Medical sciences (Basel, Switzerland)最新文献

Objective: Myxofibrosarcoma (MXF) and undifferentiated pleomorphic sarcoma (UPS) are common and aggressive subtypes of cancer differing by clinical characteristics and prognosis; however, their differential diagnosis is difficult. Elucidation of cellular and transcriptomic discrepancies between these diseases that could improve their identification was the aim of our study. Methods: We applied single-cell RNA sequencing to compare MXF and UPS by tumor cell clusters and cell-cell ligand-receptor interactions, using five tumor samples of both subtypes. Results: We identify nine major cell types in all tumors analyzed. Any significant differences in their proportions between MXF and UPS were not found. Further reclusterization of lymphoid cells showed that cytotoxic CD8+ T cell proportion was higher in the MXF samples. In UPS cancer cells, the pathways maintaining extracellular matrix components (including collagens, proteoglycans, and other proteins) were highly active, while MXF cells were characterized by high activity of growth factors and angiogenesis pathways. The ligand-receptor interactions between cancer cells and the microenvironment differed significantly between MXF and UPS. In UPS, CD80 of dendritic cells and macrophages prominently interacted with T cell co-inhibitory CTLA-4 receptors, whereas the activating CD80-CD28 interaction was predominant in MXF. Moreover, in UPS, CD44 and integrins of cytotoxic CD8+ T cells prominently interacted with COL1A1/2, while in MXF CD44, interaction with FN1, COL6A1, and LAMC1 prevailed. Conclusions: Differences were identified between UPS and MFS in the composition of lymphoid cell populations and in the intercellular interactions. This proposes deeper understanding of the biological differences between these sarcoma subtypes and may be important for the development of new therapeutic approaches, although further validation of the findings is required.

Background/Objectives: Global disability scales such as the Glasgow Outcome Scale-Extended (GOS-E) may not fully capture real-life participation after traumatic brain injury (TBI). This secondary analysis quantified mismatch between global disability and participation 5 years after moderate-to-severe TBI and identified predictors of a "good recovery, poor participation" profile. Methods: We analysed the TBIMS National Database Public Use Data Set, including adults ≥ 16 years with moderate-to-severe TBI, 5-year follow-up, and valid GOS-E, PART-O, and employment data. High versus low global outcome was defined as GOS-E 7-8 versus 3-6; good versus poor participation was defined using PART-O total (≥median vs. ≤25th percentile) plus productive role engagement. Four outcome profiles were derived and compared using 2 × 2 factorial analyses and regression. Results: The analytic cohort included 6363 participants; among those with high GOS-E, 16.8% met criteria for poor participation. Profiles with poor participation showed lower participation and lower life satisfaction and higher mood symptoms than Group A (high GOS-E, good participation), whereas those with low GOS-E but good participation showed preserved participation with greater emotional burden. Older age, lower education, minority race/ethnicity, pre-injury unemployment or retirement, longer post-traumatic amnesia, and lower 2-year GOS-E independently predicted mismatch. Sensitivity analyses using alternative GOS-E and participation cut-offs and life-satisfaction outcomes yielded similar patterns. Conclusions: Five years after moderate-to-severe TBI, good global recovery does not guarantee successful reintegration, and some individuals maintain participation despite persisting disability. Routine assessment of participation and life satisfaction alongside global disability is needed to identify high-risk profiles and target vocational and psychosocial interventions.

Glioblastoma is known as the most aggressive primary brain tumor in adults, and it is still largely not curable, with a median survival of approximately 15 months when standard multimodal therapy is applied. The standard treatment nowadays is maximal safe surgical resection, associated with radiotherapy and temozolomide. Treatment effectiveness is limited not only by an impassable blood-brain barrier (BBB) to drug delivery to the brain, but also by the heterogeneity of the tumors and intrinsic or acquired drug resistance, resulting in a certain and inescapable tumor relapse. Therefore, novel drug delivery systems are being designed to overcome the BBB and improve therapeutic efficacy. These approaches include nanoparticle-mediated delivery systems, convection-enhanced intra-tumoral infusion, implantable drug-releasing devices, and noninvasive focused ultrasound technology, which induced transient disruption of the BBB. These approaches are designed to enhance local drug exposure and reduce systemic toxicity with promising preclinical and early clinical results. However, many clinical and technical challenges remain, especially the need for safety, homogeneous drug delivery, and translation of these advances into effective clinical therapies. Current glioblastoma treatment landscape and opportunities include maturing delivery systems, novel therapeutic approaches, including targeted molecular therapies and immunotherapy, as well as personalized regimens. This multidisciplinary modality may have the capacity to help not only patients with GBM but others as well through a multimodal approach of targeted drug delivery and innovative therapy in the long run to improve clinical outcomes of GBM in patients.

Parkinson's disease (PD) is a progressive and heterogeneous neurodegenerative disorder and one of the fastest-growing causes of neurological disability worldwide. Although historically defined by motor manifestations resulting from nigrostriatal dopaminergic degeneration, PD is now recognized as a multisystem disorder. Non-motor features-including autonomic dysfunction, neuropsychiatric symptoms, cognitive impairment, and sleep-related disorders-frequently precede motor onset by years or even decades, delineating a clinically meaningful prodromal phase. The aetiology of PD reflects a complex interplay between genetic susceptibility and environmental exposures. Approximately 20% of cases are linked to identifiable pathogenic variants, most commonly in LRRK2, GBA1, and SNCA, whereas the majority arise from cumulative interactions among environmental factors, lifestyle determinants, and common genetic risk variants rather than from single causal mechanisms. Despite substantial advances in understanding disease biology, current therapies remain fundamentally symptomatic. Dopaminergic pharmacotherapy and device-aided interventions improve motor function and, in selected contexts, functional outcomes, but they do not modify disease progression. Non-motor symptoms remain a dominant driver of disability and reduced quality of life. Recent conceptual frameworks propose redefining PD as a biologically defined α-synucleinopathy. Emerging biomarkers, including α-synuclein seed amplification assays in cerebrospinal fluid and peripheral tissues, offer unprecedented opportunities to define biological disease, enable early detection, and stratify patients. However, biomarker positivity currently informs diagnosis and classification rather than prognostication or therapeutic selection, and validated intermediate endpoints linking biomarker change to sustained functional benefit remain lacking. Consequently, translation into disease-modifying therapies has been constrained by late-stage intervention, reliance on clinically defined populations, limited trial generalizability, and marked global inequities in access to advanced diagnostics and treatments. This narrative review synthesizes current evidence on PD epidemiology, diagnosis, aetiology, progression, and treatment, emphasizing gene-environment interactions, convergence on shared pathogenic pathways, limitations of existing therapeutic paradigms, and the as-yet unrealized potential of biologically informed precision care.

Childhood overweight and obesity represent a major global public health emergency, with a steadily increasing prevalence over recent decades in both developed and developing countries. Approximately one fifth of children and adolescents are overweight or obese, with marked differences across ethnic groups and geographical areas. Accurate estimation of this condition is complicated by the lack of a unique and universally accepted definition of childhood obesity, which is based on different anthropometric criteria. Although body mass index (BMI) remains the most widely used tool, growing evidence indicates that abdominal obesity, assessed by waist circumference and waist-to-height ratio, is a better predictor of cardiometabolic risk, even in children with a normal BMI. Childhood obesity is associated with several comorbidities, including arterial hypertension, non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea syndrome (OSAS). Early diagnosis and an integrated therapeutic approach are essential to reduce the risk of long-term complications. Although lifestyle modifications remain the cornerstone of treatment, new pharmacological options for pediatric obesity have been approved in recent years. This narrative review explores the impact of childhood obesity on the early development of hypertension, NAFLD, and OSAS, emphasizing the implications that can already be observed during childhood and adolescence. It examines the association between pediatric obesity and these conditions by synthesizing current epidemiological evidence, describing the underlying pathophysiological mechanisms linking excess adiposity to disease onset, and reviewing pediatric-specific diagnostic criteria as well as preventive and therapeutic strategies.

Background/Objectives: Home Enteral Nutrition Therapy (HENT) is widely used for patients with preserved gastrointestinal function who cannot maintain adequate oral intake. It can be administered through commercial formulas (CF) or artisanal preparation (AP). Methods: This was a cross-sectional, descriptive, observational study with a quantitative and qualitative approach, conducted through semi-structured interviews by the researcher herself. Patients using HENT were evaluated for nutritional status using a 24 h dietary recall, and their quality of life was assessed using a questionnaire administered during an interview with the patient and/or caregiver. Microbial characteristics of the diets were evaluated by collecting samples and performing microbiological analyses according to standard methods. Results: 22 patients participated, mostly elderly, bedridden, and dependent, with gastrostomy as the primary method of administration (72.7%) and CF as the most commonly used (54.5%). AP consisted of cooked vegetables, legumes, milk, oil, and salt, and showed low nutritional diversity and a high risk of microbiological contamination due to manual handling. Frequent complications included diarrhea (72.7%) and mechanical complications (77.7%). Despite these issues, 91% of participants rated their quality of life as acceptable. Conclusions: HENT posed significant challenges to nutritional adequacy and microbiological safety, particularly among patients using artisanal preparations. These findings highlight the need for systematic monitoring and individualized adjustments by a multidisciplinary team, along with structured caregiver training, to optimize intake, reduce complications, and improve the quality and safety of home-based enteral therapy.

Malignancy-related gastrointestinal bleeding (GIB) remains a significant clinical challenge, contributing substantially to morbidity, mortality, and healthcare utilization in patients with cancer. Up to 10% of individuals with advanced malignancies develop GIB during their disease, and these episodes are frequently characterized by a high risk of rebleeding and poor long-term hemostatic control. Tumor-associated bleeding typically arises from friable, infiltrative, and highly vascular lesions that respond suboptimally to conventional endoscopic techniques such as thermal coagulation or mechanical clipping. These limitations underscore the need for improved diagnostic accuracy and more reliable therapeutic options. Recent advances in imaging modalities, including contrast-enhanced CT studies, have enhanced the ability to localize and characterize bleeding sources in complex oncologic cases. Parallel developments in endoscopic hemostasis-such as over-the-scope clips and contact-free coagulation devices-have expanded the therapeutic armamentarium for managing malignant bleeding. Clinically, topical hemostatic powders-particularly TC-325-represent a highly effective option for achieving rapid endoscopic hemostasis, supported by the strongest comparative evidence and the highest rates of immediate bleeding control among currently available technologies. In this review, we synthesize contemporary diagnostic approaches to GIB and place particular emphasis on the evolving and emerging therapeutic strategies for malignancy-related bleeding. We also highlight innovative technologies that are reshaping clinical practice and improving management options in this challenging clinical domain.

Differentiated thyroid carcinoma (DTC) is the most common malignant endocrine tumor, with a generally favorable prognosis. Imaging, including iodine radioactive isotope scintigraphy (IRIS), is crucial for diagnosis and follow-up. While ¹³¹I has long been used for both therapeutic and diagnostic purposes, ¹²³I is reserved for diagnostic imaging due to its shorter half-life and γ emissions. This review highlights the utility of ¹²³I scintigraphy, especially in pre-treatment assessment and dosimetry for DTC. It is particularly valuable before radioiodine (RAI) ablation, providing accurate imaging in patients with iodine-refractory (IR) or biochemically incomplete response (BIR) DTC. When compared to post-therapeutic ¹³¹I scans, ¹²³I scintigraphy appears to have a lower sensitivity for detecting metastatic lesions, particularly in lymph nodes and lungs. However, its diagnostic performance compared to low-dose diagnostic ¹³¹I is more variable, with some studies suggesting superiority due to the absence of stunning. Further research is needed to standardize its use and optimize its role in guiding DTC management.