Search Results (339)

Cleft lip with or without cleft palate (CL/P) is one of the most common congenital craniofacial anomalies worldwide and presents significant functional, esthetic, and psychosocial challenges. Despite advances in multidisciplinary care and surgical reconstruction, complications such as impaired wound healing, scar formation, and growth disturbances warrant the development of novel regenerative and surgical strategies, which heavily rely on animal models at the pre-clinical stage. For the current narrative review, the literature search was performed by combining cleft phenotype terms with modeling-approach terms in six databases and was supplemented by manual review of reference lists from full-text articles. The included articles were summarized based on cleft type and the methods for cleft induction (chemically induced, genetically engineered, and surgically created). Particularly, chemical teratogens such as retinoic acid, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), corticosteroids, and 6-aminonicotinamide have been widely used to induce cleft phenotypes and elucidate environmental influences on palatogenesis, whereas genetic models have clarified the roles of key molecules and signaling pathways, including Sonic hedgehog (SHH), bone morphogenetic protein (BMP), and transforming growth factor-β (TGF-β), in the development of lip and palate. Meanwhile, the surgical models have focused on the alveolar cleft in skeletally mature animals for evaluating novel grafting materials. By comparing the strengths and limitations of existing models, this review highlights opportunities for improving experimental design and translational relevance in future cleft research. Overall, despite a wide range of CL/P animal models available, few replicate clinically relevant defect anatomy and the postnatal craniofacial deformation observed in CL/P patients, underscoring the need for the development of new models. Full article

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterized by marked heterogeneity, challenging disease monitoring and individualized treatment. Despite advances in treat-to-target strategies, unmet needs persist, particularly in assessing transmural healing and optimizing therapeutic decisions. This narrative review evaluates the role of intestinal ultrasound (IUS) as a key tool for precision medicine in IBD. IUS is a non-invasive, repeatable, and cost-effective imaging modality with diagnostic accuracy comparable to endoscopy and magnetic resonance enterography, with reported sensitivities and specificities frequently exceeding 80–90% for detecting active disease. It enables real-time assessment of transmural inflammation and complications, while parameters such as bowel wall thickness and Doppler vascularity support prognostic stratification. Early reductions in bowel wall thickness (≥25–30%) have been associated with improved treatment response, allowing identification of responders within weeks of therapy initiation. IUS informs therapeutic decision-making, including initiation, optimization, and de-escalation of advanced therapies, and may reduce reliance on invasive procedures. Integration into routine care has been associated with improved disease control and cost-effectiveness. Standardization of protocols, operator training, and prospective validation are required to establish IUS as a cornerstone of precision medicine in IBD. Full article

Background/Objectives: Peri-implant diseases, encompassing peri-implant mucositis and peri-implantitis, affect 43% and 18.8–23% of implant-bearing patients, respectively, representing significant clinical challenges in implant dentistry. While mechanical debridement remains foundational, biologically active materials offer promising adjunctive regenerative strategies. This narrative review synthesises current evidence regarding five biologically active materials: enamel matrix derivative (EMD), platelet-rich fibrin (PRF), fibroblast growth factor-2 (FGF-2), recombinant human platelet-derived growth factor-BB (rhPDGF-BB/GEM 21S^®), and polynucleotide–hyaluronic acid combinations (Regenfast^®). Methods: The relevant literature was identified using electronic databases, including MEDLINE, PubMed, Scopus, and Google Scholar. This review focused on clinical studies and randomised controlled trials with a minimum follow-up of six months investigating biologically active materials in peri-implant disease management. Material mechanisms, clinical efficacy, therapeutic limitations, and evidence quality were systematically evaluated. Attention was directed toward identifying genuine biological distinctions between peri-implant and periodontal disease contexts. Results: EMD demonstrates efficacy exclusively within multimodal surgical protocols, with isolated application yielding limited benefits. rhPDGF-BB shows superior periodontal regenerative capacity; however, dedicated peri-implantitis trials remain absent. FGF-2 exhibits paradoxical osteogenic suppression despite bone fill achievement, limiting peri-implant applicability. PRF and Regenfast^® demonstrate a mechanistically sound rationale yet lack substantive peri-implant disease validation. The critical findings revealed that peri-implant regeneration fundamentally differs from periodontal regeneration: implants lack periodontal ligament anatomy, rendering ligamentogenic differentiation-promoting agents biologically inappropriate. Conclusions: Contemporary biologically active materials demonstrate compelling periodontal efficacy yet remain inadequately validated for peri-implantitis management. This disparity reflects authentic biological distinctions rather than insufficient investigation. Until multicentre randomised controlled trials stratify efficacy across distinct peri-implant disease presentations, practitioners must prioritise evidence-based surgical fundamentals—meticulous decontamination, strategic grafting, and optimised wound healing—integrating biologically active materials judiciously within comprehensive, anatomy-respecting treatment protocols. Full article

Extracellular vesicles (EVs), particularly small extracellular vesicles (sEVs), are lipid bilayer-delimited particles involved in intercellular communication through the transfer of proteins, lipids, and nucleic acids; many products and studies in aesthetic medicine refer to these preparations as exosomes, although endosomal origin is not always demonstrated. This review examines current evidence on the mechanisms, clinical effectiveness, safety, therapeutic applications, and regulatory challenges of EV- and sEV-based interventions, complemented by an exploratory qualitative assessment of physicians’ perceptions regarding clinical implementation. A narrative review of studies indexed in Scopus and PubMed was conducted with emphasis on skin rejuvenation, hair restoration, wound healing, pigmentation disorders, and inflammatory dermatoses, and responses from 12 aesthetic physicians in Colombia were analyzed qualitatively. Available evidence suggests that EVs/sEVs may promote extracellular matrix remodeling, angiogenesis, immunomodulation, and tissue repair, with potential benefits across several aesthetic and regenerative indications. However, the literature remains heterogeneous and limited by variability in biologic sources, isolation and administration protocols, insufficient high-quality clinical trials, and unresolved regulatory issues. Reports of adverse reactions linked to unapproved products marketed as exosome-based formulations further highlight the need for stronger oversight. EVs, particularly sEVs, often referred to as exosomes in the aesthetic literature, remain a promising therapeutic platform, but safe clinical integration requires rigorous validation, technical standardization, and robust regulatory frameworks. Full article

Background and Objectives: Trauma-associated auditory dysfunction, encompassing tinnitus and hearing loss, represents a frequent yet underrecognized sequela of acoustic overexposure, blast injury, and head trauma. Despite increasing clinical awareness, the published literature exhibits substantial heterogeneity in reported prevalence estimates and recovery outcomes across different injury mechanisms. This narrative review aims to synthesize available evidence on the prevalence, clinical characteristics, recovery patterns, and prognostic factors of tinnitus and hearing loss following traumatic injury, with a particular focus on comparing outcomes across distinct trauma mechanisms and evaluating the impact of early intervention. Materials and Methods: A comprehensive literature search was conducted in PubMed, Embase, Scopus, and Web of Science for studies published between January 2010 and December 2025. The search strategy combined terms related to traumatic injury (e.g., “acoustic trauma,” “blast injury,” “traumatic brain injury,” “head trauma”) with terms related to auditory dysfunction (e.g., “tinnitus,” “hearing loss,” “auditory dysfunction”). Eligible studies included observational studies (cohort, cross-sectional, case–control) reporting original data on tinnitus and/or hearing loss prevalence, recovery outcomes, or prognostic factors in adult or mixed populations exposed to traumatic injury. A narrative synthesis was organized thematically around the key research questions. Results: The available evidence consistently indicates that tinnitus and hearing loss are frequent consequences of blast injury, acute acoustic trauma, and traumatic brain injury, although reported prevalence estimates vary considerably across studies due to differences in populations, injury mechanisms, and diagnostic criteria. Blast injury is associated with mixed hearing loss (conductive and sensorineural components), while acute acoustic trauma typically causes sensorineural hearing loss, often with a characteristic high-frequency notch. Traumatic brain injury can lead to central auditory processing deficits even when pure-tone thresholds are normal. Recovery is variable and often incomplete; tympanic membrane perforations frequently heal spontaneously, but sensorineural components often persist. Early treatment (within days to two weeks) is associated with better recovery outcomes. Conclusions: Trauma-associated tinnitus and hearing loss are highly prevalent and frequently result in persistent disability. The strong association between early treatment and improved recovery outcomes supports the implementation of prompt audiological evaluation and intervention following traumatic injury. These findings underscore the need for routine audiological screening in at-risk populations and for continued research into preventive strategies, standardised assessment protocols, and optimised treatment regimens. Full article

Background: Enterocutaneous fistulas (ECFs) and enteroatmospheric fistulas (EAFs) are rare but highly morbid complications that most commonly arise after abdominal surgery. Outcomes have improved with advances in multidisciplinary care and with increasing research on how to best manage them; however, they remain associated with significant morbidity, high mortality, and prolonged hospitalization. Optimal timing of definitive repair is unknown, with many high-volume centers waiting 6–12 months, though emerging data suggest that earlier intervention may be feasible in carefully selected patients. Given their complexity and variability in management, a comprehensive review of current evidence is needed. Methods: A narrative review of the literature was conducted with emphasis on the classification, pathophysiology, and multidisciplinary management of ECFs and EAFs. Relevant studies addressing fluid and sepsis control, nutritional optimization, wound care, pharmacologic therapies, and interventional strategies were reviewed. Results: The management of ECFs requires a staged approach focused on fluid resuscitation, sepsis control, wound management, and nutritional optimization. Spontaneous closure can occur, and is most commonly within the first two months. Nutritional optimization through enteral and/or parenteral nutrition or fistuloclysis plays a vital role in improving outcomes. Therapies such as negative pressure wound therapy, biologics, and pharmacologic agents may support spontaneous closure and fistula control. In non-healing fistulas, surgical repair remains necessary, with optimal time for surgery at least 6–12 months from fistula development. Conclusions: ECFs and EAFs remain complex surgical challenges. Outcomes have improved due to advances in nutritional support and wound management, and the emergence of minimally invasive techniques. Standardization of treatment protocols and further research into novel therapy may further enhance outcomes and limit variability in management. Full article

Critically ill obese patients with gynecological cancer represent a high-risk population with complex nutritional needs. Although excess adiposity may suggest adequate energy reserves, it often conceals sarcopenia, micronutrient deficiencies, and functional malnutrition, contributing to impaired wound healing, immune dysfunction, prolonged mechanical ventilation, increased susceptibility to infections, and adverse oncologic outcomes. Obesity-associated inflammation, insulin resistance, and tumor-driven catabolism further exacerbate metabolic stress and complicate nutritional management in the intensive care setting. Accurate nutritional assessment requires a multimodal approach incorporating body composition analysis, functional measures, and laboratory parameters, as conventional indices such as body mass index may underestimate nutritional risk. Nutritional support should be individualized and may include early enteral nutrition to preserve gut integrity, supplemental or total parenteral nutrition when gastrointestinal function is compromised, high-protein regimens, and targeted micronutrient replacement. Immunonutrition, including arginine, glutamine, omega-3 fatty acids, and nucleotides, has emerged as a promising strategy to modulate inflammation, enhance immune function, and support tissue repair. This narrative review summarizes current evidence regarding obesity-related metabolic dysfunction, nutritional assessment, enteral and parenteral nutrition, and immunonutrition in obese critically ill patients with gynecological cancer. It highlights the challenges associated with sarcopenic obesity and hidden malnutrition while providing a clinically relevant overview for intensivists, gynecologic oncologists, surgeons, and nutrition specialists. Early recognition of nutritional risk and implementation of individualized multimodal nutritional strategies may improve recovery and clinical outcomes. However, high-quality ICU-specific studies remain limited, and further prospective research is needed to establish evidence-based nutritional protocols and evaluate their impact on survival, treatment tolerance, and quality of life in this vulnerable population. Full article

Magnesium-based membranes are promising biomaterials for guided bone regeneration due to their unique properties of mechanical strength, biocompatibility, and controlled biodegradation. This scoping review aimed to map and synthesize the available evidence regarding the use of magnesium-based membranes and fixation screws in alveolar ridge regeneration and guided bone regeneration procedures. Relevant studies were identified through a literature search conducted from November 2025 to May 2026, using several databases following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Thirty-nine studies met the inclusion criteria, including in vitro studies, preclinical animal studies, clinical case reports and case series, and narrative or systematic reviews. In vitro studies demonstrated cytocompatibility and fibroblast adhesion, while moderate magnesium ion concentrations increased markers of osteogenic differentiation. Preclinical animal studies reported controlled degradation, biocompatible tissue responses, maintenance of barrier function during early healing, and findings suggesting potential osteogenic stimulation. Clinical evidence, limited to case reports and small case series, described the use of magnesium membranes in horizontal and vertical ridge augmentation, sinus lift procedures, immediate dentoalveolar regeneration, periodontal defects, and cystic lesions, with generally uneventful healing outcomes and preserved bone volume. Reported complications were mainly minor and included transient soft tissue reactions, membrane exposure, and localized gas cavity formation. However, the available evidence remains limited to low-level studies without controlled clinical trials. Current findings are insufficient to establish clinical efficacy or superiority over conventional membranes, highlighting the need for larger prospective controlled studies. The review’s findings could help researchers advance the understanding of bone regeneration and help develop new strategies to improve and further investigate bone regeneration. Full article

GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes and obesity and are increasingly relevant in periodontal and implant practice. This review covers mechanisms, preclinical and early human evidence, and practical periodontal considerations; the structured database search is conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) and the International Committee of Medical Journal Editors (ICMJE) principles. Two pathways explain GLP-1RAs’ relevance: indirect effects from better glycemic control, weight loss, and reduced inflammation; and direct tissue effects involving GLP-1R signaling and the GLP-1/dipeptidyl peptidase-4 (DPP-4) axis. Preclinical studies show reduced inflammation, osteoclast activity, and alveolar bone loss, along with improved periodontal stem cell function under hyperglycemia or inflammation via Nuclear Factor-kappaB (NF-kappaB), Wingless-related integration site (Wnt)/beta-catenin, and Mitogen-Activated Protein Kinase (MAPK) pathways. Animal studies on implants and local delivery, including exendin-4 platforms, suggest osteometabolic benefits. Human data are limited and mostly observational, and confounders include metabolic status, smoking, medication, and nutrition. Oral side effects such as xerostomia and dehydration are also noted. At present, GLP-1RA therapy should be regarded as a contextual modifier of periodontal risk and healing capacity rather than as a stand-alone periodontal therapy. Full article

Objectives: Distraction osteogenesis (DO) is an established technique for bone regeneration but is associated with prolonged consolidation time and extended external fixation. Biophysical and biologic adjuncts have been proposed to accelerate regenerative maturation. This systematic review aimed to comparatively evaluate the available clinical evidence regarding low-intensity pulsed ultrasound (LIPUS) and biologic augmentation strategies in distraction osteogenesis. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251125456). MEDLINE, Embase, Scopus, and Google Scholar were searched from inception to October 2025. Randomized controlled trials and cohort studies evaluating LIPUS, platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), culture-expanded mesenchymal stem cells, or hyperbaric oxygen therapy in distraction osteogenesis were included. Risk of bias was assessed using RoB 2 for randomized trials and structured domain-based criteria for observational studies. Due to substantial clinical and methodological heterogeneity, findings were synthesized narratively. Results: Nine studies involving 304 participants met the inclusion criteria, including randomized controlled trials and cohort studies across multiple anatomical sites and fixation techniques. Randomized trials evaluating LIPUS demonstrated inconsistent reductions in healing index and consolidation time, with no consistent effect on complication rates. Biologic adjuncts such as PRP, BMAC, and cell-based therapies showed signals of improved consolidation parameters in selected studies; however, evidence was limited by small sample sizes and methodological heterogeneity. Hyperbaric oxygen therapy lacked sufficient high-quality evidence to support routine use. Overall, the certainty of evidence was constrained by variability in study design, outcome definitions, and risk of bias. Conclusions: Although both biophysical and biologic adjuncts demonstrate compelling biological rationale, current clinical evidence in distraction osteogenesis remains heterogeneous and inconclusive. Biologic strategies may offer theoretical advantages through direct cellular and growth factor supplementation, whereas LIPUS provides non-invasive mechanotransductive stimulation; however, neither approach can currently be recommended for routine clinical use. High-quality, adequately powered trials with standardized outcome reporting are required to define their true clinical role. Level of Evidence: Level III (Systematic review of Level I–III studies). Full article

Intramyocardial hemorrhage (IMH) is a severe form of post-ischemic microvascular injury that may occur after myocardial infarction, particularly in the setting of extensive ischemia and reperfusion. IMH is closely related to microvascular obstruction (MVO), larger infarct size, impaired left-ventricular (LV) function, and adverse clinical outcomes. Cardiovascular magnetic resonance (CMR), especially susceptibility-sensitive techniques such as T2* or R2* mapping, enables in vivo detection of hemorrhagic microvascular injury and may refine post-MI risk stratification. Mechanistic and translational studies suggest that erythrocyte degradation and infarct-core iron deposition may contribute to persistent inflammation, maladaptive healing, adverse remodeling, and possibly arrhythmogenic substrate formation. However, most clinical evidence remains observational, and IMH-guided management has not yet been prospectively validated. This narrative review summarizes current evidence on the pathophysiology, imaging diagnosis, prognostic significance, and emerging therapeutic implications of IMH, while highlighting unresolved questions regarding standardized imaging, clinical implementation, and future phenotype-directed therapies. Full article

Minimally invasive spine surgery (MISS) has progressively transformed the management of spinal disorders by reducing soft-tissue disruption, perioperative morbidity, and recovery time while maintaining clinical outcomes comparable to conventional open techniques. Beyond its technical evolution, MISS has increasingly assumed a central role in the treatment of bone-related spinal conditions, including vertebral fractures, degenerative instability, metastatic disease, and osteoporosis-associated pathology. This narrative review provides a comprehensive overview of the evolution of MISS with a specific focus on its interaction with vertebral bone biology, implant stability, and fusion processes. A structured literature search of the PubMed/MEDLINE database was conducted, including English-language studies published between 1980 and June 2025 addressing MISS techniques, enabling technologies, and bone-related clinical outcomes. Current evidence suggests that MISS may preserve paraspinal vascularization and soft tissue integrity, potentially supporting bone healing and fusion, although high-quality comparative data remain limited. The effectiveness of MISS in osteoporotic and metastatic vertebral disease is closely linked to bone quality, implant anchorage, and biomechanical considerations, particularly in the context of pedicle screw fixation and interbody support. Emerging technologies—including navigation, robotics, and artificial intelligence—may enhance accuracy in implant placement and reduce bone-related complications, but robust evidence of long-term benefit is still lacking. Despite its advantages, MISS presents important limitations, including a steep learning curve, increased costs, and uncertain superiority in terms of fusion rates and long-term biomechanical stability. Future research should prioritize high-quality comparative studies focusing on bone healing, implant integration, and patient-specific factors such as bone density. MISS should therefore be interpreted not only as a surgical paradigm shift but as an evolving strategy for optimizing outcomes in bone-related spinal disorders. Full article

Background: Regenerative endodontic procedures (REPs) aim to restore pulp vitality and promote root development in immature necrotic permanent teeth. Scaffold materials provide a 3D framework to support cellular migration, proliferation, and differentiation and play a critical role in regenerative interventions. Commonly used scaffolds include PRP, PRF, and collagen; however, hyaluronic acid has also demonstrated promising treatment outcomes. Objective: To evaluate whether hyaluronic acid (HA) provides superior regenerative outcomes compared to PRP, PRF, and collagen scaffolds. Methods: A systematic electronic search was conducted across PubMed, Scopus, and EBSCOhost. A total of 952 articles were identified in the initial search, of which 19 articles were included in the final review. Due to heterogeneity, a narrative synthesis was performed. Results: PRF demonstrated the most consistent improvement in root development and dentinal wall thickening. Apical closure and periapical healing were achieved across all scaffold types. Evidence for HA was limited, with no clear superiority identified. Conclusions: Current evidence does not support the superiority of HA over established scaffolds. Further standardised clinical trials are required to make definitive comparisons on scaffold effectiveness. Full article

Osteonecrosis of the jaw (ONJ) is a multifactorial disorder characterized by impaired bone remodeling, vascular compromise, immune dysregulation, and mucosal barrier disruption. Although these mechanisms have been extensively investigated, they are often discussed separately, limiting an integrated understanding of ONJ pathogenesis. Vitamin D has emerged as a biologically relevant factor across these interconnected pathways, yet its role in ONJ remains incompletely defined. This narrative and hypothesis-generating review synthesizes current mechanistic, preclinical, observational, and clinical evidence regarding vitamin D biology and ONJ and proposes a vitamin D-centered vulnerability model in which vitamin D deficiency acts as a context-dependent modifier rather than a primary causal driver. Mechanistically, vitamin D deficiency may impair osteoblast function and mineralization, disrupt angiogenic responses, promote pro-inflammatory immune signaling, and compromise mucosal integrity, collectively creating a microenvironment susceptible to impaired healing and osteonecrosis. These effects are likely to vary across clinical settings, particularly in patients receiving antiresorptive or antiangiogenic therapies. Clinical and epidemiological studies have reported associations between low vitamin D status and increased ONJ risk or severity, while some observational studies suggest that vitamin D supplementation may be associated with improved outcomes in selected populations. However, current human evidence remains predominantly observational and subject to substantial heterogeneity and residual confounding, and direct randomized evidence is lacking. Overall, this framework provides an integrated perspective linking vitamin D biology to ONJ-related pathogenic processes and may support future mechanistic research, risk stratification, and supportive multidisciplinary management strategies. Nevertheless, the proposed model should be interpreted cautiously as hypothesis-generating and requires further validation in well-designed prospective studies and randomized controlled trials. Full article

Background/Objectives: Contemporary implant dentistry is increasingly oriented toward minimally invasive regenerative strategies designed to reduce surgical morbidity while preserving or improving clinical outcomes. Conventional bone augmentation procedures remain effective and biologically well established, but they may be associated with greater patient burden, increased risk of complications, and higher technical demands in selected clinical scenarios. This narrative review critically examines minimally invasive bone regeneration approaches in implant dentistry, with particular focus on the Bone Core Technique, the Sub-Periosteal Peri-implant Augmented Layer (SPAL) technique, and Immediate Dentoalveolar Restoration (IDR), emphasizing their biological rationale, clinical indications, surgical workflows, limitations, and reported outcomes. Methods: A structured, non-systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science to identify publications relevant to minimally invasive bone regeneration in implant dentistry. Priority was given to clinical studies, prospective cohorts, case series, technical descriptions, and biologically oriented conceptual papers addressing vascular preservation, flap limitation, donor-site morbidity, and peri-implant hard- and soft-tissue integration. Results: Available evidence suggests that minimally invasive regenerative protocols may offer favorable clinical and patient-centered outcomes only in carefully selected indications and when performed by experienced operators. The strength of support is uneven across techniques: the Bone Core Technique currently has the strongest dedicated prospective follow-up for localized peri-implant defects, SPAL is supported by limited retrospective and emerging histologic evidence, and IDR remains largely based on case reports, technique-driven descriptions, and broader immediate implant literature. Conclusions: Minimally invasive bone regeneration reflects a shift toward biologically guided and patient-centered treatment concepts in implant dentistry, but it should not be interpreted as a universal substitute for conventional augmentation. Its successful application depends on careful case selection, sound knowledge of wound healing and defect morphology, and advanced surgical and prosthetic expertise. Further research should prioritize standardized outcome measures, longer follow-up, and comparative prospective studies. Full article