Search Results (82)

Doxorubicin (DOX) is a highly effective chemotherapy drug used in the treatment of many cancers, including solid tumors, hematological malignancies, and soft tissue sarcomas. Despite its potent antitumor effects, DOX is known to have toxic effects in non-tumorous tissues, such as skeletal muscle. Potential mediators of DOX-induced skeletal muscle toxicity are reactive oxygen species (ROS). An overproduction of ROS can disrupt the balance between oxidants and antioxidants in a cell, leading to oxidative stress. Chronic oxidative stress has been shown to upregulate proteolysis, ultimately leading to muscle wasting. Exercise stands as a potent nonpharmacological therapy capable of attenuating muscle wasting by enhancing metabolic function and antioxidant defenses while suppressing harmful ROS production. This review focuses on the current understanding of the role of oxidative stress in DOX-induced skeletal muscle toxicity. In addition, we highlight the effects of various exercise types on oxidative stress and muscle remodeling during DOX chemotherapy. Full article

The N fertilization to reach high cranberry (Vaccinium macrocarpon) yields resulted in high proportions of soft berries. Our objective was to define the mineral nutrient balance of cranberry to reach a high yield of firm berries. The database comprised 393 observations on cv. ‘Stevens’. Berries were analyzed for total S, N, P, K, Ca, Mg, B, Cu, Zn, Mn, Fe, Al, and Si. Random Forest and XGBoost machine learning models were run to predict yield and firmness classes using raw concentrations, centered log ratios (clr) accounting for nutrient interactions, and weighted log ratios (wlr) that also considered the importance of each dual interaction. The wlr returned the most accurate models. The wlr standards elaborated from the high-yielding and nutritionally balanced subpopulation most often differed between the high-yield class and the high-firmness class. The wlr Cu level was significantly (p ≤ 0.01) too high to reach the high-yielding class in the nutritionally imbalanced subpopulation. There was excessive Al and shortage of Si and Mg to reach high berry firmness in the nutritionally imbalanced subpopulation (p ≤ 0.01), indicating the large influence of soil genesis on berry firmness. Despite statistical evidence, cranberry response to Al and Si corrective measures should be tested to elaborate site-specific recommendations based on soil and tissue tests. Full article

Background: Soft-tissue sarcomas (STSs) represent a heterogeneous group of malignancies with widely varying treatment responses and biological behaviors. While spontaneous necrosis (present at diagnosis) is recognized in established sarcoma grading systems, the prognostic significance of therapy-induced necrosis remains uncertain. Inconsistent definitions, methodological variability, and clinical confounders further complicate the interpretation of necrosis as an independent prognostic marker. Methods: This communication synthesizes findings from an international, multidisciplinary webinar hosted by the Sarcoma Academy, critically assessing the utility of therapy-induced necrosis in STS management. Discussions encompassed surgical, pathological, oncological, and radiological perspectives, emphasizing how necrosis is defined, measured, and contextualized in patient care. Results: Heterogeneity in STS subtypes, varied treatment protocols, and sampling inconsistencies challenge the prognostic value of post-treatment necrosis. While substantial necrosis may sometimes signal effective therapy, it can also reflect the tumor’s aggressive nature. The panel underscored the utility of measuring the percentage of viable tumor cells, rather than necrosis alone, to obtain a more standardized and reproducible measure of therapy response. Emerging approaches—such as radiomics, molecular profiling, immune-based analyses, and real-world evidence (RWE) protocols—offer promising avenues for refining prognostication and guiding personalized therapy in STS. Conclusions: A focus solely on therapy-induced necrosis is insufficient to predict outcomes in STS. Instead, a multidisciplinary framework—combining standardized pathology protocols, quantification of viable tumor cells, advanced imaging, and innovative clinical trial designs—can better capture both treatment effects and underlying tumor biology. Future collaborative studies and hybrid trial methodologies are needed to determine which STS subgroups gain the most from intensified treatments aimed at maximizing necrosis, and how to balance such interventions with surgical considerations, toxicity, and overall patient well-being. Full article

Background/Objectives: The SU2C-SARC032 randomized controlled trial (RCT) tested pembrolizumab combined with preoperative normofractionated radiotherapy as an intensified treatment for high-risk stage III resectable soft tissue sarcoma (STS), demonstrating a moderate improvement in disease-free survival (DFS) compared to preoperative radiotherapy alone, but accompanied by significantly increased toxicity, prolonged treatment durations, elevated resource source, and limited real-world applicability. To address the gap between highly controlled trial outcomes and routine clinical practice, this comparative analysis evaluated a streamlined ultra-hypofractionated preoperative radiotherapy (uhpRT) protocol using real-world data (RWD) as a potentially more balanced approach. Methods: Prospectively collected observational RWD from 54 consecutive patients with Stage III (T2 N0 M0) high-risk resectable STS treated at a single institution with uhpRT (25 Gy in 5 fractions in one week, no systemic therapy, median interval of 14 days to surgery) were analyzed. Survival endpoints (overall survival [OS], DFS, local disease-free survival [LDFS], distant disease-free survival [DDFS]), toxicity, and treatment duration were compared qualitatively with published outcomes from the SU2C-SARC032 trial’s intensified pembrolizumab arm and control arm. Results: At 2 years, the optimized uhpRT protocol achieved OS (90%), DFS (66%), and DDFS (70%) comparable to the intensified pembrolizumab arm (OS: 88%, DFS: 67%, DDFS (67%)) and clearly exceeded outcomes of the control arm (OS/DFS/DDFS: 85%/52%/52%). Importantly, the uhpRT protocol markedly reduced treatment-related toxicities (0% Grade 3/4 events vs. 56% in the intensified trial arm) and total treatment duration (<1 month vs. 3–11 months). Conclusions: These findings challenge the necessity of broad treatment intensification for high-risk localized STS, strongly supporting the concept of therapeutic optimization. Given substantial real-world variability in treatment practices and feasibility highlighted by recent research, our findings advocate for treatment strategies that prioritize realistic applicability, patient safety, and value-based care principles over pure intensification. Full article

Phosphorus is one of the most abundant minerals in the body and plays a critical role in numerous cellular and metabolic processes. Most of the phosphate is deposited in bones, 14% is present in soft tissues as various organic phosphates, and only 1% is found in extracellular space, mainly as inorganic phosphate. The plasma inorganic phosphate concentration is closely maintained between 2.5 and 4.5 mg/dL by intertwined interactions between fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), and vitamin D, which tightly regulate the phosphate trafficking across the gastrointestinal tract, kidneys, and bones. Disruption of the strict hemostatic control of phosphate balance can lead to altered cellular and organ functions that are associated with high morbidity and mortality. In the past three decades, there has been a steady increase in the prevalence of kidney failure (KF) among populations. Individuals with KF have unacceptably high mortality, and well over half of deaths are related to cardiovascular disease. Abnormal phosphate metabolism is one of the major factors that is independently associated with vascular calcification and cardiovascular mortality in KF. In early stages of CKD, adaptive processes involving FGF-23, PTH, and vitamin D occur in response to dietary phosphate load to maintain plasma phosphate level in the normal range. However, as the CKD progresses, these adaptive events are unable to overcome phosphate retention from continued dietary phosphate intake and overt hyperphosphatemia ensues. As these hormonal imbalances and the associated adverse consequences are driven by the underlying hyperphosphatemic state in KF, it appears logical to strictly control serum phosphate. Conventional dialysis is inadequate in removing phosphate and most patients require dietary restrictions and pharmacologic interventions to manage hyperphosphatemia. However, diet control comes with many challenges with adherence and may place patients at risk for inadequate protein intake and malnutrition. Phosphate binders help to reduce phosphate levels but come with a sizable pill burden and high financial costs and are associated with poor adherence and psychosocial issues. Additionally, long-term use of binders may increase the risk of calcium, lanthanum, or iron overload or promote gastrointestinal side effects that exacerbate malnutrition and affect quality of life. Given the aforesaid challenges with phosphorus binders, novel therapies targeting small intestinal phosphate absorption pathways have been investigated. Recently, tenapanor, an agent that blocks paracellular absorption of phosphate via inhibition of enteric sodium–hydrogen exchanger-3 (NHE3) was approved for the treatment of hyperphosphatemia in KF. While various clinical tools are now available to manage hyperphosphatemia, there is a lack of convincing clinical data to demonstrate improvement in outcomes in KF with the lowering of phosphorus level. Conceivably, deleterious effects associated with hyperphosphatemia could be attributable to disruptions in phosphorus-sensing mechanisms and hormonal imbalance thereof. Further exploration of mechanisms that precisely control phosphorus sensing and regulation may facilitate development of strategies to diminish the deleterious effects of phosphorus load and improve overall outcomes in KF. Full article

Background and Objectives: Total knee arthroplasty (TKA) is one of the most common medical procedures worldwide. However, 10 to 20% of patients are still dissatisfied despite implants and surgical technique advancements. Recently, several medial-stabilized TKAs have been developed in attempts to replicate the native kinematics of the knee. The aim of this scoping review on medial-stabilized TKA inserts—medial congruent (MC) and medial pivot (MP)—is to focus on their clinical outcomes and the role of the posterior cruciate ligament (PCL), aiming to systematically map the existing research and highlight current knowledge gaps. Materials and Methods: A search of the PubMed, Embase and Cochrane databases was performed to identify relevant studies on the kinematics and outcomes of medial pivot (MP) or medial congruent (MC) inserts. The following Mesh terms were used in combination with the Boolean operators “AND” and “OR”: “total knee arthroplasty”, “total knee replacement”, “medial pivot”, “medial congruence”, “outcomes” and “kinematic”. Original studies reporting on clinical outcomes assessed with validated patient-reported scales, surgical techniques and reoperation rates for any reason with a minimum follow-up of 18 months were included. Results: A total of 39 articles met the inclusion criteria, accounting for 6143 total knee replacements. The overall reoperation-free survivorship rate was 98.4% (6047 out of 6143 knees) at a weighted average follow-up of 6.3 years (range 1.5–15.2 years, SD 0.7). Both MP and MC inserts demonstrated good outcomes, with no differences between groups. Few studies evaluated the role of the PCL in MP and MC inserts, with no differences in terms of clinical outcomes between retaining and sacrificing the PCL. Conclusions: MS-TKA demonstrated good outcomes in the literature independently of the specific design (medial pivot or medial congruent). Different possible biases may be present when evaluating the outcomes of these inserts, including different types of alignment and soft tissue balancing philosophies. Full article

Conductive hydrogels, particularly those incorporating poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), have revolutionized wearable health monitoring by merging tissue-like softness with robust electronic functionality. This review systematically explores design strategies for PEDOT:PSS-based hydrogels, focusing on advanced gelation methods, including polymer crosslinking, ionic interactions, and light-induced polymerization, to engineer hierarchical networks that balance conductivity and mechanical adaptability. Cutting-edge fabrication techniques such as electrochemical patterning, additive manufacturing, and laser-assisted processing further enable precise microstructural control, enhancing interfacial compatibility with biological systems. The applications of these hydrogels in wearable sensors are highlighted through their capabilities in real-time mechanical deformation tracking, dynamic tissue microenvironment analysis, and high-resolution electrophysiological signal acquisition. Environmental stability and long-term durability are critical for ensuring reliable operation under physiological conditions and mitigating performance degradation caused by fatigue, oxidation, or biofouling. By addressing critical challenges in environmental stability and long-term durability, PEDOT:PSS hydrogels demonstrate transformative potential for personalized healthcare, where their unique combination of softness, biocompatibility, and tunable electro-mechanical properties enables seamless integration with human tissues for continuous, patient-specific physiological monitoring. These systems offer scalable solutions for multi-modal diagnostics, empowering tailored therapeutic interventions and chronic disease management. The review concludes with insights into future directions, emphasizing the integration of intelligent responsiveness and energy autonomy to advance next-generation bioelectronic interfaces. Full article

Background and Objectives: Diagnostic imaging is essential for evaluating urinary tract disorders, offering critical insights into renal pathology. This review examines the strengths, limitations, and clinical applications of various imaging modalities, with a focus on pediatric populations. Materials and Methods: A narrative review was conducted, synthesizing current literature on ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and voiding cystourethrography (VCUG). Relevant studies were selected based on diagnostic accuracy, clinical utility, and safety considerations. Results: US is the preferred first-line imaging due to its safety, accessibility, and cost-effectiveness. CT excels in detecting renal calculi, trauma, and malignancies but is limited by radiation exposure. MRI offers superior soft tissue contrast without radiation but is costly and often requires sedation. Nuclear medicine evaluates renal function and scarring, while VCUG remains the gold standard for diagnosing vesicoureteral reflux and posterior urethral valves. Conclusions: Imaging modalities are vital for diagnosing and managing urinary tract disorders, with selection based on clinical needs, patient age, and safety. Ultrasound is the primary choice for its non-invasiveness and cost-effectiveness, while CT, MRI, nuclear medicine, and VCUG provide essential structural and functional insights. A balanced approach ensures accuracy while minimizing patient risk, especially in pediatrics. Full article

Background: Reverse shoulder arthroplasty (RSA) improves shoulder function in cases of glenohumeral osteoarthritis and rotator cuff arthropathy. The design of the glenosphere influences mobility and scapular impingement. This study evaluates the impact of joint volume on the range of motion (RoM) and identifies design modifications to enhance mobility while reducing the impingement risk. Methods: Thirty-four cadaveric shoulders were implanted with the Aequalis Reversed II^® prosthesis in seven configurations: four with 36 mm spheres (centered, 2 mm eccentric, and lateralized by 5 mm and 7 mm) and three with 42 mm spheres (centered, and lateralized by 7 mm and 10 mm). The joint volumes (inferior, anteroinferior, and posteroinferior) were measured via 3D CT scans. The RoM in adduction and elbow-at-side rotations (IR1 and ER1) was recorded. A statistical analysis identified threshold joint volumes correlating with improved mobility. Results: Larger joint volumes correlated with enhanced mobility. The 42 mm spheres demonstrated better adduction and ER1 compared to those of the 36 mm spheres (p < 0.0001). An inferior volume > 5000 mm³ and anteroinferior/posteroinferior volumes >2500 mm³ were thresholds for significant mobility improvement. Lateralization (≥7 mm) or inferior eccentricity (2 mm) improved the mobility with the 36 mm spheres, with the 36 + 2 configuration offering a practical balance for smaller patients. Conclusions: Increased joint volume enhances mobility, particularly in adduction and elbow-at-side rotations. A sphere with a 2 mm inferior offset or a 42 sphere with 7 mm lateralization optimizes the RoM while minimizing impingement risks. Patient-specific considerations, including anatomy and soft tissue tension, remain essential for optimal prosthesis selection. Full article

Background: Hand fracture management requires precise diagnostic accuracy and complex decision-making. Advances in artificial intelligence (AI) suggest that large language models (LLMs) may assist or even rival traditional clinical approaches. This study evaluates the effectiveness of ChatGPT-4o, DeepSeek-V3, and Gemini 1.5 in diagnosing and recommending treatment strategies for hand fractures compared to experienced surgeons. Methods: A retrospective analysis of 58 anonymized hand fracture cases was conducted. Clinical details, including fracture site, displacement, and soft-tissue involvement, were provided to the AI models, which generated management plans. Their recommendations were compared to actual surgeon decisions, assessing accuracy, precision, recall, and F1 score. Results: ChatGPT-4o demonstrated the highest accuracy (98.28%) and recall (91.74%), effectively identifying most correct interventions but occasionally proposing extraneous options (precision 58.48%). DeepSeek-V3 showed moderate accuracy (63.79%), with balanced precision (61.17%) and recall (57.89%), sometimes omitting correct treatments. Gemini 1.5 performed poorly (accuracy 18.97%), with low precision and recall, indicating substantial limitations in clinical decision support. Conclusions: AI models can enhance clinical workflows, particularly in radiographic interpretation and triage, but their limitations highlight the irreplaceable role of human expertise in complex hand trauma management. ChatGPT-4o demonstrated promising accuracy but requires refinement. Ethical concerns regarding AI-driven medical decisions, including bias and transparency, must be addressed before widespread clinical implementation. Full article

Biopolymer hydrogel-based scaffold materials have received a lot of interest in tissue engineering and regenerative medicine because of their unique characteristics, which include biocompatibility, biodegradability, and the ability to replicate the natural extracellular matrix (ECM). These hydrogels are three-dimensional biopolymer networks that are highly hydrated and provide a supportive, wet environment conducive to cell growth, migration, and differentiation. They are especially useful in applications involving wound healing, cartilage, bone, and soft tissue regeneration. Natural biopolymers such as collagen, chitosan, hyaluronic acid, and alginate are frequently employed as the foundation for hydrogel fabrication, providing benefits such as low toxicity and improved cell adherence. Despite their potential, biopolymer hydrogel scaffolds have various difficulties that prevent broad clinical implementation. Key difficulties include the challenge of balancing mechanical strength and flexibility to meet the needs of various tissues, managing degradation rates to line up with tissue regeneration, and assuring large-scale manufacturing while retaining scaffold uniformity and quality. Furthermore, fostering appropriate vascularization and cell infiltration in larger tissues remains a significant challenge for optimal tissue integration and function. Future developments in biopolymer hydrogel-based scaffolds are likely to concentrate on addressing these obstacles. Strategies such as the creation of hybrid hydrogels that combine natural and synthetic materials, smart hydrogels with stimulus-responsive features, and 3D bioprinting technologies for accurate scaffold production show significant potential. Furthermore, integrating bioactive compounds and growth factors into hydrogel matrices to promote tissue regeneration is critical for enhancing therapeutic results. Full article

The current study began with the following question: Is smoking a balanced factor between human body systems? One of the particular features of the oral cavity is its localization at the gateway of respiratory and digestive. Morphologically, the oral cavity encompasses a complex association of soft tissues, hard tissues, salivary glands, and taste receptors. The main purpose of this study was to analyze the tobacco residues (TAR) deposited on dental materials and the alterations of artificial saliva that comes into contact with tobacco smoke, by obtaining a solution of cigarette smoke extracts (CSE) after 5, 10, 15, and 20 tobacco cigarettes. According to LC-MS analysis and FT-IR spectra, carbonyl compounds, phenols, and carboxylic acids are present in CSE, which could explain the pH decrease and acid characteristic. Moreover, the CSE solution was added to the culture medium of Mesenchymal Stem Cells (MSCs) to evaluate the cytotoxicity. The MTT study revealed decreased MSC viability; morphological changes and cell death were more intense at higher doses of CSE added to the culture medium. Scanning Electron Microscopy (SEM) indicated cellular ruffling and irregular cell surface under higher concentrations of CSE-15 and CSE-20 in culture media, which is a characteristic feature demonstrating the membrane stress. In conclusion, the present study, with its limitations, showed the negative cellular effects of tobacco cigarette smoking and the impact of this habit on the oral cavity homeostasis. Full article

Background: Pelvic fractures are among the most complex and life-threatening injuries encountered in trauma and orthopedic surgery, often resulting from high-energy trauma and leading to severe complications. This review synthesizes recent advancements in pelvic trauma care, with a focus on comparing damage control orthopedics (DCO) and early total care (ETC) strategies, operative versus nonoperative management, and outcomes of minimally invasive versus traditional ORIF techniques. Results: Our comparative analysis highlights that DCO remains the preferred approach for hemodynamically unstable patients, prioritizing rapid stabilization and reducing mortality from hemorrhage. In contrast, ETC has demonstrated superior functional recovery outcomes in stable polytrauma patients, with a 30–40% reduction in pulmonary complications and shorter ICU stays when performed within 24–48 h post-injury. Additionally, percutaneous fixation reduces soft tissue trauma and infection risk but increases the likelihood of malunion, while ORIF provides superior anatomical restoration with a higher risk of postoperative infections. Hybrid approaches, integrating percutaneous techniques with limited open reduction, show promise in minimizing operative time and complications while achieving stable fixation. Conclusions: These findings reinforce the importance of tailoring surgical strategies to patient physiology and injury patterns. DCO and ETC have distinct but complementary roles, and emerging hybrid techniques offer a middle ground that balances stability with reduced morbidity. A precision medicine approach, integrating AI-driven predictive modeling and real-world clinical data, is essential for optimizing outcomes and developing evidence-based treatment protocols. Large-scale, multicenter trials are needed to validate these approaches and establish standardized guidelines for pelvic fracture management. Full article

Implants made of titanium and its alloys are currently widely used in the human body. A series of surface modification methods developed nowadays enable titanium alloy implants to serve effectively in the human body for a long time. This paper reviews three different types of surface modification technologies for biomedical titanium alloys: physical, chemical, and biological, with particular attention to the assistance of these three technologies on the biological properties of titanium alloys. The physical method can change the surface morphology of titanium implants and prepare specific coatings for the implants, such as oxide films, bioactive molecules, drugs, etc. Chemical and biological surface modification technologies can minimize bacterial adhesion on the implant surface, improve the integration of soft tissue around the implant, prevent the occurrence of peri-implantitis, and accelerate the process of damage repair. An ideal titanium implant surface should balance the optimal surface morphology, chemical properties, and bionic characteristics to accelerate bone integration, enhance stability, and reduce peri-implant inflammation. Future research should focus on combining technologies, exploring interactions at the cellular and molecular levels, and conducting extensive in vitro and in vivo studies to verify the effectiveness and safety of modified surfaces. The progress in these fields will help overcome the existing limitations, improve the performance of implants, and obtain better clinical results. Full article

Background: The aim of this study was to evaluate the balance in extension and flexion achievable after total knee arthroplasty (TKA) using a modified kinematic alignment (KA) plan and the subsequent balance achievable after adjusting the component based on the functional alignment (FA) principle. Methods: This retrospective cohort study included 100 consecutive patients who underwent primary TKA for knee osteoarthritis through an image-based robotic system in a single center between October 2021 and February 2022. Whether modified KA or FA could achieve a balanced knee was evaluated by assessing the ligament balance in the medial and lateral compartments using a robotic system at extension and 90° flexion. Balance was defined as a difference of ≤2 mm between the compartments. Component positioning was adjusted within limits based on the functional positioning principles to achieve balance. Implant positioning and balance in extension and 90° flexion were compared between the modified KA plan (n = 100) and after FA adjustments (n = 100). Results: FA achieved significantly better balance in extension (FA, 99.0% vs. modified KA, 86.0%; p = 0.001) and flexion (98.0% vs. 43.0%; p < 0.001) than the modified KA plan. The mean difference in gap balance in extension (FA, 0.1 mm vs. modified KA, 0.6 mm; p = 0.001) and flexion (0.1 mm vs. 2.3 mm; p < 0.001) was also significant between the two techniques. The femoral component was positioned more externally rotated relative to the transepicondylar axis (FA, 2.5° vs. modified KA, 0.0°; p < 0.001) to obtain balanced targets. There were significant improvements in the patient-reported outcome measures between preoperative and postoperative assessments two years after TKA (all p < 0.05). Conclusions: FA consistently achieved superior balance in both extension and flexion following TKA compared with modified KA without altering the soft tissue envelope, leading to significant improvements in clinical outcomes at the two-year follow-up. Full article