Search Results (245)

Iron is essential for normal cellular function, but its dysregulation is increasingly recognized as a key factor in colorectal tumorigenesis. This review provides an integrated overview of iron-related biomarkers across the full spectrum of colorectal neoplasia, from preneoplastic lesions to advanced colorectal cancer (CRC). Evidence suggests that alterations in iron metabolism begin early, at the level of colorectal adenomas, where increased iron uptake and impaired export contribute to local iron accumulation and oxidative stress. As lesions progress to carcinoma, this imbalance becomes more pronounced, leading to expansion of the intracellular labile iron pool and supporting tumor growth, metabolic adaptation, and genomic instability. At the systemic level, patients often exhibit reduced circulating iron despite preserved or elevated ferritin levels, reflecting inflammation-driven functional iron deficiency. This pattern is largely mediated by dysregulation of the hepcidin–ferroportin axis. In this context, transferrin saturation and soluble transferrin receptor may provide a more accurate assessment of iron availability than ferritin alone. At the tissue level, increased expression of iron import proteins and impaired iron export promote intracellular iron retention. Excess iron further contributes to reactive oxygen species generation, leading to damage of DNA, lipids, and proteins. Clinically, iron-related biomarkers show variable diagnostic performance but may offer prognostic value. Integrating systemic and tissue biomarkers could improve risk stratification and support personalized approaches across the CRC continuum. Full article

Background and Objectives: Head and neck cancers are heterogeneous malignancies with variable biological behavior and treatment response, contributing to high morbidity and mortality. Conventional imaging techniques are limited in their ability to capture tumor biology, highlighting the need for advanced functional imaging. This review aims to evaluate the role of multiparametric magnetic resonance imaging (MRI) in characterizing the tumor microenvironment. Materials and Methods: A narrative review was conducted based on a targeted literature search of databases, including PubMed and Google Scholar. Studies addressing advanced MRI techniques for assessing tumor cellularity, vascularity, molecular features, and oxygenation were selected and analyzed. Results: Perfusion techniques, such as dynamic contrast-enhanced MRI (DCE-MRI) and arterial spin labeling (ASL), provide a quantitative assessment of tumor vascularity and show value in predicting treatment response. Diffusion-based methods, including diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI), enable evaluation of tissue cellularity and heterogeneity. Molecular approaches, such as chemical exchange saturation transfer (CEST) and amide proton transfer (APT), offer insights into protein content and proliferation. Oxygenation-sensitive techniques, such as blood oxygenation level dependent MRI (BOLD MRI) and oxygen-enhanced MRI (OE-MRI), allow non-invasive assessment of tumor hypoxia. Conclusions: Multiparametric MRI provides a comprehensive and biologically relevant evaluation of the tumor microenvironment in head and neck cancer, with potential to improve treatment prediction and support personalized therapeutic strategies. Full article

Background/Objectives: Ultrasound-guided brachial plexus blocks are widely used in upper extremity surgery. The costoclavicular block (CCB) has been defined in recent years as an alternative to the infraclavicular block (ICB) and attracts attention due to its anatomical advantages. However, studies comparing these two techniques using objective physiological parameters are limited. This study aimed to compare the effectiveness of CCB and ICB techniques by measuring tissue oxygenation with near-infrared spectroscopy (NIRS) and evaluating the role of NIRS in demonstrating block success. Methods: Eighty patients undergoing upper extremity surgery were included in this prospective, randomized, comparative study, and the patients were randomly divided into two groups: CCB (n = 40) and ICB (n = 40). Block success was evaluated using tissue oxygen saturation (StO₂) and its change (ΔStO₂) measured by NIRS in addition to sensory and motor assessments. In addition, hemodynamic parameters were recorded. Results: A statistically significant increase in StO₂ and ΔStO₂ values was observed after block application in both groups. In the costoclavicular block group, the median StO₂ increased from 78.5 [8.5] at baseline to 86.5 [9.75] at 20 min (p < 0.001), while in the infraclavicular block group, it increased from 75.0 [12.0] to 85.0 [9.0] (p < 0.001). Similarly, the ΔStO₂ values increased from 0.0 [0.0] to 9.5 [8.25] in the costoclavicular group and from 0.0 [0.0] to 11.0 [9.0] in the infraclavicular group (both p < 0.001). This increase began in the early period and paralleled sensory-motor block findings, indicating that NIRS measurements objectively reflect block success. An isolated intergroup difference in StO₂ was observed at t10 (83.92 ± 6.17 vs. 80.33 ± 7.31, p = 0.023), but no consistent intergroup superiority was demonstrated across the follow-up period. No statistically significant intergroup differences were found for ΔStO₂ at any time point (p > 0.05). The block success rates were similar between groups. The hemodynamic parameters remained stable in both groups, and no clinically significant adverse events were observed. Conclusions: CCB and ICB techniques have similar efficacy and safety profiles in upper extremity surgery. NIRS-derived StO₂ and ΔStO₂ changes appear to be promising complementary physiological markers associated with block onset. However, the present study was not designed to establish diagnostic cut-off values or predictive accuracy; therefore, NIRS should be interpreted as an adjunct to, rather than a replacement for, conventional sensory and motor block assessment. Full article

Mucosal colour assessment is widely used in veterinary medicine as an indicator of physiological states, but current approaches are characterized by inconsistent terminology, variable methodology, and differing levels of validation. This communication introduces the provisional Uldahl Standard, a conceptual framework developed to improve consistency, transparency, and reproducibility in mucosal colour assessment in terrestrial mammals. The framework integrates principles from veterinary medicine, colorimetry, and modern imaging technologies, combining perceptual, computational, and instrument-based approaches to colour analysis. Mucosal colour assessment is defined as a multidimensional process comprising colour category, light saturation level, physiological association, assessment method, and level of validation. Nine principal colour categories and eight standardised saturation modifiers were identified through a literature review and incorporated into the framework. The standard further emphasizes transparent reporting of assessment conditions, validation procedures, artefact evaluation, and analytical pathways, including examples using AI-assisted visual analysis. The framework acknowledges the inherent variability in mucosal colour assessment arising from environmental conditions, limitations of human colour perception, and differences in descriptive methods while providing a structured and comparable terminology, linked to defined levels of validation. It is anticipated that application of the proposed Uldahl Standard will provide markedly more robust and consistent descriptions of mucosal colours, which, provided they are combined with well validated clinical signs of the underlying physiology and/or pathophysiology, will greatly enhance the diagnostic power of the procedure. Full article

Circulating cell-free DNA (cfDNA) is released during tissue injury and systemic inflammation, but its association with postoperative organ injury following pediatric cardiac surgery remains incompletely defined. We evaluated the relationship between early postoperative cfDNA levels and acute kidney injury (AKI) and biochemical hepatic injury in children undergoing open-heart surgery with cardiopulmonary bypass (CPB). This retrospective observational cohort study included 50 pediatric patients (<18 years) who underwent CPB at a tertiary congenital heart center between 2017 and 2018. Plasma cfDNA concentrations were measured perioperatively, with the 6 h postoperative value analyzed as an early biomarker window. AKI was classified using Kidney Disease: Improving Global Outcomes criteria, and hepatic injury was assessed using serial liver enzyme measurements. cfDNA levels increased significantly within 6 h after CPB and were higher in patients with more severe AKI. Six-hour cfDNA concentrations correlated with postoperative creatinine, urea, alanine aminotransferase, and aspartate aminotransferase. In multivariable regression analyses adjusting for cardiopulmonary bypass duration, aortic cross-clamp time, and preoperative oxygen saturation, cfDNA at 6 h remained independently associated with AKI severity and peak liver enzyme levels. These exploratory findings suggest that early postoperative cfDNA elevation is associated with AKI severity and biochemical hepatic injury after pediatric cardiac surgery with CPB. Larger prospective studies are needed to determine its independent predictive value and clinical utility. Full article

Pediatric sepsis is a life-threatening systemic infectious response syndrome. Its core pathophysiological process involves a systemic imbalance between oxygen delivery and demand, coupled with cellular energy metabolism dysfunction, which collectively contribute to high mortality rates. Parameters of oxygen metabolism serve as critical indicators reflecting tissue perfusion and cellular oxygen utilization. Consequently, these parameters hold significant value for the early identification, severity stratification, therapeutic guidance, and prognostic evaluation of pediatric sepsis. This review systematically elucidates the pathophysiological mechanisms underlying oxygen metabolism disorders in pediatric sepsis. Furthermore, it highlights the current clinical applications and significance of key monitoring indices, including blood lactate, central venous oxygen saturation, oxygen delivery, and oxygen consumption. By integrating recent research advancements, this paper also explores therapeutic strategies aimed at optimizing oxygen metabolism, such as blood purification, microcirculation-targeted therapies, and extracorporeal membrane oxygenation. Finally, we provide future perspectives on emerging biomarkers and metabolomic approaches, aiming to establish a theoretical foundation for the optimized clinical management of pediatric sepsis. Full article

Background: Cerebral arteriovenous malformations (AVMs) are high-flow shunts in which abnormal arteriovenous connections expose draining veins to venous hypertension, arterialization, and altered oxygenation. While digital subtraction angiography (DSA) remains the reference standard for dynamic angioarchitecture, it does not directly characterize venous oxygenation or microhemorrhagic tissue changes. Objective: To synthesize current evidence on susceptibility-based MRI-susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) for characterization, risk-related features, and treatment monitoring in cerebral AVMs. Methods: Narrative review of the foundational and contemporary literature on AVM pathophysiology, SWI and QSM technical principles, and clinical applications including venous drainage depiction, microhemorrhage detection, oxygenation-related biomarkers, and post-treatment surveillance. Results: SWI provides high-resolution, non-contrast depiction of venous drainage and perinidal hemorrhagic/calcific components, improving visualization of draining veins and microhemorrhages compared with conventional MRI and complementing TOF-MRA. Arterialized draining veins may show altered SWI signal consistent with elevated venous oxygen saturation, though interpretation is indirect and influenced by flow and orientation. QSM extends susceptibility imaging by quantifying tissue susceptibility and enabling indirect estimation of venous oxygenation (SvO₂), offering a potential physiological biomarker of shunt severity and treatment response after radiosurgery or embolization. Key limitations include lack of dynamic flow timing, flow-related artifacts, orientation dependence, confounding from hemorrhage/calcification, and limited standardization and prospective validation. Conclusions: Susceptibility-based MRI does not replace DSA but meaningfully enriches multimodal AVM assessment by adding structural and physiological information-particularly venous mapping, microhemorrhage detection, and oxygenation-sensitive biomarkers. Standardized acquisition/reconstruction and prospective studies are needed to validate susceptibility-derived metrics for risk stratification and longitudinal monitoring. Full article

Reflective-mode photoplethysmography (PPG) potentially enables non-invasive physiological monitoring of heart rate and Peripheral Oxygen Saturation (SpO₂) from virtually any anatomical body site, but its performances are strongly affected by several parameters such as local perfusion, skin temperature, and microvascular bed and tissue optical properties. This study systematically evaluates the quality of reflective-mode PPG signals acquired at the finger, wrist, ear, nose, temple, upper lip, and lower lip, using two commercial PPG sensors. PPG signal quality was quantified via Skewness, Kurtosis, Perfusion Index, and Shannon entropy. Heart rate (HR) and pulse transit time (PTT) were also computed. Skewness and Perfusion Index were the most informative quality indices, revealing the finger as the site with the best signal quality and the wrist as the most challenging location. Several facial regions—including the lips, nose, and temple—showed signal quality comparable to the finger. HR estimation was most accurate using the GREEN wavelength, with the lower lip achieving the lowest error, followed by the upper lip and finger. PTT values reflected physiological differences in pulse propagation, being longest at the finger and wrist and shortest at the lips. These findings highlight the potential of non-conventional anatomical sites as alternatives to the finger and wrist for reflective-mode PPG acquisition. Full article

Background/Objectives: Peripheral(-muscle) oxygenation assessed with near-infrared spectroscopy might serve as an early marker of infection/inflammation; however, evidence of its clinical relevance is lacking so far. This study aimed to develop a peripheral(-muscle) oxygenation and perfusion score (POP-Score) using the peripheral(-muscle) tissue oxygenation index (pTOI) combined with non-invasive monitoring parameters within six hours after birth. The POP-Score was designed to explore associations with elevated C-reactive protein (CRP), as an early infection/inflammation marker, in term and late-preterm neonates. Methods: Secondary outcome parameters from a prospective observational study were analysed. Included neonates weighed ≥2000 g with respiratory distress, excluding those with umbilical artery pH < 7.20. Neonates with CRP ≥ 20 mg/L were 1:4-matched to those with CRP < 20 mg/L by gestational age (±2 weeks). For pTOI measurements, a sensor was placed for a duration of 30 s, followed by four further reapplications of the sensor, using the NIRO200NX within the first six hours after birth. The POP-Score was established using the following formula: (pTOI [%] × subcutaneous fat layer thickness [cm] × heart rate [bpm])/(arterial oxygen saturation [%] × systolic blood pressure [mmHg]). POP-Score was correlated with the highest CRP within 48 h. Results: Thirty neonates were included (median gestational age: 39.1 weeks [CRP < 20 mg/L group] vs. 37.3 weeks [CRP ≥ 20 mg/L group], p = 0.299; median birth weight: 3561 g vs. 3260 g, p = 0.058, respectively). Median POP-Scores were significantly different: 1.11 (CRP ≥ 20 mg/L) vs. 0.85 (CRP < 20 mg/L), p < 0.001. POP-Score correlated positively with CRP (r = 0.341; p = 0.070). In this small exploratory cohort, a POP-Score cut-off of 1.00 was associated with CRP ≥ 20 mg/L (100% sensitivity and 87% specificity); however, these estimates are uncertain due to the limited sample size. Conclusions: This study is the first to describe a new score for peripheral(-muscle) oxygenation and perfusion (POP-Score), which may represent a potential approach for early, non-invasive assessment but requires validation in adequately powered studies before any clinical application. Trial Registration: Clinicaltrials.gov, Trial registration number: NCT04818762, Date of Registration: 26 March 2021. Full article

Herein, we report a simple procedure regarding the photodynamic therapy (PDT) treatment as a minimally invasive modality for treating superficial bladder cancer that utilizes a photosensitizer, light, and oxygen to generate cytotoxic reactive oxygen species (ROS). This study evaluates the histopathological and morphological changes induced by PDT in an ex vivo model of low-grade (LG) pTa non-muscle-invasive bladder cancer (NMIBC). We investigated the efficacy of exogenous protoporphyrin IX (PpIX) and Rose Bengal (RB) by incubating tissue samples (n = 30) with an oxygen-saturated solution of PpIX (1–3 mM) or RB (0.3–0.5 mM) for one hour. Since the criticism of using frozen tissue in research already exists, this framing explains how to mitigate those limitations. Thus, we use oxygen-saturated solutions PpIX and oxygen-saturated solutions of RB. We discussed a few aspects related to the use of frozen tissue in PDT. Frozen tissue preserves lipids critical for assessing membrane damage and maintains higher levels of metabolic markers like antioxidant molecules like glutathione and more likely lack factors such as metabolic activity, intact cell membranes, and oxygenation. It is critical to differentiate between “artifactual” changes and the “pathological” death of cells. Thus, we used histopathological microscopy observation typically used in daily clinical investigations to characterize cells before and after PDT. Following irradiation with the light dose of 72 J/cm² (410 nm or 532 nm at 300 mW for 15 min), hematoxylin–eosin staining revealed concentration-dependent apoptotic changes, including chromatin condensation, pyknosis, and nuclear fragmentation. While both agents induced cell death, RB demonstrated faster and more intense cytotoxicity than PpIX. These findings provide microscopic evidence of PDT-induced tumor destruction and suggest that RB is a potent candidate for further preclinical evaluation. At 410 nm (deep blue/violet), light penetration in biological tissue is very shallow, typically only around 0.3 to 1 mm; therefore, in a 2 mm thick tissue sample, most of the light would be absorbed within the first millimeter, with minimal light reaching the full depth of tissues. In this protocol, the generated ROS is used to destroy tumor tissue by attacking the cellular microenvironment directly. This led to immediate membrane disruption and lipid peroxidation. The proof-of-concept is an early-stage study designed to verify that a PDT treatment is feasible, safe, and biologically active in an ex vivo model of LG pTa NMIBC. Full article

Peripheral artery disease (PAD) involves atherosclerotic obstruction of the leg arteries and impairs function and structure of lower-limb tissues. Although traditionally regarded as a large-artery (macrovascular) disorder, PAD includes significant microvascular disease in the affected musculature, together leading to impaired leg perfusion. Monitoring muscle oxygenation during exercise provides an indirect index of limb perfusion and exercise capacity, and tracking its kinetics with near-infrared spectroscopy (NIRS; a portable, non-invasive technique measuring real-time tissue oxygen saturation) helps elucidate mechanisms underlying walking limitations in PAD. We systematically searched PubMed, Web of Science, and the Cochrane Library (1985–2025) for studies employing NIRS to monitor muscle oxygenation in PAD patients before, during, and after exercise. Of 628 articles screened, 11 met the inclusion criteria. NIRS demonstrated reliability and validity for monitoring muscle oxygenation in PAD. During walking, PAD patients showed a much steeper decline in muscle oxygenation and delayed recovery to baseline. Resting muscle oxygenation did not differ between patients with PAD and controls. These dynamics reveal the pathophysiological interplay in which proximal/macrovascular and distal/microvascular disease limit oxygen delivery and utilization in skeletal muscle. Accordingly, NIRS offers a sensitive, non-invasive tool to evaluate macro- and microvascular disease burden and monitor therapeutic response in PAD. Full article

Background: Renin is a hypoperfusion marker and a good index of renin–angiotensin–aldosterone system (RAAS) activity. The purpose of this study was to evaluate whether the plasma renin concentration (PRC) can represent a tissue perfusion marker for predicting mortality in patients with circulatory shock in intensive care. Methods: This prospective study included patients aged 18 years or older who were hospitalized in the intensive care unit (ICU). A total of 69 patients were enrolled, of whom 37 had circulatory shock and were all diagnosed with septic shock according to Sepsis-3 criteria, while 32 patients did not have shock. Patient groups were compared, and survival analysis was carried out. Mortality predictions of PRC, lactate and combined tests (including PRC, mottling scores, central venous saturation of oxygen, C-reactive protein, procalcitonin, and lactate) were investigated with ROC analysis. Results: ICU 28-day mortality was 36.2% (n = 25) and was significantly higher in patients with circulatory shock than those without (CS:21, 56.8% vs. NS:4, 12.5%, respectively, p < 0.001). The survival was significantly higher in patients without circulatory shock than those with shock (17 vs. 16 days; p = 0.038). The increase in mottling score (HR: 1.64 [95%CI: 1.15–2.33]; p < 0.01) and PRC (HR = 1.01 [95%CI: 1.00–1.02]; p < 0.05) levels and the decrease in glomerular filtration rate (GFR) (HR = 0.98 [95%CI: 0.96–0.99]; p < 0.05) were associated with decreased survival times in the ICU patients (p < 0.001). Combined tests yielded better prediction of mortality than PRC level alone. Conclusions: PRC may reflect circulatory shock and predict survival in critically ill patients; however, larger prospective studies incorporating serial PRC measurements are needed before it can be recommended as an independent biomarker of mortality. Full article

Background: Adequate muscle perfusion, particularly at the level of muscle microcirculation (MM), is essential for muscle function, recovery, and tissue health. Percussive therapy (PT) is increasingly used to support recovery and injury prevention and has shown consistent benefits for range of motion and perceived recovery. However, the underlying physiological mechanisms remain insufficiently understood, and evidence regarding its effects on MM is limited. This study investigated the acute effect of a single PT session on MM and muscle oxygen saturation (SmO₂). Methods: Twenty-two healthy volunteers (24.2 ± 3.0 years) underwent a single PT application (two or four minutes) to the thigh using a handheld percussive device. MM, SmO₂, and the perceived somatosensory sensation (PSS) were assessed at baseline and at five-minute intervals up to 40 min post-application. Data were analyzed using linear mixed models adjusted for age, lower-body fat percentage, and intervention duration. Results: A significant main effect of time was found for both MM and SmO₂. MM increased significantly compared to baseline from 5 to 15 min post-application (all p < 0.001), while SmO₂ increased immediately after PT and remained elevated throughout the 40-min observation period (all p < 0.001). PSS increased significantly during the first 20 min (all p < 0.02) before returning to baseline. Conclusions: A single PT application was associated with transient increases in MM and sustained elevations in SmO₂, along with associated subjective sensations. These time-associated changes suggest that PT may enhance local muscle perfusion and therefore contribute to the understanding of its physiological mechanisms. Full article

Recently, photoacoustic (PA) imaging has made a significant impact on biomedical imaging, providing detailed information on tissue structure and function by integrating optical and acoustic techniques. PA imaging can provide functional information at the cellular (e.g., oxygen saturation, hemoglobin concentration, metabolic rate) and molecular levels, owing to its substantial advantages over conventional imaging techniques. PA imaging is particularly useful for neuroimaging, cancer detection, and cardiovascular studies. Over the last decade, there has been a tremendous amount of research and development dedicated to nanomaterials that are ideal for PA imaging. Examples of nanomaterials include carbon-based and gold nanorods, both of which demonstrate greatly enhanced light absorption capabilities in the near-infrared range. Therefore, the properties of these materials make them perfect for achieving deep penetration into tissues. In addition, they exhibit biocompatibility, tunable optical properties, and enhance the acoustic signal for PA imaging, resulting in greater accuracy and precision in PA results. Researchers working in this area have focused on developing nanomaterials with fabrication capabilities, enabling real-time visualization of therapeutic events and enhancing light absorption. This review critically examines recent advances in nanomaterials for PA imaging, emphasizing strategies for signal enhancement and evaluating their impact on imaging performance, including imaging depth, photostability, and signal intensity, as well as their suitability for biomedical applications. Furthermore, complementary approaches for PA signal enhancement are discussed to provide a broader perspective and guide the selection and design of effective contrast agents for clinical and preclinical use. Full article

Background/Objectives: Near-infrared spectroscopy measures regional oxygen saturation (RSO₂) in target tissues. Cerebral and renal RSO₂ are associated with hemodynamically significant patent ductus arteriosus (PDA) in preterm infants. The aim of this study was to determine whether liver RSO₂ is associated with PDA status. Methods: Preterm infants born before 32 weeks of gestation and/or weighing <1.5 kg were enrolled. Cerebral, renal, and liver RSO₂ values were recorded on day 2 (D2; 48–72 h), day 7 (D7; 7 ± 2 days), and day 14 (D14; 14 ± 3 days), along with the corresponding point-of-care echocardiographic findings. Results: Of the forty preterm infants enrolled (mean ± SD gestational age, 28.8 ± 2.2 weeks; birthweight, 1209.9 ± 364.2 g), 22 (55.0%) had spontaneous PDA closure, 18 (45.0%) underwent pharmacological closure, and 4 (10.0%) required surgical closure. Cerebral, renal, and liver RSO₂ values were significantly lower in infants with PDA than those without. Liver RSO₂ was significantly lower in the presence of PDA at D7 (68.19 ± 13.24 vs. 82.14 ± 5.58, p < 0.001) and D14 (59.33 ± 12.06 vs. 80.0 ± 6.48, p < 0.001). Liver RSO₂ showed a strong inverse association with a higher LA/Ao ratio (β −38.71, 95%CI −55.03 to −22.40, p <0.001) in the linear mixed model analysis. Conclusions: Liver RSO₂ was associated with different PDA statuses. Future studies exploring the potential utility of liver RSO₂ as an adjunct parameter for detecting and guiding the management of hemodynamically significant PDA in preterm infants may be warranted. Full article