Gender disparities in research trial leadership have been reported in nearly every medical specialty. The true extent of women's involvement as principal investigators (PIs) in oral and maxillofacial surgery (OMS) research trials remains unknown. The current study aims to address this knowledge gap through analyzing relevant trials registered on ClinicalTrials.gov in the 21st century. A validated search strategy, comprising procedure names and field-specific terms, was utilized to identify OMS research trials. The analysis was limited to trials where at least one PI was an oral and maxillofacial surgeon or an OMS department-affiliated researcher. Trial characteristics, including study type, phase, funding status, and investigator details were extracted from records. PI gender was determined using Genderize.io. Overall, men occupied 73.7% of PI positions for OMS research trials, and women 26.3%. Linear regression analysis revealed a significant yearly increase in proportion of women PIs over time. Geographically, women PI representation was highest in African (predominantly Egypt) and Asian institutions, and lowest in European and North American institutions. Relative to other phases, women PIs were significantly more likely to lead Phase 3 trials and less likely to lead Phase 2 trials compared to men PIs. While government funding patterns were similar between genders, women PIs were significantly less likely to lead industry-funded trials. Despite recent improvements, women remain underrepresented in OMS research trial leadership, especially in North American institutions. Targeted interventions and cultural shift are essential to fostering gender-based parity in this domain.
Severe asthma affects a minority of patients with asthma; however, it substantially impacts morbidity, health-care use, and systemic corticosteroid-related harm. Despite the increasing use of biological treatments, achievement of severe asthma remission remains elusive. Notably, real-world data on the disease burden and remission potential of severe asthma in Europe remain limited. We aimed to close this knowledge gap, offering insights with global relevance. Using data from 13 455 adults with severe asthma enrolled in the European Severe Heterogeneous Asthma Registry, Patient-centred Clinical Research Collaboration (SHARP CRC), this cross-sectional observational study evaluated the burden of severe asthma and remission-related clinical domains (exacerbations, asthma control, airflow limitation, and maintenance oral corticosteroid use) across Europe and examined their relationship with disease duration, biological therapy, and type 2 biomarkers (blood eosinophils, fractional exhaled nitric oxide [FeNO], and total IgE). Patients with severe asthma had been enrolled in national registries according to local principles and guidelines and in accordance with the European Respiratory Society/American Thoracic Society guidelines; 3% (430 of 13 885) of patients were excluded due to no consent for the international study and/or missing medication data. Patients were predominantly female (59%; 7999 of 13 453), with adult-onset asthma (82%; 8751 of 10 711), and a median disease duration of 23 years (95% CI 20-26 years). 59% (4148 of 7006) of patients had FEV1/FVC of 0·7 or less, 62% (4680 of 7568) had FEV1 lower than 80% predicted, and 89% (3519 of 3968) had at least one active disease domain. Despite 79% (10 632 of 13 453) receiving biological therapy, more than 66% (2621 of 3968) still had at least two active domains. Elevation of type 2 biomarkers persisted (89% [2806 of 3153] with at least one elevated biomarker) despite widespread biological and maintenance oral corticosteroid treatment. A subset of biologic-naive patients (35%; 1069 of 3018) exhibited a rapid accumulation of disease burden within less than 10 years, suggesting a potentially accelerated progression trajectory. This pan-European analysis of severe asthma revealed significant clinical heterogeneity and a substantial disease burden despite advanced therapies, highlighting the enduring nature of type 2 inflammation, the potential inadequacy of current remission strategies with available therapeutic approaches, and the necessity for early identification of high-risk patients. SHARP Clinical Research Collaboration and consortium partners: European Respiratory Society, GlaxoSmithKline Research and Development, Chiesi Farmaceutici Società per Azioni, Novartis Pharma Aktiengesellschaft, Sanofi-Genzyme Corporation, and Teva Branded Pharmaceutical Products R&D.
The significant environmental impact related to modern dental practices highlights the need for increased awareness and attitude shifts among future European dentists. Therefore, this study aimed to assess dental students' perceptions and knowledge levels regarding sustainability in oral healthcare across Europe. The study was conducted among 175 students from 14 dental schools in 11 European countries, who completed an online questionnaire. Most respondents were female (71%) vs. male (27%), with a mean age of 21.1 ± 2.9 years (18-33). 56% of the respondents correctly identified all three dental sustainability definitions, with no gender differences. Dental activities perceived as having the highest environmental impact were patient care (single-use cups and materials) (51%), dental equipment (18%), and dental materials (14%), with no significant gender differences. Students' top strategies to reduce environmental impact of dentistry were reducing plastic disposables (77%), using technologies like 3D printing/CAD-CAM (56%), and digital data management (55%). Dental procedures considered to have the highest carbon footprint were amalgam/composite fillings (44%), radiographs (35%), and acrylic dentures (32%). Additionally, 42% of the students expressed interest in an elective course on sustainability in dental practice. By exploring future practitioners' understanding of sustainability, this research could offer perspectives that may be useful in shaping curriculum considerations, fostering environmentally responsible clinical training, and supporting policy dialogue at institutional and European levels.
The oral microbiome has been shown to be associated with respiratory health, primarily in adult case studies or among children. This relationship has been scarcely investigated in adult population-based cohorts. To investigate the association between oral microbiome and respiratory health, more specifically asthma, chronic rhinosinusitis (CRS), lung function and fractional exhaled nitric oxide (FeNO) in a population-based cross-continental multicentre study among adults. Subgingival samples from 355 adult European Community Respiratory Health Survey participants from Norway, Australia and Estonia underwent metagenomic sequencing. Respiratory disease was defined from questionnaires and sensitisation from specific immunoglobulin E (IgE)/skin prick tests. Spirometry and FeNO were measured. The associations between alpha diversity and disease status were evaluated in cross-sectional analyses using logistic regression adjusting for sex, smoking and study centre. Differential abundance analyses were performed using analysis of compositions of microbiomes with bias correction. Alpha diversity differed by study centre and sensitisation status and was associated with non-allergic CRS (richness: 1.12, 95% CI 1.03 to 1.22). A similar though not statistically significant pattern was seen for forced vital capacity (FVC) below the lower limit of normal (LLN). Lachnospiraceae and Xanthomonas were more abundant in the oral microbiome of non-asthmatics and individuals without CRS, respectively, as compared with asthmatics and CRS patients. Several functional genes (1477-3391) and genera (54-98) were only present in the non-case groups, whereas individuals with affected respiratory health had 0-74 unique functional genes, but no unique genera present only in their respective groups. Increased alpha diversity was associated with non-allergic CRS and a similar trend was seen for FVC below LLN. Bacterial composition and functional profiles of the oral microbiome differed by respiratory health status. This study is novel in exploring functional gene profiling in relation to asthma and FeNO.
Mild autonomous cortisol secretion (MACS), the most common hormonal abnormality in adrenal incidentalomas, is associated with increased cardiometabolic risk. MACS is defined by cortisol concentrations higher than 50 nmol/L after a 1-mg overnight dexamethasone suppression test (1-mg DST). The prognostic value of a single test remains uncertain. We examined longitudinal changes in 1-mg DST results, cumulative cortisol exposure, and their associations with cardiometabolic outcomes and mortality. In this retrospective cohort study conducted in 25 adrenal centres that are part of the European Network for the Study of Adrenal Tumours consortium across 14 countries with adults (aged ≥18 years) with benign adrenal incidentalomas diagnosed from Jan 1, 2000, to Dec 1, 2020, two or more 1-mg DSTs, and follow-up of at least 36 months, we used multivariable Cox models to assess associations between longitudinal 1-mg DST results and all-cause mortality and cardiovascular and thrombotic events. Patients with Cushing's syndrome, primary aldosteronism, phaeochromocytoma, or androgen-secreting tumour at baseline; active malignancy within 36 months of incidentaloma diagnosis; or suspicion of unreliable 1-mg DST results were excluded, along with patients taking oral glucocorticoids, strong CYP3A4 modulators, adrenal enzyme inhibitors, oral oestrogen, or selective oestrogen receptor modulators. Cumulative cortisol exposure was estimated from serial 1-mg DSTs. Restricted mean survival time (RMST) quantified differences in event-free time. Data were collected from the electronic health records of all eligible patients at each participating centre. Among 2525 patients (median follow-up 80 months [IQR 49-122]), 563 (22·3%) had changes in 1-mg DST results leading to a change in diagnosis, most within 3 years of their baseline 1-mg DST. Patients with persistently abnormal 1-mg DST results (ie, MACS-to-MACS patients; n=839) were older and had a greater cardiometabolic burden than those with persistently normal results (ie, non-functioning adrenal tumours [NFAT]-to-NFAT patients; n=1103). MACS-to-MACS patients had a higher rate of worsening hypertension (adjusted hazard ratio 1·34 [95% CI 1·03-1·73]) and a shorter event-free time for worsening hypertension (10-year RMST 60·4 months [56·8-75·5] vs 86·1 months [79·1-93·4]) than NFAT-to-NFAT patients. In crude analyses, patients with higher baseline post-1-mg DST cortisol, patients with greater cumulative cortisol exposure, and MACS-to-MACS patients had shorter survival and event-free time; however, these associations were not independent of age and baseline cardiometabolic risk factors after multivariable adjustment. Longitudinal 1-mg DST changes are common. MACS-to-MACS patients had worsening hypertension, but rates of mortality and cardiovascular or thrombotic events were not significantly associated with 1-mg DST trajectories after adjustment for age and cardiovascular risk factors. These findings identify patients with persistently abnormal 1-mg DST results as a group with high cardiometabolic risk that warrants closer attention to modifiable risk factors. Prospective studies are needed to establish the clinical significance of repeated 1-mg DSTs for risk stratification. National Institute for Health and Care Research Birmingham Biomedical Research Centre, Horizon Europe 2022, and Deutsche Forschungsgemeinschaft.
Background and Objectives: This study aims to evaluate the recent literature on the oral-gut connection in the context of periodontal disease, emphasizing the significance of systemic risk associated with chronic inflammation. This review explores whether chronic inflammation resulting from periodontal disease can induce systemic conditions through alterations in the gut microbiome and whether periodontal treatment may contribute to overall health improvement. Materials and Methods: A systematic database search was performed using pre-established search strategies. Searches were conducted in three databases between 1 and 20 October 2025. A total of 578 articles were screened for eligibility based on inclusion and exclusion criteria. Two authors agreed on the selection process used. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale and the Risk of Bias 2 Tool. Results: Eleven studies were considered eligible for inclusion in the review. The gut microbiome is similar to the oral microbiome in patients with periodontitis. Gut microbial shifts may drive systemic inflammation and metabolic dysfunction. Tooth loss and gum disease are linked to alterations in the gut bacteria, potentially compromising the intestinal barrier permeability. In contrast, the presence of natural teeth may prevent oral-gut bacterial transmission. Changes in the gut microbiota are correlated with improvements in periodontal status after non-surgical periodontal therapy. Conclusions: The evidence presented in this review supports an association between periodontitis, oral-gut microbial alterations, and systemic inflammatory conditions. However, most available studies are observational, limiting causal inference. Targeted modulation of the gut microbiome may represent a promising area for future research, but its clinical applicability remains inconclusive.
Background and Objectives: Child dental neglect is a clinically significant form of maltreatment that frequently reflects broader challenges related to caregiving within the family environment. Although oral manifestations have been described in prior research, the socio-behavioral profile of responsible caregivers remains insufficiently characterized, particularly in Central and Eastern European contexts. This study aimed to identify caregiver-level socio-behavioral characteristics associated with child dental neglect and to examine their relationships with clinical outcomes. Materials and Methods: A retrospective cross-sectional analytical study was conducted on 333 children (aged 4-17 years) diagnosed with dental neglect, presenting at a municipal hospital and a private dental practice in Oradea, Romania (2020-2024). Caregiver-level variables included age, educational attainment, socioeconomic status, health condition, substance use, and family structure. Associations were analyzed using Fisher's Exact Test, Pearson Chi-Square, and Mann-Whitney U test, with Bonferroni correction applied where appropriate. Results: Most caregivers were young adults (93.1%), with low educational attainment (40.2% had no formal schooling) and high rates of alcohol use (47.1%). Low family income was present in 89.2% of cases and was significantly associated with non-adherence to the dental treatment plan (p  =  0.039). Caregivers without formal education were associated with neglect in rural areas (43.4% vs. 26.2%; p  <  0.001). Children of drug-using caregivers were significantly older at presentation (median: 12 vs. 8 years; p  =  0.014), and caregiver drug use was more prevalent in urban settings (18.0% vs. 1.8%; p  <  0.001). Over half of the children (52.9%) came from disrupted family environments. Conclusions: Dental neglect was consistently associated with young, poorly educated, and financially disadvantaged caregivers exhibiting high rates of substance use and unstable family structures. These factors may interact in complex ways, highlighting the multifactorial nature of dental neglect. Dental professionals are well positioned for early identification and have a professional and ethical responsibility to integrate child safeguarding into routine clinical practice.
Direct oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). However, real-world prescribing patterns and dosing appropriateness in low- and middle-income countries remain poorly characterized. This study evaluated patterns of oral anticoagulant use and identified clinical determinants of suboptimal prescribing in a tertiary cardiovascular center in Vietnam. We conducted a retrospective observational study of 209 patients with NVAF who received oral anticoagulation at a tertiary cardiovascular center between 2023 and 2024. Data were extracted from electronic medical records, including demographics, comorbidities, renal function, bleeding history, and prescribed anticoagulants. Multivariable logistic regression was used to identify factors associated with anticoagulant selection, defined as DOAC versus VKA use. DOAC dosing appropriateness was assessed according to the 2021 European Heart Rhythm Association Practical Guide, and predictors of potentially inappropriate dose reduction were evaluated. DOACs were prescribed in 77.0% of patients, most commonly rivaroxaban, which accounted for 55.3% of all anticoagulant prescriptions. VKAs were prescribed in 23.0% of patients. Among VKA users, 85.4% had INR values outside the therapeutic range at admission, largely due to subtherapeutic international normalized ratio values. Reduced DOAC doses were prescribed in 88 of 161 DOAC users (54.7%). Among 85 assessable reduced-dose DOAC users, 42 (49.4%) were classified as having potentially inappropriate dose reduction. In the parsimonious multivariable model, age ≥ 75 years was associated with higher odds of DOAC use (odds ratio [OR] 5.08; 95% confidence interval [CI] 1.95-13.23; p = 0.001), whereas female sex (OR 0.43; 95% CI 0.21-0.91; p = 0.027), heart failure (OR 0.23; 95% CI 0.09-0.59; p = 0.002), and prior bleeding (OR 0.20; 95% CI 0.05-0.87; p = 0.031) were associated with lower odds of DOAC use. In this single-center retrospective study from Vietnam, oral anticoagulant prescribing in patients with NVAF showed several areas for optimization, including frequent INR values outside the therapeutic range at admission among VKA users and frequent potentially inappropriate DOAC dose reduction. These findings support the need for improved dose optimization, and monitoring strategies, but should be interpreted cautiously give the observational design and inpatients data source.
Mucopolysaccharidosis type I (MPS-I) is a rare, multisystemic lysosomal storage disease (LSD) caused by mutations in the IDUA gene, which encodes the enzyme alpha-L-iduronidase. Current treatments include hematopoietic stem cell transplantation and enzyme replacement therapy (ERT), administered via weekly intravenous infusions. ERT is of limited efficacy owing to its inability to reach critical tissues such as the brain and bone. To address these limitations, this study explores a novel method to improve drug delivery to target organs and simplify administration: oral administration of enzyme encapsulated within nanostructured lipid carriers (NLC). Encapsulation of ERT within NLC enabled effective oral administration. In vitro analysis showed that our NLC formulation was as effective as intravenous ERT in correcting enzyme activity and reducing glycosaminoglycan (GAG) accumulation in fibroblasts from MPS-I patients, when administered periodically. Permeability studies confirmed passage across the intestinal barrier. Proteomic analyses demonstrated normalization of protein expression in energetic pathways related to hexose metabolism, and significant improvements in protein dysregulation in the cytoskeleton, cellular trafficking, lysosomal function, GAG biosynthesis and degradation, and the extracellular matrix. Furthermore, in vivo studies in MPS-I knockout (KO) mice demonstrated biodistribution of NLC-encapsulated enzymes to all tissues affected by the disease, including passage across the blood-brain barrier and access to poorly vascularized bone. These findings suggest that oral administration of ERT via NLC encapsulation represents a significant advancement in MPS-I treatment, enabling drug delivery to previously inaccessible areas. This study opens important avenues of research for future therapeutic strategies targeting LSDs.
The inaugural European Ovary Workshop (EOW 2025), that was held on 17-20 February 2025, in Lagos, Portugal, brought together 165 scientists, clinicians, and early career researchers from 28 countries to advance ovarian biology from fundamental mechanisms to clinical translation. The program featured 12 scientific sessions, 17 keynote lectures, 15 selected short talks, 89 flash talks, and >90 posters spanning meiosis, folliculogenesis, ovarian reserve, aging, microenvironment, bioengineering, fertility preservation, environmental toxicology, wildlife conservation, patient-public involvement in science, and ethics. A comprehensive networking program combined formal and informal activities to stimulate scientific exchange and interaction across disciplines and career stages. Post-workshop feedback (n = 86) reflected high satisfaction with scientific content (rated 4.6/5), speaker quality (4.7/5), and networking (4.4/5), while identifying opportunities to expand clinical topics, diversify model organisms, and improve poster logistics. EOW 2025 established a unique community and a biennial platform to accelerate discovery and translation in ovarian research.
The Tau Global Conference 2025, hosted by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation, convened international experts from academia, industry, government, and philanthropy to explore advances and challenges in tauopathy research. The meeting highlighted progress across tau biology, including emerging models of tau regulation, degradation, and propagation; advances in biomarker development for the diagnosis and staging of tauopathies; and evolving therapeutic strategies targeting diverse aspects of tau pathophysiology. Discussions also emphasized the importance of cross-sector collaboration, and global initiatives to address disparities in tau research. This report synthesizes key insights from the conference and underscores the critical role of interdisciplinary, biomarker-driven, and globally inclusive approaches in accelerating the translation of tau research into effective clinical applications.
Climate-induced stressors are associated with population-level mental well-being, yet reproducible workflows linking environmental data to social media sentiment remain scarce. Here, we present a protocol for analyzing spatiotemporal associations between climate-induced stressors and negative sentiment from geotagged social media data. We describe steps for preprocessing large-scale geotagged X data, performing multilingual sentiment analysis with Linguistic Inquiry and Word Count (LIWC-22), integrating climate and health indicators, and fitting a Bayesian spatiotemporal Poisson model. This protocol supports analyses of associations across diverse climate stressors and European regions. For complete details on the use and execution of this protocol, please refer to Al-Ahdal et al.1 and Al-Ahdal et al.2.
In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.
The central problem in heart failure with reduced ejection fraction (HFrEF) is reduced contractility. Existing inotropes are associated with adverse effects. In this exploratory study, we aimed to assess the safety and tolerability of AC01, a novel oral calcium-sensitising inotrope and ghrelin receptor agonist, in patients with HFrEF. In this phase 1b/2a, randomised, double-blind, placebo-controlled study, adults aged 18-80 years with heart failure for at least 6 months and an ejection fraction of 40% or lower were enrolled at 14 sites in the Netherlands, the UK, Sweden, and Italy. All patients had a transvenous implantable cardioverter defibrillator for primary prevention, with back-up pacing to protect against excessive bradycardia. Other eligibility criteria included sinus rhythm or permanent, persistent, or paroxysmal atrial fibrillation or flutter (only allowed in phase 2a), with a mean resting heart rate of 55-90 beats per min. Randomisation used permuted blocks, with block sizes of four for phase 1b and three for phase 2a. In phase 1b, patients were enrolled in four sequential dose cohorts and randomly assigned 3:1 to ascending doses of AC01 (0·1 mg, 0·3 mg, 1·0 mg, or 3·0 mg) or placebo twice daily for 7 days. In phase 2a, patients were randomly assigned 1:1:1 to parallel groups receiving 1·0 mg AC01, 3·0 mg AC01 (1·0 mg AC01 on days 1 and 2 and 3·0 mg thereafter), or placebo orally twice daily for 28 days. Patients, study personnel, outcomes assessors, those analysing the data, and the sponsor were masked to treatment assignment. The primary outcome was safety and tolerability. Safety was monitored by physical examination, vital signs, safety laboratory assessments, and 12-lead electrocardiograms (ECGs) periodically during the treatment period and until the end-of-study visit (day 12 in phase 1b and day 42 in phase 2a), and cardiac rhythm was continuously monitored remotely using a patch device until day 9 in phase 1b and until day 4 in phase 2a. Adverse or unexpected events, signs, or symptoms were recorded. This study is registered with ClinicalTrials.gov, NCT05642507, and has been completed. Between Feb 23, 2023, and Aug 28, 2025, 58 patients (53 [91%] male and five [9%] female patients with a median age of 66·0 years [IQR 60·3-72·0]) were randomly assigned: 32 in phase 1b and 26 in phase 2a. In phase 1b, four cohorts of eight patients were enrolled; in each cohort, six patients were allocated to AC01 and two to placebo, with AC01 dose cohorts of 0·1 mg, 0·3 mg, 1·0 mg, and 3·0 mg. In phase 2a, nine patients were allocated to 1·0 mg AC01, eight to 3·0 mg AC01, and nine to placebo. There were 12 AC01-related adverse events in phase 1b and 18 in phase 2a. There were no AC01-related serious adverse events; one treatment-related serious adverse event of increased high-sensitivity cardiac troponin I concentration occurred in a patient receiving placebo in phase 1b. Mild or moderate treatment-emergent adverse events were reported in 33 (80%) of 41 patients receiving AC01 and 12 (71%) of 17 patients receiving placebo. The most common treatment-emergent adverse events were hypotension, non-sustained ventricular tachycardia, dyspnoea, hyperglycaemia, dizziness or vertigo, and headache. ECG data showed no apparent signs of tachycardia, new-onset tachyarrhythmias, myocardial ischaemia, or morphological or conduction abnormalities. No case of symptomatic hypotension was reported, and there were no apparent effects of AC01 on high-sensitivity cardiac troponin I or NT-proBNP. There were no deaths during the study. In patients with HFrEF, AC01 over 28 days appeared safe and well tolerated, and no major harms were identified in this early-phase study. These findings support further investigations of AC01 in larger studies. AnaCardio.
Background and Objectives: The SARS-CoV-2 pandemic disrupted oral and maxillofacial surgery (OMS) services worldwide because of the high aerosol-generating nature of head-and-neck procedures, restricted access to elective dental care, and systemic reallocation of hospital resources. Continuous longitudinal multi-year data covering both the pandemic and the post-pandemic phases from regional Romanian (and more broadly central and southeastern European) emergency centers remain scarce. We aimed to quantify the impact of the pandemic on OMS activity in a large Romanian regional referral center and to evaluate post-pandemic resilience. Materials and Methods: We conducted a retrospective single-center study of all inpatient admissions to the OMS Clinic of a tertiary emergency hospital in western Romania between 1 January 2018 and 31 December 2024. Three periods were pre-specified: pre-pandemic (2018-2019), pandemic (2020-2022) and post-pandemic (2023-2024). A Newey-West segmented interrupted-time-series (ITS) regression and a negative-binomial monthly count model with Fourier seasonality were fitted; length of hospital stay was further analyzed with a multivariable gamma-log generalized linear model adjusted for age, sex, county, primary ICD-10 chapter and total ICD-10 codes. Variables analyzed included case volume, demographics, primary and secondary ICD-10 diagnoses, length of hospital stay (LOS), case complexity (total ICD-10 codes per admission) and in-hospital mortality. Results: A total of 11,628 inpatient admissions corresponding to 8084 unique patients (56.5% male; mean age 52.2 ± 19.2 years) were analyzed. Compared with the pre-pandemic baseline (mean 2037 admissions/year), annual volume dropped by 45.1% in 2020, 44.0% in 2021 and 32.3% in 2022, with a nadir of -76% during the first state of emergency (April 2020; n = 34 admissions). Recovery was rapid; 2024 exceeded the pre-pandemic baseline by +10.1% on raw counts and by +16.2% on admissions per 100,000 catchment population using year-specific INS denominators. The segmented ITS regression confirmed an immediate level drop of -114.2 admissions/month in March 2020 (95% CI -133.1 to -95.3; p < 0.001) and a positive post-intervention slope of +2.06 admissions/month (95% CI 1.23-2.88; p < 0.001), with observed monthly volume returning to the counterfactual projection by October 2023. The case mix shifted significantly (χ2 = 406.9, p < 0.0001); elective benign neoplasm admissions were reduced from 7.2% to 2.0%, while neoplasms of uncertain behavior nearly doubled from 15.7% to 27.5%. Case complexity increased during the pandemic (mean ICD codes 4.08 ± 2.42 vs. 3.44 ± 2.30; p < 0.001); after exclusion of administrative codes (whole Z chapter and U07.x), the difference attenuated to 3.34 vs. 3.17 codes (still p < 0.001 by Kruskal-Wallis), indicating that the largest portion of the unadjusted increase was driven by the new mandatory pre-admission SARS-CoV-2 screening code Z11.5 rather than true clinical complexity. Notably, the clinically interpretable proxy R63.3 (feeding difficulty) independently rose from 41.5% to 53.1%. The crude median LOS did not differ between the pre-pandemic and pandemic periods (3.07 vs. 3.06 d; p = 0.19) and dropped significantly post-pandemic (2.22 d; p < 0.001); however, after multivariable adjustment for case mix, age, sex, county and code count, the LOS was 15.7% shorter during the pandemic (adjusted ratio 0.84, 95% CI 0.82-0.87; p < 0.001) and 22.8% shorter post-pandemic (adjusted ratio 0.77, 95% CI 0.75-0.80; p < 0.001) relative to baseline. Conclusions: The pandemic caused a severe but transient contraction of OMS activity accompanied by increased case complexity and a marked shift away from elective surgery. Inpatient volume returned to and exceeded the pre-pandemic baseline by 2024. These results support the value of standing pandemic-preparedness protocols, sustained access to preventive dental care, and integrated tele-triage pathways for future public-health crises.
Oral administration of peptide therapeutics is limited by gastrointestinal degradation and poor epithelial permeability. Here, water-in-oil-in-water (W/O/W) double emulsions produced by microfluidics were designed to co-entrap octreotide and medium-chain triglycerides, enabling digestion-triggered generation of permeation-enhancing medium chain fatty acids. Synthesis parameters were systematically optimized to obtain stable, monodisperse droplets with defined core-shell morphology. The emulsions comprised an inner aqueous phase containing the payload, encapsulated within a Miglyol® 812 N oil phase stabilized by polyglycerol polyricinoleate (PGPR), and dispersed in an external aqueous phase stabilized by Tween® 80. The produced double emulsion had droplets of ∼190 μm in diameter with a single inner aqueous core of ∼78 μm. Lipolysis studies confirmed minimal fatty acid release under gastric conditions, but substantial release of caprylic (C8) and capric (C10) acids following small intestinal digestion, accompanied by release of payload. In Caco-2 monolayers, digested emulsions increased the apparent permeability (Papp) of fluorescein isothiocyanate-dextran (FD-4) and octreotide in a fatty acid concentration-dependent manner. Immunostaining showed occludin redistribution under permeation-enhancing conditions. Ex vivo studies with rat colonic mucosae mounted in Ussing chambers demonstrated a ∼ 4-fold increase in FD-4 permeability for the digested emulsions, comparable to matched concentrations of free fatty acids, while octreotide permeability remained unchanged. Coarse-grained molecular dynamics simulations revealed strong association of octreotide with mixed bile salt-fatty acid micelles, limiting its freely dissolved fraction, whereas FD-4 remained predominantly solvated, consistent with the experimental findings. This study demonstrates that digestion of structured double emulsions enables in situ generation of permeation enhancers while simultaneously releasing hydrophilic cargo, providing a formulation strategy for oral delivery of peptide therapeutics.
Three-dimensional finite element analysis (3D-FEA) has emerged as an essential computational tool for evaluating the biomechanical behaviors of internal fixation systems for mandibular condylar fractures. This scoping review maps and synthesizes the existing literature on 3D-FEA studies investigating the internal fixation of mandibular condylar fractures and explores, in a descriptive manner, differences in methodological focus between European and non-European research centers. PubMed and Cochrane Library databases were systematically searched following PRISMA-ScR guidelines. Original English-language research articles using 3D-FEA to evaluate internal fixation of mandibular condylar fractures were included. Data were extracted using a standardized charting form. Thirty-six studies met the inclusion criteria. European studies (n = 12) predominantly focused on development of novel plate designs and mechanical testing protocols, whereas Asian and other nationality studies (n = 24) emphasized material comparisons between titanium and bioabsorbable systems, patient-specific modeling, and loading condition analysis. Consensus findings include: (1) double-plate fixation provides superior stability; (2) among 3D plate designs, trapezoid plates demonstrate the best performance for subcondylar and condylar base fractures, whereas alpha and lambda plates may be preferable for condylar neck fractures; (3) plate positioning along the posterolateral ramus border and anterolateral sigmoid notch (A+B configuration) offers optimal biomechanical performance; and (4) contralateral molar clenching produces the highest stress concentrations. Across the included FEA studies, the A+B double-plate configuration was the most consistently reported biomechanically favorable approach for both titanium and bioabsorbable systems; the trapezoid plate performed best for subcondylar and condylar base fractures, and two-screw osteosynthesis was effective for condylar head fractures. As these findings derive from computational models, clinical validation remains necessary. Future research should focus on patient-specific modeling, clinical outcome validation, and standardization of methodological protocols.
Renal cell carcinoma (RCC) is a common manifestation in Von-Hippel Lindau (VHL) syndrome, accounting for almost 30% of the patients. However, since VHL syndrome is relatively rare, there are no clear guidelines regarding the approach to VHL patients with RCC. This article aims to provide evidence-based insights for diagnosis, treatment, and surveillance in VHL patients with RCC. The articles indexed between 1977 and 2025 in PubMed was searched. Only articles in English were included. Renal cysts are quite common in VHL patients and these cysts predispose for RCC. VHL patients are characterized with early-onset, multifocal and/or bilateral, recurrent and clear cell subtype RCC. Patients should be monitored at regular intervals. Due to recurrent characteristics of RCC, nephron-sparing surgeries should be prioritized with the aim of life-long kidney function preservation, whenever it is feasible. Focal treatments should be considered in patients for whom surgery is not suitable. In addition, belzutifan treatment has shown promising results in selected patients. In VHL patients with RCC, kidney function should be preserved whenever possible to ensure a long and high-quality life. Since these patients may develop lesions in other organs beyond kidney, surveillance with multidisciplinary approach in tertiary centers should be recommended.
Autoimmune (AI) comorbidities are common in people with multiple sclerosis (MS) and may complicate therapeutic management, particularly when dual immunosuppression is required. Cladribine, an immune reconstitution therapy approved for relapsing MS, has shown potential benefit in selected autoimmune disorders. To evaluate the prevalence of AI comorbidities in a large French MS cohort and explore the potential efficacy of cladribine in MS patients with concomitant autoimmune diseases. Retrospective multicenter registry analysis combined with a descriptive case series and literature review. Data were retrospectively extracted from the European Database for MS across five French tertiary MS centers. Adults with MS and documented autoimmune comorbidities were identified, including a subgroup treated with oral cladribine. In addition, eight detailed clinical cases of MS associated with autoimmune diseases treated with cladribine were reviewed to assess outcomes on both MS and the associated autoimmune condition. Among 11,410 people with MS, 901 had at least one autoimmune comorbidity, corresponding to a prevalence of 7.9 ± 0.25% (age 50.8 years), with a predominance of women. Of 385 cladribine-treated patients, 39 (10.1% ± 1.54%) had concurrent autoimmune disorders, although this proportion did not significantly differ from the overall cohort (p = 0.11). Eight cases involving ankylosing spondylitis (n = 3), psoriatic arthritis (n = 2), psoriasis (n = 1), rheumatoid arthritis (n = 1), and sarcoidosis (n = 1) were analyzed. Cladribine was consistently associated with MS stability, while efficacy on associated autoimmune conditions was variable, with more favorable outcomes observed in ankylosing spondylitis, psoriasis, and sarcoidosis. Autoimmune comorbidities affect approximately 8% of the French MS population and are more frequent in women. Cladribine may represent a useful therapeutic option in selected patients with concomitant autoimmune disorders, potentially limiting prolonged dual immunosuppression. Larger prospective studies are required to confirm efficacy and safety. OFSEP/EDMUS registry, ClinicalTrials.gov: NCT02889965. Cladribine as a possible treatment for MS with other autoimmune diseases A French study involving more than 11,000 people with multiple sclerosis (MS) found that around 8% also had another autoimmune disease, with women more commonly affected. Because treating both conditions can require multiple long-term immune-suppressing therapies, researchers explored whether cladribine, an approved MS treatment, could help control both diseases simultaneously. Among patients receiving cladribine, about 10% had an additional autoimmune disorder. Researchers closely reviewed eight patients with MS plus conditions including ankylosing spondylitis, psoriatic arthritis, psoriasis, rheumatoid arthritis, or sarcoidosis. The study found that MS remained stable in patients treated with cladribine. Some associated autoimmune conditions, especially ankylosing spondylitis, psoriasis, and sarcoidosis, also appeared to improve, although results were mixed for other diseases. Overall, the findings suggest that cladribine could be a useful treatment option for certain patients with both MS and autoimmune comorbidities, potentially reducing the need for multiple therapies. However, current evidence remains limited, and larger clinical studies are needed to confirm its safety and effectiveness for these additional autoimmune conditions.
Polygenic risk scores (PRS) stratify obesity risk in population cohorts, but their value within specialised paediatric obesity clinics-where genetic liability may already be saturated-remains unclear. We analysed 246 European adolescents with overweight and obesity (mean ± SD age 13.3 ± 2.2 years; 51% female; BMI 31.6 ± 4.1 kg/m2) attending a tertiary clinic in Salzburg, Austria. BMI-PRS based on people with European ancestry (PGS000027) and two cardiometabolic PRS (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR], type 2 diabetes [T2D]) were computed from Axiom-array genotypes. Distributions were compared with a population-based adult cohort from the same region (n = 2044). Associations with BMI, insulin resistance (HOMA-IR ≥ 2.5), alanine aminotransferase (ALT) and oral-glucose-tolerance parameters were examined by linear and logistic regression adjusted for age and sex. The adolescent cohort showed a right-shifted BMI-PRS distribution; the lowest quintile exceeded the adult mean (p < 0.001). Within the clinic sample, BMI-PRS neither correlated with BMI (r = -0.11; 95% CI -0.23 to 0.02) nor predicted other parameters investigated. PRS for HOMA-IR and T2D showed similarly null associations. In a genetically enriched clinical cohort, polygenic scores lose discriminatory power, delineating their optimal use for population screening rather than intra-clinic risk stratification. These data underscore the strong hereditary architecture of paediatric obesity and support context-specific application of precision-medicine tools.