Arch Bronconeumol. 2025 Mar 1:S0300-2896(25)00071-7. doi: 10.1016/j.arbres.2025.02.010. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis causes exercise limitation due to impaired lung function and other complications, which in turn increases the chance of mortality. CFTR modulators, particularly the elexacaftor/tezacaftor/ivacaftor (ETI) combination, improve lung function in children older than 6 years in real-life studies.

OBJECTIVE: This study aimed to assess the impact of ETI on aerobic capacity in children with CF aged 6-11 years under real-life conditions and to evaluate whether prior CFTR modulator treatment affects these outcomes.

METHODS: A multicenter, prospective cohort study was conducted with pediatric CF patients. Participants underwent evaluations 6-8 months before ETI (T1), at the start of ETI (T2), and 6-8 months post-treatment (T3). Primary outcomes included cardiorespiratory fitness assessed via peak oxygen consumption (VO2peak) during a cardiopulmonary exercise test (CPET), and secondary outcomes encompassed lung function, quality of life, physical activity, and functional mobility.

RESULTS: Of the 28 patients (mean age 9.02±1.59 years), 19 were ETI-naive, and 9 had prior CFTR modulator treatment. Significant improvements were observed in FEV1 (p<0.001), and several functional mobility tests (30CST, Stair Climb Test, 10MWT). However, VO2peak showed no significant changes between T1 and T3. Quality of life scores improved notably in emotional, eating, and respiratory domains, and a slight improvement was noted in physical activity levels (p=0.037).

CONCLUSIONS: ETI treatment significantly enhances lung function and certain aspects of quality of life and physical fitness in pediatric CF patients. However, it does not significantly alter aerobic capacity (VO2peak) within the observed period.

PMID:40113488 | DOI:10.1016/j.arbres.2025.02.010

Obstet Gynecol. 2025 Apr 1;145(4):e141-e142. doi: 10.1097/AOG.0000000000005865.

NO ABSTRACT

PMID:40112310 | DOI:10.1097/AOG.0000000000005865

Otolaryngol Head Neck Surg. 2025 Mar 20. doi: 10.1002/ohn.1231. Online ahead of print.

ABSTRACT

OBJECTIVE: To differentiate pediatric chronic rhinosinusitis (CRS) into clinically relevant primary and secondary phenotypes based on clinical, radiographic, and laboratory findings.

STUDY DESIGN: Retrospective chart review of patients with CRS who underwent endoscopic sinus surgery over a 5-year period.

SETTING: Tertiary referral children's hospital.

METHODS: Relevant medical and surgical history inclusive of disease onset, clinical and radiographic findings, laboratory data, and operative culture results was recorded. Data analysis resulted, where appropriate, in phenotype and endotype characterization.

RESULTS: In total, 94 patients, aged 6.8 to 22.0 years, with a mean age of 15.4 years, satisfied the inclusion criteria. Eosinophilic CRS was the most common primary phenotype (n = 19, 20.2%), and this group was the most likely to have recurrent disease requiring revision surgery. Additional primary phenotypes identified included allergic fungal rhinosinsusitis (n = 10, 10.6%) and central compartment atopic disease (n = 2, 2.1%). CRS associated with cystic fibrosis was the most common secondary CRS category (n = 13, 13.8%). Based on available data, over one-third of patients (n = 36, 38.2%) could not be categorized into a specific phenotype based on current clinical and radiologic criteria.

CONCLUSION: A phenotype and endotype-based classification system for CRS is evolving for the adult population. This study highlights that such a classification system is possible in the pediatric and adolescent age group, facilitating targeted biologic therapies at the underlying inflammatory mechanism. Further investigation is clearly required given an etiologic source of paranasal sinus inflammation could not be identified in approximately one-third of patients.

PMID:40111215 | DOI:10.1002/ohn.1231

Int J Popul Data Sci. 2025 Feb 20;8(5):2924. doi: 10.23889/ijpds.v8i5.2924. eCollection 2023.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) heterozygotes (also known as 'carriers') are people who have one mutated copy of the CFTR gene. Research into the health risks of CF carriers has been limited by a lack of large cohorts tested for CF carrier status, but routine clinical testing identifies CF carriers in the population. Such test records additionally contain large amounts of clinical information, making them a valuable research resource to not only identify CF carriers in the population but also to provide additional data not found elsewhere.

METHODS: Following governance approvals, we adapted 30 years worth of CF genetic testing records generated by the All-Wales Medical Genomics Service (AWMGS) and submitted them to the SAIL Databank for anonymised linkage.

RESULTS: Unexpected obstacles meant that a minimum amount of clinical information could be annotated ahead of linkage. The raw data were highly heterogeneous due to the records' longitudinal collection and clinical origins, making standardisation difficult. Moreover, the presence of unique identifiers in the clinical data violated the separation principle, requiring manual annotation to produce a cleaned dataset. Explicit identification of patients or their relatives throughout the records complicated split file anonymisation.

CONCLUSION: Extracting useful information from historical clinical genetic test records is a significant challenge with technical and governance aspects. The mixing of unique identifiers with clinical data in heterogeneous, unstructured free text combined with a lack of automated tools meant that manual annotation was required to adhere to the separation principle. As such, only a minimum of the available clinical data was annotatable within the project timeline and mutually exclusive access to the identifiable and pseudonymised data meant that annotations could not later be validated. Future efforts to link clinical genetic test records for research must consider these challenges in their approach.

PMID:40110575 | PMC:PMC11922013 | DOI:10.23889/ijpds.v8i5.2924

J Cyst Fibros. 2025 Mar 18:S1569-1993(25)00058-X. doi: 10.1016/j.jcf.2025.02.009. Online ahead of print.

ABSTRACT

INTRODUCTION: The Liverpool Epidemic Strain (LES) of Pseudomonas aeruginosa is one of several known strains to be transmissible between persons with cystic fibrosis (CF) (pwCF) and the only known strain to have infected large proportions of CF populations on two continents. Despite its prevalence, efforts to understand its spread have proven elusive.

METHODS: We leveraged a prospective collection of P. aeruginosa isolates from pwCF attending the Southern Alberta Adult CF clinic from 1986 to 2020 to identify all individuals with LES infection. LES isolates collected every 1-2 years from each pwCF were sequenced and compared with 171 published LES genomes by phylogenetic analysis.

RESULTS: Of 395 pwCF screened, ten pwCF infected with the LES were identified, from whom 46 LES isolates were sequenced. The earliest LES isolate was recovered in 1986, ∼2 years earlier than the previously oldest published LES isolate recovered in the UK. Phylogenetic analysis identified a diverse set of isolates at the root of the LES phylogeny that formed four clades, one of which gave rise to a "classic LES" clade. Canadian isolates formed a paraphyletic group that included the root of this clade and out of which the UK LES clade emerged. We estimated the date of the most recent common ancestor (MRCA) of the UK LES clade as 1977.

CONCLUSIONS: Our study provides genomic evidence in support of a silent epidemic of LES infection occurring in the late 1970s among pwCF first originating in Canada and being spread to the UK, where transmission markedly accelerated.

PMID:40107913 | DOI:10.1016/j.jcf.2025.02.009

J Cyst Fibros. 2025 Mar 18:S1569-1993(25)00072-4. doi: 10.1016/j.jcf.2025.03.005. Online ahead of print.

NO ABSTRACT

PMID:40107911 | DOI:10.1016/j.jcf.2025.03.005

Pediatr Pulmonol. 2025 Mar;60(3):e71048. doi: 10.1002/ppul.71048.

ABSTRACT

OBJECTIVE: To describe variants in the CFTR gene and demographic and clinical characteristics of individuals with Cystic Fibrosis (CF) from a Brazilian State pediatric reference center upon diagnosis.

METHODS: Cross-sectional retrospective cohort study of individuals with CF under 18 years old treated in a referral center between 2007 and 2023. Data was derived from medical records. A descriptive analysis of the variables at diagnosis, including pathogenic genetic variants in the CFTR gene, clinical findings, and demographic data.

RESULTS: The population of 110 patients was predominantly male (54.5%) and white (66.4%). Age at diagnosis ranged from 13 days to 17 years (median = 2 months), 78.2% were diagnosed at < 2 years, and 50.9% were diagnosed following neonatal screening. The most frequent clinical manifestations at diagnosis were steatorrhea (70.0%), persistent respiratory symptoms (58.2%), and malnutrition (36.4%). The most common CFTR variants were F508del (49.0%), G542X (7.3%), and 3120+1G>A (5.9%). Eighty-four (76.4%) were eligible to use at least 1 of the 4 CFTR modulator therapies available in Brazil, and 29 were eligible for 3 therapies because they are homozygous for F508del.

CONCLUSION: Identification of CFTR variants at diagnosis can provide many benefits to patients, such as early interventions and CFTR modulator therapy, and is feasible in Brazil. Because each country may have different distributions of CFTR variants, it is essential to evaluate these distributions as we advance methodologies for gene variant detection, particularly in the contexts of newborn screening and diagnostic testing.

PMID:40105401 | DOI:10.1002/ppul.71048

mSystems. 2025 Mar 19:e0135424. doi: 10.1128/msystems.01354-24. Online ahead of print.

ABSTRACT

Burkholderia cenocepacia is an opportunistic pathogen that has been associated with nosocomial outbreaks in hospitals and can cause severe respiratory infections among immunocompromised patients and individuals suffering from cystic fibrosis. The transmissibility and intrinsic antibiotic resistance of B. cenocepacia pose a significant challenge in healthcare settings. In this study, with the aim to identify novel drug targets to fight B. cenocepacia infections, we employed a genome-wide transposon sequencing (Tn-seq) approach to unravel fitness determinants required for survival in Galleria mellonella (in vivo infection model) and pig lung tissue (ex vivo organ model). A total of 698 and 117 fitness genes were identified for each of the models, respectively, and 62 genes were found to be important for both. To confirm our results, we constructed individual mutants in selected genes and validated their fitness in the two models. Among the various determinants identified was a rare genomic island (I35_RS03700-I35_RS03770) involved in O-antigen and lipopolysaccharide synthesis. We demonstrate that this gene cluster is required for virulence in the G. mellonella infection model but, by contrast, counteracts efficient colonization of pig lung tissue. Our results highlight the power of the Tn-seq approach to unravel fitness determinants that could be used as therapeutic targets in the future and show that the choice of the infection model for mutant selection is paramount.

IMPORTANCE: The opportunistic pathogen Burkholderia cenocepacia has been associated with nosocomial infections in healthcare facilities, where it can cause outbreaks involving infections of the bloodstream, respiratory tract, and urinary tract as well as severe complications in immunocompromised patients. With the aim to identify novel targets to fight B. cenocepacia infections, we have used a genome-wide approach to unravel fitness genes required for host colonization in a clinical strain, B. cenocepacia H111. Among the various determinants that we identified is a rare genomic island that modifies the bacterial lipopolysaccharide. Our results highlight the power of the transposon sequencing approach to identify new targets for infection treatment and show the importance of using different infection models.

PMID:40105327 | DOI:10.1128/msystems.01354-24

Infect Med (Beijing). 2025 Feb 5;4(1):100168. doi: 10.1016/j.imj.2025.100168. eCollection 2025 Mar.

ABSTRACT

Phages, including the viruses that lyse bacterial pathogens, offer unique therapeutic advantages, including their capacity to lyse antibiotic-resistant bacteria and disrupt biofilms without harming the host microbiota. The lack of new effective antibiotics and the growing limitations of existing antibiotics have refocused attention on phage therapy as an option in complex clinical cases such as burn wounds, cystic fibrosis, and pneumonia. This review describes clinical cases and preclinical studies in which phage therapy has been effective in both human and veterinary medicine, and in an agricultural context. In addition, critical challenges, such as the narrow host range of bacteriophages, the possibility of bacterial resistance, and regulatory constraints on the widespread use of phage therapy, are addressed. Future directions include optimizing phage therapy through strategies ranging from phage cocktails to broadening phage host range through genetic modification, and using phages as vaccines or biocontrol agents. In the future, if phage can be efficiently delivered, maintained in a stable state, and phage-antibiotic synergy can be achieved, phage therapy will offer much needed treatment options. However, the successful implementation of phage therapy within the current standards of practice will also require the considerable development of regulatory infrastructure and greater public acceptance. In closing, this review highlights the promise of phage therapy as a critical backup or substitute for antibiotics. It proposes a new role as a significant adjunct to, or even replacement for, antibiotics in treating multidrug-resistant bacterial infections.

PMID:40104270 | PMC:PMC11919290 | DOI:10.1016/j.imj.2025.100168

iScience. 2025 Feb 12;28(3):111999. doi: 10.1016/j.isci.2025.111999. eCollection 2025 Mar 21.

ABSTRACT

Pre-existing respiratory diseases may influence coronavirus disease (COVID-19) susceptibility and severity. However, the molecular mechanisms underlying the airway epithelial response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity in patients with chronic respiratory diseases remain unelucidated. Using an in vitro model of differentiated primary bronchial epithelial cells, we aimed to investigate the molecular mechanisms of SARS-CoV-2 infection in pre-existing cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Our study revealed reduced susceptibility of CF and COPD airway epithelia to SARS-CoV-2, relative to that in healthy controls. Mechanistically, reduced transmembrane serine protease 2 (TMPRSS2) activity potentially contributed to this resistance of CF epithelium. Upregulated complement and inflammatory pathways in CF and COPD epithelia potentially primed the antiviral state prior to infection. Analysis of a COVID-19 patient cohort validated our findings, correlating specific inflammatory markers (IP-10, SERPINA1, and CFB) with COVID-19 severity. This study elucidates SARS-CoV-2 pathogenesis and identifies potential biomarkers for clinical monitoring.

PMID:40104058 | PMC:PMC11914195 | DOI:10.1016/j.isci.2025.111999

Sci Rep. 2025 Mar 18;15(1):9264. doi: 10.1038/s41598-025-94184-x.

ABSTRACT

Measuring the quality of life in patients with cystic fibrosis is an important element of the patient care process. Many tools have been created for this measurement among adults. One of them is the Cystic Fibrosis Questionnaire-Revised 14+ (CFQ-R 14+). Its measurement properties have not been comprehensively assessed in the population of Polish adults. The aim of the study is to verify the construct validity, including structural and criterion validity, as well as internal consistency, of the Polish version of the CFQ-R 14+ in the population of adults with cystic fibrosis. We conducted a cross-sectional survey among adults with cystic fibrosis. After preparing the database, we performed a confirmatory factor analysis (CFA) followed by exploratory factor analysis (EFA) using the parallel analysis method principal axis factoring with Oblimin rotation. Intercorrelations of questionnaire factors and the occurrence of relationships among items for the general scale results was checked. We also presented basic descriptive statistics (mean, median, standard deviation, skewness, kurtosis, minimum and maximum values). The analyses included responses from 220 adult patients. CFA results did not show adequate goodness of fit (χ2(1025) = 2112.35, p < 0.001; CFI = 0.831; TLI = 0.814; RMSEA = 0.069; SRMR = 0.074). After EFA, 6 factors were extracted, considering 40 out of 50 questions of the CFQ-R 14+. CFQ-R 14+ may be useful in assessing the quality of life of Polish adult patients with cystic fibrosis. Our analysis demonstrates that the optimal factor structure of the tool in this population includes 6 scales.

PMID:40102545 | DOI:10.1038/s41598-025-94184-x

Lung. 2025 Mar 18;203(1):49. doi: 10.1007/s00408-025-00802-w.

ABSTRACT

PURPOSE: The objective was to study comparative efficacies of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, vanzacaftor-tezacaftor-deutivacaftor (VTD), elexacaftor-tezacaftor-ivacaftor (ETI), tezacaftor-ivacaftor (Tez-Iva), and lumacaftor-ivacaftor (Lum-Iva) in people with cystic fibrosis (pwCF), aged ≥ 12 years, carrying at least one F508del-CFTR-allele.

METHODS: Data from randomized controlled or randomized active comparator trials were included in this network meta-analysis which used frequentist approach for comparing the efficacy of drugs and ranking based on P-scores. Outcomes of interest were mean differences in percentage-predicted forced expiratory volume in one second (ppFEV1), CF questionnaire-revised respiratory domain (CFQ-R) scores, sweat chloride (SwCl) levels, and odds ratios (OR) for serious adverse events (SAE).

RESULTS: Data from 13 studies were analyzed. Compared to placebo, the effects of VTD and ETI on ppFEV1 were almost quadruple of Tez-Iva and Lum-Iva (VTD: 12.78 [95% confidence intervals: 6.41; 19.15] and ETI: 11.95 [7.40; 16.50]) and almost seven times of Tez-Iva and Lum-Iva for CFQ-R (VTD: 21.23 [- 28.72; 71.18] and ETI: 19.27 [10.56; 27.98]). A statistically significant difference was noted between VTD and ETI in SwCl reduction (mean difference: - 8.59 [- 15.53; - 1.65]). There were no statistically significant ORs for SAEs for any CFTR modulators but VTD, ETI, and Tez-Iva were least associated with SAEs (ORs were 0.15 [0.01; 1.79], 0.49 [0.31; 0.78], and 0.74 [0.50; 1.09], respectively, as compared to placebo). Overall, P-score ranking ranked VTD as first and ETI as second, followed by others.

CONCLUSION: VTD and ETI were more efficacious than Tez-Iva and Lum-Iva in pwCF with at least one F508del-CFTR-allele.

PMID:40102290 | DOI:10.1007/s00408-025-00802-w

Br J Sports Med. 2025 Mar 18:bjsports-2024-109184. doi: 10.1136/bjsports-2024-109184. Online ahead of print.

ABSTRACT

OBJECTIVE: To synthesise data on the associations between cardiorespiratory fitness (CRF) and health in children and adolescents, evaluate the certainty of evidence and identify knowledge gaps.

DESIGN: An overview of systematic reviews with meta-analyses. Results were pooled using forest plots and certainty of evidence evaluated with GRADE.

DATA SOURCES: Medline, Embase, Scopus, CINAHL and SPORTDiscus were searched from January 2002 to March 2024.

ELIGIBILITY CRITERIA FOR SELECTED STUDIES: Systematic reviews with meta-analyses exploring CRF and health in children and adolescents aged <18 years.

RESULTS: From the 9062 records identified, 14 reviews were included. Meta-analysed data from 125 164 observations covering 33 health outcomes were compiled, showing favourable (n=26) or null (n=7) associations with CRF. Among general populations, the associations were weak-to-moderate, with favourable links between CRF and indicators of anthropometry and adiposity, cardiometabolic and vascular health, and mental health and well-being. Among clinical populations, CRF was lower in participants with a condition compared with healthy controls, with the largest difference for newly diagnosed cancer (mean difference=-19.6 mL/kg/min; 95%CI: -21.4,-17.8). Patients with cystic fibrosis had a greater risk for all-cause mortality when comparing low CRF vs. high (relative risk=4.9; 95%CI: 1.1, 22.1). The certainty of evidence ranged from very low to moderate.

CONCLUSION: CRF shows promising links to numerous health outcomes in paediatric populations, though the low certainty of evidence calls for further research. High-quality longitudinal evidence is warranted to confirm the findings and investigate a predictive role of childhood CRF for future health.

PMID:40101938 | DOI:10.1136/bjsports-2024-109184

ACS Infect Dis. 2025 Mar 18. doi: 10.1021/acsinfecdis.4c01045. Online ahead of print.

ABSTRACT

Antimicrobial resistance (AMR) poses a major threat to human health globally. Approximately 5 million deaths were attributed to AMR in 2019, and this figure is predicted to worsen, reaching 10 million deaths by 2050. In the search for new compounds that can tackle AMR, FtsZ inhibitors represent a valuable option. In the present study, a structure-based virtual screening is reported, which led to the identification of derivative C11 endowed with an excellent minimum inhibitory concentration value of 2 μg/mL against Staphylococcus aureus. Biochemical assays clarified that compound C11 targets FtsZ by inhibiting its polymerization process. C11 also showed notable antimicrobial activity against S. aureus cystic fibrosis isolates and methicillin-resistant S. aureus strains. Derivative C11 did not show cytotoxicity, while it had a synergistic effect with methicillin. C11 also showed increased survival in the Galleria mellonella infection model. Lastly, structure-activity relationship and binding mode analyses were reported.

PMID:40100965 | DOI:10.1021/acsinfecdis.4c01045

Cell Mol Life Sci. 2025 Mar 18;82(1):121. doi: 10.1007/s00018-025-05633-9.

ABSTRACT

Cystic fibrosis (CF) is a rare disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a chloride channel with an important role in the airways. Despite the clinical efficacy of present modulators in restoring the activity of defective CFTR, there are patients who show persistent pulmonary infections, mainly due to Pseudomonas aeruginosa. Recently, we reported an unprecedented property of antimicrobial peptides i.e. Esc peptides, which consists in their ability to act as potentiators of CFTR carrying the most common mutation (the loss of phenylalanine 508) affecting protein folding, trafficking and gating. In this work, by electrophysiology experiments and computational studies, the capability of these peptides and de-novo designed analogs was demonstrated to recover the function of other mutated forms of CFTR which severely affect the channel gating (G551D and G1349D). This is presumably due to direct interaction of the peptides with the nucleotide binding domains (NBDs) of CFTR, followed by a novel local phenomenon consisting in distancing residues located at the cytosolic side of the NBDs interface, thus stabilizing the open conformation of the pore at its cytosolic end. The most promising peptides for the dual antimicrobial and CFTR potentiator activities were also shown to display antipseudomonal activity in conditions mimicking the CF pulmonary ion transport and mucus obstruction, with a higher efficacy than the clinically used colistin. These studies should assist in development of novel drugs for lung pathology in CF, with dual CFTR potentiator and large spectrum antibiotic activities.

PMID:40100363 | DOI:10.1007/s00018-025-05633-9

ACS Appl Mater Interfaces. 2025 Mar 18. doi: 10.1021/acsami.4c20874. Online ahead of print.

ABSTRACT

Bacterial biofilms present significant therapeutic challenges due to their resistance to conventional antimicrobial treatment. Mucins typically serve as a protective barrier against pathogens, yet certain bacteria, such as Pseudomonas aeruginosa (P. aeruginosa), can exploit these glycoproteins as attachment sites for biofilm formation. This study introduces boronic acid-functionalized polyethyleneimine (PEI-BA) as a promising antibiofilm agent that effectively blocks bacterial adhesion to mucin-rich surfaces. Through the multivalent presentation of boronic acid groups, PEI-BA reversibly forms boronate ester bonds with mucin glycans, creating a protective barrier. Our findings show that PEI-BA prevents bacterial attachment through a nonbactericidal mechanism, potentially reducing the risk of resistance development. Notably, PEI-BA synergizes with a conventional antibiotic, tobramycin, significantly enhancing biofilm inhibition compared to either treatment alone. Systematic evaluation of PEI-BA formulations identified optimal functionalization levels, balancing glycan-binding capability with solubility. From a biomaterials design perspective, we demonstrate how rational polymer modification can transform a potent but cytotoxic antimicrobial agent (i.e., PEI) into a safe and effective antibiofilm material, opening further possibilities for managing biofilm-associated infections in clinical settings. This work establishes boronic acid-based nanomaterials as promising candidates for biofilm prevention and antibiotic enhancement, particularly in conditions like cystic fibrosis, where mucin-bacterial interactions contribute to disease progression.

PMID:40099915 | DOI:10.1021/acsami.4c20874

Nat Biotechnol. 2025 Mar 17. doi: 10.1038/s41587-025-02616-w. Online ahead of print.

NO ABSTRACT

PMID:40097678 | DOI:10.1038/s41587-025-02616-w

Nat Nanotechnol. 2025 Mar 17. doi: 10.1038/s41565-025-01877-5. Online ahead of print.

ABSTRACT

The active transport and retention principle is an alternative mechanism to the enhanced permeability and retention effect for explaining nanoparticle tumour delivery. It postulates that nanoparticles actively transport across tumour endothelial cells instead of passively moving through gaps between these cells. How nanoparticles transport across tumour endothelial cells remains unknown. Here we show that nanoparticles cross tumour endothelial cells predominantly using the non-receptor-based macropinocytosis pathway. We discovered that tumour endothelial cell membrane ruffles capture circulating nanoparticles, internalize them in intracellular vesicles and release them into the tumour interstitium. Tumour endothelial cells have a higher membrane ruffle density than healthy endothelium, which may partially explain the elevated nanoparticle tumour accumulation. Receptor-based endocytosis pathways such as clathrin-mediated endocytosis contribute to nanoparticle transport to a lesser extent. Nanoparticle size determines the degree of contribution for each pathway. Elucidating the nanoparticle transport mechanism is crucial for developing strategies to control nanoparticle tumour delivery.

PMID:40097646 | DOI:10.1038/s41565-025-01877-5

JAMA Netw Open. 2025 Mar 3;8(3):e250908. doi: 10.1001/jamanetworkopen.2025.0908.

ABSTRACT

IMPORTANCE: Black pregnant patients are significantly more likely than their White counterparts to undergo peripartum urine drug screening (UDS) and subsequent reporting to child protective services (CPS).

OBJECTIVE: To evaluate the association of removing isolated cannabis use and limited prenatal care as order indications, combined with clinician-facing clinical decision support, with racial parity in peripartum UDS and CPS reporting.

DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study assessed 9396 pregnant patients at a single tertiary care center in a Midwestern US urban metropolitan region who delivered before (June 1, 2021, to September 31, 2022) and after (October 1, 2022, to January 31, 2024) the intervention.

EXPOSURE: Updated UDS indications combined with clinical decision support.

MAIN OUTCOMES AND MEASURES: Primary outcomes included UDS and CPS report rate by race before vs after the intervention. The secondary outcome was the rate of nonprescribed, noncannabis substance-positive UDS. Neonatal outcomes were included as balancing measures.

RESULTS: Of 9396 female patients (median [IQR] age, 29 [24-33] years; 4305 [45.8%] Black, 4277 [45.5%] White, and 814 [8.7%] other race) included in the analysis, 4639 and 4757 delivered in the preintervention and postintervention periods, respectively. There was a small but statistically significant decrease in the number of Black patients before vs after the intervention (2210 [47.6%] vs 2095 [44.0%], P = .005); there were no significant differences in other race groups, median age, or multiparity. Before the intervention, 513 (23.2%) and 228 (11.1%) Black and White patients, respectively, had UDS (P < .001) compared with 95 (4.5%) and 79 (3.6%) Black and White patients, respectively, after the intervention (P = .40). Before the intervention, an association between Black race and CPS report was observed (249 [11.3%] Black and 119 [5.8%] White patients, P < .001); there was no association between race and CPS report after the intervention (87 [4.2%] Black and 78 [3.5%] White patients, P = .67). There was no association between the intervention and the percentage of UDS results that were positive for nonprescribed, noncannabis substances (107 [2.5%] preintervention vs 88 [2.0%] postintervention; P = .14). There was no significant association between the intervention and any measured neonatal outcomes.

CONCLUSIONS AND RELEVANCE: In this quality improvement study, removal of isolated cannabis use and limited prenatal care as UDS indications, coupled with clinical decision support, was associated with improved racial equity in UDS testing and CPS reporting. The intervention was not associated with a significant change in UDS positivity for nonprescribed, noncannabis substances. These findings suggest that this intervention improved equity in UDS practices without decreasing identification of clinically relevant substance use.

PMID:40094663 | PMC:PMC11915058 | DOI:10.1001/jamanetworkopen.2025.0908

Pancreatology. 2025 Feb 28:S1424-3903(25)00043-2. doi: 10.1016/j.pan.2025.02.015. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is defined as a reduction in pancreatic exocrine secretion below a level that allows normal digestion of nutrients. Pancreatic disease and pancreatic surgery are the main causes of PEI, but other conditions can affect the digestive function of the pancreas.

METHODS: In collaboration with European Digestive Surgery (EDS), European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), European Society for Clinical Nutrition and Metabolism (ESPEN), European Society of Digestive Oncology (ESDO), and European Society of Primary Care Gastroenterology (ESPCG) the working group developed European guidelines for the diagnosis and therapy of PEI. United European Gastroenterology (UEG) provided both endorsement and financial support for the development of the guidelines.

RESULTS: Recommendations covered topics related to the clinical management of PEI: concept, pathogenesis, clinical relevance, general diagnostic approach, general therapeutic approach, PEI secondary to chronic pancreatitis, PEI after acute pancreatitis, PEI associated with pancreatic cancer, PEI secondary to cystic fibrosis, PEI after pancreatic surgery, PEI after esophageal, gastric, and bariatric surgery, PEI in patients with type 1 and type 2 diabetes, and PEI in other conditions.

CONCLUSIONS: The European guidelines for the diagnosis and therapy of PEI provide evidence-based recommendations concerning key aspects of the etiology, diagnosis, therapy, and follow-up, based on current available evidence. These recommendations should serve as a reference standard for existing management of PEI and as a guide for future clinical research. This article summarizes the recommendations and statements.

PMID:40097316 | DOI:10.1016/j.pan.2025.02.015