J Chem Inf Model. 2025 Apr 25. doi: 10.1021/acs.jcim.5c00070. Online ahead of print.

ABSTRACT

The extraction of biomedical data has significant academic and practical value in contemporary biomedical sciences. In recent years, drug repositioning, a cost-effective strategy for drug development by discovering new indications for approved drugs, has gained increasing attention. However, many existing drug repositioning methods focus on mining information from adjacent nodes in biomedical networks without considering the potential inter-relationships between the feature spaces of drugs and diseases. This can lead to inaccurate encoding, resulting in biased mined drug-disease association information. To address this limitation, we propose a new model called Dual-Feature Drug Repurposing Neural Network (DFDRNN). DFDRNN allows the mining of two features (similarity and association) from the drug-disease biomedical networks to encode drugs and diseases. A self-attention mechanism is utilized to extract neighbor feature information. It incorporates two dual-feature extraction modules: the single-domain dual-feature extraction (SDDFE) module for extracting features within a single domain (drugs or diseases) and the cross-domain dual-feature extraction (CDDFE) module for extracting features across domains. By utilizing these modules, we ensure more appropriate encoding of drugs and diseases. A cross-dual-domain decoder is also designed to predict drug-disease associations in both domains. Our proposed DFDRNN model outperforms six state-of-the-art methods on four benchmark data sets, achieving an average AUROC of 0.946 and an average AUPR of 0.597. Case studies on three diseases show that the proposed DFDRNN model can be applied in real-world scenarios, demonstrating its significant potential in drug repositioning.

PMID:40278791 | DOI:10.1021/acs.jcim.5c00070

Metabolites. 2025 Apr 9;15(4):255. doi: 10.3390/metabo15040255.

ABSTRACT

BACKGROUND/OBJECTIVES: Drug development for complex diseases such as NAFLD is often lengthy and expensive. Drug repurposing, the process of finding new therapeutic uses for existing drugs, presents a promising alternative to traditional approaches. This study aims to identify potential repurposed drugs for NAFLD by leveraging disease-disease relationships and drug-target data from the BioSNAP database.

METHODS: A bipartite network was constructed between drugs and their target genes, followed by the application of the BiClusO bi-clustering algorithm to identify high-density clusters. Clusters with significant associations with NAFLD risk genes were considered to predict potential drug candidates. Another set of candidates was determined based on disease similarity.

RESULTS: A novel ranking methodology was developed to evaluate and prioritize these candidates, supported by a comprehensive literature review of their effectiveness in NAFLD treatment.

CONCLUSIONS: This research demonstrates the potential of drug repurposing to accelerate the development of therapies for NAFLD, offering valuable insights into novel treatment strategies for complex diseases.

PMID:40278384 | DOI:10.3390/metabo15040255

Cells. 2025 Apr 11;14(8):575. doi: 10.3390/cells14080575.

ABSTRACT

Lithium is prescribed as a mood stabilizer for bipolar disorder and severe depression. However, the mechanism of action of lithium is unknown and there are major side effects associated with prolonged medication. This motivates a search for safer alternative drug repurposing candidates. Given that the drug mechanism may be encoded in transcriptional changes, we generated the gene expression profile for acute lithium treatment of cortical neuronal cultures. We found that the lithium-associated transcription response harbors a significant component that is the reverse of that seen in human brain samples from patients with major depression, bipolar disorder, and a mouse model of depression. Interrogating publicly available drug-driven expression data, we found that cardiotonic steroids drive gene expression in a correlated manner to our acute lithium profile. An analysis of the psychiatric medication cohort of the Norwegian Prescription Database showed that cardiotonic prescription is associated with a lower incidence of lithium prescription. Our transcriptional and epidemiological observations point towards cardiotonic steroids as possible repurposing candidates for lithium. These observations motivate a controlled trial to establish a causal connection and genuine therapeutic benefit in the context of depression.

PMID:40277900 | DOI:10.3390/cells14080575

Cells. 2025 Apr 8;14(8):559. doi: 10.3390/cells14080559.

ABSTRACT

Rare diseases typically evade the application of the standard drug discovery and development pipelines due to their understudied molecular etiology and the small market size. Herein, we report a rare disease-directed workflow that rapidly studies the molecular features of the disorder, establishes a high-throughput screening (HTS) platform, and conducts an HTS of thousands of approved drugs to identify and validate repositioning drug candidates. This study examines the pediatric neurological disorder caused by de novo mutations in YWHAG, the gene encoding the scaffolding protein 14-3-3γ, and the workflow discovers nuclear relocalization and a severe drop in 14-3-3γ binding to its phosphorylated protein partners as the key molecular features of the pathogenic hotspot YWHAG mutations. We further established a robust in vitro HTS platform and screened ca. 3000 approved drugs to identify the repositioning drug candidates that restore the deficient 14-3-3γ-phosphotarget interactions. Our workflow can be applied to other 14-3-3-related disorders and upscaled for many other rare diseases.

PMID:40277885 | DOI:10.3390/cells14080559

J Helminthol. 2025 Apr 25;99:e55. doi: 10.1017/S0022149X25000276.

ABSTRACT

Benzimidazoles are the most frequently prescribed therapeutic options for treating trichinellosis in clinical settings; however, they have a lot of disadvantages. Therefore, researchers are focusing on the hunt for substitute chemicals. The goal of the current study was to compare the effectiveness of albendazole and the anti-diabetic medication metformin loaded on chitosan nanoparticles in treating mice infected with various stages of T. spiralis infection. 160 mice were included in the present study and divided into 8 groups: 6 experimentally treated groups, and positive and negative control groups. For studying the intestinal and parenteral phase, each group was broken into two more subgroups (a and b) according to the time of drug administration. The effects of albendazole, albendazole-loaded NPs, metformin, metformin-loaded NPs, combined albendazole and metformin, and metformin and albendazole-loaded NPs were assessed using parasitological studies, histopathological examination, and ultrastructural examination using SEM.Statistically significant differences were detected in all studied subgroups compared to the control infected subgroup both in the intestinal and muscular phases. The greatest decrease in recovered adult worm and muscle larvae numbers was achieved by ABZ & MET/ Cs NPs. These findings were confirmed by histopathological examination. SEM examination of the tegument of T. spirals adult worms and muscle larvae showed destruction with multiple degenerative changes.Our results suggested that metformin and its combination with albendazole especially when loaded on chitosan nanoparticles could be potential therapeutic alternative drugs against trichinellosis.

PMID:40275564 | DOI:10.1017/S0022149X25000276

Nucleic Acids Res. 2025 Apr 22;53(8):gkaf346. doi: 10.1093/nar/gkaf346.

ABSTRACT

Developing customized gene-targeting therapies for the millions of individuals affected by ultra-rare diseases globally requires breaking new ground in therapeutic and regulatory innovation. To address this need, the N=1 Collaborative (N1C) was established to unite academia, industry, patients, and regulators, building an open, shared ecosystem for personalized medicines. Initially focusing on antisense oligonucleotides (ASOs) for rare, fatal neurodegenerative conditions, the N1C aims to develop frameworks that can rapidly extend to other treatment modalities and conditions. Progress in the advancement of personalized therapies has also propelled advancements in the nucleic acids field, offering critical insights into dosing, safety, and efficacy. In October 2024, the N1C convened scientific, regulatory, and advocacy leaders in ASO development for an inaugural meeting. This review report examines the current state of the scientific and clinical ecosystems enabling customized genetic therapies and explores the innovation, frameworks, and systems needed to deliver additional individualized medicines safely and at scale.

PMID:40277082 | DOI:10.1093/nar/gkaf346

Toxins (Basel). 2025 Apr 11;17(4):192. doi: 10.3390/toxins17040192.

ABSTRACT

Onabotulinumtoxin-A (onabotA) is a neurotoxin widely used for several indications, including chronic migraine (CM) preventive treatment, due to its well-demonstrated efficacy, tolerability, and safety. However, onabotA safety during pregnancy and breastfeeding remains unclear, as these populations are typically excluded from clinical trials. The action of onabotA starts locally at the injection sites, modulating the pain pathway with minimal systemic absorption, which theoretically minimizes risks to the fetus or breastfeeding infant. Preclinical studies demonstrate that onabotA does not distribute systemically in significant amounts after administration, although adverse fetal outcomes in rats and rabbits were reported when injected at high doses. Limited human data suggest that onabotA exposure during pregnancy may not be associated with major malformations or significant adverse outcomes for the fetus, especially when used at therapeutic doses for migraine prevention during the first trimester or earlier. Data on breastfeeding are even scarcer but indicate a low likelihood of drug transfer into breast milk. This narrative review highlights the available evidence on the use of onabotA in pregnancy and breastfeeding women, including real-word evidence, with a focus on the use for CM.

PMID:40278690 | DOI:10.3390/toxins17040192

J Pers Med. 2025 Apr 5;15(4):146. doi: 10.3390/jpm15040146.

ABSTRACT

Background: Pharmacogenomics (PGx) is the future of healthcare and implementation is being driven by increasing evidence. Understanding the workflow in a PGx clinic provides insight into the development and implementation of PGx services. It considers the patient's perspective, the role of the interprofessional team and the pivotal input of the pharmacist. Objectives: The purpose of this study was to describe the clinical workflow followed in selected PGx clinics. Methods: Four different sites that offer PGx clinical services (United States of America) were included. Qualitative data were collected through semi-structured interviews and observations providing valuable insights into the workflow followed in both community-based and hospital-based PGx clinics. Results: Although each setting differed, the processes were similar with setting-specific workflows and barriers. This study highlights the role of the pharmacist and the interprofessional team, the resources used for interpretation of PGx test results and the importance of patient and healthcare education. Conclusions: Understanding the workflow and the role of the interprofessional team in PGx is essential to ensure successful implementation and sustainable precision medicine practices in resource-limited settings.

PMID:40278324 | DOI:10.3390/jpm15040146

J Pers Med. 2025 Mar 27;15(4):128. doi: 10.3390/jpm15040128.

ABSTRACT

Individual variations in the active form of vitamin D (Vit.D) arise from a combination of dietary intake, sun exposure, and genetic factors, making it complex and challenging to maintain optimal levels. Among Vit.D-related genes, variations in CYP2R1 and CYP27B1 influence Vit.D synthesis, CYP24A1 regulates its inactivation, and the Vit.D receptor (VDR) mediates Vit.D signaling. These genetic variations contribute to substantial differences in Vit.D concentrations and associated clinical effects. However, there has been a lack of comprehensive, simultaneous exploration of these key genes and their clinical implications. This review provides a systematic analysis of genetic variants in Vit.D-related P450 genes identified in human clinical studies, along with in silico predictions of their functional consequences. Since multiple genes seem to influence the body's response to Vit.D, studying just one genetic variant may not fully explain Vit.D deficiency. A comprehensive evaluation of all Vit.D-related genes could offer valuable insights for advancing personalized medicine in Vit.D management. This study provides a foundation for developing a more personalized approach to Vit.D supplementation and regulation, guided by genetic information.

PMID:40278307 | DOI:10.3390/jpm15040128

Curr Oncol. 2025 Mar 31;32(4):204. doi: 10.3390/curroncol32040204.

ABSTRACT

Biological sex and gender factors significantly influence the pathogenesis, progression, and treatment response in hematologic malignancies. This comprehensive review examines sex-specific differences in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and multiple myeloma through systematic analysis of the peer-reviewed literature published between 2014-2024 and identified through structured searches of PubMed, Web of Science, and MEDLINE databases. Epidemiological data demonstrate higher disease incidence (57% male vs. 43% female in MM, 63% male vs. 37% female in AML hospitalizations for ages 18-39) and inferior outcomes in male patients across malignancy types (5-year relative survival rates of 48.8% vs. 60.4% in females with AML), while female patients exhibit superior survival despite experiencing greater treatment-related toxicities. Our analysis reveals consistent sex-specific patterns in molecular mechanisms, including distinct mutational profiles, differences in immune system function, and sex-based pharmacokinetic variations that collectively suggest the necessity for sex-differentiated treatment approaches. The review identifies reproducible patterns across diseases, particularly in cytogenetic and molecular characteristics, with females demonstrating favorable prognostic mutations in leukemias and higher rates of chromosomal abnormalities in multiple myeloma. Despite these identifiable patterns, significant knowledge gaps persist regarding the underlying mechanisms of sex-based outcome differences. Incorporating sex and gender considerations into precision medicine frameworks represents a critical advancement toward optimizing treatment strategies and improving clinical outcomes for patients with hematologic malignancies.

PMID:40277761 | DOI:10.3390/curroncol32040204

Cephalalgia. 2025 Apr;45(4):3331024251321500. doi: 10.1177/03331024251321500. Epub 2025 Apr 25.

ABSTRACT

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the GRADE approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

PMID:40277321 | DOI:10.1177/03331024251321500

Cephalalgia. 2025 Apr;45(4):3331024241305381. doi: 10.1177/03331024241305381. Epub 2025 Apr 25.

ABSTRACT

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

PMID:40277319 | DOI:10.1177/03331024241305381

Pharmacogenet Genomics. 2025 Apr 11. doi: 10.1097/FPC.0000000000000566. Online ahead of print.

ABSTRACT

OBJECTIVES: To explore the distribution of clinically relevant UGT1A1 polymorphisms and inferred UGT1A1 phenotypes in two Indigenous groups (Paiter-Suruí and Yanomami) from reservation areas in the Brazilian Amazon.

METHODS: Ninety-two Yanomami and 88 Paiter-Suruí were genotyped with a validated panel of ancestry informative markers. Individuals with >90% Native ancestry were genotyped for the promoter TA repeat (rs8175347) polymorphism and UGT1A1*6 (rs4148323) by direct sequencing, and for UGT1A1*80 (rs887829) by TaqMan allele discrimination. The UGT1A1 metabolic phenotypes were inferred from UGT1A1 diplotypes.

RESULTS: All Yanomami and 85 (96.6%) Paiter-Suruí had >92% Native ancestry. UGT1A1 genotype data from these individuals revealed: (i) the absence of both alleles with five and eight TA repeats [TA(5) and TA(8)]; (ii) TA(7) allele frequency of 0.470 in Yanomami and 0.441 in Paiter-Suruí; (iii) rs4148323 was absent in Paiter-Suruí and detected in two Yanomami (frequency 0.012); (iv) a perfect linkage disequilibrium (LD) between rs887829C>T and the promoter repeat polymorphisms in both cohorts: C allele with TA(6) and T allele with TA(7). The distribution of the inferred UGT1A1 metabolizer phenotypes did not differ between cohorts (Paiter-Suruí and Yanomami): the intermediate metabolizer was the most common (50.6-55.4%), followed by the normal (30.6-24.1%) and the slow (18.8-20.5%) phenotypes.

CONCLUSION: This is the first report on the frequency distribution of clinically relevant UGT1A1 variants and inferred UGT1A1 metabolic phenotypes in two major Native populations from indigenous reservation areas in the Brazilian Amazon, namely the Paiter-Suruí and Yanomami. The TA(5) and TA(8) repeats were absent, whereas TA(7) was common (frequency >0.50) in both cohorts. The intronic rs887829 variant (UGT1A1*80) single nucleotide variant was found in perfect LD with the promoter TA repeats. The rs4148323 SNP was absent (Paiter-Suruí) or rare (Yanomami). The frequency of high-risk UGT1A1 poor metabolizer phenotype was 1.6- to 2-fold higher in the indigenous cohorts compared to nonindigenous Brazilians.

PMID:40277150 | DOI:10.1097/FPC.0000000000000566

Curr Mol Med. 2025 Apr 24. doi: 10.2174/0115665240374044250416021616. Online ahead of print.

ABSTRACT

BACKGROUND: Chromobox 7 (CBX7) has been implicated in the progression of various malignant tumors, but its clinical relevance in lung adenocarcinoma (LUAD) remains poorly understood. This study aimed to investigate the expression, prognostic value, biological functions, and immunological role of CBX7 in LUAD.

METHODS: CBX7 expression in LUAD and adjacent normal tissues was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier curves and Cox risk regression evaluated prognostic significance. Various algorithms assessed the correlation between CBX7 and immune microenvironment. The expression of CBX7 in LUAD tissues was detected by RT-qPCR, western blotting, and immunohistochemistry. The function of CBX7 in LUAD was further investigated by in vitro and in vivo experiments.

RESULTS: CBX7 expression significantly downregulated LUAD, which was associated with aberrant DNA methylation. Decreased CBX7 expression correlated with advanced tumor stage and poor prognosis. Notably, CBX7 is associated with immune cell infiltration and immune checkpoints, highlighting its potential role in guiding immunotherapy. Functional experiments demonstrated that CBX7 overexpression suppressed the malignant phenotype of LUAD cells, while CBX7 knockdown promoted tumor progression.

CONCLUSION: We conducted a systematic analysis of the diagnostic, prognostic, and immunological significance of CBX7 in LUAD, and found that it might serve as a diagnostic marker and therapeutic target in the future.

PMID:40277108 | DOI:10.2174/0115665240374044250416021616

Metabolites. 2025 Mar 29;15(4):236. doi: 10.3390/metabo15040236.

ABSTRACT

BACKGROUND/OBJECTIVES: Amino acids (AAs) play a critical role in diseases such as cystic fibrosis where Pseudomonas aeruginosa PAO1 adapts its metabolism in response to host-derived nutrients. The adaptation influences virulence and complicates antibiotic treatment mainly for the antimicrobial resistance context. D- and L-AAs have been analyzed for their impact on quorum sensing (QS), a mechanism that regulates virulence factors. This research aimed to reconstruct the genome-scale metabolic model (GEM) of P. aeruginosa PAO1 to investigate the metabolic roles of D- and L-AAs in QS-related pathways.

METHODS: The updated GEM, iJD1249, was reconstructed by using protocols to integrate data from previous models and refined with well-standardized in silico media (LB, M9, and SCFM) to improve flux balance analysis accuracy. The model was used to explore the metabolic impact of D-Met, D-Ala, D-Glu, D-Ser, L-His, L-Glu, L-Arg, and L-Ornithine (L-Orn) at 5 and 50 mM in QS-related pathways, focusing on the effects on bacterial growth and carbon flux distributions.

RESULTS: Among the tested AAs, D-Met was the only one that did not enhance the growth rate of P. aeruginosa PAO1, while L-Arg and L-Orn increased fluxes in the L-methionine biosynthesis pathway, influencing the metH gene. These findings suggest a differential metabolic role for D-and L-AAs in QS-related pathways.

CONCLUSIONS: Our results shed some light on the metabolic impact of AAs on QS-related pathways and their potential role in P. aeruginosa virulence. Future studies should assess D-Met as a potential adjuvant in antimicrobial strategies, optimizing the concentration in combination with antibiotics to maximize its therapeutic effectiveness.

PMID:40278365 | DOI:10.3390/metabo15040236

J Imaging. 2025 Apr 21;11(4):124. doi: 10.3390/jimaging11040124.

ABSTRACT

Elexacaftor-tezacaftor-ivacaftor (ETI) has shown clinical and spirometric benefits in cystic fibrosis (CF). CT remains a vital tool for diagnosing and monitoring structural lung disease. This study aimed to assess the evolution of lung disease, as evaluated through CT, in adults with CF after at least one year of ETI treatment. This ambispective observational analysis assessed lung CT scans performed before initiating ETI and after at least one year of treatment, using the modified Bhalla scoring system. For those patients with an earlier CT scan, a pre-treatment phase analysis was performed. Epidemiological, clinical, and functional parameters were evaluated. Results: Sixty-two patients were included (35 males, median age 30.4 ± 7.87 years). After at least one year of ETI, significant improvements were observed in the global CT Bhalla score (12.2 ± 2.8 vs. 14.0 ± 2.8), peribronchial thickening (1.4 ± 0.6 vs. 1.0 ± 0.4), and mucus plugging (1.6 ± 0.7 vs. 0.8 ± 0.6) (p < 0.001). Spirometry parameters increased significantly: the percentage of the predicted forced expiratory volume in the first second (ppFEV1) increased from 66.5 ± 19.8 to 77.0 ± 20.4 (p = 0.005) and forced vital capacity (ppFVC) from 80.6 ± 16.4 to 91.6 ± 14.1 (p < 0.001). Additionally, body mass index showed a significant increase. A moderate correlation was found between the Bhalla score and spirometry results. In the pre-treatment phase (n = 52), mucus plugging demonstrated a significant worsening, whereas global CT score, other subscores, and spirometry did not change significantly. Conclusions: In adults with CF, after at least one year of ETI, a significant improvement in structural lung disease was achieved, as reflected by the CT Bhalla score.

PMID:40278040 | DOI:10.3390/jimaging11040124

Biomimetics (Basel). 2025 Apr 17;10(4):247. doi: 10.3390/biomimetics10040247.

ABSTRACT

Airway mucus plays a critical role in respiratory health, with diseases such as cystic fibrosis (CF) being characterized by mucus that exhibits increased viscosity and altered viscoelasticity. In vitro models that emulate these properties are essential for understanding the impact of CF mucus on airway function and for the development of therapeutic strategies. This study characterizes a mucus mimic composed of xanthan gum and locust bean gum, which is designed to exhibit the rheological properties of CF mucus. Mucus concentrations ranging from 0.07% to 0.3% w/v were tested to simulate different states of bacterial infection in CF. Key rheological parameters, including yield stress, storage modulus, loss modulus, and viscosity, were measured using an HR2 rheometer with strain sweep, oscillation frequency, and flow ramp tests. The results show that increasing the concentration enhanced the mimic's elasticity and yield stress, with values aligning with those reported for CF mucus in pathological states. These findings provide a quantitative framework for tuning the rheological properties of mucus in vitro, allowing for the simulation of CF mucus across a range of concentrations. This mucus mimic is cost-effective, readily cross-linked, and provides a foundation for future studies examining the mechanobiological effects of mucus yield stress on epithelial cell layers, particularly in the context of bacterial infections and airway disease modeling.

PMID:40277645 | DOI:10.3390/biomimetics10040247

Stat Med. 2025 Apr;44(8-9):e70057. doi: 10.1002/sim.70057.

ABSTRACT

Joint models for longitudinal and survival data have become a popular framework for studying the association between repeatedly measured biomarkers and clinical events. Nevertheless, addressing complex survival data structures, especially handling both recurrent and competing event times within a single model, remains a challenge. This causes important information to be disregarded. Moreover, existing frameworks rely on a Gaussian distribution for continuous markers, which may be unsuitable for bounded biomarkers, resulting in biased estimates of associations. To address these limitations, we propose a Bayesian shared-parameter joint model that simultaneously accommodates multiple (possibly bounded) longitudinal markers, a recurrent event process, and competing risks. We use the beta distribution to model responses bounded within any interval ( a , b ) $$ \left(a,b\right) $$ without sacrificing the interpretability of the association. The model offers various forms of association, discontinuous risk intervals, and both gap and calendar timescales. A simulation study shows that it outperforms simpler joint models. We utilize the US Cystic Fibrosis Foundation Patient Registry to study the associations between changes in lung function and body mass index, and the risk of recurrent pulmonary exacerbations, while accounting for the competing risks of death and lung transplantation. Our efficient implementation allows fast fitting of the model despite its complexity and the large sample size from this patient registry. Our comprehensive approach provides new insights into cystic fibrosis disease progression by quantifying the relationship between the most important clinical markers and events more precisely than has been possible before. The model implementation is available in the R package JMbayes2.

PMID:40277342 | DOI:10.1002/sim.70057

Mikrobiyol Bul. 2025 Apr;59(2):145-157. doi: 10.5578/mb.20250232.

ABSTRACT

Kistik fibrozis (KF), solunum yollarında yoğun mukus birikimi nedeniyle kronik enfeksiyonlara yol açan genetik bir hastalıktır. Pseudomonas aeruginosa, KF hastalarında sık rastlanan ve uzun süreli enfeksiyonlara ve kolonizasyona neden olan önemli bir patojendir. Bu çalışma, KF çocuk hastalarının solunum yolu örneklerinden ardışık olarak elde edilen P.aeruginosa izolatlarının antibiyotik duyarlılık profillerinin ve biyofilm oluşturma yeteneklerinin karşılaştırılmasını amaçlamıştır. Hacettepe Üniversitesi İhsan Doğramacı Çocuk Hastanesi KF Ünitesinde 2021-2023 yılları arasında prospektif olarak takip edilen KF hastalarından (n= 80) alınan solunum yolu örneklerinde üreyen ardışık kronik P.aeruginosa izolatları incelenmiştir. Bakteri tür tanımlaması MALDI-TOF MS ile yapılmış ve konvansiyonel yöntemlerle doğrulanmıştır. Antibiyotik duyarlılık testleri EUCAST önerileri doğrultusunda sıvı mikrodilüsyon ve gradiyent test yöntemleriyle gerçekleştirilmiştir. Antibiyotik direnç genleri (blaVIM, blaIMP, blaNDM, blaKPC) polimeraz zincir reaksiyonu yöntemiyle incelenmiştir. Biyofilm oluşumu, kristal viyole mikrotitrasyon plak yöntemiyle değerlendirilmiştir. Kistik fibrozis hastalarında eşlik eden en sık sistemik bulgu ekzokrin pankreas yetmezliği (n= 58) ve bronşektazi (n= 44) olarak saptanmıştır. P.aeruginosa dışında 56 hastada başka bir etkenin daha ürediği [metisiline duyarlı Staphylococcus aureus (n= 46), metisiline dirençli S.aureus (n= 31), Acinetobacter spp. (n= 2) ve tüberküloz dışı mikobakteri (n= 2)] saptanmıştır. Bu çalışmada, izolatların antibiyotik direnci seftazidime en yüksek (%3.75), kolistine en düşük (%1.25) bulunmuştur. Tobramisin, meropenem ve levofloksasine direnç %2.5 olarak saptanırken, siprofloksasine direnç tespit edilmemiştir. Antibiyotik direnç genleri açısından en sık saptanan gen blaVIM olup ilk izolatlarda %12.5, sonraki izolatlarda ise %10 oranında belirlenmiştir. Çalışmaya dahil edilen izolatların hiçbrisinde blaKPC, blaIMP ve blaNDM direnç genleri saptanmamıştır. Biyofilm oluşumu değerlendirildiğinde, ilk izolatların %77.5'inde, sonraki ardışık 80 izolatın 59 (%73.7)'unda kantitatif olarak biyofilm oluşumu gösterilmiştir. İzolatların 11 (%18.6)'inin güçlü pozitif, 33 (%55.9)'ünün orta pozitif ve 15 (%25.4)'inin zayıf pozitif biyofilm oluşturduğu saptanmıştır. Sonuç olarak, P.aeruginosa'nın KF hastalarında yüksek biyofilm oluşturma kapasitesine sahip olduğu belirlenirken antibiyotik tedavisinin mikroorganizmanın eradikasyonunda etkin rol oynamadığı saptanmıştır. Bu çalışma, ardışık izolatların biyofilm yapımı ve antibiyotik direnç paternlerinde anlamlı değişiklikler göstermediğini ortaya koymuştur. Benzer antibiyotik duyarlılık ve biyofilm yapımı gösteren ardışık P.aeruginosa izolatlarında bakterinin yok edilmesi için antibiyofilm duyarlılık testlerinin yapılması ve yeni antibiyofilm tedavi stratejilerinin geliştirilmesi önem arz etmektedir.

PMID:40277263 | DOI:10.5578/mb.20250232

Curr Opin Pulm Med. 2025 Apr 28. doi: 10.1097/MCP.0000000000001176. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Over the past decade, increased knowledge has contributed to improved medical and technical treatments across the spectrum of respiratory diseases. As a result, timing for transplant evaluation might be more challenging. In this review, the focus is on timing of lung transplant evaluation of patients from the main respiratory diseases referred. Disease-specific predictors of survival in relation to timing of transplant evaluation and alternative treatments will be reviewed.

RECENT FINDINGS: Treatment options have evolved for respiratory diseases like chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis and pulmonary arterial hypertension. These treatments have led to improved quality of life, exercise tolerance, lung function and outcome. However, the effect of these alternative treatments on transplant candidacy and knowledge on timing of lung transplant evaluation are lacking.

SUMMARY: This article reviews the current best evidence to guide clinicians regarding the optimum timing for transplant referral and highlights considerations to optimize transplant candidacy and outcomes.

PMID:40276963 | DOI:10.1097/MCP.0000000000001176