Search Results (715)

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies. Full article

Background and Clinical Significance: Serratus Anterior Muscle Pain Syndrome (SAMPS) is an underdiagnosed cause of anterior chest wall pain, often attributed to myofascial trigger points of the serratus anterior muscle (SAM) or dysfunction of the Long Thoracic Nerve (LTN), leading to significant disability and affecting ipsilateral upper limb movement and quality of life. Current diagnosis relies on exclusion and physical examination, with limited treatment options beyond conservative approaches. This case report presents a novel approach to chronic SAMPS, successfully diagnosed using Sonoguided Digital Palpation (SDP) and treated with ultrasound-guided hydrodissection of the LTN using 5% dextrose in water (D5W) without local anesthetic (LA), in a patient where conventional treatments had failed. Case Presentation: A 72-year-old male presented with a three-year history of persistent left chest pain radiating to the upper back, exacerbated by activity and mimicking cardiac pain. His medical history included two percutaneous coronary interventions. Physical examination revealed tenderness along the anterior axillary line and a positive hyperirritable spot at the mid axillary line at the 5th rib level. SDP was used to visualize the serratus anterior fascia (SAF) and LTN, and to reproduce the patient’s concordant pain by palpating the LTN. Ultrasound-guided hydrodissection of the LTN was then performed using 20–30cc of D5W without LA to separate the nerve from the surrounding tissues, employing a “fascial unzipping” technique. The patient reported immediate pain relief post-procedure, with the pain reducing from 9/10 to 1/10 on the Numeric Rating Scale (NRS), and sustained relief and functional improvement at the 12-month follow-up. Conclusions: Sonoguided Digital Palpation (SDP) of the LTN can serve as a valuable diagnostic adjunct for visualizing and diagnosing SAMPS. Ultrasound-guided hydrodissection of the LTN with D5W without LA may provide a promising and safe treatment option for patients with chronic SAMPS refractory to conservative management, resulting in rapid and sustained pain relief. Further research, including controlled trials, is warranted to evaluate the long-term efficacy and generalizability of these findings and to compare D5W to other injectates. Full article

Myelodysplastic syndromes/neoplasms (MDS) represent a biologically and clinically diverse group of myeloid malignancies marked by cytopenias, morphological dysplasia, and an inherent risk of progression to acute myeloid leukemia. Over the past two decades, the field has made significant advances in characterizing the molecular landscape of MDS, leading to refined classification systems to reflect the underlying genetic and biological diversity. In 2025, the treatment of MDS is increasingly individualized, guided by integrated clinical, cytogenetic, and molecular risk stratification tools. For lower-risk MDS, the treatment paradigm has evolved beyond erythropoiesis-stimulating agents (ESAs) with the introduction of novel effective agents such as luspatercept and imetelstat, as well as shortened schedules of hypomethylating agents (HMAs). For higher-risk disease, monotherapy with HMAs continue to be the standard of care as combination therapies of HMAs with novel agents have, to date, failed to redefine treatment paradigms. The recognition of precursor states like clonal hematopoiesis of indeterminate potential (CHIP) and the increasing use of molecular monitoring will hopefully enable earlier intervention/prevention strategies. This review provides a comprehensive overview of the current treatment approach for MDS, highlighting new classifications, prognostic tools, evolving therapeutic options, and ongoing challenges. We discuss evidence-based recommendations, treatment sequencing, and emerging clinical trials, with a focus on translating biological insights into improved outcomes for patients with MDS. Full article

Background and Objectives: Peripheral vascular access in infants is a frequent but technically challenging procedure due to the anatomical characteristics of this population. Repeated failed attempts may increase complications and emotional stress for both patients and healthcare professionals. This systematic review aimed to evaluate the efficacy and safety of ultrasound-guided peripheral vascular cannulation compared to the conventional or “blind” technique in infants. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines. The PubMed database was searched for studies published between 2017 and 2025. Studies comparing both techniques in infants under two years of age were selected, evaluating variables such as the number of punctures, first-attempt success, healthcare staff perception, associated stress, and the role of simulation in training. Results: Eleven studies were included, comprising clinical trials, observational studies, and training program assessments from different countries. Most reported a higher first-attempt success rate with the ultrasound-guided technique (often exceeding 85%), along with fewer punctures and complications, particularly among less-experienced professionals. Improvements in staff perception were also observed following structured training. The impact on stress experienced by patients and families was less frequently assessed directly, although some studies reported indirect benefits. Conclusions: Ultrasound-guided peripheral vascular cannulation appears to be more effective and safer than the conventional technique in infants, particularly in complex or critical care contexts. Its implementation requires specific training and appropriate resources but could significantly improve clinical outcomes and the pediatric patient experience. Full article

In hormone-dependent cancers, front-line treatment options include surgery and therapies that target hormone dependance. These therapies are effective initially but fail in tumors that recur, develop resistance or present at an advanced stage. Consequently, new therapeutic avenues are urgently needed. Increasing evidence implicates epigenetic modulators in tumor initiation, progression and therapeutic response, making them attractive biomarkers for patient stratification and targets for intervention. Over the past two decades, the discovery and development of small-molecule inhibitors directed against key epigenetic regulators have accelerated. This review provides a comprehensive overview of the major epigenetic targets, the inhibitors developed against them and the clinical trials currently underway in endocrine-related cancers. While epigenetic agents have shown limited benefits as monotherapies, their use in combination regimens is emerging as a strategy to overcome resistance and enhance the efficacy of existing treatments. We summarize the current landscape of combination trials, highlight early signs of clinical activity and discuss the opportunities and challenges inherent in integrating epigenetic drugs into the management of advanced endocrine-related cancers. Full article

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article

Oligometastasis represents a clinically relevant state of limited metastatic disease that could be amenable to selected local therapies in carefully chosen patients. Although initial trials such as SABR-COMET demonstrated a survival benefit with aggressive local treatment, breast cancer was underrepresented. Subsequent breast cancer-specific trials, including NRG-BR002, failed to show a clear survival benefit, highlighting uncertainties and the need for further refinement in patient selection and integration with systemic approaches. The definitions of oligometastasis continue to evolve, incorporating radiological, clinical, and biological features. Advances in imaging and molecular profiling suggest that oligometastatic breast cancer might represent a distinct biological subtype, with potential biomarkers including PIK3CA mutations and YAP/TAZ expression. Organ-specific strategies using stereotactic radiotherapy, surgery, and proton therapy have shown favorable local control in certain settings, though their impact on the overall survival remains under investigation. Emerging techniques, including circulating tumor DNA (ctDNA) analysis, are being explored to improve patient selection and disease monitoring. Ongoing trials may provide further insight into the role of local therapy, particularly in hormone receptor-positive or HER2-positive subtypes. Local and systemic strategies need to be carefully coordinated to optimize the outcomes. This review summarizes the current definitions of and evidence and therapeutic considerations for oligometastatic breast cancer and outlines potential future directions. Full article

Background: Current methods of postural control assessments and interventions to improve postural stability and thereby prevent falls often fail to incorporate the hazardous perturbation situations that frequently accompany falls. Virtual environments can safely incorporate these hazards. The purpose of the study was to identify if virtual slip and trip perturbations can be used as an exposure paradigm in place of real slip and trip perturbations to improve postural control. Methods: Fifteen healthy young adults were included in this study. Two paradigms, real gait exposure (real) and virtual environment gait exposure (virtual), consisting of real and virtual slip and trip trials, were performed by each participant in a counterbalanced order to avoid order effects. At baseline and following real and virtual paradigms, the modified clinical test for sensory integration and balance (mCTSIB), limits of stability (LOS), and single-leg stance (SLS) using BTracks balance plate were administered. Separate one-way (baseline vs. Real vs. Virtual) repeated measures analysis of variance were conducted on response variables. Results: In the posterior left quadrant of the LOS, significant differences were found after the real paradigm compared to baseline (p = 0.04). For the anterior left quadrant and total LOS, significant differences post real paradigm (p = 0.002 and p < 0.001) and virtual paradigm (p = 0.007 and p < 0.001) compared to baseline were observed. For the SLS, the left-leg significant differences were observed post real paradigm (p = 0.019) and virtual paradigm (p = 0.009) compared to BL in path length, while significant main effects were found for mean sway velocity for the left leg only (p = 0.004). For the right leg, significant differences were only observed after the virtual paradigm (p = 0.01) compared to BL. Conclusions: Both virtual and real paradigms were identified to improve postural control. The virtual paradigm led to increased postural control in the right-leg SLS condition, while the real paradigm did not, without any adverse effects. Findings suggest virtual reality perturbation exposure acutely improves postural control ability compared to baseline among healthy young adults. Full article

Background/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. Methods: This systematic review (SR) examines the relationship between vitamin D and the reduction of cancer risk and mortality, and the mechanisms involved in cancer prevention. This SR followed the PRISMA and PICOS guidelines and synthesized evidence from relevant studies. Results: Beyond genomic actions via calcitriol [1,25(OH)₂D]-receptor interactions, vitamin D exerts cancer-protective effects through mitigating inflammation, autocrine, paracrine, and membrane signaling. The findings reveal a strong inverse relationship between serum 25(OH)D levels and the incidence, metastasis, and mortality of several cancer types, including colon, gastric, rectal, breast, endometrial, bladder, esophageal, gallbladder, ovarian, pancreatic, renal, vulvar cancers, and both Hodgkin’s and non-Hodgkin’s lymphomas. While 25(OH)D levels of around 20 ng/mL suffice for musculoskeletal health, maintaining levels above 40 ng/mL (100 nmol/L: range, 40–80 ng/mL) significantly lowers cancer risks and mortality. Conclusions: While many observational studies support vitamin D’s protective role in incidents and deaths from cancer, some recent mega-RCTs have failed to demonstrate this. The latter is primarily due to critical study design flaws, like recruiting vitamin D sufficient subjects, inadequate dosing, short durations, and biased designs in nutrient supplementation studies. Consequently, conclusions from these cannot be relied upon. Well-designed, adequately powered clinical trials using appropriate methodologies, sufficient vitamin D₃ doses, and extended durations consistently demonstrate that proper supplementation significantly reduces cancer risk and markedly lowers cancer mortality. Full article

Salmonella therapies are a promising tool for the treatment of solid tumors. Salmonella can be engineered to increase their tumor infiltration, cell killing abilities, and immunostimulatory properties. However, bacterial therapies have often failed in clinical trials due to poor characterization. Mathematical models are useful for predicting the immune response to cancer treatments and characterizing the properties of bacterial invasion. Herein we develop an ordinary differential equation-based model that combines bacterial therapies with classical anti-tumor immunotherapies. Our modeling results suggest that increasing bacterial localization to the tumor is key for therapeutic efficacy; however, increased intracellular invasion and direct bacterial mediated cytotoxicity does not reduce tumor growth. Further, the model suggests that enhancing T cell-mediated cell death by both bacterial stimulation of pro-inflammatory cytokines and activation of T cells via antigen cascade is critical for therapeutic efficacy. A balance of intracellular and extracellular Salmonella leads to more effective therapeutic response, which suggests a strategy for strain design to be tested in vivo. Overall, this model provides a system to predict which engineered features of Salmonella therapies lead to effective treatment outcomes. Full article

Background/Objectives: Children with an oral presence of Candida spp. have an elevated prevalence of dental caries. As an alternative to conventional antifungal drugs, the use of biofilm-modulating strategies, such as probiotic bacteria, may be a sustainable option. Probiotics are live microorganisms that have beneficial health effects, while prebiotics are compounds in food that foster the growth or activity of the beneficial microorganisms. The aim of this paper was to review current clinical findings regarding the antifungal effects of pre- and probiotic supplements, including syn- and postbiotics, in children. Methods: We searched two databases (PubMed and Google Scholar) for controlled clinical trials published in English up to 20 April 2025, and two authors scanned the abstracts independently for relevance. The selected full-text papers were reviewed and assessed for risk of bias. Results: Four articles published between 2013 and 2025 were included in this review, covering a total number of 208 caries-active children between 3 and 14 years of age. Study designs were heterogeneous, and we observed conflicting results: two studies with probiotic streptococci failed to demonstrate any beneficial effects on the counts of salivary C. albicans, while interventions with L. plantarum and L. rhamnosus significantly reduced C. albicans compared with controls. None of the included reports displayed a low risk of bias. No clinical studies utilizing prebiotics, synbiotics, or postbiotics were retrieved. Conclusions: We found insufficient evidence concerning the antifungal effects of probiotic supplements in children. Therefore, we recommend future clinical trials to explore the ability of pre-, pro-, and postbiotic interventions to affect cross-kingdom biofilms in order to support a balanced and health-associated composition of the dental biofilm in children. Full article

Background: It is generally well-known that narration of care is critically important to high-quality nursing care. Narration of care is loosely defined as a nurse’s ability to describe to patients and families the clinical purpose behind nursing practice, what is hoped to be achieved, and the “why” (or clinical rationale) behind nursing activities. Despite the importance of narration of care, there is little practical guidance given to nurses about how to narrate care—what makes for effective or ineffective narration of care. Objective: Our aim was to develop a framework for teaching nurses and patient care assistants (PCAs) on how to effectively narrate care. In this article, we provide a practical framework for teaching nurses and PCAs how to narrate care. We describe the process of developing the framework as part of quality improvement efforts and implementing a course for eight hospitals based on the framework. Methods: Consistent with a Plan-Do-Study Act (PDSA) quality improvement approach, we developed the framework by first conducting a data and literature review, then convening a taskforce, discussing with patients on our existing committees, and finally formulating a framework. We then drafted supplementary cases and course material and implemented a course to teach nurses and PCAs how to narrate care. Results: The narration of care framework (NOC) that we developed and implemented consisted of the following five principles, which can be called RECAP as an acronym: 1. The “R” in RECAP stands for removing uncertainty. 2. The “E” in RECAP stands for explaining the environment. 3. The “C” in RECAP stands for being calm and sincere. 4. The “A” in RECAP stands for assume nothing. 5. The “P” in RECAP stands for personal connection. As for the course developed based on the RECAP principles, there was a total of 276 course offerings conducted by 30 facilitators, and 7341 nurses and PCAs completed the course. The evaluations reflected that 99% of learners believed their learning was improved by the course. Discussion: There are several multifaceted benefits to NOC: nurses’ and PCAs’ capability to narrate care well shows empathy and compassion to patients; it strengthens patient understanding and education that can lead to improved patient outcomes; and it helps allay patients’ uncertainties and anxieties. In essence, narrating care in an effective manner cultivates a strong nurse–patient therapeutic relationship. Yet, in the absence of any practical guidance, nurses and PCAs are left to develop narration skills on their own, learning by trial and error, and, in doing so, perhaps failing to meet patients’ needs and failing to fully derive the many benefits that the NOC is designed to achieve. Our hope is that, if hospital systems adopt our work, nurses and PCAs can comfortably and confidently enter the profession knowing the purpose or narrating care, its many benefits, and how to practically conduct sufficient narration, and what would constitute insufficient narration. Hospitals, in turn, can specify and clearly articulate their expectations for nurses and PCAs narrating with patients—what would make for a strong, compassionate process and what would be inadequate. For more experienced nurses, they can use the RECAP framework to reflect on their own practices and perhaps strengthen or refreshen existing skills. Conclusions: NOC is acknowledged, somewhat implicitly, as being critical to nursing and PCA practice, yet practical instruction and specified principles are lacking. We aimed to fill this gap by developing, implementing, and teaching a practical framework, armed with many tools nurses can use. Full article

Young athletes face unique nutritional challenges due to their simultaneous engagement in intensive physical training and ongoing growth and development. Standard adult-based dietary recommendations often fail to meet the specific needs of this population. While the role of macronutrients and micronutrients is well recognized, increasing attention is being paid to bioactive compounds—non-essential food-derived elements with potential health benefits. This review aims to summarize current evidence regarding the efficacy, safety, and potential benefits of bioactive compounds in the nutritional management of young athletes. Methods: A narrative review of the literature published over the last 30 years was conducted across PubMed/Medline, Embase, and Scopus databases to identify relevant studies published in English. The inclusion criteria covered original research articles, clinical trials, cohort and case-control studies, and meta-analyses focusing on individuals aged 8–20 years. Studies addressing supplementation strategies, physiological effects, and safety concerns of bioactive compounds in young athletes were selected. Preclinical data and adult-based studies were also included to contextualize molecular mechanisms and support clinical findings. Results: The review highlights that bioactive compounds such as omega-3 fatty acids, curcumin, caffeine, and creatine as well as antioxidant vitamins may play a beneficial role in improving recovery, immune function, and performance in young athletes. Of these 21 studies, 8 focused on recovery and muscle soreness, 6 addressed immune function or antioxidant/anti-inflammatory effects, and 7 investigated direct performance enhancement. However, most of the available evidence derives from adult populations, and pediatric-specific data remain limited. Concerns remain about the misuse of supplements, lack of professional guidance, and potential contamination with banned substances. Conclusions: While some bioactive compounds show promising potential to support the health and performance of young athletes, current evidence is insufficient to support routine use in this population. More pediatric-specific research is necessary to establish safety, efficacy, and appropriate supplementation protocols tailored to young athletes’ unique physiological needs. Full article

Implant primary stability is a prerequisite for obtaining osseointegration and clinical success. Insertion torque (IT) is measured during implant placement and is expressed in Ncm. It represents the quantification of the frictional force experienced by the implant as it progresses apically through a rotational motion along its axis. Usually, to achieve osseointegration, a value within the range of 20–40 Ncm is desirable. Below a threshold of 20 Ncm, implants have a decrease in survival rate, while implant stability is guaranteed above 20 Ncm. The main goal of this study was to evaluate whether high values of IT affect osseointegration, implant health, and healing, by highlighting the positive and negative effects of IT > 50 Ncm on peri-implant bone, soft tissues, and long-term stability. This scoping review considered randomized clinical trials, observational studies, and cohort studies. Studies failing to meet the predefined inclusion criteria were excluded from the analysis. The review process adhered to the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) guidelines. Ultimately, a total of 11 studies were included in the final synthesis. Based on the studies included, the literature suggests that high values of IT guarantee adequate primary stability and better osseointegration. However, high IT is significantly associated with greater marginal bone loss, depending on bone density. Accordingly, IT values > 50 Ncm may provoke greater compressive forces with a negative impact on the jawbone. An elevated strain on the bone can induce necrosis and ischemia, due to an alteration of circulation, which in turn is responsible for marginal bone loss and reduced osseointegration. Lack of osseointegration ultimately leads to an early implant failure. As concerns soft tissue recession, a higher decrease is measured in implants placed with high-insertion torque. Nonetheless, additional clinical trials are warranted to assess long-term outcomes, quantify the incidence of these complications, and explore the impact of emerging clinical variables. Full article