Biology (Basel). 2025 Mar 25;14(4):338. doi: 10.3390/biology14040338.

ABSTRACT

Endosymbiosis can be considered a regressive or degenerative evolutionary process characterized at the genomic level by genome erosion and degeneration due to high mutational pressure toward AT (adenine and thymine) bases. The genomic and biological complexity of endosymbionts must be lower than that of the free-living bacteria from which they evolved. In the present work, we contrasted whether two proposed metrics for measuring genomic complexity in both types of bacteria, GS and BB, reflect their complexity, expecting higher values in free-living bacteria than in endosymbionts. On the other hand, we endeavored to delve into the factors that contribute to the reduction in metric values in endosymbionts, as well as their eventual relationship with six genomic parameters associated with functionality. This study aimed to test the robustness of these proposed metrics in a well-known biological scenario, such as the endosymbiosis process.

PMID:40282203 | DOI:10.3390/biology14040338

Pharmaceuticals (Basel). 2025 Apr 13;18(4):565. doi: 10.3390/ph18040565.

ABSTRACT

Objectives: The multidisciplinary city-hospital Oncoral follow-up of cancer outpatients has been set up to ensure the safety of oral anticancer drugs (OADs). The aim of this study was to assess Oncoral by Relative Dose Intensity (RDI) in patients with hematological malignancies treated with ibrutinib as a model. Methods: The study included all outpatients treated with ibrutinib and followed in Oncoral between January 2016 and June 2020. Patients benefited from interviews leading to pharmacist and nurse interventions (PNI) on drug-related problems as adverse events (AE), drug-drug interactions (DDI), and drug intake. Results: In total, 83 patients were enrolled. At least one PNI was performed for 86.7%, focusing on drug intake and DDIs (54.5%), the management of AEs (27.0%), and community-hospital coordination (18.5%). Major DDIs with ibrutinib were found in 10 patients, with at least one moderate interaction in 28%. Grade 3-4 AEs mainly concerned cytopenia and infection. Adherence tended to decrease after the first 6 months. At 6 months, the mean RDI was 93.7 ± 11.3%; RDI reductions occurred in 43% patients. RDI was lower in patients who discontinued treatment before day 90 and worsened over time in patients still being treated at month 6 (Friedman's test, p < 0.01). Age and gender were predictors of early treatment termination (OR 1.10 [1.03; 1.19] and 6.44 [1.65; 37.21]). The estimates of 30-month OS and PFS were 73.8% (95% CI [64.7%; 84.2%]) and 61.8% (95% CI [51.8%; 73.7%]). Conclusions: The Oncoral follow-up is a secure, coordinated pathway assessed by RDI. Multidisciplinary follow-up should be the gold-standard for outpatients receiving OADs.

PMID:40284000 | DOI:10.3390/ph18040565

Pharmaceuticals (Basel). 2025 Apr 8;18(4):543. doi: 10.3390/ph18040543.

ABSTRACT

Background: Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by the presence of marked eosinophilia resulting in end organ damage. The diagnostic approach is multidisciplinary and treatment goals include reductions in flares and eosinophils with minimal drug-related side effects. Results: Eleven patients (n = 11) with a diagnosis of idiopathic HES were included in the study [M/F: 6/5, median age: 54 (95% CI: 38.2 to 68.5), smokers/never smokers: 5/6]. Asthma was present in the majority of them (n = 8, 72.7%); four patients (n = 4, 36.4%) presented with eosinophilic pleural effusions, two patients (n = 2, 18.2%) with cardiac arrhythmias, and one with bilateral eyelid angioedema. Eight patients (72.7%) were treated with mepolizumab (300 mg/month) and three (27.3%) with benralizumab (30 mg/4 weeks). The median values of eosinophils at baseline and 12 months after initiation of biologic agent were 3000 (95% CI: 2172 to 11,365) K/μL and 50 (95% CI: 3 to 190) K/μL, respectively, p = 0.0002. All patients with concomitant asthma (n = 8) experienced elimination of asthma flares, asthma control (ACQ < 0.75), functional improvement (mean ΔFEV1: 857 ± 594 mL), and an 82% reduction in oral corticosteroids, p = 0.0001. Materials and Methods: Patients with highly characterized idiopathic HES treated with anti-eosinophilic agents between 1 October 2019 and 1 October 2023 were retrospectively included in the study. The aim of this study was to present clinical, laboratory, and functional features and outcomes in patients with thoroughly investigated idiopathic HES treated with biologic agents targeting eosinophils. Conclusions: Biologic agents in patients with idiopathic HES-following thorough diagnostic investigation-are both safe and effective, sparing the toxicity of immunosuppressive agents. Real-life data from larger registries are greatly anticipated.

PMID:40283978 | DOI:10.3390/ph18040543

Genes (Basel). 2025 Apr 15;16(4):453. doi: 10.3390/genes16040453.

ABSTRACT

BACKGROUND/OBJECTIVES: Lung cancer has a high mortality rate worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent. Carboplatin and paclitaxel are key treatments for NSCLC; however, adverse drug reactions (ADRs) pose significant challenges. This study examined the impact of genetic variations in ABCB1 and ABCC2 genes on the incidence of ADRs and survival in NSCLC patients treated with carboplatin and paclitaxel.

METHODS: Variants were identified using RT-PCR, and ADRs classified according to the Common Toxicity Criteria for Adverse Events, Version 4.03.

RESULTS: The ABCB1 rs1128503 (c.1236C>T) CC genotype was associated with a higher chance of nausea (OR: 3.5, 95% CI 1.367-9.250, p = 0.0093), vomiting (OR: 13.553, 95% CI 1.705-107.723, p = 0.0137), and a higher risk of death in CT or TT genotypes (HR: 1.725, 95% CI 1.036-2.871, p = 0.0361). The ABCC2 rs717620 (c.-24C>T) TT genotype was associated with increased ALP levels (OR: 14.6, 95% CI 1.234-174.236, p = 0.0335). The ABCB1 rs2032582 non-CC genotypes (TT+AA+TA+CA+CT) were associated with an increased risk of death (HR: 1.922, 95% CI 1.093-3.377, p = 0.0232). Patients with hypocalcemia (HR: 2.317, 95% IC 1.353-3.967, p = 0.022), vomiting (HR: 3.047, 95% IC 1.548-5.997, p = 0.0013), and diarrhea (HR: 2.974, 95% IC 1.590-5.562, p = 0.0006) were associated with lower overall survival.

CONCLUSIONS: The data suggest that ABCB1 variants may influence gastrointestinal ADRs and patient survival, highlighting the importance of pharmacogenomics in predicting ADRs and drug resistance. This approach offers more precise pharmacotherapy, reduces ADRs, and enhances the patients' quality of life and survival.

PMID:40282412 | DOI:10.3390/genes16040453

Eur J Paediatr Neurol. 2025 Apr 15;56:46-50. doi: 10.1016/j.ejpn.2025.03.016. Online ahead of print.

ABSTRACT

Leukodystrophies, a group of genetic disorders primarily affecting brain white matter, were once considered untreatable. Advances in MRI and genetic diagnostics now allow most patients to receive a genetic diagnosis, and emerging treatments are shifting the field from therapeutic nihilism to cautious optimism. Allogenic haematopoietic stem cell transplantation (HSCT), used since the 1980s, has shown efficacy in specific leukodystrophies, such as adrenoleukodystrophy and metachromatic leukodystrophy, when administered early. Gene therapy has become a viable option, with ex vivo approaches like atidarsagene autotemcel providing promising outcomes for early-onset MLD. Trials for gene replacement and antisense oligonucleotide therapies are ongoing for several leukodystrophies, including Canavan disease and Alexander disease. Certain treatments, such as guanabenz for Vanishing White Matter, target disease-specific dysregulated molecular pathways. Despite these advances, challenges remain, including the ultrarare nature of most leukodystrophies, limited natural history data, high treatment costs, and barriers to accessibility. Future developments, including newborn screening and close international collaboration, aim to enhance early diagnosis, refine treatment timing, and expand access to innovative therapies.

PMID:40279833 | DOI:10.1016/j.ejpn.2025.03.016

Sci Data. 2025 Apr 25;12(1):695. doi: 10.1038/s41597-025-04981-2.

ABSTRACT

Drug-target interactions constitute the fundamental basis for understanding drug action mechanisms and advancing therapeutic discovery. While existing drug-target databases have contributed valuable resources, they exhibit structural and functional fragmentation due to heterogeneous data sources and annotation standards. Building upon the high-confidence drug-gene interactions curated in HCDT 1.0, we present HCDT 2.0, a comprehensive and standardized resource that expands the scope through multiomics data integration. This update incorporates three-dimensional interactions including drug-gene, drug-RNA and drug-pathway interactions. The current version contains 1,284,353 curated interactions: 1,224,774 drug-gene pairs (678,564 drugs × 5,692 genes), 11,770 drug-RNA mappings (316 drugs × 6,430 RNAs), and 47,809 drug-pathway links (6,290 drugs × 3,143 pathways), alongside 16,317 drug-disease associations. To enhance biological interpretability, we further integrated pathway-gene and RNA-gene regulatory relationships. In addition, we integrated 38,653 negative DTIs covering 26,989 drugs and 1,575 genes. This integrative framework not only addresses critical gaps in cross-scale data representation but also establishes a robust foundation for systems pharmacology applications, including drug repurposing, adverse event prediction, and precision oncology strategies.

PMID:40281032 | DOI:10.1038/s41597-025-04981-2

Acta Neuropathol Commun. 2025 Apr 25;13(1):84. doi: 10.1186/s40478-025-01986-1.

ABSTRACT

Prolactinoma is the most prevalent pituitary neuroendocrine tumor and dopamine agonists (DAs) targeting dopamine D2 receptor (DRD2) are recommended as the first-line treatment. However, varying degrees of DA resistance limit patient benefit. Our study used transcriptome sequencing of surgical tumor samples and found abnormal cholesterol metabolism in prolactinoma, especially in DA-resistant tumors. We found that cholesterol significantly enhanced the resistance of prolactinoma MMQ cell lines to cabergoline in vitro and in vivo xenografts. Further, cholesterol did not affect the total protein level of DRD2, but changed the distribution of DRD2 with downregulation of its membrane abundance and upregulation of cytoplasmic localization. Mechanistically, immunoprecipitation combined with mass spectrometry revealed cholesterol increased binding affinity between DRD2 and stress granules (SGs) core proteins, such as G3BP1. Western blot experiment of G3BP1 and fluorescent probe were used to confirm the formation of SGs after cholesterol treatment in MMQ cells and tumor xenografts, as well as in surgical tumor samples. Interfering the formation of SGs by overexpressing of USP10 and using the small molecule ISRIB reversed cholesterol's effect on DRD2 cellular distribution and DA resistance in MMQ cells. Finally, a non-specificity inhibitor of SGs, anisomycin identified by drug repositioning analysis, could attenuate cholesterol-induced cabergoline resistance in vitro. Taken together, our findings suggest that abnormal cholesterol metabolism reduces DRD2 membrane localization via stress granules formation, which may be an important reason for the DA resistance of prolactinoma patients.

PMID:40281543 | DOI:10.1186/s40478-025-01986-1

Sci Rep. 2025 Apr 25;15(1):14436. doi: 10.1038/s41598-025-98894-0.

ABSTRACT

Extracellular vesicles (EVs) are important mediators of intercellular communication and play key roles in the regulation of pathophysiological processes. In diabetic kidney disease (DKD), it has been reported that macrophages recruited in the mesangial region may play pathogenic roles through inducing local inflammation in glomeruli. We focused on EV-mediated crosstalk between mesangial cells (MC) and macrophages as a novel therapeutic target for DKD. EVs released from MC induced inflammation in macrophages and the effect was enhanced under high-glucose conditions. For discovering novel therapeutic agents which can inhibit such EV-mediated mechanisms, drug repositioning is considered as an effective tool. We established a unique screening strategy and screened agents to aim at maximizing their specificity and potency to inhibit EV mechanisms, along with minimizing their toxicity. We succeeded in identifying alvespimycin, an HSP90 inhibitor. Treatment of diabetic rats with alvespimycin significantly suppressed mesangial expansion, inflammatory gene activation including macrophage markers, and proteinuria. The inhibitory effect on EV uptake was specific to alvespimycin compared with other known HSP90 inhibitors. MC-derived EVs are crucial for inflammation by intercellular crosstalk between MC and macrophages in DKD, and alvespimycin effectively ameliorated the progression of DKD by suppressing EV-mediated actions, suggesting that EV-targeted agents can be a novel therapeutic strategy.

PMID:40281012 | DOI:10.1038/s41598-025-98894-0

Biomed Pharmacother. 2025 Apr 24;187:118079. doi: 10.1016/j.biopha.2025.118079. Online ahead of print.

ABSTRACT

This study investigated a novel immunization therapy for pre-clinical aggressive metastatic breast cancer using immunogenic cell lysates derived from 4T1-luc cells treated with cisplatin and methotrexate, addressing the critical need for improved treatments given the poor prognosis associated with breast cancer metastasis and its significant mortality rate. Methotrexate, a conventional cytotoxic agent, demonstrated a previously unrecognized capacity to induce immunogenic cell lysates, presenting a potential drug repositioning opportunity. In a murine model of stage IV metastatic breast cancer, immunization with these lysates significantly reduced primary tumor growth and lung metastasis, as assessed by bioluminescence imaging. Immunization also modulated immune cell populations, reducing splenomegaly and hepatomegaly, and partially reversing the immunosuppressive phenotype associated with 4T1-luc tumor growth, as evidenced by cytokine profiling (IL-6 and IFN-γ) and flow cytometry analysis of CD4 + and CD8 + T cell subpopulations. Specifically, methotrexate-treated lysates induced a significant shift in CD4 + T cells towards an effector phenotype. These findings highlight the potential of this immunotherapy approach to improve breast cancer treatment outcomes and warrant further investigation.

PMID:40280032 | DOI:10.1016/j.biopha.2025.118079

Trends Cardiovasc Med. 2025 Apr 23:S1050-1738(25)00052-0. doi: 10.1016/j.tcm.2025.04.003. Online ahead of print.

NO ABSTRACT

PMID:40280353 | DOI:10.1016/j.tcm.2025.04.003

Hum Genomics. 2025 Apr 25;19(1):44. doi: 10.1186/s40246-025-00753-6.

ABSTRACT

BACKGROUND: Statins are essential for managing cardiovascular disease (CVD), but adverse effects often lead to treatment discontinuation and non-adherence, underscoring the need for personalized approaches. This study aimed to evaluate the influence of pharmacogenomic (PGx) variants and demographic factors on statin-associated adverse effects in a multiethnic cohort from the United Arab Emirates (UAE).

METHODS: This sub-analysis of the EmHeart Study included 675 patients using rosuvastatin or atorvastatin. Patients were genotyped for SLCO1B1 and ABCG2 actionable variants using real-time PCR. Data on demographics, comorbidities, and statin use were extracted from electronic health records. Adverse events, including statin-associated muscle symptoms (SAMS) and liver enzyme elevation, were tracked over 12 months. Associations were analyzed using chi-square tests and logistic regression.

RESULTS: Rosuvastatin users carrying the ABCG2 rs2231142 variant had a threefold increased risk of liver enzyme elevation, particularly among East Asian patients (P < 0.005). Atorvastatin users with the SLCO1B1 rs4149056 variant exhibited a twofold increased risk of SAMS, with higher rates observed in females and Arabs (P < 0.05). The combination of rosuvastatin with ezetimibe further exacerbated risks of SAMS and liver enzyme elevation.

CONCLUSION: This study highlights the importance of genetic testing and demographic factors, such as ethnicity and gender, in tailoring statin therapy to minimize adverse effects. Despite extensive research on PGx-guided statin prescribing, clinical implementation remains limited. Integrating PGx testing into routine practice and enhancing physician awareness of genetic and demographic risk factors can improve the safety, efficacy, and adherence of lipid-lowering therapies in diverse populations.

PMID:40281622 | DOI:10.1186/s40246-025-00753-6

Pharmacogenomics J. 2025 Apr 25;25(3):12. doi: 10.1038/s41397-025-00371-4.

ABSTRACT

Pharmacogenomic testing for CYP2C19 helps personalise clopidogrel therapy and reduces the risk of experiencing a secondary myocardial infarction in individuals with impaired CYP2C19 function. Routine testing, however, is uncommon and it is proposed that the key requirements and processes of testing services are poorly understood. This scoping review aimed to explore the literature for CYP2C19 testing services for clopidogrel and identify their commonalities to inform the design and delivery of future services. In total, 37 eligible studies describing services across hospital and community settings were retrieved. Key elements of delivery included a multi-disciplinary approach involving physicians and pharmacists, provision of pre-implementation training and education, and electronic communication of test results. Result integration into clinical decision support systems improved the practical application of pharmacogenomic testing. The identification of the key requirements and processes may be used by institutions looking to design and deliver CYP2C19 testing services to guide clopidogrel therapy.

PMID:40280918 | DOI:10.1038/s41397-025-00371-4

Chem Biol Interact. 2025 Apr 23:111526. doi: 10.1016/j.cbi.2025.111526. Online ahead of print.

ABSTRACT

Pharmacogenetic (PGx) testing can be used to help guide drug therapy and decrease or avoid the risk of adverse drug reactions. CYP2D6 is an important pharmacogene in pharmacogenomics testing panels. However, phenoconversion, whereby an individual's ability to metabolize a drug does not match the genotype-predicted metabolizer status, is a confounding factor to the accurate application of PGx testing results to patient care. To address this issue, CYP2D6 expression between and within genotype-predicted CYP2D6 metabolizer phenotype groups was compared using WGS and RNA-Seq data from 134 normal liver tissue donors obtained from the GTEx program. Wide variability in CYP2D6 mRNA levels was observed within metabolizer phenotype groups. The median expression level for ultrarapid metabolizers (UMs) was 738.9 TPM (transcripts per million; 196.8-778.9 TPM), 212.5 TPM (32.1-666.5 TPM) for normal metabolizers (NMs), 219.6 TPM for intermediate metabolizers (IMs) (22-389.8 TPM), and 121.2 TPM for poor metabolizers (PMs) (9.3-298.2 TPM). The PM and UM phenotypes were significant predictors of CYP2D6 expression (p=0.0004 and p=0.019, respectively). Interestingly, expression of the gene encoding human serum albumin (ALB) was also a significant predictor of CYP2D6 expression (p=0.0003). Data from 50 patients with hepatocellular carcinoma obtained from the TCGA program showed no significant difference in expression between tumor tissue (median=119.7 TPM, range 0.16-817.7 TPM) and normal matched tissue (median=143.3 TPM, range 26.2-810.7 TPM). Transcriptional regulation of CYP2D6 expression may contribute to differences in drug response and risk for CYP2D6 phenoconversion. Efforts to understand the role of gene expression to predict CYP2D6 phenoconversion may inform the use of PGx testing in the clinical setting.

PMID:40280382 | DOI:10.1016/j.cbi.2025.111526

Life Sci. 2025 Apr 23:123661. doi: 10.1016/j.lfs.2025.123661. Online ahead of print.

ABSTRACT

AIMS: Arbutin (ARB), a natural polyphenol isolated from the bearberry plant Arctostaphylos uva-ursi, has been studied for its diverse pharmacological activities including anti-diabetic, cardioprotective and anti-inflammatory effects. This study aimed to evaluate arbutin's diuretic activity, focusing on its impact on aldosterone synthase gene expression and its toxicity profile.

MATERIAL AND METHODS: Acute toxicity was assessed using single doses ranging from 500 to 9000 mg/kg and sub-acute toxicity with doses of 375 and 750 mg/kg over 14 days. To evaluate acute diuretic activity, ARB was administered in three doses (25, 50 and 75 mg/kg i.p) alongside standard groups, furosemide (FUR) 10 mg/kg i.p and Spironolactone (SPIR) 25 mg/kg i.p. In sub-acute diuretic study, treatment was administered for seven days, followed by blood collection and adrenal dissection for gene expression analysis.

KEY FINDINGS: Acute toxicity studies revealed that ARB is well-tolerated up to 8000 mg/kg with no significant changes in organ and body weight. However, sub-acute studies showed minor changes in leukocyte count, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and triglycerides (TGs) at high doses while histopathological evaluations revealed no severe organ damage. The diuretic index and electrolyte analysis confirmed the potential of ARB as diuretic and saluretic with reduced risk of hyperuricemia and hyperkalemia. Gene expression studies showed non-selective downregulation of aldosterone synthase gene (CYP11B2) and 11β-hydroxylase (CYP11B1). While the effects on 17α-hydroxylase (CYP17A1) were less pronounced than SPIR, indicating fewer possible anti-androgenic effects.

SIGNIFICANCE: Our findings suggest that ARB is a promising diuretic agent with a favorable safety profile.

PMID:40280300 | DOI:10.1016/j.lfs.2025.123661

J Allergy Clin Immunol. 2025 Apr 23:S0091-6749(25)00457-9. doi: 10.1016/j.jaci.2025.04.017. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles.

OBJECTIVE: To identify phenotypes (metabotypes) in children with moderate-to-severe asthma through integrative fecal and serum metabolome analysis.

METHODS: Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step ≥3 were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomics profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity Network Fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.

RESULTS: Integrative fecal and serum metabolome analysis of 92 children with moderate-to-severe asthma (median age: 11.5 years, 34% female) revealed three metabotypes. Metabotype1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype2 had higher odds of asthma control, the highest percentage of children with ≥4 months of breastfeeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and with elevated serum acylcarnitines and ω-3 fatty acids. Metabotype3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.

CONCLUSIONS: Metabotypes in children with moderate-to-severe asthma are linked to asthma control, distinct fecal microbiota and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.

PMID:40280190 | DOI:10.1016/j.jaci.2025.04.017

J Pharm Biomed Anal. 2025 Apr 19;263:116910. doi: 10.1016/j.jpba.2025.116910. Online ahead of print.

ABSTRACT

Systemic arterial hypertension, affecting more than 1 billion people worldwide, necessitates widespread use of antihypertensive and diuretic medications. However, the potential toxicity related to exposure of these medications is not always fully understood, potentially leading to underestimates of deaths related to cardiovascular drugs. Additionally, the growing interest in monitoring adherence to antihypertensive medications necessitates the development of specific analytical methods suitable for both clinical and forensic applications. In this study, we developed a novel, high-throughput quantitative method for the simultaneous analysis of 21 antihypertensive and diuretic drugs mainly in human plasma using liquid chromatography with tandem mass spectrometry. This method has several advantages, including minimal sample volume requirement, a one-step sample preparation using an Ostro® plate, and a chromatographic run time of 7 min. The method was successfully validated on 11 criteria following the European Medicines Agency's guidances. The method was successfully applied to authentic samples from 62 clinical cases and 76 post-mortem cases, with two cases of severe intoxications more precisely described. The first case describes an attempted suicide by candesartan (2558 ng/mL in plasma) combined with celiprolol (18 ng/mL) and amlodipine (161 ng/mL). The second case is a diuretic-contaminated dietary supplement poisoning with plasma concentrations of 40 ng/mL for furosemide and 36 ng/mL for hydrochlorothiazide. The authors present a simple, fast, and sensitive quantification method for the analysis of 21 antihypertensive and diuretic drugs, with concentration values reported in both living subjects and post-mortem cases to aid in the often-challenging interpretation of cardiotropic drug concentrations.

PMID:40280085 | DOI:10.1016/j.jpba.2025.116910

Lung. 2025 Apr 25;203(1):57. doi: 10.1007/s00408-025-00811-9.

ABSTRACT

PURPOSE: Combined lung-liver transplant (CLLT) is a complex yet life-saving procedure for patients with simultaneous end-stage lung and liver disease. Given the geographical allocation change to the lung allocation score (LAS) in 2017 and the recent SARS-CoV-2 outbreak in 2019, we aim to provide an updated analysis of the patient selection and outcomes of CLLTs.

METHODS: The UNOS registry was used to identify all patients who underwent CLLT between January 2014 and June 2023. To account for the changes made to LAS in 2017, baseline characteristics and outcomes were compared between era 1 (before 2017) and era 2 (after 2017). Risk factors for mortality were analyzed using the Cox regression hazard models. Recipient survival of up to 3 years was analyzed using the Kaplan-Meier method.

RESULTS: 117 CLLTs were performed (77.8% in era 2). Donor organs experienced significantly longer ischemic times (p = 0.039) and traveled longer distances (p = 0.025) in era 2. However, recipient (p = 0.79) and graft (p = 0.41) survival remained comparable at up to 3 years post-transplant between eras. CLLTs demonstrated similar long-term survival to isolated lung transplants (p = 0.73). Higher recipient LAS was associated with an increased mortality risk (HR 1.14, p = 0.034). Recipient diagnosis of idiopathic pulmonary fibrosis carried a 5.03-fold risk of mortality (p = 0.048) compared to those with cystic fibrosis.

CONCLUSION: In the post-2017 LAS change era, CLLTs are increasingly performed with comparable outcomes to isolated lung transplants. A careful, multidisciplinary approach to patient selection and management remains paramount to optimizing outcomes for this rare patient population.

PMID:40281222 | DOI:10.1007/s00408-025-00811-9

Br Dent J. 2025 Apr;238(8):648-654. doi: 10.1038/s41415-024-8269-8. Epub 2025 Apr 25.

ABSTRACT

Objectives To measure past dental caries experience in people with cystic fibrosis and to compare the results with a control group of people without cystic fibrosis.Methods A cross-sectional study of 92 adults with cystic fibrosis and 92 adults without cystic fibrosis was undertaken in Cork University Dental School and Hospital. The median age for study group and control group participants was 31 years and 27 years, respectively. All participants completed a detailed questionnaire before undergoing a clinical examination that recorded demographic, social and oral health variables. Caries was recorded using the Decayed, Missing and Filled Teeth (DMFT) index. All data were statistically analysed using the Wilcoxon rank-sum test, chi-squared test and Fisher's test. Negative binomial models were also used to analyse data.Results The study group had a higher mean DMFT score compared to the control group (6.52, 0.99, 0.41, 3.89 versus 5.33, 0.18, 0.11, 3.68). While the study group had a higher DMFT, the only component that was statistically significant between the groups was the Decayed Teeth component (p <0.001).Conclusion In this study, the cohort of people with cystic fibrosis had more caries than people without cystic fibrosis. Further research is required to establish if underlying systemic conditions, social and behavioural factors, or a combination of the aforementioned are responsible for a higher caries experience in this study group.

PMID:40281172 | DOI:10.1038/s41415-024-8269-8