Int J Mol Sci. 2024 Mar 31;25(7):3893. doi: 10.3390/ijms25073893.

ABSTRACT

Cystic fibrosis (CF) is an inherited genetic disorder which manifests primarily in airway disease. Recent advances in molecular technologies have unearthed the diverse polymicrobial nature of the CF airway. Numerous studies have characterised the genus-level composition of this airway community using targeted 16S rDNA sequencing. Here, we employed whole-genome shotgun metagenomics to provide a more comprehensive understanding of the early CF airway microbiome. We collected 48 sputum samples from 11 adolescents and children with CF over a 12-month period and performed shotgun metagenomics on the Illumina NextSeq platform. We carried out functional and taxonomic analysis of the lung microbiome at the species and strain levels. Correlations between microbial diversity measures and independent demographic and clinical variables were performed. Shotgun metagenomics detected a greater diversity of bacteria than culture-based methods. A large proportion of the top 25 most-dominant species were anaerobes. Samples dominated by Staphylococcus aureus and Prevotella melaninogenica had significantly higher microbiome diversity, while no CF pathogen was associated with reduced microbial diversity. There was a diverse resistome present in all samples in this study, with 57.8% agreement between shotgun metagenomics and culture-based methods for detection of resistance. Pathogenic sequence types (STs) of S. aureus, Pseudomonas aeruginosa, Haemophilus influenzae and Stenotrophomonas maltophilia were observed to persist in young CF patients, while STs of S. aureus were both persistent and shared between patients. This study provides new insight into the temporal changes in strain level composition of the microbiome and the landscape of the resistome in young people with CF. Shotgun metagenomics could provide a very useful one-stop assay for detecting pathogens, emergence of resistance and conversion to persistent colonisation in early CF disease.

PMID:38612702 | DOI:10.3390/ijms25073893

Int J Mol Sci. 2024 Mar 27;25(7):3713. doi: 10.3390/ijms25073713.

ABSTRACT

The interaction between extracellular vesicles (EVs) and SARS-CoV-2, the virus causing COVID-19, especially in people with cystic fibrosis (PwCF) is insufficiently studied. EVs are small membrane-bound particles involved in cell-cell communications in different physiological and pathological conditions, including inflammation and infection. The CF airway cells release EVs that differ from those released by healthy cells and may play an intriguing role in regulating the inflammatory response to SARS-CoV-2. On the one hand, EVs may activate neutrophils and exacerbate inflammation. On the other hand, EVs may block IL-6, a pro-inflammatory cytokine associated with severe COVID-19, and protect PwCF from adverse outcomes. EVs are regulated by TGF-β signaling, essential in different disease states, including COVID-19. Here, we review the knowledge, identify the gaps in understanding, and suggest future research directions to elucidate the role of EVs in PwCF during COVID-19.

PMID:38612524 | DOI:10.3390/ijms25073713

Diagnostics (Basel). 2024 Apr 3;14(7):763. doi: 10.3390/diagnostics14070763.

ABSTRACT

Cystic fibrosis (CF) is a chronic and potentially life-threatening condition, wherein timely diagnosis assumes paramount significance for the prompt initiation of therapeutic interventions, thereby ameliorating pulmonary function, addressing nutritional deficits, averting complications, mitigating morbidity, and ultimately enhancing the quality of life and extending longevity. This review aims to amalgamate existing knowledge to provide a comprehensive appraisal of contemporary diagnostic modalities pertinent to CF in the 21st century. Deliberations encompass discrete delineations of each diagnostic modality and the elucidation of potential diagnostic quandaries encountered in select instances, as well as the delineation of genotype-phenotype correlations germane to genetic counseling endeavors. The synthesis underscores that, notwithstanding the availability and strides in diagnostic methodologies, including genetic assays, the sweat test (ST) retains its position as the preeminent diagnostic standard for CF, serving as a robust surrogate for CFTR functionality. Prospective clinical investigations in the realm of CF should be orchestrated with the objective of discerning novel diagnostic modalities endowed with heightened specificity and sensitivity.

PMID:38611676 | DOI:10.3390/diagnostics14070763

Cancers (Basel). 2024 Apr 5;16(7):1420. doi: 10.3390/cancers16071420.

ABSTRACT

Shwachman-Diamond syndrome (SDS) is one of the most common inherited bone marrow failure syndromes. SDS is characterized by hypocellular bone marrow, with a severe impairment of the myeloid lineage, resulting in neutropenia, thrombocytopenia, and, more rarely, anemia. Almost 15% of patients with SDS develop myelodysplastic syndrome or acute myeloid leukemia as early as childhood or young adulthood. Exocrine pancreatic insufficiency is another common feature of SDS. Almost all patients with SDS show failure to thrive, which is associated with skeletal abnormalities due to defective ossification. Considering these observations, it remains unfeasible to use the common growth charts already available for the general population. To address this issue, we report how we drew up growth charts of patients with SDS aged 0 to 18 years. We analyzed height, weight, and body max index (BMI) in 121 Italian patients with SDS. Results indicated that the 50th and 3rd percentiles of weight and height of the pediatric general population correspond to the 97th and 50th percentiles of patients with SDS aged 0-18 years, respectively. In addition, the percentage increment in weight of subjects aged 14-18 years was higher in patients with SDS than in the general population. SDS-specific growth charts, such as those described here, afford a new tool, which is potentially useful for both clinical and research purposes in SDS.

PMID:38611098 | DOI:10.3390/cancers16071420

J Clin Med. 2024 Apr 2;13(7):2050. doi: 10.3390/jcm13072050.

ABSTRACT

Background: Previous studies found high but very variable levels of tetranor-PGEM and PGDM (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF). This study aims to assess the role of cyclooxygenase COX-1 and COX-2 genetic polymorphisms in PG production and of PG metabolites as potential markers of symptoms' severity and imaging findings. Methods: A total of 30 healthy subjects and 103 pwCF were included in this study. Clinical and radiological CF severity was evaluated using clinical scoring methods and chest computed tomography (CT), respectively. Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. Variants in the COX-1 gene (PTGS1 639 C>A, PTGS1 762+14delA and COX-2 gene: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were also analyzed. Results: PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Conclusions: These results suggest that urinary PG level testing can be used as a biomarker of CF severity. COX genetic polymorphisms are not involved in the variability of PG production.

PMID:38610815 | DOI:10.3390/jcm13072050

BMC Oral Health. 2024 Apr 12;24(1):446. doi: 10.1186/s12903-024-04227-4.

ABSTRACT

BACKGROUND: Oral health impacts systemic health, individual well-being, and quality of life. It is important to identify conditions that may exacerbate oral disease to aid public health and policy development and promote targeted patient treatment strategies. Developmental defects can increase an individual's risk of dental caries, hypersensitivity, premature tooth wear, erosion, and poor aesthetics. As part of an ongoing study assessing oral health in adults with cystic fibrosis at Cork University Dental School and Hospital, a systematic review of available literature was conducted to assess the prevalence of enamel defects in people with cystic fibrosis.

AIMS: To critically evaluate the literature to determine if the prevalence of developmental defects of enamel is higher in people with cystic fibrosis (PwCF).

METHODS: Data Sources: Three online databases were searched Embase, Scopus, and Web of Science Core Collection. Studies that examined an association between cystic fibrosis and developmental defects of enamel were included in this systematic review.

RESULTS: The initial search identified 116 publications from the following databases Embase, Web of Science Core Collection, and Scopus. Eleven studies were included for qualitative analysis. Nine studies concluded that PwCF had a higher prevalence of enamel defects than control people and one study found no difference in cystic fibrosis (CF) status. All studies had a risk of bias that may influence study results and their interpretation.

CONCLUSIONS: The results of the systematic review show a consistent pattern that PwCF have a higher prevalence of DDE than people without CF. Genetic dysfunction, chronic systemic infections, and long-term antibiotic use are possible aetiological causes. This review highlights the need for future studies to investigate if DDEs are caused by the underlying CFTR mutation or as a consequence of disease manifestations and/or management.

PMID:38609911 | DOI:10.1186/s12903-024-04227-4

Eur Respir J. 2024 Apr 12:2301689. doi: 10.1183/13993003.01689-2023. Online ahead of print.

ABSTRACT

BACKGROUND: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use.

METHODS: Prospective observational study using data from the EMBARC Registry between January 2015 and April 2022. Pre-specified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs.

RESULTS: 16 723 people with bronchiectasis from 28 countries were included in the study. Mean age was 67 years (interquartile range 57-74 years, range 18-100 years) and 61% were females. Seventy-two percent of the participants reported daily sputum expectoration and 52% (95% CI 51-53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the patients and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Patients who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in patients with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe.

CONCLUSIONS: Only half of the people with bronchiectasis in Europe use airway clearance management. Use and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

PMID:38609097 | DOI:10.1183/13993003.01689-2023

Eur Respir J. 2024 Apr 12:2301554. doi: 10.1183/13993003.01554-2023. Online ahead of print.

ABSTRACT

INTRODUCTION: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the EMBARC registry, we tested whether sputum colour would be associated with disease severity and clinical outcomes.

METHODS: Prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalizations for severe exacerbations and mortality during up to 5 years follow-up.

RESULTS: 13 484 patients were included in the analysis. More purulent sputum was associated with lower FEV1, worse quality of life, greater bacterial infection, and a higher bronchiectasis severity index.Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (1.0 reference), patients with mucopurulent sputum experienced significantly more exacerbations (Incident rate ratio (IRR) 1.26 95%CI 1.19-1.33, p<0.0001), while the rates were even higher for patients with purulent (IRR 1.45 95%CI 1.36-1.55, p<0.0001), and severely purulent sputum (IRR 1.54 95%CI 1.26-1.89, ted with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.29 (95%CI 1.19-1.39, p<0.0001), 1.73 (95%CI 1.58-1.90, p<0.0001) and 2.01 (95%CI 1.54-2.63, p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. . Mortality was significantly increased with increasing sputum purulent, hazard ratio 1.12 (95%CI 1.01-1.24, p=0.027), for each increment in sputum purulence.

CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

PMID:38609095 | DOI:10.1183/13993003.01554-2023

Free Radic Biol Med. 2024 Apr 10:S0891-5849(24)00388-5. doi: 10.1016/j.freeradbiomed.2024.04.217. Online ahead of print.

ABSTRACT

Hypothiocyanous acid (HOSCN) is an endogenous oxidant produced by peroxidase oxidation of thiocyanate (SCN-), an ubiquitous sulfur-containing pseudohalide synthesized from cyanide. HOSCN serves as a potent microbicidal agent against pathogenic bacteria, viruses, and fungi, functioning through thiol-targeting mechanisms, independent of currently approved antimicrobials. Additionally, SCN- reacts with hypochlorous acid (HOCl), a highly reactive oxidant produced by myeloperoxidase (MPO) at sites of inflammation, also producing HOSCN. This imparts both antioxidant and antimicrobial potential to SCN-. In this review, we discuss roles of HOSCN/SCN- in immunity and potential therapeutic implications for combating infections.

PMID:38608822 | DOI:10.1016/j.freeradbiomed.2024.04.217

Pediatr Pulmonol. 2024 Apr 12. doi: 10.1002/ppul.26982. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is caused by CF transmembrane conductance regulator (CFTR) gene mutations producing dysfunctional CFTR proteins leading to progressive clinical disease. Elexacaftor-tezacaftor-ivacaftor (ETI) remarkably improves lung disease but is associated with substantial weight gain.

STUDY DESIGN AND METHODS: We performed a single-center longitudinal study predicting 6-month weight gain after ETI initiation. We used linear mixed effects modeling (LME) to determine association of ETI treatment with changing body mass index (BMI). Using linear regression, we examined BMI prediction models with distinct combinations of main effects to identify a model useful for patient counseling. We used up to eight commonly observed clinical characteristics as input variables (age, sex, percent predicted FEV1 [FEV1%], F508del homozygous state, pancreatic sufficiency, HgbA1c, prior modulator use and prior year number of pulmonary exacerbations).

RESULTS: We evaluated 154 patients (19-73 years old, 54% female, FEV1% = 19-121, 0-6 prior year pulmonary exacerbations). LME demonstrated an association between ETI use and weight increases. Exhaustive testing suggested a parsimonious linear regression model well-fitted to data that is potentially useful for counseling. The two variable model shows that on average, BMI decreases by 0.045 (95% Confidence Interval [CI] = -0.069 to -0.021, p < 0.001) for every year of age and increases by 0.322 (CI = 0.142 to 0.502, p = 0.001) for each additional prior year exacerbation at the time of ETI initiation.

INTERPRETATION: Young patients with many prior year pulmonary exacerbations likely have the largest 6 month weight gain after starting ETI.

PMID:38607242 | DOI:10.1002/ppul.26982

Pediatr Pulmonol. 2024 Apr 12. doi: 10.1002/ppul.26997. Online ahead of print.

NO ABSTRACT

PMID:38607232 | DOI:10.1002/ppul.26997

Bioinform Adv. 2024 Apr 3;4(1):vbae028. doi: 10.1093/bioadv/vbae028. eCollection 2024.

ABSTRACT

SUMMARY: The 19th ISCB Student Council Symposium (SCS2023) organized by ISCB-SC adopted a hybrid format for the first time, allowing participants to engage in-person in Lyon, France, and virtually via an interactive online platform. The symposium prioritized inclusivity, featuring on-site sessions, poster presentations, and social activities for in-person attendees, while virtual participants accessed live sessions, interactive Q&A, and a virtual exhibit hall. Attendee statistics revealed a global reach, with Europe as the major contributor. SCS2023's success in bridging in-person and virtual experiences sets a precedent for future events in Computational Biology and Bioinformatics.

AVAILABILITY AND IMPLEMENTATION: The details of the symposium, speaker information, schedules, and accepted abstracts, are available in the program booklet (https://doi.org/10.5281/zenodo.8173977). For organizers interested in adopting a similar hybrid model, it would be beneficial to have access to details regarding the online platform used, the types of sessions offered, and the challenges faced. Future iterations of SCS can address these aspects to further enhance accessibility and inclusivity.

PMID:38606186 | PMC:PMC11007116 | DOI:10.1093/bioadv/vbae028

J Cyst Fibros. 2024 Apr 10:S1569-1993(24)00045-6. doi: 10.1016/j.jcf.2024.04.002. Online ahead of print.

NO ABSTRACT

PMID:38604889 | DOI:10.1016/j.jcf.2024.04.002

J Cyst Fibros. 2024 Apr 10:S1569-1993(24)00043-2. doi: 10.1016/j.jcf.2024.03.014. Online ahead of print.

NO ABSTRACT

PMID:38604888 | DOI:10.1016/j.jcf.2024.03.014

PLoS Pathog. 2024 Apr 11;20(4):e1012154. doi: 10.1371/journal.ppat.1012154. Online ahead of print.

ABSTRACT

Candida albicans chronically colonizes the respiratory tract of patients with Cystic Fibrosis (CF). It competes with CF-associated pathogens (e.g. Pseudomonas aeruginosa) and contributes to disease severity. We hypothesize that C. albicans undergoes specific adaptation mechanisms that explain its persistence in the CF lung environment. To identify the underlying genetic and phenotypic determinants, we serially recovered 146 C. albicans clinical isolates over a period of 30 months from the sputum of 25 antifungal-naive CF patients. Multilocus sequence typing analyses revealed that most patients were individually colonized with genetically close strains, facilitating comparative analyses between serial isolates. We strikingly observed differential ability to filament and form monospecies and dual-species biofilms with P. aeruginosa among 18 serial isolates sharing the same diploid sequence type, recovered within one year from a pediatric patient. Whole genome sequencing revealed that their genomes were highly heterozygous and similar to each other, displaying a highly clonal subpopulation structure. Data mining identified 34 non-synonymous heterozygous SNPs in 19 open reading frames differentiating the hyperfilamentous and strong biofilm-former strains from the remaining isolates. Among these, we detected a glycine-to-glutamate substitution at position 299 (G299E) in the deduced amino acid sequence of the zinc cluster transcription factor ROB1 (ROB1G299E), encoding a major regulator of filamentous growth and biofilm formation. Introduction of the G299E heterozygous mutation in a co-isolated weak biofilm-former CF strain was sufficient to confer hyperfilamentous growth, increased expression of hyphal-specific genes, increased monospecies biofilm formation and increased survival in dual-species biofilms formed with P. aeruginosa, indicating that ROB1G299E is a gain-of-function mutation. Disruption of ROB1 in a hyperfilamentous isolate carrying the ROB1G299E allele abolished hyperfilamentation and biofilm formation. Our study links a single heterozygous mutation to the ability of C. albicans to better survive during the interaction with other CF-associated microbes and illuminates how adaptive traits emerge in microbial pathogens to persistently colonize and/or infect the CF-patient airways.

PMID:38603707 | DOI:10.1371/journal.ppat.1012154

Heliyon. 2024 Mar 29;10(7):e28984. doi: 10.1016/j.heliyon.2024.e28984. eCollection 2024 Apr 15.

ABSTRACT

BACKGROUND: Molecular diagnosis of cystic fibrosis (CF) is challenging in Mexico due to the population's high genetic heterogeneity. To date, 46 pathogenic variants (PVs) have been reported, yielding a detection rate of 77%. We updated the spectrum and frequency of PVs responsible for this disease in mexican patients.

METHODS: We extracted genomic DNA from peripheral blood lymphocytes obtained from 297 CF patients and their parents. First, we analyzed the five most frequent PVs in the Mexican population using PCR-mediated site-directed mutagenesis. In patients with at least one identified allele, CFTR sequencing was performed using next-generation sequencing tools and multiplex ligation-dependent probe amplification. For variants not previously classified as pathogenic, we used a combination of in silico prediction, CFTR modeling, and clinical characteristics to determine a genotype-phenotype correlation.

RESULTS: We identified 95 PVs, increasing the detection rate to 87.04%. The most frequent variants were p.(PheF508del) (42.7%), followed by p.(Gly542*) (5.6%), p.(Ser945Leu) (2.9%), p.(Trp1204*) and p.(Ser549Asn) (2.5%), and CFTRdel25-26 and p.(Asn386Ilefs*3) (2.3%). The remaining variants had frequencies of <2.0%, and some were exclusive to one family. We identified 10 novel PVs localized in different exons (frequency range: 0.1-0.8%), all of which produced structural changes, deletions, or duplications in different domains of the protein, resulting in dysfunctional ion flow. The use of different in silico software and American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) criteria allowed us to assume that all of these PVs were pathogenic, causing a severe phenotype.

CONCLUSIONS: In a highly heterogeneous population, combinations of different tools are needed to identify the variants responsible for CF and enable the establishment of appropriate strategies for CF diagnosis, prevention, and treatment.

PMID:38601560 | PMC:PMC11004572 | DOI:10.1016/j.heliyon.2024.e28984

J Pediatr Pharmacol Ther. 2024 Apr;29(2):135-139. doi: 10.5863/1551-6776-29.2.135. Epub 2024 Apr 8.

ABSTRACT

OBJECTIVES: As cystic fibrosis (CF) lung disease progresses, the airways become infected with opportunistic pathogens, such as Pseudomonas aeruginosa (PA). In October 2019, the US Food and Drug Administration approved elexacaftor/tezacaftor/ivacaftor (ETI), a highly effective modulator therapy (HEMT), for individuals 12 years and older with 1 copy of the F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation. ETI increases the amount of and function of CFTR in the respiratory epithelium, improving mucociliary clearance and reducing static airway mucus, a major trigger for chronic infection and inflammation.

METHODS: A retrospective analysis of inhaled tobramycin (iTOB) prescriptions between January 1, 2016, and December 31, 2021, was performed. This captured data before and after ETI approval at Children's Mercy Kansas City (CMKC). The number of individuals with new PA acquisition and individuals considered -chronically infected was analyzed.

RESULTS: The number of eradication prescriptions declined in 2020 and 2021, with 15 (7%) and 12 (5%) -individuals prescribed therapy for those years, respectively. A similar pattern was observed for -prescriptions for chronic infection. A reduction was seen in 2020 and 2021, with 28 (13%) and 20 (9%) individuals -prescribed therapy for the respective years.

CONCLUSIONS: The CMKC experienced a decrease in the number of courses of iTOB prescribed during the last 6 years. The reasons for this are likely multifactorial and may include the implementation of standardized PA surveillance and eradication protocols, the effect of HEMT on mucociliary clearance and airway microbiology, and the poorly understood effects of the SARS-CoV-2 pandemic on the epidemiology of respiratory infections.

PMID:38596420 | PMC:PMC11001205 | DOI:10.5863/1551-6776-29.2.135

ERJ Open Res. 2024 Apr 8;10(2):00897-2023. doi: 10.1183/23120541.00897-2023. eCollection 2024 Mar.

ABSTRACT

BACKGROUND: Asthma is the most common chronic childhood respiratory condition globally. Inhaled corticosteroid (ICS)-formoterol reliever-based regimens reduce the risk of asthma exacerbations compared with conventional short-acting β2-agonist (SABA) reliever-based regimens in adults and adolescents. The current limited evidence for anti-inflammatory reliever therapy in children means it is unknown whether these findings are also applicable to children. High-quality randomised controlled trials (RCTs) are needed.

OBJECTIVE: The study aim is to determine the efficacy and safety of budesonide-formoterol reliever alone or maintenance and reliever therapy (MART) compared with standard therapy: budesonide or budesonide-formoterol maintenance, both with terbutaline reliever, in children aged 5 to 11 years with mild, moderate and severe asthma.

METHODS: A 52-week, multicentre, open-label, parallel group, phase III, two-sided superiority RCT will recruit 400 children aged 5 to 11 years with asthma. Participants will be randomised 1:1 to either budesonide-formoterol 100/6 µg Turbuhaler reliever alone or MART; or budesonide or budesonide-formoterol Turbuhaler maintenance, with terbutaline Turbuhaler reliever. The primary outcome is moderate and severe asthma exacerbations as rate per participant per year. Secondary outcomes are asthma control, lung function, exhaled nitric oxide and treatment step change. Assessment of Turbuhaler technique and cost-effectiveness analysis are also planned.

CONCLUSION: This will be the first RCT to compare the efficacy and safety of a step-wise budesonide-formoterol reliever alone or MART regimen with conventional inhaled ICS or ICS-long-acting β-agonist maintenance plus SABA reliever in children. The results will provide a much-needed evidence base for the treatment of asthma in children.

PMID:38590934 | PMC:PMC11000271 | DOI:10.1183/23120541.00897-2023

Oncoimmunology. 2024 Apr 4;13(1):2338951. doi: 10.1080/2162402X.2024.2338951. eCollection 2024.

ABSTRACT

Recently, we showed that an autologous DC-based vaccine induces an increase in immunosuppressive PD-L1+ tumor-associated macrophages (TAM) both in the tumor and the tumor draining lymph nodes, thereby blunting the efficacy of therapeutic immunization. Only the combination of the DC vaccine with anti-PD-L1 immune checkpoint inhibition, but not the use of antibodies targeting PD-1 alone, was able to set off CD8+ cytotoxic T lymphocyte (CTL)-mediated tumor suppression in mice. In sum, we delineated a PD-L1 checkpoint blockade-based strategy to avoid TAM-induced T cell exhaustion during DC vaccine therapy.

PMID:38590800 | PMC:PMC11000604 | DOI:10.1080/2162402X.2024.2338951

Front Pediatr. 2024 Mar 25;12:1376360. doi: 10.3389/fped.2024.1376360. eCollection 2024.

ABSTRACT

INTRODUCTION: Due to improvements in perinatal care, survival rates of preterm infants have improved during the last decades. However, these infants remain at risk of developing cardiovascular sequelae later in life. This study aimed to investigate the cardiac biomarkers and left ventricular systolic function in former preterm infants in comparison with term controls at preschool age.

METHODS: The study included children aged 5-7 years old born below 32 weeks of gestational age. The control group consisted of same-age children born at term. Basic data of study participants were collected using questionnaires and follow-up databases. During the study visit, we recorded anthropometric data and blood pressure readings, determined high-sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentrations, and calculated fractional shortening (FS) and left ventricular mass (LVM).

RESULTS: Term-born (n = 25; median gestational age, 40.1 weeks) compared with preterm-born infants (n = 80; median gestational age 29.6 weeks) showed no significant differences in the median concentration of hs-cTnT [median, 3.5 (IQR 3.5; 3.5) vs. 3.5 (3.5; 3.5) ng/L, p = 0.328] and the median concentration of NT-pro-BNP [median, 91.0 (IQR 40.8; 150.3) vs. 87.5 (50.1; 189.5) ng/L, p = 0.087]. FS and LVM/LVMI were not significantly different between the two groups.

CONCLUSION: At preschool age, we observed no significant differences in cardiac biomarkers and left ventricular systolic function in preterm infants. Further studies are warranted to explore the potential of cardiac biomarkers as a prognostic tool for subclinical cardiac alterations after preterm birth.

PMID:38590770 | PMC:PMC10999603 | DOI:10.3389/fped.2024.1376360