Search Results (39)

Dysregulated microRNA (miR) expression has emerged as a potential prognostic tool in head and neck squamous cell carcinoma (HNSCC), but the clinical value of miR-34a remains unclear. This systematic review, meta-analysis, and trial sequential analysis (TSA) evaluated the association between tumor tissue miR-34a expression and survival outcomes in HNSCC. Following a protocol registered in PROSPERO (n. CRD420251238772), PubMed/MEDLINE, Scopus, ScienceDirect, CENTRAL, Google Scholar, and grey literature sources were searched for studies reporting overall survival (OS) or disease-free survival (DFS) stratified by miR-34a expression in HNSCC or its subsites. Hazard ratios (HRs) were extracted directly or reconstructed from Kaplan–Meier (KM) curves using the Tierney method, supported by a dedicated Python application (KM2HR). Four retrospective studies, corresponding to six study/site-specific cohorts and 318 patients, met the inclusion criteria. For OS (four cohorts), the fixed-effects model yielded a pooled HR of 2.25 (95% CI 1.48–3.41) for low versus high miR-34a expression, indicating worse survival in the low-expression group. However, the random-effects model attenuated the association (HR 1.32, 95% CI 0.32–5.54), with substantial heterogeneity (I² ≈ 77%). For DFS (two studies), the fixed-effects model suggested poorer outcomes with low miR-34a (HR 2.92, 95% CI 1.24–6.88), whereas the random-effects model reversed the direction of effect with extremely wide confidence intervals (HR 0.19, 95% CI ≈ 0.00–129.34; I² = 91%). TSA for OS (accrued information size 225 patients; estimated power ≈66%) crossed the monitoring boundary but did not reach the a priori information size, supporting only a tentative signal. A bioinformatic exploration of the TCGA HNSCC cohort (n = 522) showed a non-significant trend towards worse OS with low miR-34a (HR 1.24, 95% CI 0.93–1.65) and was excluded from pooling. Overall, low tumor miR-34a expression appears to be associated with poorer OS, but the evidence is limited by retrospective design, small sample size, and marked heterogeneity. miR-34a is a promising biomarker for prognostic stratification in HNSCC, yet larger, prospective, site-specific studies with standardized assays, pre-defined cut-offs, and appropriate adjustment for HPV status and clinical covariates are required before clinical implementation can be recommended. Full article

Background: China and India represent a large proportion of the Asian birth cohort and have produced extensive but heterogeneous evidence on neonatal hearing screening. This scoping review summarizes studies published between 2005 and 2025 on otoacoustic-emission-based neonatal hearing screening programs in these countries, with emphasis on program implementation, screening coverage, the prevalence of congenital and bilateral hearing loss, follow-up, and intervention pathways. Methods: Searches were conducted in PubMed, Scopus, and Google Scholar using predefined keywords. Studies reporting screening protocols, coverage, prevalence, or follow-up outcomes were included. The standard English language filter was used. A total of 19 papers were considered for this review. Results: The data from the two assessed Asian states show two clearly different screening implementation profiles. In China, universal hearing screening has evolved into a large-scale and increasingly standardized system, supported by technical specifications and regional or municipal databases. The reported screening coverage was 85.8% in early rural programs, 93.6% in Shanghai, and 97.9% in Liuzhou. National institutional surveys indicate that UNHS has now been substantially implemented in many regions. Reported hearing loss prevalence estimates generally ranged from 1.66 to 3.43 per 1000 newborns, although follow-up and regional equity remain problematic, especially in rural settings. In India, the evidence is dominated by tertiary-hospital feasibility studies rather than a uniformly implemented national program. Reported hearing loss prevalence estimates varied more widely, from 0.29 to 5.60 per 1000 screened newborns, largely reflecting differences in study design, screening timing, referral completion, and population risk profile. Across both countries, OAE-based two-stage or sequential OAE + AABR protocols reduced referral rates and improved case identification, but loss to follow-up remained a recurrent limitation. Conclusions: China and India provide complementary models of neonatal hearing screening expansion. China demonstrates the effects of system-level scale-up, whereas India highlights the feasibility and constraints of hospital-based implementation in a highly diverse healthcare environment. Future priorities include stronger follow-up systems, harmonized reporting standards, and broader dissemination of outcome data through peer-reviewed publications. Full article

Newly hired workers in construction, industrialized building production, and other built-environment operations often face elevated safety and ergonomic risk while learning manual tasks. At the same time, many onboarding programs still rely on observation, verbal coaching, and checklist-based sign-off, which can be difficult to standardize across supervisors and sites. This study presents the development and field evaluation of a data-driven training system that integrates markerless motion capture, machine-learning-assisted ergonomic risk scoring, and Lean/continuous-improvement (CI) routines to provide structured coaching during onboarding. A single-site, non-randomized quasi-experimental sequential-cohort design compared a traditional onboarding cohort with a subsequent app-supported cohort (n = 20 each). Primary outcomes were time to qualification, training cost, and task accuracy. Secondary site-level indicators were safety compliance and musculoskeletal (MSK) injury outcomes. Compared with the traditional cohort, the app-supported cohort reached qualification sooner (5.85 ± 1.50 vs. 18.60 ± 3.50 calendar months), at lower cost (SR 29,250 ± 7602 vs. SR 93,000 ± 17,348 per employee), and with higher task accuracy (88.60 ± 5.70% vs. 60.65 ± 10.60%). Welch’s t-tests showed statistically significant differences across all primary outcomes (all p < 0.001), although the standardized effect sizes were very large and should be interpreted cautiously given the modest sample and non-randomized design. Safety compliance (+68%) and MSK injuries (−25%) are reported only as descriptive site-level indicators because denominator and exposure data were not available for inferential analysis. The study contributes a practical intervention model linking ergonomic sensing to coaching cues, auditable training logs, A3 problem solving, and standard work refinement. The findings suggest that this integrated approach is promising for built-environment onboarding, but multi-site studies with stronger comparative designs, individual-level reporting, and fuller algorithmic documentation are needed. Full article

Background: The flipped classroom is an innovative student-centered teaching approach frequently applied in nursing education. The success of the approach relies on students coming prepared to class. Faculties play a critical role in facilitating students’ pre-class preparation. Objective: The objective of this study was to elicit nursing students’ preferred designs for pre-class preparation in large-group, flipped-classroom teaching in evidence-based practice, and to use these insights to inform practical, faculty-driven changes to course design and delivery. Methods: An action research study was conducted among bachelor’s students in nursing at a Norwegian university college. Data were collected through questionnaires with closed and open-ended questions, focus group interviews, and class meetings. Descriptive statistics and thematic analysis were applied to analyze data. Data were analyzed sequentially, and findings provided guidance for further actions. Results: The action was carried out and evaluated in two cohorts. The thematic analysis revealed one main theme—students need motivation for pre-class preparation—and three associated sub-themes: (1) Information: Communicate relevance and provide timely reminders, (2) Organization: Learning platform and workload, and (3) Engage learners: Diverse, interactive and aligned learning activities. Conclusions: Faculties can support motivation through clear communication of relevance, a well-organized learning platform, activating pre-class activities, and timely reminders. Successfully accommodating pre-class preparation for large-group teaching also appears to require coordinated faculty engagement and a shared commitment to student-centered approaches. Further evaluation is needed to determine which specific configurations work best in different contexts. Full article

Background: The keratorefractive lenticule extraction (KLEx) procedure has gained popularity because of its safety and effectiveness; however, its predictability remains variable, as it may be over- or under-corrected. This study aimed to evaluate visual and refractive outcomes following the utilisation of VISULYZE-generated nomograms (Carl Zeiss Meditec AG, Jena, Germany) and OcuLign cyclotorsion alignment tools (Carl Zeiss Meditec AG, Jena, Germany). Methods: This retrospective consecutive cohort study included patients undergoing KLEx, grouped into four sequential treatment phases: PRE-NOMOGRAM, NOMOGRAM, OCULIGN & NOMOGRAM, and OCULIGN. Results: A total of 688 patients (1264 eyes) were included. The OCULIGN group showed numerically higher efficacy, with 83.0% achieving post-operative (PO) uncorrected distance visual acuity (UDVA) 20/20 or better, with no loss of corrected distance visual acuity (CDVA) lines, and 67.0% gaining one line. Predictability and accuracy were high across groups, with the OCULIGN group demonstrating a strong correlation between attempted and achieved spherical equivalent (R² = 0.9908), and 95.5% of eyes within ±0.50 D. Early PO outcomes suggested minimal refractive shift at one month. The NOMOGRAM group demonstrated numerically improved astigmatism correction (100.0% within ≤0.50 D), while the OCULIGN & NOMOGRAM group showed high precision in axis alignment. However, baseline imbalances were present, and between-group differences were relatively small. Conclusions: The use of OcuLign cyclotorsion alignment and VISULYZE-generated nomograms was associated with favourable visual and refractive outcomes following KLEx. However, given the retrospective, sequential design, imbalanced baseline, and limited follow-up duration, these findings should be interpreted cautiously. Further prospective, randomised studies with longer follow-up are required to confirm these observations. Full article

Introduction: Pancreatic cancer is one of the most lethal malignancies worldwide, and its incidence continues to rise. Periodontitis, a highly prevalent chronic inflammatory disease, has been linked to several systemic conditions, including a potential increase in pancreatic cancer risk. However, the available epidemiological evidence remains heterogeneous and fragmented. Objective: To evaluate whether periodontitis is associated with an increased risk of pancreatic cancer through a systematic review and meta-analysis of observational studies. Materials and Methods: A comprehensive search was conducted in PubMed, EMBASE, Web of Science, Scopus, the Cochrane Library, ClinicalTrials.gov, and the WHO regional databases, following PRISMA guidelines. Cohort, case–control, and cross-sectional studies assessing periodontitis through clinical parameters, radiographic measures, or tooth loss—and reporting pancreatic cancer risk (HR, RR, or OR)—were included. Risk of bias was assessed using the Newcastle–Ottawa Scale. Random-effects meta-analyses, meta-regressions, leave-one-out sensitivity analyses, influence diagnostics, publication bias assessment, and Trial Sequential Analysis (TSA) were performed. Results: Eight observational studies (primarily cohort designs) (n = 476,245 participants) met the inclusion criteria. Periodontitis was associated with an increased risk of pancreatic cancer (pooled HR = 1.56; 95% CI: 1.28–1.89), with moderate heterogeneity (I² = 55.5%). Sensitivity and influence analyses confirmed the robustness of the estimate. TSA showed a consistent trend, although the cumulative evidence remains insufficient for a definitive conclusion. Conclusions: Observational evidence suggests a modest statistical association between periodontitis and pancreatic cancer risk. However, the absolute risk increase is very small, and Trial Sequential Analysis indicates that cumulative evidence remains insufficient to establish causality or to support preventive or clinical recommendations. Further large-scale prospective studies with standardized periodontal assessments are required. Full article

Background: Contemporary coronary artery bypass grafting (CABG) is often performed in patients with diffuse atherosclerosis, severe calcification, prior percutaneous coronary intervention (PCI), and fragile myocardium, creating intraoperative scenarios that can compromise target selection, anastomotic quality, and completeness of revascularization. We synthesize operative strategies and outcomes across five predefined “complex CABG” scenarios. Methods: A focused literature review was performed targeting intraoperative CABG challenges in adult patients. Two reviewers independently screened titles/abstracts and selected studies describing operative details, technical considerations, or outcomes relevant to (1) intramyocardial/embedded coronaries, (2) severely calcified or diffuse disease requiring reconstruction, (3) small-caliber targets/flow-limited grafting, (4) iatrogenic right ventricular (RV) injury, and (5) failed PCI/stent-related surgical management. Disagreements were resolved through discussion and consensus. Results: Thirty core publications were synthesized across five complex intraoperative CABG scenarios (intramural/embedded coronaries n = 7; calcified/diffuse disease n = 7; small-caliber/flow-limited targets n = 7; iatrogenic RV injury n = 5; failed PCI/stent-related management n = 5). Intramural/embedded targets: reported intramyocardial LAD prevalence ranged from 2.2–13%, and studies emphasized structured localization strategies with a small but real risk of ventricular injury depending on technique. Severely calcified/diffuse disease: reconstructive approaches (endarterectomy, patch angioplasty, long-segment LAD reconstruction) were used to create graftable beds when standard anastomosis was not feasible, with series reporting acceptable early mortality and generally high early-to-midterm patency when paired with planned antithrombotic and imaging follow-up strategies. Small-caliber targets: vessel size alone did not preclude durable grafting when flow was optimized, with evidence supporting flow-augmenting designs (e.g., sequential grafting) and intraoperative flow verification to reduce low-flow failure in limited runoff beds. Iatrogenic RV injury: bailout techniques prioritized rapid hemostasis while preserving LAD/graft patency using buttressed closure concepts designed for constrained exposure and ongoing bleeding risk. Failed PCI/stent-related pathology: long stented segments shifted operative planning from distal target selection to target reconstruction (stentectomy/endarterectomy with long-segment LAD reconstruction), with angiographic follow-up cohorts demonstrating feasible revascularization but variable patency by territory and lesion extent. Conclusions: Complex CABG is best approached as structured, anatomy-driven problem-solving: deliberate target localization, creation of a graftable bed when needed, flow-augmenting graft design, and predefined bailout options. Standardized comparative studies are needed to define optimal strategies across these common clinically important scenarios. Full article

Background/Objectives: The Korean Genome and Epidemiology Study (KoGES) is a large population-based cohort designed to investigate chronic disease risk using long-term dietary and health data. However, comprehensive amino acid information for estimating long-term intake from food frequency questionnaire (FFQ) data remains limited. This study aimed to develop and validate a standardized, rule-based algorithm for food matching and substitution and to construct an amino acid database applicable to the KoGES FFQ. Methods: The algorithm sequentially evaluated food name concordance, preparation forms, substitutability of similar foods, and differences in energy, macronutrients, and moisture (±20%). Amino acid composition data were derived from domestic and international food composition tables and published literature, with protein–nitrogen conversion factors applied by food group. Results: Amino acid information was established for 475 FFQ food items covering 19 amino acids. Of the database values, 31.0% were analytical, 64.2% were calculated, and 4.8% were substituted. Overall database coverage across all amino acid–food item combinations was 98.8%. The constructed database was applied to dietary data from the second follow-up (Phase 3) of the KoGES Ansan and Ansung community-based cohorts, showing that total amino acid intake accounted for 86.7% of total protein intake, reflecting the inclusion of non-protein nitrogen in conventional protein estimates. Based on the Estimated Average Requirement (EAR) criteria, the proportions of participants with intakes below the EAR for protein and essential amino acids varied across age and sex groups. Overall and in both men and women, lysine showed the highest proportion of participants below the EAR, whereas tryptophan showed the lowest proportion. Conclusions: This standardized algorithm provides a reproducible framework for constructing amino acid databases and can be applied to large-scale cohort and dietary survey data. Full article

Background/Objectives: Vaccination against respiratory viruses—such as respiratory syncytial virus (RSV), pneumococcal disease, influenza, and COVID-19—may reduce the risk of adverse outcomes in older adults with cardiovascular disease. This study conducted a scoping review of the effects of respiratory vaccines in older adults with cardiovascular disease. Methods: We included studies evaluating adults aged ≥ 60 years with cardiovascular disease who received different types of respiratory vaccines. Eligible designs comprised clinical trials, observational cohort studies, and other relevant studies. Editorials, commentaries, and non-original publications were excluded. A comprehensive and targeted literature search was conducted in PubMed, Scopus, EMBASE, and Web of Science from database inception through January 2026. Results: A total of 25 studies were included, encompassing 1,782,787 adults aged ≥ 60 years with cardiovascular disease who received various respiratory vaccines. RSV vaccines were associated with a lower incidence of cardiorespiratory hospitalization and stroke among vaccinated individuals. Pneumococcal vaccines showed that sequential dual vaccination strategies were associated with a lower risk of cardiovascular events. Influenza vaccination was associated with improved cardiovascular outcomes, lower mortality, and reduced adverse events. COVID-19 vaccines were associated with reductions in mortality and hospitalizations. These benefits are particularly relevant in an older population with a high burden of comorbidities; therefore, complete vaccination schedules, including booster doses, should be considered a central strategy for prevention and comprehensive management in this high-risk group. Conclusions: Vaccination against respiratory viruses in older adults with cardiovascular disease demonstrates an overall favorable/acceptable profile of efficacy and safety, with reductions in mortality, hospitalizations, and cardiovascular events, without a significant increase in serious adverse events. Full article

Background: Vandetanib and cabozantinib are the approved first-line antiangiogenic multikinase inhibitors (aaMKIs) for metastatic medullary thyroid carcinoma (MTC); however, real-world data on their comparative efficacy, optimal sequencing, and outcomes beyond the first-line setting remain limited. We report multicenter real-world outcomes from a large Turkish cohort. Methods: In this retrospective multicenter cohort study, we analyzed data from 24 oncology referral centers across Türkiye. Patients with histologically confirmed metastatic MTC who received systemic therapy between December 2011 and December 2024 were included. The primary endpoint was progression-free survival (PFS), assessed separately for first-line (PFS1) and second-line (PFS2) therapy. Overall survival (OS) and prognostic factors were evaluated using Kaplan–Meier and Cox proportional hazards analyses. Results: A total of 115 patients were included (median age 47.4 years; 63.5% male). In the first-line setting, vandetanib (47.8%) and cabozantinib (30.4%) were the most frequently used agents. Median PFS1 was 40.8 months with vandetanib and was not reached with cabozantinib; both were significantly superior to chemotherapy (median PFS1 4.9 months; log-rank p < 0.001). In the second-line setting, median PFS2 was not reached with cabozantinib and was 32.5 months with vandetanib. Sequential use of cabozantinib and vandetanib across the first two lines was associated with a median time to second progression of 114 months, compared with 39 months in patients receiving any other TKI combination (p = 0.003). Second-line use of cabozantinib or vandetanib was independently associated with improved OS (HR 0.40, 95% CI 0.16–0.98; p = 0.046). On multivariate analysis, younger age (HR 0.16, 95% CI 0.03–0.72; p = 0.017) and bone metastasis (HR 0.29, 95% CI 0.11–0.73; p = 0.009) were independent prognostic factors for OS. Conclusions: In this real-world cohort of patients with metastatic MTC, cabozantinib and vandetanib demonstrated durable efficacy across treatment lines, substantially outperforming alternative TKIs and chemotherapy. Sequential use of both approved aaMKIs was associated with prolonged disease control. These findings suggest a potential association between access to both agents and improved outcomes. They are consistent with their central role in treatment sequencing, particularly in settings with limited access to selective RET inhibitors. Given the retrospective design and small subgroup sizes, these results should be interpreted as exploratory and hypothesis-generating. Full article

Background: Adolescent migraine is highly prevalent and associated with substantial functional and psychosocial burden. Conventional oral preventives are widely used off-label with limited pediatric efficacy and frequent tolerability problems. Real-world data on calcitonin gene-related peptide (CGRP) monoclonal antibodies in adolescents are scarce. Methods: We conducted an exploratory, retrospective cohort analysis of depersonalized routine-care data from adolescents with migraine in the German Pain e-Registry. Patients were eligible if they had at least one 6-month episode with high-evidence conventional oral preventives (HECP) and one 6-month episode with a CGRP monoclonal antibody (CGRP-mAb), each with baseline and follow-up documentation, enabling intra-individual descriptive comparisons. The primary endpoint was a pragmatic composite of 6-month treatment persistence and ≥50% reduction in monthly migraine days (MMD). Secondary outcomes included MMD, MMD with acute medication (MMDAM), migraine-related sick-leave days (MMSLD), disability (MIDAS), and patient-reported psychosocial outcomes. Results: A total of 422 adolescents contributed 1448 HECP and 422 CGRP-mAb episodes. Premature discontinuation occurred in 68.8% (HECP) and 11.9% (CGRP-mAb) of episodes; corresponding 6-month persistence was 30.6% and 88.2%, respectively. Mean MMD decreased from 11.7 to 9.4 during HECP episodes and from 11.6 to 4.4 during CGRP-mAb episodes. A ≥50% MMD reduction occurred in 25.4% (HECP) and 70.9% (CGRP-mAb) of episodes; the composite endpoint was met in 23.7% and 69.9%, respectively. CGRP-mAb episodes were associated with numerically larger improvements across secondary outcomes. Conclusions: In this high-burden adolescent cohort, CGRP-mAb treatment episodes were associated with higher persistence and broader improvements than prior conventional preventive episodes. Given the retrospective, non-randomized, sequential design, these findings are hypothesis-generating and do not constitute evidence of comparative effectiveness. Controlled pediatric trials and long-term safety studies are warranted. Full article

Background: Transvaginal radiofrequency ablation (TRFA) is a minimally invasive, uterus-preserving technique for symptomatic uterine fibroids. This study evaluates its two-year clinical and volumetric outcomes, safety profile, patient satisfaction, and reintervention rates. Methods: In this single-center, retrospective, single-arm observational cohort study, 121 premenopausal women underwent outpatient TRFA under general anesthesia between 2018 and 2023. Follow-up visits at 1, 6, 12, and 24 months assessed fibroid volume reduction, symptom improvement using the Uterine Fibroid Symptom and Quality of Life Questionnaire (UFS-QoL), vascularity, satisfaction, complications, and the need for reintervention. A total of 169 fibroids were treated. Results: TRFA resulted in progressive fibroid shrinkage, with a mean volume reduction of 57.97% at 6 months and 60.75% at 24 months, accompanied by sustained improvement in UFS-QoL scores (from 30.19 at baseline to 14.97 at 24 months). Patient satisfaction was high (96.61%). Complications were infrequent and predominantly mild, and recovery was rapid, with short postoperative analgesia (mean 2.87 days) and limited sick leave (mean 3.34 days). The two-year reintervention rate was 24.79%, with a substantial proportion corresponding hysteroscopic procedures planned a priori as part of a sequential therapeutic strategy. Among 22 pregnancies recorded after TRFA, 81.82% resulted in term deliveries with favorable neonatal outcomes although fertility was not a predefined study endpoint. Conclusions: TRFA appears to be a safe, effective, and well-tolerated minimally invasive treatment for symptomatic uterine fibroids, offering durable symptom relief and significant volume reduction and rapid recovery, and encouraging reproductive outcomes. Within the limitations of its single-arm observational design, these results support TRFA as a valuable uterus-preserving therapeutic option. Full article

Background: Previous attempts to classify lymphoma subtypes based on metabolic features extracted from ¹⁸F-FDG PET imaging have been hindered by inconsistencies in imaging protocols, scanner types, and inter-institutional variability. To overcome these limitations, we propose a multimodal deep learning framework that integrates harmonized PET imaging features with structured clinical information. The proposed framework is designed to perform hierarchical classification of clinically meaningful lymphoma subtypes through two sequential binary classification tasks. Methods: We collected multi-center data comprising ¹⁸F-FDG PET images and structured clinical variables of patients with lymphoma. To mitigate domain shifts caused by different scanner manufacturers, we integrated a Scanner-Conditioned Normalization (SCN) module, which adaptively harmonizes feature distributions using manufacturer-specific parameters. Performance was validated using internal and external cohorts, with the statistical significance of performance gains assessed via DeLong’s test and bootstrap-based CI analysis. Results: The proposed model achieved an area under the curve (AUC) of 0.89 (internal) and 0.84 (external) for Hodgkin lymphoma versus non-Hodgkin lymphoma classification and 0.84 (internal) and 0.76 (external) for diffuse large B-cell lymphoma versus follicular lymphoma classification (p > 0.05). These results were obtained using a multimodal model that integrated anterior and lateral maximum intensity projection (MIP) images with clinical data. Conclusions: This study demonstrates the potential of a deep learning-based approach for lymphoma subtype classification using non-invasive ¹⁸F-FDG PET imaging combined with clinical data. While further validation in larger, more diverse cohorts is necessary to address the challenges of rare subtypes and biological heterogeneity, LymphoMAP serves as a meaningful step toward developing assistive tools for early clinical decision-making. These findings underscore the feasibility of using automated pipelines to support, rather than replace, conventional diagnostic workflows in personalized lymphoma management. Full article

Background/Objectives: This study reports on findings from the first preconception screening performed in Russia and provides a comprehensive discussion of the significant results and challenges faced during the implementation of the project. Methods: Using a targeted sequencing panel of 33 genes (associated with 29 autosomal recessive and 4 X-linked diseases), we analyzed 165 couples considering pregnancy. The screening design also included analysis of the frequent pathogenic variants in the SMN1, DMD, CFTR, and CYP21A2 genes that may not be detected through the next-generation sequencing approach. The sequential screening protocol, wherein the female partner was tested first, was used. Results: The results revealed that 35.8% of women (n = 59) were carriers of at least one pathogenic or likely pathogenic (P/LP) variant, with 7.9% of women (n = 13) carrying variants in two or more genes. Notably, the analysis identified 5 deletions of exon 7 in the SMN1 gene, 1 deletion of the CYP21A2 gene, and 1 large duplication in the DMD gene in female participants. The most frequently identified pathogenic variants occurred in the CYP21A2, GJB2, SERPINA1, and ATP7B genes. The screening identified six couples (3.6% of the cohort) at high risk of having a child with an autosomal recessive or X-linked genetic disorder. Conclusions: This pilot study confirms the high clinical utility of the gene panel, effectively evaluating reproductive risk in couples without a known family history of monogenic diseases. The findings indicate that the observed frequencies of identified gene variants differ from those theoretically expected, with a notable percentage of identified couples being at relatively high risk. Furthermore, these results highlight the indispensable role of comprehensive genetic counseling both before and after testing to ensure an appropriate preconception testing algorithm and informed reproductive decision-making. Full article

Background: Periodontitis and oral dysbiosis have been linked to systemic inflammation and carcinogenesis. Among oral pathogens, Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) are biologically plausible contributors to colorectal cancer (CRC) via inflammatory and immunomodulatory pathways. However, the magnitude and consistency of these associations remain uncertain. Objective: To evaluate whether periodontitis and key oral pathogens are associated with CRC risk and prognosis through a systematic review, meta-analysis, and trial sequential analysis (TSA). Methods: We searched PubMed, Scopus, and Web of Science from inception to December 2024 following PRISMA 2020. Eligible observational studies assessed periodontitis exposure or detection of oral bacteria in relation to CRC incidence or survival. Effect estimates (RRs/HRs) were log-transformed and pooled using random-effects models; heterogeneity was quantified with I². TSA was conducted to appraise information size and the stability of the primary association. Risk of bias was evaluated with ROBINS-I/QUIPS as appropriate. PROSPERO: CRD420251168522. Results: Five studies evaluating periodontitis/oral-pathogen exposure and CRC incidence yielded a 70% higher risk (HR = 1.70; 95% CI: 1.33–2.19; I² = 0%). Detection of Fn was associated with approximately threefold higher risk of CRC (RR = 3.20; 95% CI: 1.76–5.82; p < 0.001). Pg presence was linked to worse overall survival (HR ≈ 2.4; p < 0.01). TSA suggested that the accrued evidence for the primary incidence association is likely sufficient to reduce random errors; nevertheless, interpretability is constrained by the small number of observational studies and between-study differences in exposure and outcome ascertainment. Conclusions: Current evidence indicates that periodontitis and oral pathogens—particularly Fn and Pg—are significantly associated with CRC development and progression. These findings support the clinical relevance of the oral–gut axis and underscore oral health as a potentially modifiable factor in cancer prevention. Further large, well-designed prospective cohorts and mechanistic studies are warranted to strengthen causal inference. Full article