Search Results (1,255)

Accurate knowledge of a patient’s anatomy during every treatment fraction in proton therapy is an important prerequisite to ensure a correct dose deposition in the target volume. Adaptive proton therapy aims to detect those changes and adjust the treatment plan accordingly. One way to trigger a daily re-planning of the treatment is to take a proton radiograph from the beam’s-eye view before the treatment to check for possible changes in the water equivalent thickness (WET) along the path due to daily changes in the patient’s anatomy. In this paper, the Two-Plane Imaging System (TPIS) is presented, comprising two ATLAS IBL silicon pixel-detector modules developed for the tracking detector of the ATLAS experiment at CERN. The prototype of the TPIS is described in detail, and proof-of-principle WET images are presented, of two-step phantoms and more complex phantoms with bone-like inlays (WET 10 to 40$\mathrm{m}$$\mathrm{m}$). This study shows the capability of the TPIS to measure WET images with high precision. In addition, the potential of the TPIS to accurately determine WET changes over time down to 1$\mathrm{m}$$\mathrm{m}$ between subsequently taken WET images of a changing phantom is shown. This demonstrates the possible application of the TPIS and ATLAS IBL pixel-detector module in adaptive proton therapy. Full article

Backgrounds: High-volume (HV) metastatic castration-sensitive prostate cancer (mCSPC) is an aggressive disease. Despite this, we aimed to assess the metastatic patterns associated with a favorable prognosis in HV disease with bone metastasis (BM), including BM’s coexistence with lung metastasis (LM). Methods: We retrospectively analyzed 379 patients with synchronous mCSPC. They were categorized using the CHAARTED criteria as low-volume (LV) or HV with BM, classified based on extent of the disease from 1 to 4 (HV-EOD1–4) with or without LM. Multivariate Cox models for overall survival and castration-resistance-free survival assessed the prognostic values of HV-EOD1–4 compared with LV disease and the presence of LM. Site-specific radiographic progression at the time of castration-resistant prostate diagnosis was assessed in patients with BM and LM. Results: Multivariate analyses for overall survival showed no prognostic value of HV-EOD1 (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.43–1.85; p = 0.77), HV-EOD2 (HR 1.17; 95% CI 0.69–1.99; p = 0.57), and LM (HR 1.29; 95% CI 0.80–2.07; p = 0.29). In the analyses, HV-EOD ≤ 2 and LM did not influence castration resistance-free survival. LM showed a significantly lower incidence of radiographic progression to castration-resistant prostate cancer than BM (6.0% vs. 29.9%, p < 0.001). Conclusions: This study indicates the prognostic heterogeneity of HV disease considering BM and LM. These findings may aid in determining the treatment intensity for mCSPC. Full article

Suture anchors are widely used for tendon and ligament repair, but their fixation strength is compromised in osteoporotic bone and limited bone volume such as the coracoid process. Existing designs are prone to penetration and insufficient cortical engagement under such conditions. In this study, we developed a novel short expandable-wing (SEW) suture anchor (Ti6Al4V) designed to enhance pull-out resistance through a deployable wing mechanism that locks directly against the cortical bone. Finite element analysis based on CT-derived bone material properties demonstrated reduced intra-bone displacement and improved load transfer with the SEW compared to conventional anchors. Mechanical testing using matched artificial bone surrogates (N = 3 per group) demonstrated significantly higher static pull-out strength in both normal (581 N) and osteoporotic bone (377 N) relative to controls (p < 0.05). Although the sample size was limited, results were consistent and statistically significant. After cyclic loading, SEW anchor fixation strength increased by 25–56%. In a 3D-printed anatomical coracoclavicular ligament reconstruction model, the SEW anchor provided nearly double the fixation strength of the hook plate, underscoring its superior stability under high-demand clinical conditions. This straightforward implantation protocol—requiring only a 5 mm drill hole without tapping, followed by direct insertion and knob-driven wing deployment—facilitates seamless integration into existing surgical workflows. Overall, the SEW anchor addresses key limitations of existing anchor designs in small bone volume and osteoporotic environments, demonstrating strong potential for clinical translation. Full article

Background and Objectives: Adequate buccal bone thickness is critical for long-term peri-implant health and stability. When residual alveolar bone volume is insufficient, guided bone regeneration (GBR) is a widely adopted technique. While non-resorbable membranes provide structural support, they carry a higher risk of complications and require secondary surgery. Resorbable collagen membranes, offer promising biological properties and easier clinical handling, yet clinical data remain limited. This prospective cohort study aimed to evaluate the clinical and radiographic outcomes of horizontal GBR using a native, non–cross-linked resorbable porcine pericardium membrane fixed with titanium pins, in conjunction with simultaneous implant placement. Materials and Methods: Eighteen patients (26 implants) with horizontal alveolar defects (<6 mm) underwent implant placement and GBR with deproteinized bovine bone mineral and a porcine pericardium collagen membrane. Horizontal bone gain and buccal bone thickness were measured at baseline and 6 months post-operatively. Post-operative complications, patient-reported outcomes (PROMs), and peri-implant tissue health were assessed up to 1 year post-loading. Results: Mean bone gain was 2.95 ± 0.95 mm, and all sites achieved a buccal bone thickness ≥ 1.5 mm. No membrane-related complications occurred. PROMs revealed low morbidity. At 1-year follow-up, marginal bone loss averaged 0.54 ± 0.7 mm, mean probing depth was 2.79 ± 0.78 mm, 92% of sites exhibited keratinized mucosa ≥ 2 mm. Conclusions: Native resorbable porcine pericardium membranes, when combined with DBBM and mechanical stabilization, seem to be effective for horizontal bone regeneration. Full article

Background/Objectives: In oral and maxillofacial surgery, apicoectomy is a standard procedure for treating persistent periapical infections after insufficient conservative treatment. Traditional techniques rely on direct visualization, while navigated methods offer advantages in precision and safety. This in vitro study compared conventional apicoectomy with dynamically guided navigation. The aim was to assess the feasibility, accuracy, and safety of dynamic navigation and to determine whether it reduces complication risks, improves surgical predictability, and minimizes bone loss. Methods: Ten experienced surgeons performed both techniques on custom-designed models. Operation time was assessed, as well as cavity volume, resected root length, incision width and height, and preservation of adjacent structures. Results: The navigated approach demonstrated significantly improved accuracy in root-end resection, with a reduction in access cavity volume (p < 0.001). No significant differences were found in operation time (p = 0.499), resection length (p = 0.054), or incision dimensions (p > 0.05). The risk of damaging adjacent structures was not significantly different between the two methods. Conclusions: Dynamic navigation for apicoectomy can offer an alternative in cases requiring high precision to conventional techniques. However, the routine clinical implementation of dynamic navigation remains limited due to the extensive preoperative planning required. The necessity for additional planning increases complexity, time, and cost. Full article

This randomized controlled clinical trial compared a conventional combined screw- and cement-retained prosthesis (CSCRP) workflow (control group) with a fully digital cementless screw-retained prosthesis (CL-SRP) system (test group) for single posterior implant restorations. A total of 40 implants in 35 patients were allocated to either workflow. Clinical procedure times, prosthetic accuracy, peri-implant soft tissue changes, and marginal bone loss (MBL) were assessed. The test group demonstrated significantly shorter total prosthetic time (p < 0.001) and impression-taking time (p < 0.001) compared with the control group. Prosthetic adjustment time (p = 0.211) and adjustment volume (p = 0.474) did not differ significantly. Gingival shape changes were likewise not statistically significant (p = 0.966). MBL was significantly lower in the test group (p < 0.05). From a prosthetic standpoint, both workflows yielded clinically acceptable outcomes; however, the digital CL-SRP approach improved procedural efficiency and early peri-implant bone preservation without compromising prosthetic quality. This trial had inherent limitations, including a short follow-up duration, a relatively small sample size, combined test conditions, and restriction to single posterior implants. Therefore, further long-term studies are warranted to confirm durability and broader clinical applicability. Full article

Background/Objectives: Gaucher disease type 1 is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the GBA1 gene. Although enzyme replacement therapy has improved patient outcomes, there is limited long-term real-world data on taliglucerase alfa. This study aimed to evaluate the long-term efficacy and safety of taliglucerase alfa in both treatment-naïve and previously treated patients with Gaucher disease type 1 over a 10-year period. Methods: This prospective, single-centre cohort study involved 29 patients (13 treatment-naïve and 16 previously treated with imiglucerase) who received taliglucerase alfa from 2015 to 2024. Clinical, hematological, visceral, skeletal, and biochemical parameters were assessed at baseline and at 12, 60, and 120 months. Biomarkers included chitotriosidase and glucosylsphingosine. Safety was evaluated through adverse event reporting and anti-drug antibody testing. Results: Hemoglobin and platelet counts improved or remained stable in all patients. By 60 months, liver volume had normalised in treatment-naïve patients (mean reduction: 23.1%), while spleen volume had decreased by up to 47.3%. Lyso-Gb1 levels decreased by 86.1% in patients who had not previously received treatment and by 59.5% overall, with a strong correlation to adherence. Bone mineral density improved in most cases. 137 adverse events were reported, 24% of which were mild infusion-related reactions. Anti-drug antibody developed in two patients, including one with a reduced therapeutic response. Conclusions: Taliglucerase alfa offers sustained long-term clinical, hematological and biochemical benefits in both treatment-naïve and previously treated Gaucher disease type 1 patients, with a favorable safety profile. Glucosylsphingosine proved to be a highly sensitive biomarker for monitoring therapeutic efficacy and detecting treatment response. Full article

Background/Objectives: The process of designing and fabricating bone tissue engineering scaffolds is a multi-faceted and intricate process. The scaffold is designed to attach cells to the required volume of regeneration to subsequently migrate, grow, differentiate, proliferate, and consequently develop tissue within the scaffold which, in time, will degrade, leaving just the regenerated tissue. The fabrication of tissue scaffolds requires adapting the properties of the scaffolds to mimic, to a large extent, the specific characteristics of each type of bone tissue. However, there are some significant limitations due to the constrained scaffolds’ architecture and structural features that inhibit the optimization of bone scaffolds. Methods: To overcome these shortcomings, new computational approaches for scaffold design have been adopted through currently adopted computational methods such as finite element analysis (FEA), computational fluid dynamics (CFD), and fluid–structure interaction (FSI). Results: This paper presents a narrative review of the state of the art in the field of parametric numerical modeling and computational fluid dynamics geometry-based models used in bone tissue engineering. Computational methods for scaffold design improve the process of constructing scaffolds and contribute to tissue engineering. Conclusions: This paper highlights the benefits of computational methods on employing scaffolds with different architectures and inherent characteristics that can potentially contribute to a favorable environment for hosting cells and predict their behavior and response. By recognizing these benefits, researchers can enhance and optimize scaffold properties for future advancements in tissue engineering research that will lead to more accurate and robust outcomes. Full article

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Background/Objective: Clinical statistics show that bacterial infection is a major driver of implant failure. To enhance antibacterial performance, some metallic elements, such as silver (Ag), zinc (Zn), and copper (Cu), are commonly used to modify the titanium surface. Despite the promising antibacterial performance of Ag, concerns persist regarding dose-dependent cytotoxicity, systemic accumulation, and potential effects on local bone metabolism. This review aimed to investigate the effects of incorporating or coating titanium (Ti) implant surfaces with Ag on bone formation around implants. Methods: A search was undertaken using three main databases (PubMed, Web of Science, and Scopus). The search was limited to studies published within the last 20 years that involved animal experiments using endosseous implants coated with or incorporating Ag. Meta-analyses were performed for bone-to-implant contact (BIC), bone formation (BA), and bone volume (BV/TV) around the implant in control and test groups. The compared groups were subjected to similar implant surface treatments aside from the presence of silver in the test group. Results: Sixteen studies met the inclusion criteria in this study and were included. The analysis of BIC values revealed a statistically significant overall effect in favor of silver-coated implants (Z = 2.01, p = 0.04), along with 95% confidence intervals (CIs). The BA analysis found no significant difference between silver-coated and control implants (Z = 1.09, p = 0.28). The BV/TV analysis also showed no statistically significant overall difference (Z = 0.35, p = 0.73). Conclusions: In animal models, silver-coated Ti implants improve bone–implant contact without altering peri-implant bone volume metrics. Full article

In recent years, apatite-based materials have garnered significant interest, particularly for applications in tissue engineering. Apatite is most commonly employed as a coating for metallic implants, as a component in composite materials, and as scaffolds for bone and dental tissue regeneration. Among its various forms, hydroxyapatite (HAP) is the most widely used, owing to its natural occurrence in human and animal hard tissues. An emerging area of research involves the use of fluoride-substituted apatite, particularly fluorapatite (FAP), which can serve as a direct fluoride source at the implant site, potentially offering several biological and therapeutic advantages. However, substituting HAP with FAP may lead to unforeseen changes in material behavior due to the differing physicochemical properties of these two calcium phosphate phases. This study investigates the effects of replacing hydroxyapatite with fluorapatite in ceramic–polymer composite materials incorporating β-1,3-glucan as a bioactive polymeric binder. The β-1,3-glucan polysaccharide was selected for its proven biocompatibility, biodegradability, and ability to form stable hydrogels that promote cellular interactions. Nitrogen adsorption analysis revealed that FAP/glucan composites had a significantly lower specific surface area (0.5 m²/g) and total pore volume (0.002 cm³/g) compared to HAP/glucan composites (14.15 m²/g and 0.03 cm³/g, respectively), indicating enhanced ceramic–polymer interactions in fluoride-containing systems. Optical profilometry measurements showed statistically significant differences in profile parameters (e.g., Rp: 134 μm for HAP/glucan vs. 352 μm for FAP/glucan), although average roughness (Ra) remained similar (34.1 vs. 27.6 μm, respectively). Microscopic evaluation showed that FAP/glucan composites had smaller particle sizes (1 μm) than their HAP counterparts (2 μm), despite larger primary crystal sizes in FAP, as confirmed by TEM. XRD analysis indicated structural differences between the apatites, with FAP exhibiting a reduced unit cell volume (524.6 ų) compared to HAP (528.2 ų), due to substitution of hydroxyl groups with fluoride ions. Spectroscopic analyses (FTIR, Raman, ³¹P NMR) confirmed chemical shifts associated with fluorine incorporation and revealed distinct ceramic–polymer interfacial behaviors, including an upfield shift of PO₄³⁻ bands (964 cm⁻¹ in FAP vs. 961 cm⁻¹ in HAP) and OH vibration shifts (3537 cm⁻¹ in FAP vs. 3573 cm⁻¹ in HAP). The glucan polymer showed different hydrogen bonding patterns when combined with FAP versus HAP, as evidenced by shifts in polymer-specific bands at 888 cm⁻¹ and 1157 cm⁻¹, demonstrating that fluoride substitution significantly influences ceramic–polymer interactions in these bioactive composite systems. Full article

Background/Objectives: The maintenance of peri-implant soft tissue health is critical for the long-term success of implant therapy, particularly in edentulous patients rehabilitated with mandibular overdentures. Leukocyte- and platelet-rich fibrin (L-PRF) has been proposed as an autologous biomaterial to enhance peri-implant tissue quality. This randomized controlled clinical trial evaluated the effect of L-PRF on peri-implant mucosal thickness in edentulous patients treated with mandibular implant-retained overdentures. Methods: Edentulous patients received two interforaminal implants to retain a mandibular overdenture and were randomly assigned to a test group (L-PRF applied during surgery) or a control group (standard protocol without L-PRF). Clinical measurements of keratinized mucosal thickness and width were recorded at baseline, 12 weeks, and 24 weeks. Volumetric analyses of soft and hard tissue changes were performed using digital superimposition of STL models. The trial was conducted in accordance with the Declaration of Helsinki and approved by the Scientific Ethics Committee of the Aconcagua Health Service. All participants provided written informed consent. Results: A significant increase in keratinized mucosal thickness was observed in the L-PRF group at 12 and 24 weeks compared with baseline (p < 0.01). No significant differences were detected between the groups in soft tissue volume (p = 0.12) or bone volume (p = 0.45). Mucosal width remained stable in both groups throughout follow-up. Conclusions: The application of L-PRF at implant placement resulted in a significant gain in peri-implant mucosal thickness, suggesting a soft tissue modulating effect. Enhancing keratinized mucosal thickness during implant surgery may improve peri-implant tissue quality and support long-term stability of mandibular overdentures. Full article

Background/Objectives: Mastoid obliteration (MO) after canal wall down (CWD) tympanoplasty for chronic otitis media with cholesteatoma (COMC) enables simultaneous surgical management of the pathology and shaping of a new external ear canal (EEC) that is similar to the natural one. The aim of the present work is to describe the results of a new MO technique that involves using homologous bone (HB) material and a Palva flap (“Cupeta technique”). Methods: A retrospective study was conducted on 12 patients undergoing MO for COMC, either during the same operation or in a second-time surgery after CWD. The surgical technique, patient demographics, audiometric data, the EEC volume, and clinical outcomes were analyzed. Results: The MO technique resulted in good outcomes in terms of healing at three months after surgery. Fewer clinical complications were observed compared with similar MO methods described in the literature. HB reabsorption was observed in two patients and was defined as only partial. Measurements of the EEC volume were normal in all patients. The preoperative and postoperative hearing thresholds were similar. Conclusions: Performing MO with the Cupeta technique after CWD is a suitable surgical management method for COMC and demonstrates good clinical postoperative results. We plan to conduct further studies with a longer follow-up and a larger group of patients in order to confirm our findings. Full article

Background: Orthodontically driven osteogenesis (ODO) is a surgical tunnel modification of periodontally accelerated osteogenic orthodontics (PAOO), combining selective corticotomy with bone grafting in sequential and/or segmental fashion. This is a minimally invasive approach that enhances periodontal health and allows orthodontic tooth movement beyond the original alveolar envelope. Considering the lack of long-term three-dimensional data on orthodontically driven osteogenesis (ODO), this study aims to quantitatively assess the long-term stability of alveolar bone and buccal cortical thickness following ODO, using CBCT imaging. The null hypothesis is that ODO does not result in significant changes in alveolar bone volume or cortical thickness over a seven-year follow-up period. Methods: Twenty patients (13 females, 7 males; mean age 27.4 ± 5.3 years) who had undergone orthodontically driven osteogenesis (ODO) using a minimally invasive tunnel approach and segmental corticotomy protocol followed by clear aligner therapy were retrospectively evaluated. The mean follow-up period after treatment was 7 years (range: 5–15 years). Cone beam computed tomography (CBCT) scans were obtained at one year postoperatively (T1) and again at the long-term follow-up visit (T2). Buccal bone thickness measurements were taken at standardized levels (3 mm, 5 mm, and 7 mm apical to the cementoenamel junction) and compared between T1 and T2 to evaluate bone stability over time. In addition, histologic evaluation of the previously grafted area was performed in two patients: one sample was collected during an alveolar ridge augmentation procedure six months after ODO, and the other during orthognathic surgery eight months after ODO. The samples were analyzed to assess new bone formation and integration of graft material. Results: Radiographic analysis showed long term stability of the new bone support. Histologic examination showed newly formed lamellar and reticular bone. Bone marrow showed no inflammatory infiltration, and bone particles were still detectable but incorporated in the newly created bone. Conclusions: Based on these findings, ODO appears to be a promising technique that could induce stable bone osteogenesis. A larger cohort study can enhance the evidence of these promising results to popularize this technique. Full article

Osteoporosis is a common skeletal disease characterized by decreased bone density, leading to bone fragility and fractures, especially in menopausal women. The purpose of this study is to confirm the anti-osteoporosis activity of stem cell extracellular vesicles (EVs) as a material of regenerative medicine. Mesenchymal stem cells have a potential to differentiate into osteocytes, so directly reconstruct bone tissue or facilitate bone regeneration via paracrine effects. Paracrine effects are mediated by functional molecules delivered in EVs released from stem cells. EVs containing high concentrations of growth factors (GFs) and neurotrophic factors (NFs) were attained via hypoxia culture of human amniotic membrane stem cells (AMSCs). From the EVs with a mean diameter of 77 nm, 751 proteins and 15 species of lipids were identified. Sprague-Dawley rats were ovariectomized, and eight weeks later, intravenously injected with EVs at doses of 1 × 10⁸, 3 × 10⁸ or 1 × 10⁹ particles/100 μL/body, weekly for eight weeks. One week after the final administration, the serum and bone parameters related to bone density were analyzed. Serum 17β-estradiol, alkaline phosphatase, and calcium levels that decreased in ovariectomized rats were restored by EVs in a dose-dependent manner. Bone parameters such as bone mineral density, bone mineral content, bone volume/tissue volume ratio, trabecular number, trabecular space, and bending strength were also improved by treatment with EVs. Such effects were confirmed by morphological findings of micro-computed tomography. Taken together, it is suggested that AMSC-EVs containing high concentrations of GFs and NFs preserve bone soundness by promoting bone regeneration and inhibiting bone resorption. Full article