JCEM Case Rep. 2025 May 21;3(7):luaf114. doi: 10.1210/jcemcr/luaf114. eCollection 2025 Jul.

ABSTRACT

Cystic fibrosis (CF), a genetic disorder caused by pathogenic variants in the CFTR gene, is associated with various complications including cystic fibrosis-related diabetes (CFRD). CFRD is an entity distinct from type 1 or type 2 diabetes. We report a rare case of diabetic ketoacidosis (DKA) in a pediatric patient with CFRD, occurring during a significant pulmonary exacerbation. The patient's management involved addressing fluid and electrolyte imbalances, careful monitoring of nutritional status, and correction of hyperglycemia with insulin. This case serves as a reminder to consider DKA in the differential diagnosis of patients with CF presenting with respiratory distress, even in the absence of typical symptoms such as polyuria and polydipsia.

PMID:40401175 | PMC:PMC12093047 | DOI:10.1210/jcemcr/luaf114

Respir Med Case Rep. 2025 Apr 19;55:102214. doi: 10.1016/j.rmcr.2025.102214. eCollection 2025.

ABSTRACT

We report three cases of bronchiectasis caused by homozygous WFDC2 variants. The ages at diagnosis of bronchiectasis were 18, 24, and 16 years, and all patients had a history of chronic sinusitis since childhood. Despite low nasal nitric oxide levels, the radiologic features resembled those of cystic fibrosis, characterized by bronchiectasis predominantly in the upper lobes. All patients experienced frequent exacerbations and respiratory dysfunction, even with long-term macrolide therapy. Consequently, two of the three patients required lung transplantation. Considering the possibility of founder mutations, WFDC2 variants should be included in diagnostic panels for patients with sinopulmonary disease in Asian populations.

PMID:40401042 | PMC:PMC12093231 | DOI:10.1016/j.rmcr.2025.102214

J Thorac Dis. 2025 Apr 30;17(4):1832-1843. doi: 10.21037/jtd-2024-2069. Epub 2025 Apr 27.

ABSTRACT

BACKGROUND: Ex vivo lung perfusion (EVLP) of donor lungs not otherwise acceptable for transplantation can provide outcomes similar to standard-criteria lung transplantation and has been reported to increase transplant volume by approximately 20% in some transplant centers. Evidence to support decisions about use of EVLP is limited, so expert opinion can be a useful decision aid. This study developed expert consensus recommendations for EVLP with acellular perfusate using a modified Delphi method.

METHODS: A panel of 18 physicians with expertise in lung transplantation and EVLP who practice in North America completed three surveys on EVLP: Survey 1 used open-ended questions; Survey 2 used primarily Likert-scale questions; and Survey 3 repeated Survey 2 while providing panelists with the Survey 2 results. A follow-up meeting after Survey 3 probed open questions.

RESULTS: The primary goal for EVLP is expanding the number of donor lungs available for transplant. Lungs that are acceptable after EVLP are equivalent to lungs that met standard criteria initially. Lungs with unclear or marginal quality should be placed on EVLP for evaluation, including lungs received from third party organizations with incomplete or concerning information. Decisions on whether to put lungs on EVLP require nuanced clinical judgement and should consider compliance and deflation, the ratio of PaO2 to fraction of inspired oxygen (P/F ratio), peak inspiratory pressure (PIP), edema on imaging, and bronchoscopy, with additional parameters considered as appropriate if lung quality is unclear. EVLP lungs are appropriate for transplant if all relevant parameters are acceptable and may be appropriate if some parameters are borderline depending on clinical judgment. Decisions about transplanting EVLP lungs should consider radiography, delta PO2, overall movement, STEEN Solution™ loss, bronchoscopy, peak airway pressure, and palpation, along with other parameters as appropriate. Key open areas for research include evidence-based criteria for lung selection and assessment, the role of biomarkers, and enhanced techniques and perfusion solutions. In addition, the role of EVLP is unclear in lungs with pulmonary emboli and lungs procured with normothermic regional perfusion (NRP), as is the maximal duration of cold ischemia time (CIT).

CONCLUSIONS: Decisions about EVLP require nuanced consideration of numerous parameters. Expert opinion from this study may help optimize use of EVLP.

PMID:40400975 | PMC:PMC12090176 | DOI:10.21037/jtd-2024-2069

Cureus. 2025 Apr 21;17(4):e82692. doi: 10.7759/cureus.82692. eCollection 2025 Apr.

ABSTRACT

This narrative review aims to describe the evolution, classification, nutritional composition, and clinical applications of enteral infant formulas, with an emphasis on pediatric patients who are unable to be breastfed or follow conventional feeding methods. The primary objective is to analyze the different types of formulas available - polymeric, hydrolyzed, elemental, and blenderized - and their indications based on clinical scenarios and specific patient needs. The methodology used was a non-systematic narrative review. Relevant scientific literature was selected through a targeted search of databases such as PubMed, Scopus, ScienceDirect, and Google Scholar, including publications from the last 20 years in both English and Spanish. Key search terms included "enteral nutrition," "infant formula," "nutritional therapy," and "pediatric enteral feeding." The article traces the historical development of infant nutrition, from breastfeeding and wet nursing to modern enteral formulas. It explains the macronutrient composition of each formula type, their preparation methods, palatability, osmolality, and caloric density. Clinical considerations and recommended formulas for specific diseases - such as obesity, cow's milk allergy, Crohn's disease, eosinophilic esophagitis, necrotizing enterocolitis, short bowel syndrome, and cystic fibrosis - are discussed in detail. Additionally, the review outlines the regulatory context in the United States and Europe, noting that these products are classified as medical foods and not pharmaceuticals, and are thus subject to distinct safety, composition, and labeling requirements. The review concludes that although breastfeeding remains the gold standard in infant nutrition, enteral formulas are indispensable in many clinical situations. Future research is expected to focus on the development of more targeted, functional, and personalized formulas to address the needs of vulnerable pediatric populations.

PMID:40400894 | PMC:PMC12094131 | DOI:10.7759/cureus.82692

Cureus. 2025 Apr 20;17(4):e82655. doi: 10.7759/cureus.82655. eCollection 2025 Apr.

ABSTRACT

Background and objective Dornase alpha can be considered an alternative therapy when the standard therapy fails, but evidence of nebulization through artificial airways for persistent pulmonary atelectasis is limited. The study aimed to determine the efficacy of dornase alpha nebulization on persistent atelectasis in non-cystic fibrosis patients with and without artificial airways. Methodology A retrospective cross-sectional study was conducted on patients admitted to the Pediatric Intensive Care Unit (PICU) of King Fahad Medical City (KFMC) between February 2020 and October 2023. The pre- and post-treatment MRAS (Modified Radiologically Assisted Score) was used to determine the treatment efficacy. The independent t-test and chi-square test were used for statistical analysis. Multivariate regression analysis was applied after estimating the propensity score to adjust baseline characteristics to reduce selection and indication bias. A value of p<0.05 was taken to indicate statistical significance. Results Dornase alpha was not an independent positive predictor of MRAS score improvement (B=0.326, p=0.757, Exp(B)=1.385) beyond other variables. However, the dornase group (n = 132) significantly improved the mean MRAS score by 6.08+2.69 compared to the non-dornase group's (n=143) mean MRAS score of 5.14+2.4, with a moderate effect size (Cohen's d=0.364, 95% CI: 0.126 to 0.603; p=0.03) in resolving persistent atelectasis. Conclusion Dornase alpha did not independently improve MRAS scores in pediatric patients with persistent atelectasis, controlling for selection/indication bias and confounding variables. The observed differences in MRAS improvement in the initial analysis were most likely due to baseline differences.

PMID:40400792 | PMC:PMC12094807 | DOI:10.7759/cureus.82655

Clin Pharmacokinet. 2025 May 21. doi: 10.1007/s40262-025-01507-2. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Following the development of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (ivacaftor, tezacaftor, elexacaftor, and lumacaftor), the prognosis for people diagnosed with cystic fibrosis (pwCF) has improved. Understanding the pharmacokinetics (PK) of CFTR modulators is crucial to provide optimal care, particularly in special cystic fibrosis (CF) populations such as pwCF with hepatic impairment, pancreatic insufficiency, those who are pregnant or lactating, or who are children. We aim to provide an overview of the PK of CFTR modulators in these populations.

METHODS: A systematic literature search was carried out in PubMed and Embase on 20 June 2024. Studies were considered relevant when information on PK or exposure of CFTR-modulating drugs was available.

RESULTS: PwCF with mild/moderate hepatic impairment do not exhibit substantially higher exposure to CFTR modulators compared with those without liver involvement or healthy individuals. Similarly, exocrine pancreatic insufficiency has no effect on the PK of CFTR modulators in adult pwCF. In contrast, pediatric pwCF are exposed to higher levels of CFTR modulators relative to adults, as children receive higher weight-based doses (mg/kg) to ensure equivalent therapeutic efficacy.

CONCLUSIONS: The PK of CFTR modulators have been more extensively studied in adults, pwCF with mild/moderate hepatic impairment, and children. However, ensuring adequate dosing remains challenging. Knowledge gaps persist for adults with severe hepatic impairment (Child-Pugh Class C), children with CF-induced hepatic impairment, and pregnant or lactating pwCF. Future research addressing these gaps, through incorporating routine clinical data, is crucial for improving clinical guidelines and optimizing dosing regimens, thereby advancing towards evidence-based utilization of CFTR modulators.

PMID:40399734 | DOI:10.1007/s40262-025-01507-2

Ther Drug Monit. 2025 May 21. doi: 10.1097/FTD.0000000000001340. Online ahead of print.

ABSTRACT

Acute exacerbations of cystic fibrosis (CF) diminish quality of life and, if inadequately treated, can be life-threatening. The pathophysiological alterations associated with CF result in modified antibiotic pharmacokinetics. Moreover, the viscous mucus in the lungs limits pathogen exposure to drugs, rendering successful antibiotic treatment challenging. A 23-year-old female patient with CF was repeatedly admitted for intravenous antibiotic therapy for acute exacerbation of Pseudomonas aeruginosa infection. In the context of altered pharmacokinetics in CF, therapeutic drug monitoring of meropenem and piperacillin revealed consistently low plasma levels of both drugs. Targeted plasma levels were ultimately achieved through continuous high-dose infusions, based on therapeutic drug monitoring and subsequent dose adjustments.

PMID:40397762 | DOI:10.1097/FTD.0000000000001340

Microbiol Spectr. 2025 May 21:e0281124. doi: 10.1128/spectrum.02811-24. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic human pathogen that can also infect mammals, invertebrates, and plants. Protease IV (PIV) is a secreted protease shown to be important in mammalian cornea, lung, and wound models of infection. It also contributes to P. aeruginosa virulence in many invertebrate models. Previous studies have shown that the expression of the gene encoding PIV is higher at 25°C than at 37°C. Thus, we hypothesized that piv would be more important for P. aeruginosa virulence at 25°C than at 37°C. To test this, we first demonstrated that more PIV is secreted by P. aeruginosa PAO1 cells grown at 25°C than at 37°C. We then determined the survival of larvae of the greater wax moth Galleria mellonella infected by PAO1 and an isogenic Δpiv mutant at both 25°C and 37°C. We found no significant difference in virulence between PAO1 and Δpiv at either 25°C or 37°C, although both strains were more virulent at 37°C than 25°C as measured by a decrease in median survival time. P. aeruginosa possesses an arsenal of virulence factors besides PIV, and thus loss of this single virulence factor may not result in attenuation in the highly susceptible G. mellonella larvae.IMPORTANCEPathogenesis of the important opportunistic pathogen Pseudomonas aeruginosa is often investigated using model organisms. Larvae of the greater wax moth, Galleria mellonella, are a popular non-mammalian model organism for P. aeruginosa infections that have been used to study highly attenuated mutants and characterize their defects in virulence. Our study shows that small differences in the virulence of P. aeruginosa, such as those caused by deleting the gene encoding a single virulence factor, may not be detectable in the G. mellonella model of infection. This is an important finding for researchers considering the choice of model organisms for virulence studies.

PMID:40396793 | DOI:10.1128/spectrum.02811-24

Pediatr Pulmonol. 2025 May;60(5):e71140. doi: 10.1002/ppul.71140.

NO ABSTRACT

PMID:40396441 | DOI:10.1002/ppul.71140

Pediatr Pulmonol. 2025 May;60(5):e71134. doi: 10.1002/ppul.71134.

ABSTRACT

OBJECTIVES: This study aims to study the healthcare (HC) costs associated with cystic fibrosis (CF) in children diagnosed prenatally (ANT), through newborn screening (NBS), after birth due to meconium ileus (MI), or later based on symptoms (LS). Additionally, it seeks to clinically characterize children with CF (chCF) with different trajectories of HC costs.

STUDY DESIGN: A retrospective observational study was conducted on data from the French CF Registry (FCFR) and the French National Claims Database (SNDS) linked from 2006 to 2021. HC costs related to CF diagnosis circumstances were estimated per year of life among chCF up to age 10. Group-based trajectory modeling was performed to identify subgroups with similar cost trajectories.

RESULTS: Between 2006 and 2011, data from 1065 chCF were recorded in the FCFR. Nine hundred seventy-three (91.4%) were matched with SNDS, and 779 (73.1%) had at least 10 years of follow-up. During the first year, HC costs of chCF diagnosed with NBS were lower than for those diagnosed with MI and ANT (all p < 0.05). However, by the tenth year HC were no longer different between groups. Three groups with different cost trajectories were identified. Groups with the highest costs had a lower lung function at 6 and 10 years and the lowest weight and height z-scores at 2 and 10 years (all p < 0.05).

CONCLUSION: NBS is associated with the lowest HC costs during the first year of life.

PMID:40396435 | DOI:10.1002/ppul.71134

iScience. 2025 Apr 16;28(5):112453. doi: 10.1016/j.isci.2025.112453. eCollection 2025 May 16.

ABSTRACT

Constipation causes significant morbidity in patients with cystic fibrosis (CF). Using CF patient (F508del) derived ex vivo ileal and distal colonic/rectal enteroids as a model and the Forskolin Induced Swelling Assay (FIS), we compared CFTR mediated fluid secretion in human enterocytes across the crypt-villus axis. CFTR expression and FIS decreased as enterocytes differentiated from crypt to become partially differentiated and then mature villus cells. While there was no FIS response in undifferentiated (crypt enterocytes) F508del-CF enteroids, partially differentiated F508del-CF enteroids had a swelling response to forskolin (cAMP) and linaclotide (cGMP), which was ∼48%, and ∼67% of the response in healthy enteroids, respectively, and was prevented by a CFTR inhibitor. Also, linaclotide and a general phosphodiesterase (PDE) inhibitor independently enhanced the combined CFTR-modulator-induced FIS response from partially differentiated F508del-CF enteroids. These findings demonstrate that partially differentiated ileal and distal colonic F508del-CFTR enteroids can be stimulated to secrete fluid by cAMP and cGMP.

PMID:40395669 | PMC:PMC12090326 | DOI:10.1016/j.isci.2025.112453

J Cyst Fibros. 2025 May 19:S1569-1993(25)01466-3. doi: 10.1016/j.jcf.2025.04.011. Online ahead of print.

ABSTRACT

BACKGROUND: The role of autoimmune beta-cell damage in cystic fibrosis-related glucose abnormalities remains unclear. This study evaluates the prevalence of pancreatic islet autoantibodies (AABs) by glycemic status and age, and assesses the risk of developing cystic fibrosis-related diabetes (CFRD) in people with cystic fibrosis (pwCF).

METHODS: A random-effects meta-analysis examined AABs against glutamic acid decarboxylase (GADA), insulin (IAA), islet cell (ICA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) in pwCF (CRD42023482663). Prevalence, odds ratios (OR), and 95 % confidence intervals (CI) were calculated with subgroup analyses by glycemic status and age.

RESULTS: Analysis of 20 studies (2229 pwCF) found an overall islet AAB positivity rate of 4 % (CI: 2-9 %) and multiple positivity at 1 % (CI: 0-11 %). IAA had the highest prevalence at 6 % (CI: 3-14 %), and ICA the lowest at 1 % (CI: 0-9 %). Islet AAB prevalence trended higher in CFRD than non-CFRD patients and in children than adults. CFRD was significantly associated with islet AAB positivity, notably for GADA (OR 4.63, CI: 3.42-6.28), ICA (OR 3.57, CI: 1.05-12.18), and IA-2A (OR 2.36, CI: 1.29-4.34). Any and multiple AAB positivity were similarly correlated to CFRD (OR 2.82, CI: 1.22-6.51 and OR 2.71, CI: 1.49-4.93).

CONCLUSIONS: Pancreatic islet AABs are present in 1-6 % of pwCF and increase the risk of CFRD by 2.36 to 4.63 times. While there's a suggested link, limited study quality and inconsistent testing warrant cautious interpretation. Further robust studies are needed to confirm these findings and improve screening strategies.

PMID:40393876 | DOI:10.1016/j.jcf.2025.04.011

mBio. 2025 May 20:e0054125. doi: 10.1128/mbio.00541-25. Online ahead of print.

ABSTRACT

The opportunistic pathogen Pseudomonas aeruginosa causes debilitating lung infections in people with cystic fibrosis, as well as eye, burn, and wound infections in otherwise immunocompetent individuals. Many of P. aeruginosa's virulence factors are regulated by environmental cues, such as temperature and cell density. One such virulence factor is protease IV. Prior studies have shown that piv expression is higher at ambient temperatures (22°C-28°C) compared to human body temperature (37°C) and also upregulated by the LasRI quorum sensing system, although it is unclear how. We found that piv expression was thermoregulated at stationary phase, but not exponential phase, and that piv is thermoregulated at the level of transcription. Using a transcriptional reporter for piv, we show that LasR activates piv expression more at 25°C at stationary phase than at 37°C. We show that key components of the LasRI quorum sensing system are not upregulated at 25°C, suggesting that LasR regulatory activity is not higher intrinsically at this temperature. We also identified sequences within the piv promoter that are important for its thermoregulation. We propose that LasR upregulates piv more at 25°C than at 37°C. The finding that temperature controls LasR regulation of piv highlights the complex nature of gene regulatory systems in P. aeruginosa.IMPORTANCEPseudomonas aeruginosa is a versatile opportunistic pathogen capable of causing many different types of infections that are often difficult to treat, such as lung infections in people with cystic fibrosis. Temperature regulates the expression of many virulence factors that contribute to P. aeruginosa's ability to cause infection, yet our mechanistic understanding of virulence factor thermoregulation is poor. In this study, we show that the virulence factor protease IV is thermoregulated at the level of transcription through the quorum sensing regulator, LasR. Mechanistic studies of virulence factor thermoregulation will expand our understanding of how P. aeruginosa experiences different environments, including the mammalian host. Our work also highlights the importance of growth conditions in studying gene regulation, as it better elucidates the regulation of protease IV by LasR, which was previously not well understood.

PMID:40391957 | DOI:10.1128/mbio.00541-25

JAC Antimicrob Resist. 2025 May 19;7(3):dlaf077. doi: 10.1093/jacamr/dlaf077. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance (CFTR) gene, resulting in the secretion of hyperviscous mucus. Infective exacerbations are a major determinant of morbidity and mortality in CF patients. These infections are clinically challenging, and antimicrobial treatment should effectively target the organisms and be delivered early to improve survival. Ceftobiprole is a fifth-generation cephalosporin antibiotic that is not indicated for the treatment of CF. However, due to its activity against common causes of infective exacerbations in CF such as Staphylococcus aureus, including MRSA, and Pseudomonas aeruginosa where resistance has not developed, it has utility for managing infective exacerbations.

OBJECTIVES: To describe the use of ceftobiprole in the treatment of infective exacerbations in CF.

PATIENTS AND METHODS: Ten patients with CF (age 24-63; six male and four female) were treated with ceftobiprole for infective exacerbations following discussion within the multi-disciplinary team. In most patients, ceftobiprole was given concomitantly with other antibiotics.

RESULTS: All patients had positive sputum cultures for S. aureus (including nine MRSA), and seven patients had concomitant P. aeruginosa infection. Ceftobiprole treatment was associated with improved lung function, and markers of systemic inflammation decreased for most patients, with some variation. There was good tolerability in all but four patients.

CONCLUSIONS: Ceftobiprole presents a therapeutic option for susceptible infections in CF patients with limited treatment options. Its broad-spectrum coverage may help to reduce polypharmacy. However, further clinical studies are needed.

PMID:40391172 | PMC:PMC12086531 | DOI:10.1093/jacamr/dlaf077

Sci Rep. 2025 May 19;15(1):17394. doi: 10.1038/s41598-025-02296-1.

ABSTRACT

Iron deficiency (ID) is frequent in adult patients with cystic fibrosis (pwCF). The effect of elexacaftor-tezacaftor-ivacaftor (ETI) on iron metabolism has rarely been reported. We aimed to study the trends and variables associated with iron store modulation under ETI. We conducted a prospective adult cohort in two referral centres for pwCF. Iron supplementation during the follow-up was an exclusion criterion. Clinical, biological data and pulmonary function tests were collected prospectively at ETI initiation (V0) and after 1 year of ETI (V12). The presence of Pseudomonas aeruginosa in forced sputum was assessed at V0 and V12. 220 (87 women) pwCF among the 278 screened were included. At V0, ID prevalence was 58% and was significantly associated with female sex and lower forced expiratory volume (FEV1). At V12, ID prevalence decreased significantly from 58 to 31% (p = 0.001). A significant decrease of C reactive protein and total globulins was found at V12. 60% of patients with ID at V0 achieved normalization of iron status at V12 with a significant association with the increase of FEV1 (moderate size effect: 0.68). A lower decrease of C reactive protein was significantly associated with the onset of ID in a small sample of patients (p < 0.001). The disappearance of Pseudomonas aeruginosa in sputum at V12 was not correlated to the evolution of iron status under ETI. ETI was associated with a decrease of ID prevalence, and improvement of pulmonary function and a correction of systemic inflammation.

PMID:40389628 | DOI:10.1038/s41598-025-02296-1

Dtsch Med Wochenschr. 2025 Jun;150(12):703-712. doi: 10.1055/a-2145-7495. Epub 2025 May 19.

ABSTRACT

Bronchiectasis is a worldwide inflammatory disease with different epidemiology and heterogenous etiology. The disease burden is high for patients and economic costs can be immense. So far there are no special disease modifying drugs available for patients with bronchiectasis other than cystic fibrosis. With rising numbers of newly diagnosed patients (prevalence 120/100000 in Germany) due to different reasons (idiopathic, postinfectious, genetic, asthma, COPD etc.) the awareness for this once called orphan disease should rise - not only among pulmonologists but also among general care practitioners. This article focuses on diagnostic algorithms and multimodal treatment options based on the latest studies and the recently published German bronchiectasis guideline from May 2024. It outlines what general care practitioners can do for their patients, what they should consider when treating an exacerbation and that special surveillance of these patients is needed in centers with expertise in this disease due to its complexity. With upcoming treatment options just as disease modifying drugs like DDP-1 inhibitors or inhaled antibiotics one can expect a change in disease treatment and outcome. Therefore, it is more and more important to raise awareness for bronchiectasis starting at the very basis when patients present at their general care practitioner with recurring productive cough, exacerbations, and further cardinal symptoms of bronchiectasis disease.

PMID:40388981 | DOI:10.1055/a-2145-7495

Expert Rev Respir Med. 2025 May 19. doi: 10.1080/17476348.2025.2508313. Online ahead of print.

ABSTRACT

INTRODUCTION: Non-cystic-fibrosis bronchiectasis (NCFB) is an airway disorder with a growing world-wide prevalence that affects predominantly older and female individuals and is associated with high symptom burden and significant healthcare expenditure. Brensocatib is a novel orally bioavailable, selective, and reversible dipeptidyl peptidase 1 (DPP1) inhibitor that leads to a sustained inhibition of neutrophil serine protease activity in both whole blood and sputum.

AREAS COVERED: This drug profile summarizes the role of inflammation in the pathophysiology of bronchiectasis. The mechanism of action of brensocatib in reducing neutrophil-related inflammation is described. We then summarize existing efficacy and safety data from Phase 2 and Phase 3 studies of brensocatib in patients with bronchiectasis, in which the rate of exacerbation was the primary endpoint. Finally, we summarize the current marketplace for brensocatib, including the unmet for effective therapies for bronchiectasis, and the status of other potential treatments undergoing clinical trials.

EXPERT OPINION: Brensocatib is the first-in-class DPP1 inhibitor that shows promise as a treatment for patients with bronchiectasis.

PMID:40387478 | DOI:10.1080/17476348.2025.2508313

JPGN Rep. 2025 Mar 17;6(2):146-152. doi: 10.1002/jpr3.70007. eCollection 2025 May.

ABSTRACT

This is a prospective, multicenter study of a cohort of 224 cystic fibrosis (CF) patients treated with CF transmembrane conductance regulator (CFTR) modulators (CFTRm). Our aim was to prospectively analyze the effect of CFTRm treatment on fat-soluble vitamin serum levels. Demographic and clinical data were recorded, and fat-soluble vitamin levels were analyzed at baseline, and at 6 and 12 months after starting treatment. Two groups were analyzed separately: patients receiving dual therapy lumacaftor/ivacaftor or tezacaftor/ivacaftor (Lum/Tez+Iva), and those on triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI). We found that treatment with ETI produced a significant increase in vitamin D and A levels within the first 6 months, which was maintained at 12 months. However, with dual therapy, we observed an increase only in vitamin A levels within the first 6 months, which was not maintained at 12 months. No differences were found in vitamin E serum levels between the groups.

PMID:40386324 | PMC:PMC12078071 | DOI:10.1002/jpr3.70007

JPGN Rep. 2025 Mar 17;6(2):213. doi: 10.1002/jpr3.70011. eCollection 2025 May.

NO ABSTRACT

PMID:40386322 | PMC:PMC12078063 | DOI:10.1002/jpr3.70011

JCEM Case Rep. 2025 May 15;3(7):luaf104. doi: 10.1210/jcemcr/luaf104. eCollection 2025 Jul.

ABSTRACT

Glucagon-like peptide-1 (GLP-1) agonists are widely used in the management of type 2 diabetes and obesity, with their therapeutic scope expanding to address cardiometabolic and cardiorenal conditions. However, their increasing use has been associated with potential adverse effects, including acute pancreatitis (AP). The exact prevalence of GLP-1 agonist-induced AP remains uncertain and reliable predictors for its onset have yet to be identified. We present 3 cases of class-associated predilection for GLP-1 analog-associated AP in patients with carrier states for hemochromatosis (HC) and cystic fibrosis. Case 1 is a heterozygous carrier for the C282Y HC pathogenic variant. Case 2 is a heterozygous carrier of the Delta F508 deletion of the cystic fibrosis transmembrane regulator (CFTR) gene. Case 3 is compound heterozygous carrier of a single CFTR intron 9 poly T allele pathogenic variant (5T/7T/8T), as well as a single pathogenic variant of the C282Y HC gene. Our observation suggests that carrier states for cystic fibrosis and HC may predispose individuals to GLP-1 agonist-associated AP. Genetic testing for these carrier states should be considered among patients with GLP-1 agonist-associated AP to provide more support and data for this as a potential true risk factor.

PMID:40384889 | PMC:PMC12078934 | DOI:10.1210/jcemcr/luaf104