Insights Imaging. 2025 Jul 5;16(1):153. doi: 10.1186/s13244-025-01998-4.

ABSTRACT

The vanishing pancreas is a frequently overlooked condition which can result from partial or complete dorsal pancreatic agenesis, intra-pancreatic fat deposition (IPFD) and pancreatic atrophy caused by chronic pancreatitis. A variety of diseases, including cystic fibrosis, maturity-onset diabetes of the young type 8, Shwachman-Diamond syndrome, and Johanson-Blizzard syndrome, can manifest as IPFD. Dorsal pancreatic agenesis can, albeit rarely, coexist with abnormalities or tumors. This review aimed to summarize the various causes that may result in partial or complete vanishing pancreas on computed tomography/magnetic resonance imaging (CT/MRI). We provide a comprehensive review of these imaging findings and their corresponding clinical characteristics, which are crucial for ensuring an accurate diagnosis. CRITICAL RELEVANCE STATEMENT: By reviewing various causes of pancreatic vanishing, we summarize these imaging findings and their corresponding clinical characteristics, which is crucial for ensuring an accurate diagnosis and patient management. KEY POINTS: Imaging findings of partial or complete pancreatic vanishing reveal a hypodense pancreas (resembling fat density) or visibility of only the pancreatic head and proximal body. Pancreatic vanishing can result from dorsal pancreatic agenesis, intra-pancreatic fat deposition, and atrophy caused by chronic pancreatitis. Intra-pancreatic fat deposition is associated with genetic and systemic diseases.

PMID:40616703 | DOI:10.1186/s13244-025-01998-4

BMC Med Ethics. 2025 Jul 4;26(1):86. doi: 10.1186/s12910-025-01250-0.

ABSTRACT

BACKGROUND: There is an ongoing global debate regarding the return of individual genetic findings (IGF) in the field of biobanking. Various models for returning these findings are actively discussed, and strategies for their implementation are increasingly being developed in the context of biobanks. This study aims to analyze the perspectives of the public and experts on returning IGF to biobank participants in Lithuania. Additionally, it seeks to contribute to the discussion on identifying the most appropriate IGF return strategy for Lithuanian biobanks.

METHODS: We conducted an empirical study based on a mixed methods approach involving semi-structured interviews with experts and a representative online survey of the general population with a sample of 700 participants. The mixed methods study was conducted in Lithuania in 2021. Both experts and the general population were asked to give their opinion on hypothetical IGF cases with four different scenarios: [1] “Lynch syndrome” [2], “Possession of a pathogenic variant associated with Huntington’s disease” [3], “Possession of a pathogenic variant associated with cystic fibrosis”, and [4] “Increase in genetic risk of type 2 diabetes”.

RESULTS: 81–92% of the study participants willing to cooperate with a biobank expressed interest in receiving all types of IGF included in the survey from the biobank. The qualitative study revealed a less uniform opinion among experts regarding the appropriateness of returning these findings. While experts unanimously agreed that biobank participants should be informed about findings indicating an increased risk of treatable monogenic diseases (such as Lynch syndrome), their opinions diverged on the return of other findings (such as possession of a pathogenic variant associated with Huntington’s disease or cystic fibrosis or increase in genetic risk of type 2 diabetes).

CONCLUSIONS: Specifying the current strategy for returning IGF to biobank participants in Lithuania, without expanding the definition of clinically actionable information, is crucial for improving the return of such information to biobank participants. To achieve this, at least two approaches—or a combination of them—can be taken: preparing and using a list of genes and diseases, such as the one outlined in the American College of Medical Genetics guidelines, or applying frameworks and guidelines, like the one proposed by Berg and colleagues, to evaluate the criteria for determining the clinical actionability of IGF.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12910-025-01250-0.

PMID:40616130 | PMC:PMC12231843 | DOI:10.1186/s12910-025-01250-0

BMC Pulm Med. 2025 Jul 4;25(1):325. doi: 10.1186/s12890-025-03707-9.

ABSTRACT

BACKGROUND: Clinical trials in cystic fibrosis (CF) disproportionately over-represent non-Hispanic, White individuals. Barriers and facilitators to enrolling racially and ethnically minoritized individuals with CF are not well understood. This study explored research coordinator (RC) perspectives on recruitment and enrollment of minoritized people with CF (PwCF) into clinical trials.

METHODS: A cross-sectional survey was administered to RCs in the CF Therapeutics Development Network (CF TDN), eliciting perceived barriers and facilitators to inclusion of minoritized PwCF in clinical research. Respondents were categorized based on their self-reported experience discussing and successfully enrolling minoritized PwCF into clinical trials.

RESULTS: Among 48 respondents, the majority (n = 31, 64%) had little to no experience discussing CF clinical trials with minoritized PwCF. Respondents who had a moderate or great deal of experience (n = 20, 91%) identified that having a trusted clinical team member first introduce the study to PwCF as the most common strategy for recruitment. Experienced respondents also identified the importance of having team members who speak the same language or are the same culture as the minoritized PwCF (n = 17, 35%). Respondents who had little to no experience successfully enrolling minoritized PwCF into clinical trials cited low numbers of minoritized patients at their study center as an important consideration (n = 31, 47%). Among all levels of experience, respondents emphasized language barriers in enrollment including need for adequate translation services and printed materials in the PwCF's primary language.

CONCLUSION: Our study identified modifiable barriers that may be addressed at the level of trial design and study center. This study highlights the importance of trusted, culturally competent research teams and underscores the importance of language accessibility in recruitment in clinical trials.

PMID:40615798 | DOI:10.1186/s12890-025-03707-9

Sci Rep. 2025 Jul 4;15(1):23965. doi: 10.1038/s41598-025-08459-4.

ABSTRACT

Investigating the interplay between polymicrobial colonization and host response in the context of chronic infections is a complex issue. The interaction between Staphylococcus aureus and Pseudomonas aeruginosa, which frequently co-infect patients with chronic diseases like cystic fibrosis (CF), can be either competitive or coexistent. How these interaction states can influence the host response remains an open question for which relevant infection models are needed. In this study, we investigated co-infections by P. aeruginosa and S. aureus in zebrafish (Danio rerio), a non-mammalian model well established for the study of the host innate immune response. Using a wound infection method and a trio of strains co-isolated from a CF patient, we provide an in vivo co-infection model that recapitulates the competitive and coexistent bacterial interactions observed in vitro. The inflammatory response, monitored through the expression of specific cytokines at the infection site or in the whole larvae, was stronger with P. aeruginosa than S. aureus in the context of mono-infection. Upon co-infection, a competitive or coexistent interaction between P. aeruginosa and S. aureus appeared to slightly modulate this response. Moreover, the RT-qPCR profile of cytokine response observed in zebrafish larvae was similar to the one observed after infection of human lung epithelial cells. Thus, the zebrafish embryo appears as a relevant model to study persistent co-infection with P. aeruginosa and S. aureus, offering unique opportunities to address the host response in this polymicrobial context.

PMID:40615487 | DOI:10.1038/s41598-025-08459-4

J Cyst Fibros. 2025 Jul 3:S1569-1993(25)01517-6. doi: 10.1016/j.jcf.2025.06.003. Online ahead of print.

ABSTRACT

Cystic fibrosis is a lifelong progressive disease in which lung disease is the main prognostic factor, where starting early treatment is crucial for improving long-term outcomes. Therefore, new treatment should be available as early as possible. However, choosing appropriate and feasible clinical trial endpoints in children under 2 years of age presents significant challenges. Most studies in this age group have extrapolated pulmonary efficacy from older age groups, focusing on safety, pharmacokinetics, and biomarker response. As lung health is near normal in infants, demonstrating absence of pulmonary decline requires large sample sizes and extended study duration, which may not be feasible for standard regulatory trials. To address this gap, the European Cystic Fibrosis Society Clinical Trials Network developed a consensus document evaluating direct pulmonary endpoints for therapeutic pulmonary studies in this young age group. The pulmonary endpoints evaluated include multiple-breath washout (MBW); chest computed tomography (CT); chest magnetic resonance imaging (MRI); airway infection and inflammation. Relevant literature, pitfalls, practice guidelines, and recommendations are presented. None of the pulmonary endpoints evaluated are currently suitable to serve as a primary efficacy endpoint in children below 2 years of age, as this will require large numbers and long follow-up. For clinical trials in infants with CF, pharmacokinetics, pharmacodynamics, safety and tolerability should remain the primary endpoints, with pulmonary endpoints as secondary or exploratory outcomes. Post authorization studies are essential to evaluate long-term pulmonary benefits, including MBW, structural lung assessment (e.g. CT and MRI), and markers of pulmonary inflammation to fully understand the impact of early therapy initiation in this young population.

PMID:40615279 | DOI:10.1016/j.jcf.2025.06.003

Respir Med. 2025 Jul 2:108243. doi: 10.1016/j.rmed.2025.108243. Online ahead of print.

ABSTRACT

Brensocatib is an oral inhibitor of dipeptidyl peptidase 1, an enzyme that activates neutrophil serine proteases. Its potential to reduce neutrophil-driven inflammation has generated interest across a range of chronic inflammatory and respiratory conditions, particularly non-cystic fibrosis bronchiectasis. As the body of evidence supporting brensocatib continues to expand, there is a clear need for a comprehensive, rigorous, and practical narrative review to consolidate current knowledge and highlight gaps for future research. The aim of this narrative review was to systematically examine and synthesize the existing literature on brensocatib, including its pharmacology, therapeutic applications, clinical trial outcomes, safety profile, and ongoing research efforts. A systematic search was performed across major databases, EMBASE, MEDLINE, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov, through April 2025. Studies involving brensocatib in preclinical or clinical contexts were thoroughly reviewed to evaluate its efficacy and safety. Data were extracted on study design, population, dosage, outcomes, adverse events, and key findings. The most extensively studied indication was non-CF bronchiectasis, where brensocatib demonstrated a reduction in exacerbation rates and neutrophil protease activity. Preliminary evidence also suggests potential applications in cystic fibrosis, chronic obstructive pulmonary disease (COPD), and other neutrophilic conditions. An evaluation of the safety data indicates that the adverse events reported are generally mild to moderate in severity. Brensocatib demonstrates potential as a novel anti-inflammatory therapy targeting neutrophil-mediated disease mechanisms. Further research is needed to evaluate its long-term efficacy, safety across a broader population, and its role in combination therapies.

PMID:40614835 | DOI:10.1016/j.rmed.2025.108243

Mol Ther Nucleic Acids. 2025 Jun 2;36(3):102580. doi: 10.1016/j.omtn.2025.102580. eCollection 2025 Sep 9.

ABSTRACT

Cigarette smoking is associated with COVID-19 prevalence and severity, but the mechanistic basis for how smoking alters SARS-CoV-2 pathogenesis is unknown. A potential explanation is that smoking alters the expression of the SARS-CoV-2 cellular receptor and point of entry, angiotensin-converting enzyme 2 (ACE-2), and its cofactors including transmembrane protease serine 2 (TMPRSS2). We investigated the impact of cigarette smoking on the expression of ACE-2, TMPRSS2, and other known cofactors of SARS-CoV-2 infection and the resultant effects on infection severity in vitro. Cigarette smoke extract (CSE) exposure increased ACE-2 and TMPRSS2 mRNA expression compared to air control in ferret airway cells, Calu-3 cells, and primary human bronchial epithelial (HBE) cells derived from normal and chronic obstructive pulmonary disease (COPD) donors. CSE-exposed ferret airway cells inoculated with SARS-CoV-2 had a significantly higher intracellular viral load versus vehicle-exposed cells. Likewise, CSE exposure increased both SARS-CoV-2 intracellular viral load and viral replication in both normal and COPD HBE cells over vehicle control. Apoptosis was increased in CSE-exposed, SARS-CoV-2-infected HBE cells. Knockdown of ACE-2 via an antisense oligonucleotide (ASO) reduced SARS-CoV-2 viral load and infection in CSE-exposed ferret airway cells that was augmented by co-administration of camostat mesylate to block TMPRSS2 activity. Smoking increases SARS-CoV-2 infection via upregulation of ACE2 and TMPRSS2.

PMID:40612711 | PMC:PMC12221736 | DOI:10.1016/j.omtn.2025.102580

Biochemistry (Mosc). 2025 Jun;90(6):773-785. doi: 10.1134/S0006297924604672.

ABSTRACT

Prime editing is a highly promising strategy for treating hereditary disorders due to its superior efficiency and safety profile compared to the conventional CRISPR-Cas9 systems. This study is dedicated to development of a causal therapy for cystic fibrosis by targeting the F508del variant of the CFTR gene using prime editing, as this specific deletion accounts for a substantial proportion of cystic fibrosis cases. While prime editing has shown remarkable precision in introducing targeted genetic modifications, its application in AT-rich genomic regions, such as the one containing the F508del variant, remains challenging. To overcome this limitation, we systematically evaluated 24 pegRNAs designed for two distinct prime editing systems, PEmax and PE2-NG. Efficiency of the F508del variant correction reached 2.81% (without normalization for transfection efficiency) in the airway basal cells from the patients with homozygous F508del mutation. However, the average transfection efficiency was only 11.9%, emphasizing critical need for the advancements in delivery methodologies. These findings highlight potential of prime editing as an approach for treating cystic fibrosis, while also underscoring necessity for further optimization of both editing constructs and delivery vectors to achieve clinically relevant correction levels.

PMID:40609995 | DOI:10.1134/S0006297924604672

FEMS Microbiol Lett. 2025 Jul 3:fnaf066. doi: 10.1093/femsle/fnaf066. Online ahead of print.

ABSTRACT

Chronic respiratory tract infections with Pseudomonas aeruginosa frequently occur in patients with cystic fibrosis, chronic obstructive pulmonary disease, and bronchiectasis. A hallmark of these conditions is the accumulation of mucus plugs, creating oxygen-limited niches. Within these microenvironments, P. aeruginosa undergoes cellular modifications that may alter its antibiotic sensitivity. Although the acute effects of anoxia are well studied, the impact of prolonged anoxic exposure on antibiotic sensitivity remains unclear. In this study, we developed anoxic-conditioned P. aeruginosa strains by passaging a laboratory strain for 22 days in an anoxic environment. We performed time-kill assays with both parental and anoxic-conditioned strains in anoxic and aerobic environments, using ceftazidime, ciprofloxacin, colistin, and tobramycin. The anoxic-conditioned strains exhibited increased susceptibility to tobramycin and reduced sensitivity to colistin and ceftazidime. These differences were attributed to altered killing rates (as with tobramycin) or reduced regrowth under anoxic conditions (as with colistin). For ciprofloxacin, a steeper killing rate was observed against the anoxic-conditioned strains, but 24-hour outcomes were similar to the parental strain. Overall, our findings demonstrate that long-term anoxia alters antibiotic sensitivity in P. aeruginosa differently than acute anoxia, with important implications for treating chronic infections in oxygen-limited environments.

PMID:40608522 | DOI:10.1093/femsle/fnaf066

Ann Am Thorac Soc. 2025 Jul 3. doi: 10.1513/AnnalsATS.202501-063PS. Online ahead of print.

NO ABSTRACT

PMID:40607955 | DOI:10.1513/AnnalsATS.202501-063PS

Front Chem. 2025 Jun 18;13:1575479. doi: 10.3389/fchem.2025.1575479. eCollection 2025.

ABSTRACT

An efficient, reliable, and cost-effective sensor of 2,3-butanedione, an organic compound with a distinctive buttery aroma, is here developed through the production of a sensible layer based on a tin oxide semiconductor decorated with platinum nanoparticles. The resulting material is subjected to characterization and testing to evaluate its capability to sense 2,3-butanedione, which is known to be responsible for health risks upon inhalation, including the potential to cause lung disease, and to be detected in the breath of individuals with cystic fibrosis. The results demonstrate that the developed sensor provides high sensitivity and selectivity for 2,3-butanedione in specific experimental conditions, featuring advantages such as simplicity, portability, and rapid response. In addition, it shows great potential for on-site safety and health applications, providing a practical solution for real time monitoring.

PMID:40606551 | PMC:PMC12213707 | DOI:10.3389/fchem.2025.1575479

J Child Neurol. 2025 Jul 3:8830738251346626. doi: 10.1177/08830738251346626. Online ahead of print.

NO ABSTRACT

PMID:40605553 | DOI:10.1177/08830738251346626

Sci Rep. 2025 Jul 2;15(1):23198. doi: 10.1038/s41598-025-05051-8.

ABSTRACT

Sweat analysis is best recognized as a procedure for the diagnosis of cystic fibrosis. However sweat contains a large number of solutes, so it has great potential to phenotypically profile individuals. We aimed to evaluate the use of aminoacids in sweat as biomarkers by measuring their concentrations in relation to those in circulation. Healthy adults were recruited to provide concurrent blood and sweat samples collected by standard methods. This included the collection of sweat under an oil barrier on a subset to evaluate potential contamination from transdermal sources. For most aminoacids only weak correlations were noted, as well as large differences introduced by the sweat collection conditions. Only for Valine, Alanine and Threonine we found significant correlations. This suggests to us that these amino acids might be more amenable to modeling of their partitioning for further development as surrogates of circulating levels. Among aminoacid characteristics assessed, only molecular weight seemed to influence partitioning into sweat. Overall our study demonstrates that the partitioning of aminoacids into sweat is complex and in need of additional research. This should also be taken as a cautionary note about the further development of aminoacids in sweat as biomarkers.

PMID:40603951 | DOI:10.1038/s41598-025-05051-8

Int J Behav Med. 2025 Jul 2. doi: 10.1007/s12529-025-10382-x. Online ahead of print.

ABSTRACT

BACKGROUND: Among people with cystic fibrosis (CF), health behaviors and mental health have been associated with general social support. We used egocentric network analysis to assess the specific impact of social network variables on treatment adherence, depression, anxiety, and perceived stigma among adults with CF. Our goal is to identify the social network factors which may be driving adherence, anxiety, depression, and perceived stigma among adults with CF toward developing targeted network-based interventions.

METHOD: Our primary outcome, adherence to individual-level treatment regimens, was assessed using composite prescription refill history (cMPR), self-reported airway clearance therapy (ACT), and consumption of all prescriptions. Secondary outcomes were assessed via patient completion of the Patient Health Questionnaire-9 (PHQ-9) for depression, the General Anxiety Disorder-7 (GAD-7) for anxiety, and the CF Stigma Scale for perceived stigma. Participants also completed a social network interview to collect data on personal-level networks. Controlling for participant age, sex, race, relationship status, work status, and CF disease severity, we explored the impact of network variables on our primary and secondary outcomes using regression analysis. All models were run twice to assess both core and strong network ties.

RESULTS: Regression analysis of 104 participants showed that strong network ties serving as health discussants and health regulators were positively associated with stronger adherence, while financial dependence and network density were associated with decreased adherence. Network alters having higher education levels, strong trust in doctors, and support for daily activities were associated with lower depression, anxiety, and perceived stigma. Participants having a higher proportion of network members who hassled them and had lower trust and/or greater variability in trust in doctors experienced higher depression, anxiety, and perceived stigma.

CONCLUSION: Findings show that network-based variables including close ties to health discussants, network members' education levels, and health beliefs, as well as having network members providing support for daily activities may be driving specific aspects of adherence, symptoms of depression and anxiety, and perceived stigma among adults with CF. These findings may thus allow us to leverage social networks in the development of novel interventions to improve adherence and mental health and reduce perceived stigma for people with CF.

PMID:40603690 | DOI:10.1007/s12529-025-10382-x

npj metabolic health and disease.. 2024 Aug 13;2(1):22. doi: 10.1038/s44324-024-00024-3.

ABSTRACT

Human metabolism is complex, and is impacted by genetics, cohabitation, diet, health, and environmental inputs. As such, we applied untargeted LC-MS metabolomics to 1425 saliva samples from a diverse group of elementary school-aged children and their caregivers collected during the Family Life Project, of which 1344 were paired into caregiver/child dyads. We compared metabolomes within and between homes, performed population-wide "metabotype" analyses, and measured associations between metabolites and salivary biomeasures of inflammation, antioxidant potential, environmental tobacco smoke (ETS) exposure, metabolic regulation, and heavy metals. Children and caregivers had similar salivary metabolomes, and dyad explained most metabolomic variation. Our data clustered into two groups, indicating that "metabotypes" exist across large populations. Lastly, several metabolites-putative oxidative damage-associated or pathological markers-were correlated with the above-mentioned salivary biomeasures and heavy metals. Implications of the family environment's effects on metabolomic variation at population, dyadic, and individual levels for human health are discussed.

PMID:40603689 | DOI:10.1038/s44324-024-00024-3

Sci Rep. 2025 Jul 2;15(1):23392. doi: 10.1038/s41598-025-06075-w.

ABSTRACT

The colonization and persistence of Pseudomonas aeruginosa in chronically diseased lungs are driven by various virulence factors. However, pulmonary infections in cystic fibrosis (CF) patients are predominantly polymicrobial. While Achromobacter xylosoxidans is an opportunistic pathogen in these patients, its impact on P. aeruginosa virulence during co-infection remains largely unknown. This study investigated P. aeruginosa interaction with two clonally related A. xylosoxidans strains, Ax 198 and Ax 200, co-isolated from CF sputum. We found that the interaction was strain-dependent, with Ax 200 significantly reducing P. aeruginosa virulence in a zebrafish model, providing the first in vivo evidence of this interaction. Proteomic analysis revealed that P. aeruginosa proteome was differently impacted by the two A. xylosoxidans strains, with Ax 200 altering proteins involved in biofilm formation, swimming motility, iron acquisition, and secretion systems. These findings were validated by phenotypic assays, confirming that A. xylosoxidans affected major P. aeruginosa virulence phenotypes, including biofilm formation, swimming motility, and siderophore production. Genetic analysis confirmed that distinct regulatory mechanisms, including iron cycle pathways, may account for the strain-dependent effects. These findings reveal a novel multi-target competitive mechanism through which A. xylosoxidans significantly disrupts P. aeruginosa virulence.

PMID:40603430 | DOI:10.1038/s41598-025-06075-w

J Cyst Fibros. 2025 Jul 1:S1569-1993(25)01519-X. doi: 10.1016/j.jcf.2025.06.005. Online ahead of print.

ABSTRACT

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved pulmonary and extrapulmonary manifestations of cystic fibrosis (CF). ETI clinical trials excluded lung transplant (LTx) recipients and current post-transplant prescribing practices are not evidence-based. We sought to identify the prevalence of new ETI prescriptions among CF LTx recipients in the United States (U.S.) and factors associated with ETI prescription after LTx.

METHODS: We performed a retrospective cross-sectional study of LTx recipients through December 2022 using the Cystic Fibrosis Foundation Patient Registry. Recipients were alive as of October 2019, had an ETI-eligible genotype, and were not prescribed ETI before LTx. Logistic regression was used to assess factors associated with ETI prescription. CF Center prescribing patterns were categorized based on the proportion of LTx recipients who were prescribed ETI after LTx at each center.

RESULTS: Overall, 488/1666 (29.3 %) of patients were prescribed ETI after LTx. The presence of sinus disease (OR 2.12, 95 % CI 1.51-2.99) and BMI<18.5 kg/m2 (OR 1.52, 95 % CI 1.13-2.04) were positively associated with ETI prescription after LTx. CF center prescribing pattern ["middle prescribing": OR 0.19, 95 % CI 0.14-0.26; "low prescribing": OR 0.02, 95 % CI 0.01-0.04; "high prescribing": reference group] and zero F508del alleles (OR 0.18, 95 % CI 0.07-0.49; 1 or 2 alleles: reference group) were negatively associated with ETI prescription after LTx.

CONCLUSIONS: ETI was newly prescribed to almost 30 % of eligible LTx recipients in the U.S. Even when including patient clinical characteristics in the model, CF center prescribing pattern was one of the strongest factors associated with ETI prescription after LTx.

PMID:40603159 | DOI:10.1016/j.jcf.2025.06.005

Am J Hematol. 2025 Jul 2. doi: 10.1002/ajh.27756. Online ahead of print.

ABSTRACT

Hereditary hemorrhagic telangiectasia (HHT) is the second-most common inherited bleeding disorder worldwide, afflicting one in 4000-5000 people, and is the most morbid inherited bleeding disorder of women. HHT causes recurrent severe epistaxis, chronic gastrointestinal bleeding, heavy menstrual bleeding, and arteriovenous malformations in the lung, liver, and brain that cause serious bleeding and nonbleeding complications. There are no approved treatments worldwide, and the direct medical costs of HHT have not been well-characterized. We utilized the Komodo Healthcare Map claims database to create a large sample of US patients diagnosed with HHT, including a subgroup with anemia and a subgroup receiving hematologic support (iron infusions and/or red cell transfusions). We quantified mean per patient per year (PPPY) and total population inpatient, outpatient, and pharmacy costs in 2022 and 2023. The mean PPPY costs for all HHT patients (n = 24 407; n = 23 524), those with anemia (n = 13 856; n = 13 192) and those receiving hematologic support (n = 6191; n = 5818) were approximately $19 000, $27 000, and $40 000, respectively, across years, representing > $450 000 000 in annual healthcare costs in the sample. The leading cost drivers were related to treatment for bleeding and its consequences. While accounting for nearly 60% of HHT patients, those with anemia accounted for ~80% of direct medical costs. Across the majority of leading inpatient, outpatient, and pharmacy cost drivers, patients with anemia and anemia treatment accounted for 75%-100% of cost. The PPPY costs of HHT are comparable to, or exceed, those of other rare, resource-intensive serious diseases, including sickle cell disease, muscular dystrophy, and cystic fibrosis.

PMID:40600700 | DOI:10.1002/ajh.27756

Front Med (Lausanne). 2025 Jun 17;12:1577363. doi: 10.3389/fmed.2025.1577363. eCollection 2025.

ABSTRACT

PURPOSE: Burkholderia multivorans, a Gram-negative bacterium, often infect patients with severe immunocompromised and cystic fibrosis. B. multivorans infection is challenging to treat due to its ability to disrupt the action of multiple antimicrobial agents through intrinsic and acquired resistance mechanisms. A better understanding of the pulmonary microbial spectrum of B. multivorans infection is crucial for the prevention and treatment of B. multivorans.

CASE PRESENTATION: This case series reviewed the respiratory microbiome structure and alternations during the treatment of B. multivorans infection through metagenomic next-generation sequencing (mNGS). Analysis of mNGS data of 19 pharyngeal secretion samples collected from the 3 COVID-19 patients at different time points showed that the relative abundance of B. multivorans was fluctuated and eventually increased, indicating the possible development of drug resistance. A total of 40 antibiotic-resistant genes (ARGs) were detected. Significantly, the levels of CEOA, CEOB, and OPCM were consistent with the trends in the relative abundance of B. multivorans. Besides, we described nine previously uncharacterized non-synonymous mutations in PenA of B. multivorans. These mutations lead to amino acid changes Thr32Ala, Ala43Ser, Gln105Arg, Asn202Ser, Gln219Arg, Gly241Ala, Val259Ala, Thr279Ala, and Ser298Ile that may associate with resistance to β-lactam antibiotics.

CONCLUSION: This report shed light on the importance of rapidly diagnosis and treatment of B. multivorans infection. mNGS serve as a powerful microbial detection tool that provides a comprehensive, sensitive, and rapid method for pathogen detection and drug resistance analysis.

PMID:40600049 | PMC:PMC12209342 | DOI:10.3389/fmed.2025.1577363

Front Pharmacol. 2025 Jun 17;16:1528905. doi: 10.3389/fphar.2025.1528905. eCollection 2025.

ABSTRACT

Pseudomonas aeruginosa infection has become a widespread problem in patients with cystic fibrosis (CF). A safe and effective manufacturing method is required to produce antibiotic dry powder inhalations (DPIs) which can be effectively delivered to treat lung infections. In this study, an excipient-free tobramycin inhalable powder was prepared using spray freeze-drying (SFD) method. The mass median aerodynamic diameters (MMAD) of optimized inhalable powder prepared by SFD was 1.30 µm, and the fine particle fractions (FPF) reached 83.31%. In both in vitro and in vivo safety and activity studies, the inhalable powder showed excellent safety performance at both animal and cellular levels, with a minimum inhibitory concentration (MIC) of 0.5 μg/mL. Compared with intravenous injection, inhalation of excipient-free tobramycin inhalable powder had a better effect in the infected mouse model because of its amorphous state. This study demonstrates that excipient-free tobramycin inhalable powder with good delivery and deposition performance can be successfully obtained using the SFD method. Inhalation of excipient-free tobramycin inhalable powder has the potential to be a promising strategy for treating pulmonary infections caused by P. aeruginosa in patients with CF.

PMID:40599797 | PMC:PMC12208834 | DOI:10.3389/fphar.2025.1528905