stroke and spinal cord ischaemia. We aim to evaluate post-procedural outcomes and complication rates.

MATERIALS AND METHODS: A single-centre retrospective observational study was conducted for BAE cases performed between January 2002-June 2022 in a London teaching hospital. Data was collected from electronic medical records and Picture Archiving Communications System (PACS). Primary outcomes were measured, and statistical analysis was performed to identify risk factors for haemoptysis recurrence.

RESULTS: One hundred eleven patients underwent 141 procedures with technical success achieved in 87.8% and clinical success in 84.8%. The most common causes of haemoptysis were aspergilloma (24.8%), bronchiectasis (19.1%) and malignancy (11.3%). Haemoptysis recurrence occurred in 65 cases (46%) with 20 patients undergoing repeat embolisation. Aspergillosis, cystic fibrosis, and non-tuberculous pneumonia were identified as risk factors for recurrent haemoptysis (p < 0.005). Pre-procedure MDCTA did not improve technical success. The rate of stroke in the cohort was 6.4% (9 cases), which is more so than quoted in the literature. Four of these patients presented with apical cavitations secondary to infection (aspergilloma or bacterial pneumonia).

CONCLUSIONS: BAE is an effective endovascular treatment in patients with massive and recurrent haemoptysis. However, there is a well-documented risk of recurrent symptoms and early mortality, particularly in the setting of aspergilloma, cystic fibrosis and non-tuberculous pneumonia. The risk of stroke should not be underestimated. Patients should be counselled appropriately during informed consent prior to embarking on BAE.

PMID:40531240 | DOI:10.1186/s42155-025-00551-0

Adv Anat Pathol. 2025 Jun 16. doi: 10.1097/PAP.0000000000000502. Online ahead of print.

ABSTRACT

The list of genetically defined causes of cholestatic liver diseases continues to expand; it currently includes mutations affecting bile acid synthesis, basolateral and apical membrane transporters, bile duct development, canalicular tight junctions, and bile acid conjugation, among others. The most frequently identified mutations in large multi-institutional studies of cholestasis occur in JAG1, ATP8B1, ABCB11, ABCB4, SERPINA1, and CFTR. Mutations in JAG1, SERPINA1, and CFTR cause Alagille syndrome, alpha-1 antitrypsin deficiency, and cystic fibrosis, respectively. Mutations in ATP8B1, ABCB11, and ABCB4 cause a spectrum of diseases that range from the episodic, nonprogressive benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy to the severe and rapidly progressive familial intrahepatic cholestasis. These cholestatic disorders present a wide range of symptoms and overlapping clinical features. However, in contemporary practice, diagnosis is often easily and rapidly established by clinically available comprehensive gene panels. In addition to diagnosis, these panels also aid in the discovery of novel genes or variants as potential causes of cholestasis. Genetic mutations may also be responsible for drug-induced cholestasis, as the liver plays a vital role in metabolism of drugs and xenobiotics. Uptake into hepatocytes and elimination into the bloodstream or bile of drugs and xenobiotics involve transporters across the basolateral and apical hepatocellular membranes, respectively. Therefore, mutations in any of the transporters lead to impaired metabolism and/or elimination of these substances. Furthermore, a large number of drugs and xenobiotics have a transcriptional or functional inhibitory effect on transporters such as BSEP and MDR3, setting the stage for the all-too-common drug-induced cholestasis.

PMID:40530431 | DOI:10.1097/PAP.0000000000000502

Front Pediatr. 2025 Jun 2;13:1604037. doi: 10.3389/fped.2025.1604037. eCollection 2025.

ABSTRACT

BACKGROUND: Growing evidence indicates that prematurity adversely affects lung function, even in early childhood, thus, a routine respiratory follow-up was implemented in our clinical setting. The aim of this study was to evaluate the acceptance of this examination and assess the feasibility of forced expiratory maneuvers and bronchodilator responsiveness test (BRT) in former preterm infants at preschool age and to present initial results.

METHODS: In November 2022, a respiratory follow-up was implemented for former preterm infants born at less than 32 weeks of gestation or with a birth weight below 1,500 g, who were born between 2016 and 2019 at Innsbruck Medical University Hospital. The evaluation included a standardized clinical examination, collection of medical history, spirometry, and a BRT.

RESULTS: A total of 107 former preterm infants (median gestational age 29.9 (28.1; 31.1) weeks and mean birthweight 1,250.5 (±355.6) grams performed spirometry. Successful spirometry was achieved by 93 (86.9%) children. Among these, 64 (59.8%) had normal pulmonary function and were symptom-free, however, ten (15.6%) showed a positive BRT. Twenty-nine children (27.1%) exhibited pathological test results and/or respiratory symptoms, with 13 (44.8%) of them testing positive for bronchial hyper-responsiveness. Fourteen children (13.1%) did not meet the quality control criteria for spirometry but were symptom-free.

CONCLUSION: Our study demonstrated that a respiratory follow-up for preterm infants is highly accepted and feasible at preschool age. Up to 30% of infants were identified with impaired lung function and subsequently received appropriate management, highlighting the importance of standardized and routine respiratory follow-up for these children.

PMID:40530186 | PMC:PMC12171263 | DOI:10.3389/fped.2025.1604037

JHLT Open. 2025 May 26;9:100299. doi: 10.1016/j.jhlto.2025.100299. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Ex vivo lung perfusion (EVLP) has been clinically applied as a lung preservation and assessment tool prior to lung transplantation (LTx) and is evolving to become a platform to deliver cellular and gene therapies or inactivate pathogens. Here we aimed to investigate the utility of our recently reported rat EVLP-to-LTx model as the smallest ever experimental survival model of EVLP-to-LTx and to compare late graft endpoints between strain combinations.

METHODS: We tested three strains as normothermic EVLP donors: Fisher 344 (F344), Lewis (LEW), and Wistar Kyoto (WKy) rats. Then we tested three strain combinations of EVLP-to-LTx (F344-to-WKy, F344-to-LEW, and LEW-to-LEW) to compare histologic and radiologic changes.

RESULTS: F344 and LEW, but not WKy rat lungs, tolerated 4 hours of normothermic EVLP. F344-to-WKy EVLP-to-LTx developed significant histologic (as measured by acute lung injury score, ISHLT A and B grade rejection score) and radiologic (volume and mean Hounsfield units of aerated lung graft analyzed by computed tomography at day 7 after EVLP-to-LTx) changes in the lung allograft. In this strain combination, progressive deterioration with time was noted up to day 28, while F344-to-LEW grafts exhibited only mild injuries similar to LEW-to-LEW. In addition, flow cytometric analyses of F344-to-WKy EVLP-to-LTx revealed a sharp rise in activation marker expression in lung graft T cells beginning at day 3.

CONCLUSIONS: Our F344-to-WKy EVLP-to-LTx model generates reproducible and clinically relevant histological, radiological, and immunological results similar to those seen in humans. The model is therefore well suited to experimental EVLP studies with long-term follow-up prior to moving to large animal and human studies.

PMID:40530004 | PMC:PMC12173122 | DOI:10.1016/j.jhlto.2025.100299

Lancet Reg Health Am. 2025 Jun 5;47:101142. doi: 10.1016/j.lana.2025.101142. eCollection 2025 Jul.

ABSTRACT

BACKGROUND: Attaining the Paris Agreement goal of limiting global temperature rise to below 1.5-2 °C requires the healthcare sector to achieve net-zero emissions by 2050. This necessitates adopting diverse strategies, including replacing carbon-intensive metered-dose inhalers (MDIs) with more environmentally sustainable dry powder inhalers (DPIs) and soft mist inhalers (SMIs). While several European countries have successfully made this transition, patterns of MDI use and barriers to adopting sustainable alternatives in the United States remain poorly understood. Thus, we assessed inhaler utilization, costs, and insurance coverage among U.S. older adults.

METHODS: Using 100% fee-for-service Medicare data with pharmacy benefit (2008-2022), we described utilization trends and costs by device types and drug classes, including inhaled corticosteroids [ICS] and short-/long-acting beta-agonists [S/LABA]. Using the COVERAGE Search database, we extracted formulary data from Part D plans in 10 large US states and described insurance coverage, formulary tier placement (categorizing drugs by costs), prior authorization (requiring insurer approval for coverage), and step therapy (requiring initial trial of lower-cost drugs).

FINDINGS: Of 160,845,280 inhalers dispensed to 10,494,068 older adults (mean age 74 ± 7 years; 38% male; 85% White), 51% were MDIs. Of these MDIs, 88% were SABA and ICS. Median deductible-phase out-of-pocket costs were $3-9 for SABA MDIs vs. $42-49 for DPIs/SMIs and $3-4 for ICS MDIs vs. $3-116 for DPIs/SMIs. Only 18% and 50% of 2530 Part D plans covered SABA and ICS DPIs, respectively. Among the covering plans, >70% placed DPIs for SABA or ICS in higher-cost tiers, with 32-58% requiring prior authorization or step therapy.

INTERPRETATION: MDIs, primarily as SABA or ICS, accounted for over half of inhalers dispensed to US older adults. Most insurance plans excluded sustainable alternatives for SABA/ICS. When covered, additional approval steps and/or higher patient costs were posed. Multi-level efforts are needed to ensure affordable access to sustainable alternatives, as demonstrated in European countries.

FUNDING: Funding for this study was provided by the National Institutes of Health and the National Institute on Aging (1R01AG060232-01A1).

PMID:40529851 | PMC:PMC12173656 | DOI:10.1016/j.lana.2025.101142

J Pediatr Gastroenterol Nutr. 2025 Jun 17. doi: 10.1002/jpn3.70096. Online ahead of print.

ABSTRACT

Acute severe colitis (ASC) is a relatively frequent manifestation in children with ulcerative colitis and one of the few emergencies in paediatric gastroenterology. A standardized proactive approach based on tight monitoring and timely medical and surgical interventions may improve patients' outcomes. We aimed to update the previous ASC guidelines using detailed recommendations and practice points, based on a systematic review of the literature and consensus of experts. These guidelines update is a joint effort of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organization. A systematic search was performed in Pubmed Ovid Medline, Embase and Cochrane databases using 13 predefined PICO (patient, intervention, comparison, outcomes) based questions and 30 non-PICO based questions. Grading methodology was based on the Oxford Centre for Evidence-Based Medicine-Levels of evidence. The questions were addressed by working subgroups following an iterative consensus voting process, including three online voting meetings and one face-to-face meeting. A total of 36 recommendations and 72 practice points were endorsed with a consensus rate of at least 88% for all statements, regarding initial evaluation, monitoring, medical and surgical treatment of ASC in children. Several topics have been revised since the previous 2018 guidelines and differ from corresponding published adult guidelines. These guidelines present a comprehensive overview of the management of ASC in children, offering practical recommendations and practice points aiming to standardize clinical and surgical treatment and improve outcomes of this severe scenario.

PMID:40528309 | DOI:10.1002/jpn3.70096

Ann Med. 2025 Dec;57(1):2516697. doi: 10.1080/07853890.2025.2516697. Epub 2025 Jun 17.

ABSTRACT

INTRODUCTION: Several severe disorders, such as inherited diseases (e.g. cystic fibrosis and beta thalassemia), genetic diseases (e.g. malignant tumors and diabetes), and infectious diseases (e.g. HIV) are pose significant challenges to human health.

BACKGROUND: Over the past few decades, researchers have been working on gene therapies, and currently, terrible dreams have come true. To date, the Food and Drug Administration (FDA) has approved multiple gene therapies such as Kynamro for familial hypercholesterolaemia, Exondys51 for duchenne muscular dystrophy, Spinraza for spinal muscular atrophy, etc., rest for cancer, infectious diseases, and rare diseases.

DISCUSSION: The authors have summarized recent advances in gene therapy, its background, molecular basis (e.g. viral and non-viral vectors), gene-editing techniques (e.g. CRISPR/Cas9, TALEN, ZFN), and its foremost applications in severe disorders, such as cancer, monogenic disorders (e.g. spinal muscular atrophy), polygenic disorders (e.g. autism), neurogenic disorders (e.g. Parkinson disease and Alzheimer's disease), and infectious diseases (e.g. HIV).

CHALLENGES: In addition, we explored the major challenges faced by gene therapies during targeted delivery, immunogenicity, efficacy, and safety.

CONCLUSION: To date, most of the promising approaches, such as different vectors, target cell populations, and both in vivo and ex vivo have paved the foundation for applications of gene therapies. Additionally, advances in enhancing the immune system that would certainly lower the healthcare costs. This review highlights the translatory potential of gene therapy in revolutionizing the treatment landscape for severe disorders.

PMID:40526097 | DOI:10.1080/07853890.2025.2516697

Health Educ Behav. 2025 Jun 17:10901981251346812. doi: 10.1177/10901981251346812. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) affects over 100,000 people worldwide. Despite advances in CF care, sexual and reproductive health (SRH) care continues to lag behind other care priorities. Although partners of females with CF play a critical role in providing support and care, their perspectives of SRH care remain unexplored. During a mixed-methods study, interviews were conducted with 20 partners of females with CF, transcribed verbatim, and analyzed using thematic analysis to determine SRH-related knowledge, experiences, preferences, and concerns. Findings indicate limited progression in CF-related SRH care. Patient-initiated discussions, paternalistic provider views, and a perceived lack of provider collaboration reinforce outdated notions that parenthood in CF is not an option. Partners provide tangible, daily support to reduce disease burden for females with CF and desire inclusion in the decision-making unit. Incorporating partners in SRH discussions and providing SRH-specific training for CF clinicians are imperative to improve patient-centered care.

PMID:40525817 | DOI:10.1177/10901981251346812

Pediatr Pulmonol. 2025 Jun;60(6):e71156. doi: 10.1002/ppul.71156.

ABSTRACT

BACKGROUND: Prior studies have documented improvement in pancreatic status after ivacaftor and lumacaftor/ivacaftor in a small number of patients with cystic fibrosis (CF). There is paucity of data with similar improvement after initiation of elexacaftor/tezacaftor/ivacaftor (ETI).

METHODS: In this cross-sectional study, we retrospectively reviewed the change in fecal elastase-1 (FE-1) at least 6 months after initiation of ETI in children less than 12 years of age. Children who demonstrated a change in FE-1 of ≥ 100 µg/g from the baseline after ETI therapy (post-ETI FE-1 minus pre-ETI FE-1) were termed as responders and those with a change in FE-1 < 100 µg/g post-ETI (or no change in FE-1) were termed as nonresponders.

RESULTS: Thirty-five children had post-ETI FE-1 value at least 6 months after its initiation and were included for final review. The mean change (±SD) in FE-1 post-ETI from the baseline in the entire cohort was 47.2 ± 89.5. Seven children had a change in FE-1 of ≥ 100 µg/g or more post-ETI (responders). Two of these seven patients had a change in FE-1 of ≥ 200 µg/g post-ETI. Twenty-three had no change or change < 100 µg/g post-ETI (nonresponders). Another five children who did not have a baseline FE-1 and had post-ETI FE-1 < 10 µg/g were also added to the nonresponders cohort increasing the total number to 28. The pre- and post-ETI body mass index was significantly higher in the responder group compared to the nonresponders.

CONCLUSION: In our cohort of 35 children, 7 (20%) were noted to have a positive change in FE-1 from the baseline value of ≥ 100 µg/g post-ETI. Further prospective multicenter studies will help identify predictive factors associated with improvement in FE-1 after initiation of CFTR-directed modulator therapies.

PMID:40525743 | DOI:10.1002/ppul.71156

Pediatr Pulmonol. 2025 Jun;60(6):e71168. doi: 10.1002/ppul.71168.

NO ABSTRACT

PMID:40525717 | DOI:10.1002/ppul.71168