Healthcare (Basel). 2025 Apr 22;13(9):965. doi: 10.3390/healthcare13090965.

ABSTRACT

Introduction: Cystic fibrosis (CF) is a chronic genetic disease affecting the respiratory and digestive systems. Multidisciplinary care is vital for managing CF's complex complications. This study investigates the potential role of a Case Manager (CM) in improving care coordination and patient outcomes at the CF Unit of Careggi University Hospital. Methods: A survey among 34 CF Unit healthcare professionals assessed the perceptions of integrating a CM. The survey included demographic questions and 12 Likert scale items on the CM's role in care continuity, team collaboration, and treatment adherence. Responses were collected anonymously and analyzed using descriptive statistics. Results: The response rate was 100%, with strong support for the CM role, averaging 4.5/5 across Likert scales. Respondents highlighted the CM's value in coordinating care, managing time-sensitive tasks, and improving communication with external care providers. Telemedicine was positively rated, particularly for reducing hospital visits and supporting the remote monitoring of CF patients treated. Discussion: Findings indicate that integrating a CM could enhance multidisciplinary CF care by improving communication and treatment adherence. Challenges, including team readiness and training, were noted. Future studies will focus on patient satisfaction and clinical outcomes following the integration of CM, with special attention to the role of telemedicine in CF care.

PMID:40361743 | DOI:10.3390/healthcare13090965

JAMA Netw Open. 2025 May 1;8(5):e2510077. doi: 10.1001/jamanetworkopen.2025.10077.

ABSTRACT

IMPORTANCE: Illegal fentanyl is driving overdose mortality, and fentanyl test strips (FTS) can be used to test drugs for fentanyl at the point of consumption. Evidence on whether FTS use is associated with overdose risk reduction behaviors is encouraging, but largely limited to smaller, single-site studies.

OBJECTIVE: To determine whether self-reported baseline FTS use among people who use drugs (PWUD) was associated with overdose risk reduction behaviors and nonfatal overdose over a 28-day follow-up.

DESIGN, SETTING, AND PARTICIPANTS: Multisite, observational cohort study of PWUD conducted from May to December 2023 as an ancillary study of the HEALing Communities Study, which consists of fixed and mobile direct service provision sites in 14 community partner organizations distributing FTS. Participants lived in Kentucky, New York, or Ohio and reported using heroin, fentanyl, cocaine, methamphetamine, or nonprescribed opioids, benzodiazepines, or stimulants within 30 days before baseline. Participants were followed up for a maximum of 37 days.

EXPOSURE: Baseline FTS use.

MAIN OUTCOME AND MEASURES: The primary outcome was a composite score measuring the self-reported number and frequency of using 8 overdose risk reduction behaviors. Secondary outcomes included multiple measures (eg, self-reported nonfatal overdose).

RESULTS: The study included 732 participants (median [IQR] age, 41 [34.0-48.0] years; 369 [50.4%] male; 64 [8.9%] Black or African American, 587 [81.3%] White, and 71 [9.8%] other races); 414 reported baseline FTS use and 318 did not. Compared with nonusers, a higher percentage of baseline FTS users were from Ohio and White, while a lower percentage were from New York and Hispanic and/or Black. In adjusted analyses, PWUD who used FTS had a mean daily composite score for overdose risk reduction behaviors that was 0.86 (95% CI, 0.34-1.38) units higher across follow-up compared with nonusers (score for FTS users, 7.37; nonusers, 6.51). There was no difference in self-reported nonfatal overdoses between the 2 groups (mean daily risk for FTS users, 0.02; nonusers, 0.02; risk ratio, 1.20; 95% CI, 0.70-2.06).

CONCLUSIONS AND RELEVANCE: In this cohort study, baseline FTS use was associated with greater engagement in overdose risk reduction behaviors during follow-up, but not with the risk of nonfatal overdose during follow-up, suggesting PWUD who use FTS may also engage in a broader set of harm reduction strategies.

PMID:40358945 | PMC:PMC12076174 | DOI:10.1001/jamanetworkopen.2025.10077

Hum Gene Ther. 2025 May 13. doi: 10.1089/hum.2024.260. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. While CRISPR-based CFTR editing approaches have shown proof-of-concept for functional rescue in primary airway basal cells, induced pluripotent stem cells, and organoid cultures derived from patients with CF, their efficacy remains suboptimal. Here, we developed the CuFiCas9(Y66S)eGFP reporter system by integrating spCas9 and a non-fluorescent Y66S eGFP mutant into CuFi-8 cells, an immortalized human airway epithelial cell line derived from a patient with CF with homozygous F508del mutations. These cells retain the basal cell phenotype in proliferating cultures and can differentiate into polarized airway epithelium at an air-liquid interface (ALI), enabling both visualized detection of gene editing and electrophysiological assessment of CFTR functional restoration. Using this system, recombinant adeno-associated virus (rAAV)-mediated homology-directed repair (HDR) was evaluated in proliferating cultures. A correction rate of 13.5 ± 0.8% was achieved in a population where 82.3 ± 5.6% of cells were productively transduced by AAV.eGFP630g2-CMVmCh, an rAAV editing vector with an mCherry reporter. Dual-editing of F508del CFTR and Y66S eGFP was explored using AAV.HR-eGFP630-F508(g03) to deliver two templates and single guide RNAs. eGFP+ (Y66S-corrected) cells and eGFP- (non-corrected) cells were sorted via fluorescence-activated cell sorting and differentiated at an ALI to assess the recovery of CFTR function. Despite a low F508 correction rate of 2.8%, ALI cultures derived from the eGFP- population exhibited 25.2% of the CFTR-specific transepithelial Cl- transport observed in CuFi-ALI cultures treated with CFTR modulators. Next-generation sequencing revealed frequent co-editing at both genomic loci, with sixfold higher F508 correction rate in the eGFP+ cells than eGFP- cells. In both populations, non-homology end joining predominated over HDR. This reporter system provides a valuable platform for optimizing editing efficiencies in proliferating airway basal cells, particularly for development of strategies to enhance HDR through modulation of DNA repair pathways.

PMID:40359132 | DOI:10.1089/hum.2024.260

J Physiol Biochem. 2025 May 13. doi: 10.1007/s13105-025-01082-x. Online ahead of print.

ABSTRACT

Neutrophil extracellular traps (NETs), web-like complex structures secreted by neutrophils, have emerged as key players in the modulation of immune responses and the immunopathogenesis of immune disorders. Initially described for their antimicrobial function, NETs now play a part in the fundamental processes of cancer biology, including cancer initiation, metastatic dissemination, and immune evasion strategies. NETs hijack anti-tumor immunity by entrapping circulating cancer cells, fostering the growth of tumors, and reorganizing the tumor microenvironment such that it is pro-malignancy. Emerging evidence emphasizes the role of NETosis coupled with non-coding RNAs-long non-coding RNAs (lncRNAs) and microRNAs (miRNAs)-as key regulators of gene expression and controllers of processes vital for cancer growth, such as immune response and programmed cell death processes like apoptosis, necroptosis, pyroptosis, and ferroptosis. Aberrantly expressed non-coding RNAs have been attributed to immune dysregulation and excessive NET production, promoting tumor growth. NETs are also associated with a myriad of pathological conditions, such as autoimmune disorders, cystic fibrosis, sepsis, and thrombotic disorders. New therapeutic approaches-such as DNase therapy and PAD4 inhibitors-target NET production and their degradation to modify immune function and the efficiency of immunotherapies. Further clarification of the intricate interactions of NETosis, lncRNAs, and miRNAs has the potential to establish new strategies for the suppression of the growth of tumors and preventing immune evasion. This review seeks to elucidate the interactions between NETosis and the regulatory networks involving non-coding RNAs that significantly contribute to the immunopathogenesis of cancer.

PMID:40358898 | DOI:10.1007/s13105-025-01082-x

Front Cell Infect Microbiol. 2025 Apr 28;15:1560634. doi: 10.3389/fcimb.2025.1560634. eCollection 2025.

ABSTRACT

INTRODUCTION: Rarely does Pandoraea occur in bloodstream infections (BSI), although it's typically found in cystic fibrosis. This study aims to decipher the genetic map and obtain insights of clinical symptoms into Pandoraea from BSI patients.

METHODS: 30 suspected BSI patients' diagnostic records and medical histories were recorded. Pandoraea spp. isolates were collected and subjected to antimicrobial susceptibility testing, Sanger sequencing and Whole-genome sequencing (WGS).

RESULTS: Of the 30 clinical cases, five (16.67%) ultimately died, whereas 25 (83.33%) are alive. 30 purified Pandoraea isolates showed high degree of MIC values to Meropenem, Amoxicillin and Potassium Clavulanate, Gentamicin, and Ceftazidime. Then, all isolates were identified as P. pneumonica based on the 16S rRNA-based phylogenetic analysis. Among 28 genomes of them, the average genome size and average GC contents were 5,397,568 bp, and 62.43%, respectively. However, WP1 displayed high similarity (90.6%) to reference Pandoraea sp. LMG 31114. Genetic differences between the tested isolates and LMG 31114 suggested that the outbreak's causative pathogen could be a novel cluster of P. pneumonica. The genomes accumulated mutations at an estimated rate of 1.3 × 10-7 mutations/year/site. Moreover, 26 clinical isolates within the P. pneumonica cluster were formed in July 2014, revealing a tendency to develop regional endemic patterns.

CONCLUSION: BSI caused by this novel cluster of P. pneumonica is linked to significant morbidity and mortality. Such cluster remains a critical public health challenge due to their regional epidemiological patterns and antibiotic treatment risk. This study contributed to the basis on pathogen identification, disease diagnosis, and BSI treatment.

PMID:40357401 | PMC:PMC12066476 | DOI:10.3389/fcimb.2025.1560634

Front Cell Infect Microbiol. 2025 Apr 28;15:1566495. doi: 10.3389/fcimb.2025.1566495. eCollection 2025.

ABSTRACT

The leading cause of death for people with cystic fibrosis (pwCF) continues to be due to respiratory-related illnesses. Both wound repair and immune cell responses are dysregulated in the CF airways, creating a cycle of unresolved injury and perpetuating inflammation. PwCF are predisposed to colonization and infections with opportunistic bacteria like Pseudomonas aeruginosa (Pa), the most common adult pathogen in CF. Pa possesses key virulence factors that can exacerbate chronic inflammation and lung injury. With the approval of highly effective modulator therapies like elexacaftor/tezacaftor/ivacaftor (ETI), pwCF eligible for ETI have seen drastic improvements in lung function and clinical outcomes, including an increased life expectancy. While modulator therapies are improving bronchial epithelial cellular processes in wound repair and some areas of immunity, many of these processes do not reach a non-CF baseline state or have not been thoroughly studied. The effect of modulator therapy on Pa may lead to a reduction in infection, but in more longitudinal studies, there is not always eradication of Pa, and colonization and infection frequency can return to pre-modulator levels over time. Finally, in this review we explore the current state of additional treatments for CF lung disease, independent of CFTR genotype, including anti-inflammatories, phage-therapies, and Pa vaccines.

PMID:40357395 | PMC:PMC12066499 | DOI:10.3389/fcimb.2025.1566495

Front Med (Lausanne). 2025 Apr 28;12:1571506. doi: 10.3389/fmed.2025.1571506. eCollection 2025.

ABSTRACT

Tannerella forsythia infection was common in oral diseases but less reported in lung diseases. This report presents a patient with bronchiectasis who was infected by Tannerella forsythia and subsequently hospitalized with symptoms including fever, progressive cough, sputum production, and shortness of breath. A chest computed tomography (CT) scan revealed multiple bilateral pulmonary bronchiectasis with signs of infection. Metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid primarily detected Tannerella forsythia. Treatment with Piperacillin-tazobactam and ornidazole resulted in a favorable outcome. This case first reported a patient with extensive bronchiectasis infected by Tannerella forsythia and provided an effective treatment.

PMID:40357303 | PMC:PMC12066332 | DOI:10.3389/fmed.2025.1571506

J Neurol Surg B Skull Base. 2024 May 23;86(3):373-376. doi: 10.1055/s-0044-1787155. eCollection 2025 Jun.

NO ABSTRACT

PMID:40351885 | PMC:PMC12064296 | DOI:10.1055/s-0044-1787155

Therap Adv Gastroenterol. 2025 May 8;18:17562848251337515. doi: 10.1177/17562848251337515. eCollection 2025.

ABSTRACT

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, progressive type 2 inflammatory disorder of the esophagus, characterized by abnormal eosinophil accumulation in esophageal epithelium. Undiagnosed or undertreated EoE leads to increased risk of fibrostenosis, strictures, and food impaction due to persistent inflammation, deeply impacting patients' health-related quality of life (HRQoL).

OBJECTIVES: To gather insights on comprehensive assessment of EoE, comprising clinical, endoscopic, histological outcomes, adaptive behaviors and HRQoL; to define proper evaluation of disease control and impact of continuous versus noncontinuous treatment to reach full disease control. Finally, to validate an algorithm for disease control, switching criteria, and follow-up.

DESIGN: Literature review, survey, and panel expert opinion building by a multidisciplinary Italian EoExpert Panel (EoExpert) of nine specialists from various Italian institutions.

METHODS: Non-systematic literature review, followed by a survey including 21 questions on the different topics. Results were then discussed and validated by EoExpert.

RESULTS: The current diagnostic pathway often does not allow early detection of EoE patients, especially in the presence of adaptive behaviors and unawareness of EoE best practices. In addition, there is a lack of a shared "control" definition. EoExpert reviewed, shared, and recommended two novel management tools for EoE, represented by I.M.P.A.C.T. Questionnaire to uncover adaptive behaviors and S.C.O.P.E. (Symptoms Control, Observation, Pathological Evaluation) scheme for comprehensive treatment efficacy evaluation. EoExpert's recommendations were gathered and turned into a therapeutic management algorithm for the definition of disease control and switching criteria.

CONCLUSION: This document provides a standardized approach to EoE management in pediatric and adult settings, highlighting the importance of timely diagnosis in a multidisciplinary setting, of using unified criteria for assessment of disease control through the adoption of a comprehensive approach and of following up patients. These recommendations highlight the critical role of increased awareness and standardized care in EoE clinical setting for lifelong management.

PMID:40351381 | PMC:PMC12062651 | DOI:10.1177/17562848251337515

Chest. 2025 May 9:S0012-3692(25)00574-4. doi: 10.1016/j.chest.2025.05.005. Online ahead of print.

ABSTRACT

BACKGROUND: Limited data exists to inform and appropriately counsel female lung transplant (LuT) recipients regarding post-transplant pregnancy.

QUESTION: What are the modifiable factors that impact pregnancy outcomes in female LuT recipients?

STUDY DESIGN AND METHODS: Retrospective observational analysis was performed on female LuT recipients who reported post-transplant pregnancies to the Transplant Pregnancy Registry International (TPRI).

RESULTS: Fifty-three recipients transplanted from 1991-2021 reported 72 pregnancies to TPRI. Predominant indications for transplant were cystic fibrosis (60%) and pulmonary hypertension (19%). Contraceptive use post-transplant was 36%. The majority of recipients (54%) had unplanned pregnancies. The livebirth rate was 62% resulting in 46 livebirths. Approximately 60% were premature (<37 weeks gestational age, GA) and low birth weight (LBW, <2500 grams). Birth defects were seen in 7 (16%) children; none with mycophenolic acid (MPA) embryopathy. Three neonatal deaths resulted from extreme prematurity; 43 remaining children are healthy. Twenty recipients (38%) have died a median of 23.6 years post-LuT. Recipients with transplant-to-conception interval ≤2 years had no difference in mortality compared to >2 years (HR 1.26 95% CI 0.50-3.12, p=0.625). Recipients whose first pregnancy post-transplant was unplanned had lower survival (HR 7.02, 95% CI 1.35-36.45, p=0.020). Newborns of LuT recipients with planned compared to unplanned pregnancies have higher median GA (36.9 versus 34 weeks, p=0.025) and birthweight (2639 versus 2155 grams, p=0.047), and significantly lower risk of LBW for singletons (OR 0.26, 95% CI 0.07-0.94, p=0.036).

INTERPRETATION: Successful pregnancy after lung transplantation is achievable, however not without risks for mother and offspring. Planned pregnancies resulted in higher GA and birth weight liveborn and had lower post-pregnancy mortality. TPRI data show 54% of recipients reported unplanned pregnancies, an obvious area for improvement. Planning pregnancy is the most modifiable factor for mitigating risks.

PMID:40350146 | DOI:10.1016/j.chest.2025.05.005

ACS Infect Dis. 2025 May 11. doi: 10.1021/acsinfecdis.5c00226. Online ahead of print.

ABSTRACT

Infections in the lungs of cystic fibrosis (CF) patients are often polymicrobial in nature, typically comprising Pseudomonas aeruginosa and Staphylococcus aureus. Compounds that act as an antimicrobial agent against one of these pathogens, and as an antibiotic adjuvant against the other, could provide a valuable approach to treating such infections, however a model that mimics the unique environment found with the CF lung is required for the identification and characterization of such molecules. To address this, we employed a S. aureus/P. aeruginosa coculture screening model in synthetic sputum, and identified compounds from our in-house library that simultaneously have potent anti-S. aureus activity, and potentiate colistin against colistin-resistant P. aeruginosa. The two lead compounds, 12F1 and 12G9, control growth of both species when dosed alongside sub-inhibitory concentrations of colistin, highlighting the potential of using a single molecule as both an antibiotic and antibiotic adjuvant to target multiple species in polymicrobial infections, as well as the importance of conducting activity screens in clinically relevant media.

PMID:40349215 | DOI:10.1021/acsinfecdis.5c00226

Chest. 2025 May;167(5):1282-1284. doi: 10.1016/j.chest.2024.09.036.

NO ABSTRACT

PMID:40348513 | DOI:10.1016/j.chest.2024.09.036

Patient Educ Couns. 2025 May 5;137:108822. doi: 10.1016/j.pec.2025.108822. Online ahead of print.

ABSTRACT

OBJECTIVES: Cystic fibrosis (CF) causes progressive respiratory disease and premature death. Lung transplantation (LTx) is an important treatment consideration for people with CF (PwCF). Among PwCF, does preparedness for LTx and knowledge about LTx improve by reading personal narratives from CF LTx recipients ("CF Stories")?

METHODS: Adults with CF were recruited and presented with online CF Stories. Pre- and post-intervention questionnaires assessed LTx preparedness, knowledge, and decisional conflict. Deductive thematic analysis of study visits was conducted.

RESULTS: Twenty-five participants were included. Pre-intervention, 24 % (6/25) reported feeling "very prepared" to discuss LTx. Among the remaining 19, preparedness improved post-intervention for 74 % (n = 14, 95 % CI: 51-88 %), with 42 % (n = 8, 95 % CI: 23-64 %) transitioning to feeling "very prepared." Baseline transplant knowledge was high (100 % questions correct) among 48 % (12/25) of participants; among the remaining 13, 92 % (n = 12, 95 % CI: 67-99 %) scored 100 % post-intervention. Decisional conflict improved for 67 % of participants (16/24), with a mean individual Decisional Conflict Scale change of -9.4 (95 % CI: -2.8, -15.9; p = 0.01). Thematic analysis revealed that participants valued practical LTx insights and relatable stories, identifying key medical information for LTx discussions.

CONCLUSIONS: CF Stories improved knowledge and preparedness for LTx discussions.

PRACTICE IMPLICATIONS: Personal narratives could enhance preparedness for LTx discussions and decision-making for PwCF.

PMID:40347548 | DOI:10.1016/j.pec.2025.108822

Indian J Med Res. 2025 Mar;161(3):207-214. doi: 10.25259/IJMR_1754_2024.

ABSTRACT

Background & objectives Availability of sweat chloride analysis, the gold standard test for diagnosis of Cystic Fibrosis (CF) faces significant challenges in India. This study aimed to compare sweat conductivity using Sweat-Chek™ Sweat Analyzer against sweat chloride analysis using the 926 Sherwood chloride analyser and assess if sweat conductivity test can guide CF diagnosis in resource-poor settings. Methods In this retrospective study sweat chloride analysis and sweat conductivity were simultaneously performed on samples collected via Macroduct® system from patients referred for sweat testing. CF diagnosis was based on sweat chloride levels: ≥60 mmol/l confirmed CF, 30-59 mmol/l was borderline, and <30 mmol/l excluded CF. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and area under curve (AUC) were calculated via ROC curve. Spearman's rho was employed to analyse the correlation between methods. Results Both tests were performed on 118 children of which 106 samples were adequately collected. CF was diagnosed in 11 children. Sweat conductivity ≥ 80 mmol/l diagnosed CF with 100 per cent sensitivity, specificity, PPV, and NPV. Likewise, a value ≤ 49 mmol/l predicted absence of CF with 100 per cent sensitivity, 91.36 per cent specificity, 78.13 per cent PPV, and 100 per cent NPV. Spearman's rho of 0.93 (P< 0.001) showed a strong correlation between the two methods. Intermediate conductivity values also correlated well (rs 0.62, P< 0.003) with intermediate sweat chloride levels. Interpretations & conclusions Sweat conductivity reliably identified CF in the study population including those children with borderline levels, suggesting the possibility of its use in resource-limited settings where sweat chloride analyzers are unavailable.

PMID:40347500 | DOI:10.25259/IJMR_1754_2024

Clin Transl Sci. 2025 May;18(5):e70245. doi: 10.1111/cts.70245.

ABSTRACT

Elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves treatment outcomes for people with cystic fibrosis (pwCF) with at least one F508del allele. In 2023, the Food and Drug Administration approved ETI for children with CF aged 2-5 years. However, real-world pharmacokinetic-pharmacodynamic data for ETI in pediatric and adult populations are still limited. This study aimed to characterize the population PK of ETI in children with CF (chCF) and evaluate current dosing recommendations. Population PK modeling was conducted using Monolix software on 150 ETI concentrations obtained from therapeutic drug (TDM) monitoring in 96 children with CF aged 2-18 years, as part of the MODUL-CF study. Area under the curve was derived from individual Bayesian pharmacokinetic estimates. A one-compartment model with a lag time, first-order absorption, and elimination best described the PK of elexacaftor/ivacaftor, while the PK of tezacaftor followed a one-compartment model with first-order absorption and elimination. A large between-subject variability was observed. The effect of body weight was significant on apparent clearance and volume of distribution parameters using allometric scaling. Children weighing 30-40 kg who received the adult-recommended dose showed higher drug exposure compared to adults with cystic fibrosis. This is the first study to describe the population pharmacokinetics of ETI in chCF aged 2-18 years, revealing high between-subject variability for all three drugs. In this context, TDM is likely essential for managing ETI exposure levels and guiding dosing adjustments. The appropriateness of current dosing recommendations for children under 12 years old weighing 30-40 kg remains to be clarified.

PMID:40347054 | DOI:10.1111/cts.70245

Diabetes Technol Ther. 2025 May 9. doi: 10.1089/dia.2025.0075. Online ahead of print.

ABSTRACT

Background: Studies investigating the safety and efficacy of automated insulin delivery (AID) systems in people with cystic fibrosis-related diabetes are limited. There are no published studies investigating the tubeless Omnipod 5 (OP5) AID system. Methods: This dual-center retrospective cohort study compared 14 days of baseline continuous glucose monitoring (CGM) data with days 1-90 and 91-180 post-OP5 initiation. Multivariable mixed-effects linear regression models were used to assess changes in glycemic metrics. Results: Among the 26 individuals with sufficient data initiating OP5, 65% were female, with a median age of 27.3 years and median diabetes duration of 10.9 years. Six (23%) had a history of solid organ transplant, and 2 (8%) were receiving enteral tube feeds. Participants transitioned to OP5 from multiple daily injections (54%), prior Omnipod generation (31%), or another AID system (15%). CGM time in range (70-180 mg/dL) increased from 54% (95% confidence interval [CI]: 45.0, 63.0) to 64% (95% CI: 57, 71.8, P < 0.001) during the first 90 days and to 62.7% (95% CI: 54.9, 70.5, P < 0.001) during 91-180 days. Time above range (TAR) 181-250 mg/dL and TAR >250 mg/dL improved at 1-90 days and 91-180 days compared with baseline (P = 0.001 and P = 0.002, respectively). There were no significant changes in time below range (54-69 mg/dL, <54 mg/dL) or coefficient of variation. Two individuals discontinued OP5 within 14 days due to persistent hypoglycemia. One adult experienced a hypoglycemic seizure after 3 months of use. Conclusions: Use of the OP5 system in youth and adults with CFRD led to significant improvements in multiples measures of hyperglycemia without a change in CGM-measured hypoglycemia over a 6-month period, although patient experience with hypoglycemia may limit sustained use. Given the unique comorbidities and pathophysiology of CFRD, these results emphasize the need for future studies to investigate the safety and efficacy of AID devices in this patient population.

PMID:40346784 | DOI:10.1089/dia.2025.0075

Arch Bronconeumol. 2025 Apr 28:S0300-2896(25)00140-1. doi: 10.1016/j.arbres.2025.04.004. Online ahead of print.

NO ABSTRACT

PMID:40345955 | DOI:10.1016/j.arbres.2025.04.004

Ocul Surf. 2025 May 7:S1542-0124(25)00066-7. doi: 10.1016/j.jtos.2025.05.005. Online ahead of print.

ABSTRACT

The tear film is a complex structure with rich interactions with the human body. A growing body of evidence suggests that measuring changes in protein, lipid, or other metabolite concentration in the tear film can be used to help detect disease. Particularly in the era of precision medicine, the tear film serves as a promising source of non-invasive insights into systemic health for early diagnosis and treatment. This paper analyzes the latest research in tear film biomarkers for systemic diseases. The review was conducted through PubMed and Embase databases using the PRISMA protocol and includes 54 articles. This paper first reviews the anatomy and physiology of tear film, as well as the latest proteomic analysis techniques on the tear film. We then provide a disease-by-disease review on the tear film as a biomarker including 5 articles related to Alzheimer's Disease, 10 articles related to Cancers, 1 article related to Cystic Fibrosis, 1 article related to Migraines, 4 articles related to Multiple Sclerosis, 15 articles related to Parkinson's Disease, 7 articles related to Rheumatoid Arthritis, and 11 articles related to Thyroid Disease. This paper highlights the promising results of these studies yet also reviews the challenges with limited sample sizes, reproducibility, and biological understanding of biomarkers. We conclude this paper with insights for future work to ensure clinical validity and generalizability. Ultimately, the tear film is a clinically accessible, complex structure that provides a wealth of information that may contribute to a more comprehensive understanding of systemic health.

PMID:40345388 | DOI:10.1016/j.jtos.2025.05.005

ACS Chem Biol. 2025 May 9. doi: 10.1021/acschembio.4c00562. Online ahead of print.

ABSTRACT

The fungus Aspergillus fumigatus and the bacterium Burkholderia cenocepacia cause fatal respiratory infections in immunocompromised humans and patients with lung disease, such as cystic fibrosis (CF). In dual infections, antagonistic interactions contribute to increased mortality. These interactions are further altered by the presence of antimicrobial and antifungal agents. However, studies performed to date on chemical interactions between clinical B. cenocepacia and A. fumigatus have focused on pathogens in isolation and do not include the most abundant chemical signal, i.e., clinically administered therapeutics, present in the lung. Here, we characterize small molecule-mediated interactions between B. cenocepacia and A. fumigatus and their shift in response to trimethoprim exposure by using metabolomics and mass spectrometry imaging. Using these methods, we report that the production of several small-molecule natural products of both the bacteria and the fungus is affected by cocultivation and exposure to trimethoprim. By systematic analysis of metabolomics data, we hypothesize that the B. cenocepacia-encoded ham gene cluster plays a role in the trimethoprim-mediated alteration of bacterial-fungal interactions. We support our findings by generating a genetically modified strain lacking the ham gene cluster and querying its interaction with A. fumigatus. Using comparative analyses of the extracts of wild-type and knockout strains, we report the inactivation of a bacterially produced antifungal compound, fragin, by A. fumigatus, which was verified by the addition of purified fragin to the A. fumigatus culture. Furthermore, we report that trimethoprim does not inhibit fungal growth, but affects the biochemical pathway for DHN-melanin biosynthesis, an important antifungal drug target, altering the pigmentation of the fungal conidia and is associated with modification of ergosterol to ergosteryl-3β-O-l-valine in coculture. This study demonstrates the impact of therapeutics on shaping microbial and fungal metabolomes, which influence interkingdom interactions and the expression of virulence factors. Our findings enhance the understanding of the complexity of chemical interactions between therapeutic compounds, bacteria, and fungi and may contribute to the development of selective treatments.

PMID:40344688 | DOI:10.1021/acschembio.4c00562

Ann Am Thorac Soc. 2025 May 9. doi: 10.1513/AnnalsATS.202501-093OC. Online ahead of print.

ABSTRACT

RATIONALE: FEV1 and its longitudinal change are mortality risk-factors. Visit-to-visit-FEV1-variation is a risk-factor for death in cystic fibrosis but has not been studied in other cohorts.

OBJECTIVE: Assess if longitudinal visit-to-visit-FEV1-variation is a mortality risk-factor in World Trade Center (WTC) exposed FDNY rescue/recovery workers.

METHODS: Linear mixed-effects regression of all post-9/11/2001 FEV1 measurements defined time-effect on longitudinal-FEV1-decline (FEV1-slope) and its standard error (visit-to-visit-FEV1-variation). Cox proportional hazards and logistic models adjusted for age and smoking assessed the association between FEV1 related risk-factors and mortality. Receiver operating characteristic area under the curve (ROC-AUC) assessed predictive model performance.

MEASUREMENTS AND MAIN RESULTS: Among 11,745 workers with ≥3 FEV1 measurements, 575 (4.9%) died. When all FEV1-related risk-factors were combined, each 5 mL/year increase in visit-to-visit-FEV1-variation increased mortality 2.1-fold (HR=2.14; 95%CI=1.84-2.48); each 10%predicted reduction in the last-longitudinal-FEV1 increased mortality 15% (HR=1.15; 95%CI=1.09-1.21), but each 10ml/year longitudinal-FEV1-decline was not associated with mortality (HR=1.04; 95%CI=0.99-1.10). The ROC-AUC of a fully adjusted multivariable cumulative mortality model was 0.82 (95%CI=0.80-0.84); for unadjusted visit-to-visit-FEV1-variation, AUC was 0.80 (95%CI=0.78-0.82); for last-longitudinal-FEV1 AUC was 0.61 (95%CI=0.59-0.64) and for longitudinal-FEV1-decline AUC was 0.58 (95%CI=0.56-0.61). In the 1,988/11,745(16.9%) with high-WTC-exposure defined as arrival at the WTC-site before noon on 9/11/2001, the risk of high-visit-to-visit-FEV1-variation (top-quartile, ≥10.35 ml/year) increased 25% (OR=1.25; 95%CI=1.12-1.40).

CONCLUSIONS: Visit-to-visit-FEV1-variation is a mortality risk-factor in FDNY rescue and recovery workers with greater accuracy for predicting cumulative mortality than either last-longitudinal-FEV1 or longitudinal-FEV1-decline. Further investigation in other cohorts is needed to assess the generalizability of this rarely studied mortality risk-factor.

PMID:40343979 | DOI:10.1513/AnnalsATS.202501-093OC