Search Results (2,663)

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Objective: The accurate visualization of root canal systems on periapical radiographs is critical for successful endodontic treatment. This study aimed to evaluate and compare the effectiveness of several image enhancement algorithms—including a novel Total Variation–Contrast-Limited Adaptive Histogram Equalization (TV-CLAHE) technique—in improving the detectability of root canal configurations in mandibular incisors, using cone-beam computed tomography (CBCT) as the gold standard. A null hypothesis was tested, assuming that enhancement methods would not significantly improve root canal detection compared to original radiographs. Method: A retrospective analysis was conducted on 60 periapical radiographs of mandibular incisors, resulting in 420 images after applying seven enhancement techniques: Histogram Equalization (HE), Contrast-Limited Adaptive Histogram Equalization (CLAHE), CLAHE optimized with Pelican Optimization Algorithm (CLAHE-POA), Global CLAHE (G-CLAHE), k-Caputo Fractional Differential Operator (KCFDO), and the proposed TV-CLAHE. Four experienced observers (two radiologists and two dentists) independently assessed root canal visibility. Subjective evaluation was performed using an own scale inspired by a 5-point Likert scale, and the detection accuracy was compared to the CBCT findings. Quantitative metrics including Peak Signal-to-Noise Ratio (PSNR), Signal-to-Noise Ratio (SNR), image entropy, and Structural Similarity Index Measure (SSIM) were calculated to objectively assess image quality. Results: Root canal detection accuracy improved across all enhancement methods, with the proposed TV-CLAHE algorithm achieving the highest performance (93–98% accuracy), closely approaching CBCT-level visualization. G-CLAHE also showed substantial improvement (up to 92%). Statistical analysis confirmed significant inter-method differences (p < 0.001). TV-CLAHE outperformed all other techniques in subjective quality ratings and yielded superior SNR and entropy values. Conclusions: Advanced image enhancement methods, particularly TV-CLAHE, significantly improve root canal visibility in 2D radiographs and offer a practical, low-cost alternative to CBCT in routine dental diagnostics. These findings support the integration of optimized contrast enhancement techniques into endodontic imaging workflows to reduce the risk of missed canals and improve treatment outcomes. Full article

Background/Objectives: Nowadays, intravascular lithotripsy (IVL) has emerged as a novel technique for treatment of vascular calcifications, first in coronary and then in peripheral arteries. In the current literature there is little evidence that describes IVL as an effective and safe solution in treating severe aortic and aorto-iliac calcifications. The aim of this study is to report current available data about the use of IVL in treating aortic and aorto-iliac calcified lesions and its application in facilitating other endovascular procedures. Methods: the present review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Guidelines. Preliminary searches were conducted on MEDLINE and Pubmed from January 2015 to February 2025. Studies were divided into 3 main categories depending on the location of calcifications and the type of treatment: IVL in visceral and infrarenal obstructive disease (group 1), IVL in aorto-iliac obstructive disease (group 2), IVL used to facilitate other endovascular procedures. Main primary outcomes in the perioperative period were technical and clinical successes and perioperative complications. Primary outcomes at 30 days and mid-term (2 years) were overall survival, limb salvage rate, primary patency, primary assisted patency, secondary patency, and residual stenosis. Results: Sixteen studies were identified for a total of 1674 patients. Technical and clinical successes were 100%, with low rates of perioperative complications. Dissection rate reaches up to 16.1% in some studies, without any differences compared to plain old balloon angioplasty (POBA) alone (22.8%; p = 0.47). At 30 days, limb salvage and survival rates were 100%. At 2 years, primary patency, assisted primary patency, and secondary patency were 95%, 98%, and 100%, respectively, with no difference compared to IVL + stenting. Conclusions: IVL has emerged as a novel approach to treat severe calcified lesions in visceral and aorto-iliac atherosclerotic disease and to facilitate other endovascular procedures. This technique seems to offer satisfactory early and mid-term outcomes in terms of primary, primary assisted patency, and secondary patency with low complication rates. Full article

Background/Objectives: The advent of tyrosine kinase inhibitors (TKIs) revolutionized the management of chronic myeloid leukemia (CML), achieving survival rates near those of the general population. Despite this success, prolonged therapy presents challenges, including physical, emotional, and financial burdens. Treatment-free remission (TFR), defined as sustained deep molecular response (DMR) after discontinuing TKIs, has emerged as a viable clinical goal. This study evaluates real-world data from the Canary Islands Registry of CML (RCLMC) to explore outcomes, predictors, and the feasibility of TFR. Methods: This retrospective observational study included 393 patients diagnosed with CML-CP between 2007 and 2023. Molecular response was monitored according to international guidelines. Survival probabilities were estimated using the Kaplan–Meier method. Logistic regression analysis was performed to identify predictors of molecular relapses after TKI discontinuation. Results: Of the 383 patients who received TKI treatment, 58.3% achieved molecular response grade 2 (MR2) (BCR-ABL1 ≤ 1%), 95.05% achieved MR2, and 50.5% reached MR4 within the first year. Of the 107 patients attempting TFR, 73.2% maintained remission at 36 months. Relapses occurred in 24 patients, all regaining molecular response upon reintroduction of TKIs. No cases of disease progression were observed. Conclusions: Our findings support the feasibility and safety of TFR in a real-world clinical setting for well-selected patients, with outcomes consistent with international studies. The study underscores the importance of molecular monitoring and patient-specific strategies to optimize outcomes. Full article

Objective: Cervical pregnancy (CP) accounts for less than 1% of all ectopic pregnancies. The standard of management for CP is still under detailed investigation; however, among the known treatment methods, super-selective uterine artery embolization (UAE) and the use of methotrexate (MTX) have emerged as effective and minimally invasive options in recent years. Our aim is to present our center’s experience and provide available evidence evaluating the efficacy of UAE in the treatment of CP. Materials and Methods: This single-center and retrospective study evaluated the procedural and clinical outcomes of patients with CP who underwent endovascular uterine embolization with MTX between 2017 and 2024. Both procedural and clinical efficacy and safety, as well as the rate of complications and long-term outcomes, were noted. Results: A total of nine patients were diagnosed with CP (imaging examination included transvaginal ultrasound and/or magnetic resonance imaging) and referred for endovascular treatment. The mean age of the patients was 36.7 years, and the mean gestational age on admission was 9 weeks. In all cases, selective catheterization of supplying vessels and subsequent embolization with a mixture of methotrexate and gel sponge was carried out. The technical success rate was 100% with no complications. Follow-up ultrasound confirmed the disappearance of the flow signal around the intracervical gestational sac in all cases. Conclusions: In conclusion, this retrospective study demonstrated the procedural and clinical safety and efficacy of uterine artery embolization in patients with cervical pregnancy. This is why endovascular therapy should be proposed to these individuals and be included in treatment options discussed during multidisciplinary boards. Full article

The high incidence of melanoma leading to a poor prognosis rate endorses the development of alternative and innovative approaches in the treatment of melanoma. Therefore, the present study aims to develop and characterize, in terms of physicochemical features and biological impact, an aqueous suspension of magnetite (Fe₃O₄) coated with β-cyclodextrin (Fe₃O₄@β-CD) as a potential innovative alternative nanosystem for melanoma therapy. The nanosystem exhibited physicochemical characteristics suitable for biological applications, revealing a successful complexation of Fe₃O₄ NPs with β-CD and an average size of 18.1 ± 2.1 nm. In addition, the in vitro evaluations revealed that the newly developed nanosystem presented high biocompatibility on a human keratinocyte (HaCaT) monolayer and selective antiproliferative activity on amelanotic human melanoma (A375) cells, inducing early apoptosis features when concentrations of 10, 15, and 20 μg/mL were employed for 48 h and 72 h. Collectively, the Fe₃O₄@β-CD nanosystem reveals promising features for an adjuvant approach in melanoma treatment, mainly due to its β-cyclodextrin coating, thus endorsing a potential co-loading of therapeutic drugs. Furthermore, the intrinsic magnetic core of Fe₃O₄ NPs supports the magnetically based cancer treatment strategies. Full article

Background/Objectives: Pneumatic dilation (PD) is a widely used treatment modality in the management of achalasia. It is particularly relevant in regions where many centers lack access to advanced therapeutic modalities. Therefore, we aimed to assess the effectiveness and safety of PD in our local region. Methods: This study retrospectively analyzed patients with achalasia that underwent PD from 1/2013 to 12/2019. The diagnosis of achalasia was established on the grounds of clinical symptoms, radiological and endoscopic findings, and esophageal manometry. Data on patient’s clinical characteristics, dilation technique and postprocedural follow-up were collected and statistically analyzed. Procedure effectiveness was defined as the postprocedural Eckardt score ≤ 3. Results: PD significantly reduced frequency of dysphagia, regurgitation, and retrosternal pain (p < 0.001). Body-weight increased significantly one month and one year after the procedure (p < 0.001). The procedural success rate was 100%. No severe complications were reported. Conclusions: PD is an effective and safe treatment modality in the management of achalasia. The study limitations include a single center design with the small number of participants, not all of whom underwent manometry, gender disproportion, absence of non-responders, and a short follow-up. Full article

Background: Diabetes mellitus is associated with worse outcomes after cardiac arrest. Hyperglycemia, diabetes treatments and other long-term sequalae may contribute to this association. We sought to determine the acute effect of diabetes on the return of spontaneous circulation (ROSC) and post-arrest cardiac function in a rat cardiac arrest model. Methods: Eighteen male Wistar rats were utilized, and 12 underwent the induction of type II diabetes for 10 weeks through a high-fat diet and the injection of streptozotocin. The carotid artery flow and femoral arterial pressure were measured. Seven minutes of asphyxial cardiac arrest was induced. An external cardiac compression was performed via an automated piston. Post-ROSC, epinephrine was titrated to a mean arterial pressure (MAP) of 70 mmHg. Data was analyzed using the Mann–Whitney test. The significance was set at p ≤ 0.05. Results: The rate of the ROSC was significantly lower in animals with diabetes, 50% compared to 100% in non-diabetics. Additionally, it took significantly longer to achieve the ROSC in diabetics, p = 0.034. In animals who survived, the cardiac function was reduced, as indicated by an increased epinephrine requirement, p = 0.041, and a decreased cardiac output at the end of the experiment, p = 0.017. The lactate, venous and arterial pressures, heart rate and carotid flow did not differ between groups at 2 h. Conclusions: Diabetes negatively affects the survival from cardiac arrest. Here, the critical difference was the rate of the conversion to a life-sustaining rhythm and the achievement of the ROSC. The post-ROSC cardiac function was depressed in diabetic animals. Interventions targeted at improving defibrillation success may be important in diabetics. Full article

Background/Objectives: Anterior dental trauma in adolescents presents complex restorative challenges due to ongoing craniofacial development and high aesthetic expectations. This study evaluated the long-term clinical performance of feldspathic ceramic veneers and lithium disilicate crowns used in the anterior region following dental trauma in adolescents. Methods: A total of 209 restorations were placed in 85 adolescents (50 females, 35 males), aged 11.1–17.9 years (mean age: 15.1 years). Of these, 144 were lithium disilicate crowns, and 65 were feldspathic ceramic veneers. All restorations were fabricated using minimally invasive protocols and followed up for periods ranging from 3 to 60 months. Outcomes were assessed based on standardized clinical criteria for success and failure. Results: Lithium disilicate crowns exhibited superior long-term performance, with the majority of failures occurring in feldspathic veneers (p < 0.001), primarily due to chipping or structural fracture. Age and gender had no statistically significant influence on failure rates. Conclusions: Both feldspathic and lithium disilicate ceramic restorations represent viable treatment options for anterior dental trauma in adolescents. However, lithium disilicate demonstrates greater mechanical reliability, particularly in teeth with significant hard tissue loss. These results support the use of durable ceramic materials in adolescent restorative protocols involving dental trauma. Full article

Current work investigates the fabrication and performance of nanocomposite membranes, modified with varying concentrations of hybrid nanostructures comprising titanium nanowires coated with iron nanoparticles (TiO₂ NWs-Fe₂O₃), for the removal of Naphthol Blue Black (NBB) dye from industrial wastewater. A series of analytical tools were employed to confirm the successful modification including scanning electron microscopy and EDX analysis, porosity and hydrophilicity measurements, Fourier-transform infrared spectroscopy, and X-Ray Diffraction. The incorporation of TiO₂ NWs-Fe₂O₃ has enhanced membrane performance significantly by increasing the PWF and improving dye retention rates of nanocomposite membranes. At 0.7 g of nanostructure content, the modified membrane (M8) achieved a PWF of 93 L/m²·h and NBB dye rejection of over 98%. The flux recovery ratio (FRR) analysis disclosed improved antifouling properties, with the M8 membrane demonstrating a 73.4% FRR. This study confirms the potential of TiO₂ NWs-Fe₂O₃-modified membranes in enhancing water treatment processes, offering a promising solution for industrial wastewater treatment. These outstanding results highlight the potential of the novel PES-TiO₂ NWs-Fe₂O₃ membranes for dye removal and present adequate guidance for the modification of membrane physical properties in the field of wastewater treatment. Full article

Background: Peripancreatic collections (PPCs) are a frequent and severe complication of acute and chronic pancreatitis, as well as pancreatic surgery, often requiring interventions to treat and prevent infection, gastric obstruction, and other complications. Endoscopic ultrasound (EUS)-guided drainage has emerged as a minimally invasive alternative to surgical and percutaneous approaches, offering reduced morbidity and shorter recovery times. However, the effectiveness of EUS-guided drainage in post-surgical PPCs remains underexplored. Methods: This retrospective, single-center study evaluated the technical and clinical outcomes of EUS-guided drainage in patients with PPCs between October 2021 and December 2024. Patients were categorized as having post-pancreatitis or post-surgical PPCs. Technical success, clinical success, complications, recurrence rates, and the need for reintervention were assessed. Results: A total of 50 patients underwent EUS-guided drainage, including 42 (84%) with post-pancreatitis PPCs and 8 (16%) with post-surgical PPCs. The overall technical success rate was 100%, with clinical success achieved in 96% of cases. Lumen-apposing metal stents (LAMSs) were used in 84% of patients, including 7.1% as a dual-gate salvage strategy after the failure of double-pigtail drainage. The complication rate was 24%, with infection being the most common (16%). The recurrence rate was 25%, with no significant difference between post-pancreatitis and post-surgical cases. Patients with walled-off necrosis had a significantly higher reintervention rate (35%) than those with pseudocysts (18%; p = 0.042). Conclusions: EUS-guided drainage is a highly effective and safe intervention for PPCs, including complex post-surgical cases. The 100% technical success rate reinforces its reliability, even in anatomically altered post-surgical collections. While recurrence rates remain a consideration, EUS-guided drainage offers a minimally invasive alternative to surgery, with comparable outcomes in both post-pancreatitis and post-surgical patients. Future multi-center studies should focus on optimizing treatment strategies and reducing recurrence in high-risk populations. Full article

Background: Non-adherence to anti-tuberculosis treatment remains a major obstacle to increasing tuberculosis treatment success rates and enhancing healthcare expenditure. The aim of this study was to identify determinants contributing to non-adherence to anti-tuberculosis treatment in a public primary healthcare clinic in South Africa. Method: A cross-sectional study was carried out to collect data from 65 participants using face-to-face interviews with a structured questionnaire. Data were analyzed using SPSS. Results: Of the 65 participants interviewed, 41 (63.08%) were males and 24 (36.92%) were females. A total of 45 (69.23%) were adherents and 20 (30.77%) were non-adherents. Gender was the major predictor of non-adherence with more males committed to treatment than females with a significant association (X² = 65.00 and p of <0.001). Conclusions: The major contributing factors to non-adherence were long dis-tances to the clinics, a lack of family support, and unemployment. Comprehensive programs addressing these multifactorial factors are needed for successful treatment and eradication of tuberculosis. Full article

Background/Objectives: Global warming and rising CO₂ concentrations pose significant challenges to plant systems. Amid these pressures, this study contributes to understanding how tropical species respond by simultaneously evaluating reproductive and genetic traits. It specifically investigates the effects of maternal exposure to warming and elevated CO₂ on progeny physiology, genetic diversity, and population structure in Stylosanthes capitata, a resilient forage legume native to Brazil. Methods: Maternal plants were cultivated under controlled treatments, including ambient conditions (control), elevated CO₂ at 600 ppm (eCO₂), elevated temperature at +2 °C (eTE), and their combined exposure (eTEeCO₂), within a Trop-T-FACE field facility (Temperature Free-Air Controlled Enhancement and Free-Air Carbon Dioxide Enrichment). Seed traits (seeds per inflorescence, hundred-seed mass, abortion, non-viable seeds, coat color, germination at 32, 40, 71 weeks) and abnormal seedling rates were quantified. Genetic diversity metrics included the average (A) and effective (Ae) number of alleles, observed (Ho) and expected (He) heterozygosity, and inbreeding coefficient (Fis). Population structure was assessed using Principal Coordinates Analysis (PCoA), Analysis of Molecular Variance (AMOVA), number of migrants per generation (Nm), and genetic differentiation index (Fst). Two- and three-way Analysis of Variance (ANOVA) were used to evaluate factor effects. Results: Compared to control conditions, warming increased seeds per inflorescence (+46%), reduced abortion (−42.9%), non-viable seeds (−57%), and altered coat color. The germination speed index (GSI +23.5%) and germination rate (Gr +11%) improved with warming; combined treatments decreased germination time (GT −9.6%). Storage preserved germination traits, with warming enhancing performance over time and reducing abnormal seedlings (−54.5%). Conversely, elevated CO₂ shortened GSI in late stages, impairing germination efficiency. Warming reduced Ae (−35%), He (−20%), and raised Fis (maternal 0.50, progeny 0.58), consistent with the species’ mixed mating system; A and Ho were unaffected. Allele frequency shifts suggested selective pressure under eTE. Warming induced slight structure in PCoA, and AMOVA detected 1% (maternal) and 9% (progeny) variation. Fst = 0.06 and Nm = 3.8 imply environmental influence without isolation. Conclusions: Warming significantly shapes seed quality, reproductive success, and genetic diversity in S. capitata. Improved reproduction and germination suggest adaptive advantages, but higher inbreeding and reduced diversity may constrain long-term resilience. The findings underscore the need for genetic monitoring and broader genetic bases in cultivars confronting environmental stressors. Full article

Chronic postsurgical or posttraumatic pain (CPSP) is a persistent pain condition lasting beyond three months after tissue injury, often associated with neuropathic features and pathological angiogenesis. This study investigated the feasibility, safety, and therapeutic potential of transarterial embolization (TAE) in patients with CPSP arising from prior musculoskeletal surgeries or interventions. Six patients with refractory pain and imaging evidence of abnormal neovascularization were retrospectively reviewed. TAE was performed using imipenem/cilastatin particles to selectively target pathological vasculature. Eleven procedures were conducted, achieving 100% technical and clinical success. Mean Numeric Rating Scale scores improved significantly from 7.8 at baseline to 1.3 at final follow-up (p < 0.001). No major adverse events occurred, and follow-up imaging demonstrated resolution of inflammation in selected cases. These results support the role of TAE as a minimally invasive treatment option for intervention-related CPSP involving the musculoskeletal system, and further prospective studies are warranted. Full article

Background: There has been a reduction in successful H. pylori eradication rates recently, which is largely attributed to increasing antibiotic resistance. In areas of high dual clarithromycin and metronidazole resistance such as ours, Maastricht VI/Florence guidelines recommend bismuth quadruple therapy (BQT) as first line of therapy; however, the availability of bismuth was poor in Ireland until recently. Similarly, tetracycline, a component of BQT, is restricted locally, with doxycycline (D) being approved and reimbursed for most indications. Aims: To assess the efficacy of BQT-D therapy for H. pylori eradication in an Irish cohort. Methods: All patients testing positive for H. pylori in three Irish referral centres by urea breath test, stool antigen, or histology were treated prospectively with BQT-D (bismuth subcitrate 120 mg QDS, metronidazole 400 mg TDS, doxycycline 100 mg BD and esomeprazole 40 mg BD) for 14 days. Eradication was evaluated with a urea breath test (UBT) >4 weeks after therapy cessation or by stool antigen testing, as available. Outcomes were recorded and analysed according to demographics and H. pylori treatment history of the patients. Results: 217 patients completed post-eradication testing. Of which, 124 (57%) were female, with a mean age 52 years. 180 patients (83%) were treatment-naïve. A total of 165/180 (92%) of the treatment-naïve patients had successful eradication. There was no association between eradication and gender or age in this cohort (p = 0.3091, p = 0.962 respectively). A total of 29 patients received this therapy as second-line therapy, of which 22 (76%) had successful eradication. Eight patients received the regimen as rescue therapy, with seven (88%) having successful eradication. No serious adverse events were reported. Eleven individuals (6.5%) commented on the complicated nature of the regimen, with 11 tablets being taken at five intervals daily. Conclusions: BQT-D as first-line therapy for H. pylori infection is highly effective in a high dual-resistance population, achieving >90% eradication. BQT-D as a second-line treatment performed less well. Our data support BQT-D as a first-line treatment. Full article