Introduction: Personalized dental therapies are becoming increasingly achievable through advancements in digital technologies. The integration of patient-specific data and artificial intelligence (AI) is revolutionizing diagnosis, treatment planning, and the execution of oral rehabilitation, allowing for progress toward precision dentistry.
Methods: This study outlines a digital workflow for individualized dental treatment, starting with the full digitalization of the patient. Intraoral scans, CBCT imaging, and facial scanning were combined to create a virtual patient model. This integrated digital representation enabled comprehensive diagnostic evaluation and esthetic–functional treatment planning. Furthermore, AI-based systems were incorporated for diagnostic support and prosthetic planning.
Results: The virtual patient model allowed clinicians to simulate various therapeutic scenarios and optimize treatment strategies based on anatomical, functional, and esthetic criteria. The use of AI tools enhanced diagnostic accuracy, facilitated early detection of pathologies, and supported decision-making in complex rehabilitations. Patient-specific digital planning improved communication with both patients and interdisciplinary teams, leading to more predictable outcomes.
Conclusions: The integration of digital technologies and AI in dentistry enables highly personalized, precise, and efficient treatments. The creation of a virtual patient through comprehensive digitalization, combined with AI-enhanced planning, represents a significant step forward in individualized oral rehabilitation and sets the foundation for the future of precision dental care.

INTRODUCTION: The disruption of microbiota metabolism, measured by changes in the serum concentrations of clinically relevant aromatic metabolites, appears to play a crucial role in the occurrence of complications following cardiac surgery [DOI:10.3390/biomedicines11051335].

The aim of this study was to assess the potential of modulating the microbial metabolism using specific antibiotics to prevent infectious and inflammatory complications after cardiac surgery.

MATERIAL AND METHODS: Patients (n = 58) who underwent cardiac surgeries under artificial circulation were involved in a randomized prospective interventional study [ClinicalTrials.gov identifier: NCT04921436. Registered May 24, 2021].

Patients in group I (n = 30) received modulation of microbial metabolism through antibiotics that inhibited protein synthesis (a combination of semi-synthetic antibiotics from the tetracycline and macrolide groups); the patients in group II did not experience such modulation (n = 28).

Blood serum samples were collected three times, prior to and on the 3rd and 6th days after the surgery, and analyzed for their clinical parameters and concentrations of clinically significant aromatic acids.

RESULTS: Six and eight patients developed postoperative complications, including zero and five cases of pneumonia, in groups I and II, respectively. The range of identified microorganisms in group II was considerably broader. Group I (compared to group II) exhibited a more pronounced reduction in the concentration of 4-hydroxyphenylacetic acid when comparing the values prior to surgery to those on the third and sixth days (p = 0.016 and 0.005, respectively). The total concentration of aromatic metabolites on the third day, as well as 4-hydroxyphenylacetic acid on the sixth day, showed strong predictive value concerning the occurrence of complications (sensitivity of 100% for both parameters; specificity of 82% and 93%, respectively).

CONCLUSIONS: The preventive administration of antibiotics that inhibit microbial protein synthesis effectively diminishes the severity of microbiota metabolic dysfunction and lowers pneumonia incidence in the early stages following surgery.

Objective: We wished to systematically summarize critical peri-procedural nursing strategies for a middle-aged patient with decompensated liver cirrhosis and esophagogastric variceal bleeding (EGVB) undergoing interventional treatments—specifically percutaneous transhepatic variceal embolization (PTVE) and a transjugular intrahepatic portosystemic shunt (TIPS)—and to develop evidence-based nursing protocols aimed at reducing complications and improving outcomes.

Methods: Nursing interventions were implemented within a multidisciplinary framework, emphasizing 1. Comprehensive preoperative assessment and preparation; 2. Real-time intraoperative coordination and monitoring; and 3. Rigorous postoperative management to prevent rebleeding, hepatic encephalopathy, and infection. Specialized care included precise puncture site management, continuous portal pressure monitoring, individualized nutritional support, psychological counseling, and targeted health education. The nursing plan was dynamically adjusted based on the patient’s clinical status.

Results: Following PTVE and TIPS, bleeding was effectively controlled; hemoglobin levels increased from 39 g/L to 85 g/L; liver function (total protein, albumin) progressively improved; and no severe complications (puncture site hematoma, hepatic encephalopathy, or stent thrombosis) occurred. Patient satisfaction reached 98%. The patient was discharged stably 24 days postoperatively and remained healthy during the 1-year follow-up.

Conclusion: Effective perioperative nursing for interventional EGVB management requires 1. Precise monitoring and proactive complication prevention; 2. Integrated multidisciplinary collaboration; and 3. Specialized attention to the portal pressure dynamics, coagulation parameters, and psychological well-being . This protocol establishes a replicable nursing model for similar cases.

Introduction: Menke-Hennekam syndrome (MKHK) is an ultra-rare neurodevelopmental disorder first described in 2016 and linked to variants in exons 30-31 of CREBBP and EP300 genes, which are key regulators of chromatin remodeling. Precision genomic diagnosis is essential given MKHK’s clinical heterogeneity. We report a 3-year, 2-month-old male with severe global neurodevelopmental delay, feeding difficulties, failure to thrive, hypodontia, hirsutism, hypertonia, and distinctive facial features, with no relevant family history. His complex presentation underscored the need for individualized molecular investigation to guide prognosis and potential personalized interventions.

Methods: Clinical exome sequencing was performed using the Illumina NextSeq 2000 platform, while Sanger sequencing was used to validate candidate variants. Extensive bioinformatics analysis and a systematic meta-analysis of reported MKHK cases were conducted.

Results: We identified a novel de novo heterozygous variant, NM_004380.3:c.5368T>C p.(Cys1790Arg), in exon 31 of the CREBBP gene, located in the TAZ2 domain. This variant was classified as pathogenic, according to the ACMG 2015 and ACGS 2020 guidelines, using the criteria PM2 (supporting), PM1 (moderate), PP3 (strong) and PS2 (strong). The variant was absent from gnomAD database, located in a mutational hotspot, while in silico predictive tools (including Revel, AlphaMissense, Varity, SIFT, MutationTaster, among others) strongly supported its pathogenicity. Meta-analysis revealed that cysteine substitutions account for over 18% of MKHK cases, particularly clustering within the ZZ and TAZ2 domains.

Conclusions: This finding enriches the personalized genomic understanding of MKHK, emphasizes the diagnostic importance of domain-specific variants, and highlights the utility of early precision diagnosis. Recognizing domain-specific pathogenic mechanisms may enable tailored management strategies and support the development of targeted therapies in the future.

Introduction

Metabolomic studies can be used to stratify patients with systemic inflammatory response syndrome and sepsis. Changes in the concentrations of aromatic microbial metabolites and inflammation biomarkers are considered to identify sepsis as a manifestation of the most severe metabolic dysfunction.

Aim

To evaluate the diagnostic value of inflammation biomarkers and aromatic microbial metabolites in children during the treatment of malignant oncological diseases.

Materials and methods

The study included patients with various malignant oncological diseases (leukemia, lymphoma, nephroblastoma, ependymoma, etc.) without complications (n = 40); patients with inflammatory and infectious complications (n = 31); and, as a control group, healthy children who participated in a routine medical examination (n = 18). In all groups, biomarkers associated with inflammation were determined: C-reactive protein (CRP), procalcitonin (PCT), and presepsin (PSP), as well as aromatic metabolites associated with sepsis: phenyllactic (PhLA), hydroxyphenyllactic (p-HPhLC), and hydroxyphenylacetic (p-HPhA) acids.

Results

Children with malignant oncological diseases had profound metabolic dysfunction compared to healthy children, regardless of the presence of systemic inflammatory response syndrome (SIRS) or sepsis. The sum of sepsis-associated aromatic microbial metabolite concentrations in children was 2.2 (1.5; 2.6) μmol/L in the control group versus 1.5 (1.1; 1.8) μmol/L in cancer patients (p-value=0.001). High diagnostic ability of procalcitonin and presepsin for detecting sepsis was observed: AUROC=0.875, with a cutoff value (Youden index) of 0.913 ng/ml, and AUROC=0.774, with a cutoff value (Youden index) of 526 pg/ml, respectively.

Conclusion

Decreased concentrations of sepsis-associated aromatic microbial metabolites in cancer patients indicate microbiota dysfunction, which may indicate the need for its timely targeted correction. This study also reveals the high diagnostic ability of procalcitonin and presepsin for detecting sepsis.

Aim: The aim of the study was to evaluate choroidal and peripapillary retinal nerve fiber layer thickness (pRNFLT) in individuals with vasovagal syncope (VVS).

Method: A total of 67 consecutive patients with VVS and 61 healthy control subjects were enrolled this study. The choroidal thickness (CT) at fovea, nasal to fovea and, temporal to fovea and pRNLFT measurements assessed by swept source optical-coherence tomography (SS-OCT).

Results: The mean foveal CT (408.7 ± 92.5 μm vs. 342.1 ± 60.2 μm, p< 0.01), mean nasal CT (385.2 ± 88.3 μm vs. 329.2 ± 47.6 μm, p< 0.001), and mean temporal CT (379.5 ± 51.6 μm vs. 321.48 ± 43.2 μm, p< 0.03) were statistically thicker in patients with VVS compared to healthy controls. There was no statistically significant difference in global and all quadrants of pRNFLT measurements between study groups.

Conlusion: In conclusion, we showed that patients with VVS exhibited greater CT across all measured regions when compared to healthy controls. Conversely, there were no signifi-cant variations observed in the thickness of the pRNFL. These findings imply that the choroidal blood flow could be influenced by changes in local neurotransmitter levels in individuals suffering from VVS. This interplay underscores the connection between car-diovascular health and CT alterations, suggesting a need for monitoring in individuals with frequent syncopal episodes to prevent complications and maintain ocular health. Further investigation into these dynamics may yield insights beneficial for clinical practice regarding VVS and ocular health.

Rhinorrhea associated with viral upper respiratory tract infections or reaction to aeroallergens affects all human beings and has been associated with loss of quality of life. Pulmonary fluid accumulation in acute lung injury is a leading cause of hospital admission and death from lower respiratory tract infection and sepsis.

Methods:

In this narrative review, evidence supporting the hypotheses that both rhinorrhea and inflammation-related pulmonary fluid accumulation are due to the dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is presented, and novel concepts of the patho-mechanisms involved are explained.

Results: Upper and lower airway as well as alveolar surface liquid volumes are shown to be dependent on CFTR. Its function is regulated directly by cytokines in allergic- and infection-related inflammation and through increased hydrostatic tissue pressure secondary to vasodilatation in enclosed spaces within the upper airway and in heart failure in pulmonary interstitial spaces. The regulation of upper airway fluid secretion manifested in allergic inflammation and viral infections by rhinovirus and respiratory syncytial virus can be explained by CFTR activation and alveolar fluid accumulation by the inactivation of CFTR through cytokine-induced microRNA and Na/K ATPase inhibition. Therapeutic interventions reducing CFTR dysfunction through anti-inflammatory and CFTR modulating strategies are introduced.

Conclusions: Excessive fluid secretion in the upper respiratory tract induced by viruses and allergy as well as increased lung water in local and systemic inflammation can be explained by CFTR dysfunction opening avenues for supportive treatment.

Introduction

Pharmacogenomic testing (PGt) is increasingly incorporated in clinical practice, with multiple tests available to guide drug administration. The application of PGt in routine clinical care varies considerably across healthcare systems. This study focused on assessing the impact of routine PGt implementation at a high patient volume Internal Medicine clinic in Greece.

Methods

142 patients (98 females, 44 males; ranging 24-91 years) were enrolled in a pilot PGt screening program approved by the “Attikon” University Hospital Research Committee, assessing CYP2C9, CYP2C19, SLCO1B1, and VKORC1 gene variants. Inclusion criteria comprised age >18 years, and the capacity for autonomous decision making.

Results

In 139/142 (98%) cases a pharmacogenetically informative variant was identified. In 33/142 cases, official recommendations were available for the optimization of drug selection and dosing for medications used during their hospitalization. Of these, in 4 cases, recommendations were available for >1 of the prescribed drugs. Overall, recommendations related to 3 major drug classes: alimentary tract (17 cases), cardiovascular (12 cases), and nervous system (4 cases). These included omeprazole (8), pantoprazole (6), lansoprazole (3), atorvastatin (8), rosuvastatin (2), clopidogrel (1), simvastatin (1), escitalopram (2), and amitriptyline/perphenazine (2). In 22/33 cases they involved CYP2C19, while in 11/33 cases they related to SLCO1B1 variants. The strength of these recommendations according to PharmGKB varied across ‘strong’ (4), ‘moderate’ (19), and ‘optional’ (10).

Conclusion

In summary, genotyping of CYP2C9, CYP2C19, SLCO1B1, and VKORC1 led to actionable findings for 98% of the patient population. In 24% of cases recommendations for optimization of currently administered treatments were available – 12% of which were marked as ‘strong’. This study provides insights into the distribution of clinically relevant pharmacogenomic variants within the Greek population and highlights the potential clinical utility of integrating targeted PGt into routine care in Internal Medicine clinics. Knowledge of patient-specific allele frequency data, combined with frequently used medications, may inform evidence-based establishment of new policies.

Marfan syndrome (MFS) is an autosomal genetic disease caused by FBN1 mutation. Patients with the same FBN1 mutation type exhibit different phenotypes, which indicates that there are extra risk factors. Mitochondrial dysfunction was observed in the aorta of both MFS patients and Marfan murine models. Single-nucleotide variants in mitochondrial DNA (mtDNA) may have harmful consequences on a cell. However, the association of mtDNA mutations with MFS has been unclear. Here, we used targeted mtDNA sequencing to detect whole-blood mtDNA mutations from 48 healthy controls and 77 MFS patients, including 7 mother–offspring pedigrees. Three rare mtDNA mutations, m.279T>C, m.2361G>A and m.3316G>A, were filtered in a family whose predominant phenotype was eye lesions. The MFS patients with these mutations had more severe symptoms than family members without the mutation. m.9738G>A was identified in a family whose dominant phenotype was aortic manifestation. A sporadic case with this rare mutation site had aortic aneurysm. We also described the mutation frequency and mutation rate in MFS. The frequency of all solid variants, nonsynonymous variants, pathogenic or likely pathogenic variants and variants of uncertain significance were more abundant in MFS patients compared to the control group. The mutation rate of the coding region, MT-rRNA and MT-tRNA were higher in the MFS group. These data demonstrate frequent mitochondrial mutation in MFS and suggest that the mtDNA mutation might be a potential modifier and diagnostic indicator of MFS phenotypes.

Glioblastoma multiforme (GBM) is the most aggressive and common brain tumor, with an annual incidence of 3.19 per 100,000 people. Chemoresistance is a major issue in the treatment of GBM with therapeutics like temozolomide (TMZ), especially because of the challenges in making chemotherapeutics that can overcome the blood–brain barrier. Cancer stem cells, mechanisms of protein folding, drug pumps, and the tumor microenvironment have been noted as contributing to chemoresistance in GBM, but its precise molecular mechanisms remain unknown. Differential gene expression data from GSE140441 and GSE98126 was extracted from GEO2R, and we investigated the genes differentially expressed at the p<0.05 level between a control group of non-resistant subtypes and an experimental group of GBM cells cultured in TMZ to determine which could confer chemoresistance. The differentially expressed genes were identified and compiled using the dplyr package in R. These genes were submitted for DAVID functional annotation clustering. Clusters were analyzed for their significance at p<.05. From the differential expression studies, 1,980 genes were identified and used to conduct DAVID functional annotation clustering. From these genes, 101 functional annotation clusters were identified. Notably, many clusters responsible for mRNA regulation, as well as the clusters regulating conjugation of ubiquitin-like protein (p=1.2E-17) and cadherin binding (p=1.9E-5) clusters, were significantly differentially expressed in chemoresistant GBM. Targeting pathways related to conjugation of ubiquitin-like protein and cadherin binding, as well as other mechanisms of protein breakdown, might further our understanding of the mechanism of chemoresistance in GBM while also improving the clinical utility of treatments. Certain FDA-approved drugs that target both the ubiquitin-like protein degradation pathway and DNA synthesis, including mitoxantrone, 6-mercaptopurine, and 6-thioguanine, should be explored for possible use as drugs to sensitize chemoresistant GBM. Inhibition of the cadherin binding pathway may also be a novel method of overcoming adaptive mechanisms in GBM.