Search Results (360)

Multiple myeloma is a complex hematologic malignancy characterized by significant biological heterogeneity, a relapsing–remission clinical course, and a continuously evolving therapeutic landscape. Accurate and timely laboratory assessment is central to disease management, supporting diagnosis, risk stratification, evaluation of treatment response, and long-term monitoring. Despite major advances in therapy, a critical need remains for laboratory tools that can detect disease with greater sensitivity, capture spatial and clonal tumor heterogeneity, and reflect the true depth of treatment response beyond conventional serological and bone marrow-based criteria. Recent laboratory innovations have the potential to transform myeloma care by enabling earlier detection, more accurate prognostication, and personalized therapeutic strategies. This review focuses specifically on innovative laboratory technologies for the diagnosis of multiple myeloma and the evaluation of treatment response. Within this scope, we examine the current diagnostic approaches and the role of high-throughput technologies for measurable residual disease assessment. We explore the emerging role of liquid biopsy approaches, including circulating tumor cells, cell-free DNA/RNA, and mass spectrometry for ultrasensitive detection of monoclonal proteins. We further discuss novel molecular biomarkers and the integration of artificial intelligence and machine learning tools to enhance data interpretation. The innovations reviewed here represent a shift in the contribution of laboratory medicine to myeloma care, offering a more precise, less invasive, and biologically informative framework for targeted and adaptive clinical decisions. Full article

Upper tract urothelial carcinoma (UTUC) is a relatively rare malignancy, far less frequent than its counterpart in the bladder, but with a more aggressive course, worse prognosis and unique diagnostic challenges. Despite the histological and molecular similarities between upper and lower tract urothelial tumours, UTUC has many key distinct traits, both clinical and genomic, and must be viewed as a separate entity from bladder urothelial carcinoma (BUC). Ureteroscopy with biopsy is the only means to obtain tissue for histo-logical confirmation of diagnosis and more accurate tumour grading, but is not always feasible or preferable because it carries the risk of potentially severe complications. Aside from the widely available but poorly sensitive urine cytology, a large variety of urine-based diagnostics are increasingly investigated as non-invasive alternatives to ureteroscopy. Fluorescence in situ hybridization (FISH) is the most widely used molecular assay for the diagnosis and monitoring of UTUC, but has failed, as of yet, to display a comparable diagnostic accuracy to the existing gold standards of computed tomography urography (CTU) and ureteroscopy. We herein aimed to comprehensively review all published data on the performance of FISH for the detection of UTUC, in comparison to urine cytology and other assays, while further commenting on the existing challenges and future perspectives in the field of urine-based diagnostics. Across all studies (n = 29) which were included in this review, the sensitivity and specificity of FISH ranged from 36.8% to 100.0% (mean: 75.5%; median: 78.9%) and 34.4% to 100.0% (mean: 84.9%; median: 89.9%), respectively, in the overall patient population, while in the low- versus high-grade subgroups, the sensitivity of FISH ranged from 30.0% to 90.0% (mean: 55.6%; median: 60%) versus 50.0% to 100.0% (mean: 77.9%; median: 78.8%). Furthermore, FISH showed superi-or sensitivity and similar or lower specificity in comparison to cytology, in the over-whelming majority of studies, while Xpert^®BC Detection showed the highest sensitivity values among all evaluated assays, reaching 100% even in the low-grade subgroup, albeit at the cost of a significantly reduced specificity. Despite the adequate overall sensitivity and specificity of FISH, its suboptimal performance in the detection of low-grade UTUC seems to preclude its use as a stand-alone screening test. Full article

Background/Objectives: Objective, non-invasive biomarkers are needed to track anterior cruciate ligament (ACL) graft maturation and support individualized return-to-sport decisions. This study evaluated a single-session multiparametric quantitative MRI (qMRI) protocol for longitudinal assessment of ACL graft microstructural evolution and its association with patient-reported outcomes. Methods: Twenty-eight patients undergoing primary ACL reconstruction with hamstring autografts underwent multiparametric qMRI (T1, T2*, R2*, and PD mapping) at 1, 3, 6, and 12 months. The contralateral native ACL served as a within-subject control. IKDC, Lysholm, and VAS scores were recorded at each visit. Linear mixed-effects models were used to test longitudinal changes. Correlations of baseline-normalized changes between adjacent visits were used to evaluate imaging–clinical associations. Results: All qMRI parameters changed significantly over time (all p < 0.001). At 1 month, T1, PD, and T2* were lower and R2* higher than the contralateral native ACL (all p < 0.001). Thereafter, T1, PD, and T2* increased and R2* decreased, with most metrics approaching contralateral values by 3–6 months (all p < 0.05), and changes entered a plateau after 6 months (all p > 0.05). IKDC, Lysholm, and VAS improved over time (all p < 0.001), mainly before 6 months. Greater early T2* increases and R2* decreases (1–3 months) were associated with less pain relief and smaller Lysholm improvement (p < 0.05); no significant associations were observed from 6–12 months. Conclusions: Single-session multiparametric qMRI sensitively captures ACL graft maturation and highlights 3–6 months as a critical remodeling window, providing objective biomarkers to complement clinical assessment for individualized rehabilitation monitoring and return-to-sport timing. Full article

Continuous, in vivo drug and biomarker measurements could transform healthcare, enabling both the high-precision personalization of drug dosing and the real-time monitoring of health status. A practical realization of this vision, however, requires an improved understanding of the relationship between concentrations measured in the easily accessible dermal interstitial fluid (ISF) that correlate with the plasma concentrations that guide clinical decision making. As a preliminary step towards this goal, here we have used electrochemical, aptamer-based (EAB) sensors to perform seconds-resolved vancomycin measurements in the plasma and subcutaneous ISF of live rats. Concentrations of the antibiotic in the ISF vary rather little between different subcutaneous sites and, after the very rapid initial distribution phase is complete, they are well correlated with the plasma concentrations (mean R² = 0.88). Likewise, a simple, two-compartment, two-parameter model describes our six paired plasma and ISF drug time courses quantitatively. Together, these findings provide further evidence of the viability of the drug concentration measurements performed in the subcutaneous or dermal ISF as a less invasive approach to real-time drug monitoring in individual patients. Full article

Background: Heart transplantation remains the definitive therapy for selected patients with end-stage heart failure, but outcomes are limited by acute rejection, chronic allograft injury, and cardiac allograft vasculopathy. Endomyocardial biopsy (EMB) remains the reference standard for rejection surveillance but is invasive and imperfectly captures diffuse myocardial injury. Cardiovascular magnetic resonance (CMR) offers noninvasive, multiparametric assessment of graft structure, function, tissue composition, and perfusion. We aimed to review current evidence supporting CMR in post-heart transplant surveillance and to evaluate the performance of serial CMR for acute cellular rejection in a prospective cohort. Methods: We performed a focused narrative review of the literature on CMR for detection of acute rejection, assessment of chronic allograft injury and prognosis, and evaluation of cardiac allograft vasculopathy and microvascular disease. In parallel, we conducted a prospective observational study of adult heart transplant recipients undergoing early post-transplant CMR (CMR1) and follow-up CMR (CMR2) with temporally matched EMB. Multiparametric CMR included cine imaging, native T1 and T2 mapping, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). Clinically significant acute cellular rejection was defined as ISHLT grade ≥ 2R. Results: Eighteen recipients were included (median 53 days to CMR1 and 192 days to CMR2). Baseline CMR parameters correlated with invasive hemodynamic and biomarkers. Two patients had biopsy-proven ≥2R rejection at follow-up. T2 values at CMR2 were significantly higher in rejection versus non-rejection patients (59.0 ± 1.4 ms vs. 51.1 ± 1.9 ms; p = 0.015), with greater LGE burden in rejection (p = 0.029). In longitudinal analyses, rejection was associated with divergent patterns of cardiac remodelling and tissue characterization, including increases in indexed ventricular volumes and T2 over time, whereas non-rejection patients demonstrated stable ventricular volumes and a decline in T2. Conclusions: Multiparametric CMR, anchored by T2 mapping, provides clinically meaningful, non-invasive information for acute rejection surveillance after heart transplantation and complements EMB within a personalized, risk-adapted follow-up framework. Establishing individualized baseline CMR phenotypes and monitoring longitudinal changes may support more personalized, less invasive graft surveillance strategies. Larger multicentre prospective studies are needed to define standardized implementation pathways. Full article

Background: Stable isotope-based analytical methods have brought about a significant transformation in the study of energy nutrient metabolism, enabling precise in vivo measurement of metabolic fluxes at systemic, tissue, and organ-specific levels in both healthy and diseased states. The regulation of these metabolic fluxes is governed by dynamic interactions between proteins, lipids, carbohydrates, and their precursors—such as glucose, fatty acids, and amino acids—as well as final metabolic products. Discussion: Advanced analytical technologies, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), which can offer enhanced precision, have been developed for investigating nutrient metabolism and fluxes in humans, providing precise information on metabolic pathways. These techniques have primarily utilized stable isotopes, such as ²H, ¹³C, ¹⁵N, and ¹⁸O, which have largely replaced radioactive isotopes and are now central to metabolic research. These isotopes have been used to label glucose, fatty acids, or amino acids—the main biomolecular precursors—enabling detailed investigation at systemic, tissue, and organ-specific levels of carbohydrate, lipid, and protein metabolism, and revealing pathway alterations associated with diseases conditions, such as diabetes, non-alcoholic fatty liver disease, cardiovascular disorders, and cancer. The use of deuterium oxide (D₂O) has allowed for long-term metabolic studies, providing a cost-effective and less invasive means to monitor metabolic changes over days to months. Total daily energy expenditure can be measured in free living conditions by the doubly stable isotopes ²H- and ¹⁸O-labeled water method. Stable isotope tracing, combined with advanced imaging and modeling, has also been instrumental in assessing body composition, energy expenditure, and nutrient bioavailability. Collectively, these methods have expanded our understanding of human physiology and disease, supporting the development of novel diagnostic tools, the identification of new biomarkers, and the tailoring of nutritional and therapeutic interventions. Conclusions: This review aimed to provide an overview of the applications of stable isotopes for the study of energy nutrient metabolic pathways. The ongoing integration of stable isotope approaches with artificial intelligence, omics technologies, and miniaturized detection techniques could promise to further refine our understanding of human metabolism and drive advances in personalized medicine. Full article

Background: Extracorporeal membrane oxygenation (ECMO) is commonly used for temporary support in patients with severe cardiogenic shock and may serve as a bridge to heart transplantation. In recent years, outcomes have improved with better timing, patient management and advances in ECMO technology. Case presentation: We describe the case of a 61-year-old man who developed refractory cardiogenic shock after an extensive acute myocardial infarction complicated by recurrent ventricular arrhythmias. After an initial period of stabilization following complex percutaneous coronary intervention, the patient suddenly deteriorated with acute pulmonary edema and severe hypoxemia. A peripheral femoro-femoral veno-arterial ECMO with distal limb perfusion was promptly implanted using the ECMOLIFE system and the Landing Advance system (Eurosets s.r.l., Medolla, MO, Italy) to stabilize the patient and enable continuous monitoring. Due to severe left ventricular distension, surgical left ventricular venting was performed through a minimally invasive approach. ECMO support allowed rapid hemodynamic stabilization without major complications. During ECMO support, the patient remained stable and after less than 48 h a suitable donor heart became available. The patient was safely transferred to a transplant center while on ECMO and successfully underwent heart transplantation. Conclusions: This case shows that early ECMO implantation, combined with appropriate ventricular unloading and careful management with an advanced monitoring system, can be an optimal support as a bridge to heart transplantation. Limiting the duration of ECMO support and ensuring timely referral to a transplant center may improve outcomes in patients with refractory cardiogenic shock. Full article

Background/Objectives: Phyllodes tumors are rare fibroepithelial neoplasms of the breast, accounting for less than 1% of all breast tumors and approximately 2–3% of breast fibroepithelial tumors. They can be benign, borderline, or malignant, depending on cellular atypia and stromal invasion. Although most display local behavior, malignant forms can metastasize hematogenously, most frequently to the lungs, bones, and liver, with lymph node metastases being exceptional. Case Presentation: We analyzed the case of a 47-year-old woman with a phyllodes breast tumor weighing approximately 5 kg. The tumor evolved slowly over five years, followed by accelerated growth, cutaneous necrosis, superinfection, and severe anemia. Total mastectomy was performed, and histopathological examination confirmed the diagnosis of a malignant phyllodes tumor. Five months after surgery and adjuvant radiotherapy, the patient developed laterocervical metastases with thyroid invasion and life-threatening tracheal compression, an extremely rare presentation for this type of tumor in adults. Discussion/Conclusions: This case illustrates the aggressive and unpredictable behavior of malignant phyllodes tumors and underscores the necessity of careful oncological monitoring and a multidisciplinary approach, given their potential for dissemination to unusual locations. Full article

Sepsis and septic shock remain major causes of morbidity and mortality in critically ill patients. Hemodynamic management is a cornerstone of treatment, yet the optimal monitoring strategy to guide resuscitation is still debated. The progressive decline in the use of invasive techniques, such as pulmonary artery catheterization, has favored the development of less-invasive and non-invasive monitoring approaches. Recent technologies allow continuous assessment of cardiovascular function through arterial waveform analysis, non-invasive blood pressure monitoring, and predictive algorithms, while increasing attention has been directed toward the evaluation of tissue perfusion and oxygenation. This reflects the recognition that normalization of macrocirculatory variables does not necessarily ensure adequate microcirculatory perfusion in sepsis. This narrative review summarizes current evidence on less-invasive hemodynamic and tissue perfusion monitoring in sepsis and septic shock, discussing their physiological rationale and potential role within contemporary, multimodal resuscitation strategies. Full article

Mangrove extent has increased in many regions under strengthened conservation policies and large-scale restoration programs. Nevertheless, mangrove ecosystems continue to face multiple pressures, including limited total area, habitat degradation, biodiversity decline, and biological invasion, and localized deterioration in ecosystem structure and function has been increasingly reported. Despite extensive mapping efforts, the spatiotemporal dynamics of mangrove degradation—particularly in tidally influenced environments—remain insufficiently understood. Focusing on the Nanliu River Delta, the largest deltaic mangrove system in the Northern Beibu Gulf of China, this study integrates long-term Landsat time-series imagery (1990–2025) with deep learning to quantify both mangrove extent change and canopy degradation. To mitigate tidal inundation effects, a NDVI Pseudo-P75 compositing strategy was applied using Google Earth Engine (GEE), enabling consistent observation of mangrove canopies across tidal stages. Global Mangrove Watch v4 (GMW-V4) and HGMF2020 mangrove dataset for China were used as reference labels to train a ResNet34–UNet segmentation framework incorporating Digital Elevation Model (DEM) constraints. The model achieved high classification performance, with an IoU of 0.822 for mangroves and 0.981 for background, yielding a mean IoU of 0.902. The resulting maps, following manual verification, provided a robust basis for spatiotemporal and degradation analyses. Canopy condition was further assessed using the Enhanced Vegetation Index (EVI), which is less prone to saturation in high-biomass mangrove stands. Results show that mangrove area in the Nanliu River Delta expanded from 266 ha in 1990 to 1414 ha in 2025, with the annual expansion rate after 2005 being nearly seven times higher than that before 2005. Despite this net gain, a cumulative loss of 347.45 ha was recorded, primarily during 1990–2000, with approximately 70% converted to aquaculture and coastal engineering. Spatial analysis revealed that mangrove expansion occurred predominantly seaward, whereas both mangrove loss and canopy degradation exhibited an inverse J-shaped relationship with seawall proximity. More than 80% of mangrove loss occurred within 200 m of seawalls, indicating concentrated anthropogenic encroachment, while 75.6% of canopy degradation was observed within 350 m, potentially reflecting landward forest senescence. These results indicate a transition in dominant threats from permanent land conversion in the late 20th century to more subtle, internal functional degradation in recent decades, underscoring the need to complement extent-based assessments with canopy condition monitoring in mangrove conservation and management. Full article

In current clinical medicine, urinary profiling and blood tests are the primary toxicological exposure assessments for endocrine-disrupting chemicals (EDCs), including atrazine. Recent research suggests that analog monitoring of EDC concentrations and metabolites in sweat may be a less invasive, yet equally reliable method for conducting toxicological exposure assessments. However, no systematic reviews have identified whether concentrations of atrazine in sweat serve as a valid biomarker of environmental exposure. Thus, we performed a systematic review of the peer-reviewed literature to assess (1) if there is a correlation between the concentration of atrazine present in blood and urine and evaluate the evidence for sweat-based biomonitoring and (2) whether atrazine concentrations in sweat are a reliable and valid measurement of atrazine exposure based on the current state of evidence in the peer-reviewed literature. Databases included PubMed, Embase, Google Scholar, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and WHO Global Index Medicus. Stratified by exposure context, the average blood concentration of atrazine and atrazine metabolites in acute poisoning patients was 261 ng/mL, and the average blood concentration in prenatal exposure contexts was 31.68 ng/mL maximum in the included studies. While physicochemical properties of atrazine metabolites, particularly deisopropylatrazine (DIA), suggest potential suitability for sweat-based monitoring, empirical validation through controlled sweat collection studies is required before this approach can be recommended for clinical or occupational use. The results of the systematic review were heterogeneous, and a narrative review was conducted. To conclude, no studies have examined the concentration of atrazine in sweat and whether sweat can be used as a statistically valid toxicological assessment of atrazine exposure. Full article

This article presents a scalable IoT-based architecture for continuous and passive monitoring of human behavior in home environments, designed as a technical foundation for future dementia risk assessment systems. The architecture addresses three fundamental challenges: achieving room-level spatial localization without privacy-invasive methods, balancing temporal resolution with bandwidth efficiency in continuous data streams, and enabling multi-institutional model development under GDPR constraints. The system integrates (1) wearable BLE sensors with infrared room-level localization; (2) edge computing gateways with local preprocessing and machine learning; (3) a three-channel data architecture that simultaneously achieves full 1 s temporal resolution for machine learning training, low-latency real-time visualization, and 41.2% network bandwidth reduction; and (4) a federated learning framework enabling collaborative model development without data sharing between institutions. Technical validation in two apartments (three participants, 7 days) demonstrated: 97.6% room-level localization accuracy using infrared beacons; less than 7 s end-to-end latency for 99.5% of critical events; and 98.5% deduplication accuracy in multi-gateway configurations. Federated learning simulation demonstrates algorithmic convergence (84.3% IID, 79.8% non-IID) and workflow feasibility, establishing a foundation for future production deployment. Cost analysis shows approximately €490 for initial implementation and approximately €55 monthly operation, representing substantially lower costs than existing research systems. The work establishes architectural and technical feasibility, as well as system-level economic viability, of continuous home monitoring for behavioral analysis within the evaluated residential scenarios. Clinical validation of diagnostic capabilities through longitudinal studies with validated cognitive assessments and patients with mild cognitive impairment remains to be studied in future work. Full article

Background: Despite recent breakthroughs in pharmacological treatment for Alzheimer’s disease, high costs and the complex procedure to monitor safety have limited access for many patients. Less invasive and more accessible non-pharmacological therapies that support neuroplasticity and slow cognitive decline are needed. Processing Inner Strength Toward Actualization (PISTA) stimulation applies structured tactile input to promote cortical–subcortical activation. This study evaluated the long-term effects of PISTA on cognition and pain in older adults with mild cognitive impairment or early dementia. Methods: This single-arm, prospective trial enrolled 100 outpatients aged 47–70 years at outset (50 women, 50 men) with no control group. Participants received clinician-supervised PISTA stimulation three times weekly for 48 months. Each 30 min session delivered rhythmic tactile input calibrated to individual sensory thresholds. Cognitive performance was assessed monthly using the Mini-Mental State Examination (MMSE). Perceived pain was measured monthly with the Numeric Pain Rating Scale. Outcomes were analyzed using ANCOVA, adjusting for age, sex, and baseline cognitive status. Results: Cognitive scores improved significantly across all age strata, with a mean annual MMSE increase of 0.75 points (95% CI: 0.26–1.21; p < 0.0025). Pain intensity decreased in parallel (mean reduction: 0.56 points; 95% CI: 0.34–0.78; p < 0.001). Improvements in cognition and pain were moderately correlated (r = 0.38). The greatest combined benefits occurred in participants aged 55–62 years. No serious adverse events were observed during the 48-month trial. Conclusions: PISTA stimulation produced sustained improvement in cognition and reduced perceived pain, supporting its promising role as a safe, non-invasive adjunct for neurodegenerative cognitive decline. These findings suggest peripheral sensory activation as a promising driver of functional neuroplasticity and warrant verification in randomized, controlled trials. Full article

Landfills represent areas of pronounced anthropogenic disturbance, with substantial impacts on local vegetation. The composition and structure of plant communities serve as indicators of eco-system alteration and may function as reservoirs of species with potential utility in ecological restoration. This study provides the first detailed assessment of vegetation structure on a closed MSW landfill in Kokshetau (Akmola Region, northern Kazakhstan; semi-arid steppe/forest-steppe setting) and demonstrates an integrative, restoration-oriented monitoring and target-setting workflow, including a localized phytoremediation screening framework integrating field performance, ecological indicator values, and literature-based functional traits, with a risk/governance filter. A total of 76 vascular plant species were recorded during the field survey, predominantly comprising annual herbaceous taxa adapted to highly disturbed environments. The families Asteraceae and Poaceae were the most species-rich, while Chenopodiaceae and Brassicaceae were also notably represented. Meadow-steppe species constituted the majority (45.5%) of the phytosociological spectrum. Multivariate ecological and statistical analyses revealed that community composition was primarily influenced by the degree of disturbance (p = 0.016), rather than soil pH, with Cannabis sativa and Bassia scoparia emerging as key indicators of less disturbed sectors, contrasting with actively disturbed dumping areas. Consequently, restoration efforts should prioritize mesophytic species adapted to open, sunlit habitats and capable of establishing on slightly alkaline soils, while accounting for site-specific constraints to support long-term vegetation recovery. Notably, Artemisia absinthium and Bassia scoparia were identified as candidate taxa for phytoremediation-oriented restoration, based on their in situ ecological performance and literature-reported traits, albeit with limitations due to allergenic pollen and invasive tendencies, respectively. These findings support phytoremediation strategy design on disturbed landscapes by emphasizing regionally adapted species selection that balances ecological suitability with potential ecological risks. Full article

Retinoblastoma is a prevalent pediatric malignant tumour of the retina, primarily caused by biallelic inactivation of the RB1 gene or, less commonly, amplification of the MYCN oncogene. It has a global incidence of approximately 1 in 15,000–18,000 live births and predominantly affects children under five years of age. Trefoil factor 1 (TFF1) is a small, secreted peptide from the trefoil family, mainly expressed in the gastrointestinal mucosa, where it plays an essential role in mucosal protection, repair, and cellular differentiation. Beyond its physiological functions, aberrant TFF1 expression has been implicated in tumour progression and oncogenic signalling across several cancers. TFF1 is not expressed in healthy human retina but is significantly expressed in retinoblastoma tissues, with higher levels correlating with advanced disease stage, high-risk histopathologic features (HRPFs) and metastasis, poor differentiation, and unfavourable prognosis, suggesting a potential role of TFF1 in the pathogenesis and progression of retinoblastoma. Furthermore, in addition to tumour biopsy, its detection in the aqueous humour indicates its potential utility as a non-invasive biomarker for tumour activity and treatment monitoring. Although the precise molecular mechanisms underlying TFF1’s function in retinoblastoma remain unclear, evidence suggests that it may modulate tumour aggressiveness through effects on cell proliferation, apoptosis, and tumour microenvironmental signalling, supporting its promise as a prognostic biomarker and potential therapeutic target. This review consolidates the current advances in the role of TFF1 in retinoblastoma and critically examines its emerging significance as a potential clinical biomarker, molecular mediator, and novel therapeutic target for retinoblastoma. Full article