Search Results (111)

Background/Objectives: diabetic foot osteomyelitis (DFO) is a serious complication characterized by bone infection that can involve cortical structures, bone marrow, and surrounding soft tissues. Its prevalence ranges from 20% in moderate diabetic foot infections to over 50% in severe cases, making accurate diagnosis essential in guiding timely and effective management. in this study, we aimed to evaluate the diagnostic accuracy achieved by combining the probe-to-bone (PTB) test, plain radiography, and blood biomarkers—including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)—in the diagnosis of DFO. Methods: we conducted a diagnostic accuracy study involving 128 patients with diabetic foot ulcers and clinical suspicion of DFO. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for individual tests and for their diagnostic combinations. Results: the combination of PTB and biomarkers yielded a sensitivity of 75%, a specificity of 24%, a positive predictive value of 69%, and a negative predictive value of 29%. Similarly, the combination of PTB and plain radiography showed a sensitivity of 76%, a specificity of 23%, a positive predictive value of 62%, and a negative predictive value of 38%. When the three diagnostic modalities were analyzed together, the sensitivity reached 75%, and the specificity reached 23%. Conclusions: the combination of PTB and inflammatory biomarkers demonstrated moderate effectiveness and diagnostic performance comparable to PTB combined with radiography. These findings suggest that biomarkers may serve as a practical and accessible diagnostic adjunct in settings where imaging availability is limited or radiographic interpretation is challenging. Full article

Type 2 diabetes mellitus (T2DM) is characterised by chronic hyperglycaemia and accumulation of advanced glycation end products (AGEs), driving interest in food-derived peptides as safer multifunctional modulators. Coconut milk is a promising source, but its anti-hyperglycaemic and anti-glycation potential remains largely unexplored. Here, proteins from coconut cream, skimmed and insoluble fractions of coconut milk were enzymatically hydrolysed, and the resulting peptides were profiled by nano-ESI-Orbitrap-LC-MS/MS. One hundred and fourteen peptides were identified and screened in silico against α-glucosidase, α-amylase, aldose reductase and the receptor for AGEs (RAGE). Two peptides, MQIFVK and ADVFNPR, showed the most favourable docking scores and physicochemical properties. However, ADVFNPR inhibited all 3 diabetic targets & RAGE. Molecular dynamics analysis showed that both peptides bind stably to the diabetic targets. Both peptides were synthesised and evaluated in vitro. ADVFNPR significantly inhibited α-glucosidase, α-amylase and aldose reductase with lower IC₅₀ values and displayed competitive inhibition kinetics. It also scavenged methylglyoxal, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide radicals at low EC₅₀ values, and showed low hemolytic activity in human erythrocytes. These findings indicate that coconut milk contains multifunctional peptides with anti-hyperglycaemic, anti-glycation and antioxidant activities that may be further developed as food-derived adjuncts for managing T2DM and glycation-related complications. Full article

Objective: We sought to assess the diagnostic performance of quantitative bone SPECT/CT standardized uptake values (SUVs) in diabetic foot osteomyelitis (DFO) and their associations with inflammatory biomarkers. Methods: We retrospectively reviewed 150 consecutive patients who underwent three-phase bone scintigraphy and foot SPECT/CT (November 2016–December 2024) for DFO before antibiotic treatment; 117 with complete imaging and laboratory data were analyzed. Lesion and contralateral SUVs (SUVmax, SUVmean) were compared. Receiver operating characteristic (ROC) curves were used to determine discrimination and optimal cut-offs (Youden index). Associations with biomarkers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), CRP/albumin (ESR × CRP) and hematologic/coagulation indices including mean corpuscular hemoglobin (MCH) and activated partial thromboplastin time (aPTT) were evaluated using Spearman correlations. Results: Lesion uptake and contralateral uptake were SUVmax 10.94 ± 7.36 vs. 3.62 ± 1.70; SUVmean 4.38 ± 3.63 vs. 0.93 ± 0.50. Discrimination was excellent; SUVmax was AUC 0.921 (cut-off 4.47; sensitivity 0.93; specificity 0.75) and SUVmean was AUC 0.961 (cut-off 1.49; sensitivity 0.91; specificity 0.89). CRP and ESR showed weak but consistent positive correlations with SUVs (ρ ≈ 0.25–0.30). The ESR × CRP value correlated most strongly (e.g., with SUVmean ρ = 0.35), and CRP/albumin showed a modest positive association. MCH (ρ ≈ −0.20) and aPTT (ρ ≈ −0.37) were inversely related. Conclusions: Quantitative SPECT/CT provides excellent lesion–contralateral discrimination in DFO. SUVs—particularly SUVmean—track inflammatory burden, supporting their use as practical quantitative adjuncts to clinical and laboratory assessment. Study-specific cut-offs are promising but require local validation. Full article

Mature erythrocytes are traditionally regarded as anucleate cells lacking nuclear DNA. However, evidence shows they retain residual genetic material, including mitochondrial DNA (mtDNA) and RNA fragments. This review explores the role of such genetic material in cellular function, diagnostics, and erythropoiesis. A comprehensive literature review was conducted, focusing on (i) erythropoiesis, (ii) enucleation of erythroid precursors, (iii) the presence of DNA in red blood cells (RBCs), and (iv) RNA fragments such as messenger RNA (mRNA), microRNA (miRNA), and other non-coding RNAs. Mature RBCs harbor small amounts of DNA and diverse RNA species. Residual DNA can act as damage-associated molecular patterns (DAMPs), triggering immune responses when released under stress or injury. RNA fragments reflect the transcriptional activity of precursor cells and have been linked to potential diagnostic applications. Studies suggest that RBC-derived RNA signatures may serve as non-invasive biomarkers for diseases such as diabetes, cardiovascular conditions, and hematological disorders. These profiles mirror changes in erythropoiesis and provide insights into systemic pathophysiology. Residual genetic material in RBCs extends their role beyond oxygen transport. It contributes to immune modulation and may provide novel diagnostic and therapeutic opportunities, enhancing disease detection and understanding of erythropoiesis. Full article

Hemoglobin A1C (HbA1C), a non-enzymatically glycated form of adult hemoglobin (HbA0), is a widely used biomarker for diabetes. Its concentration is strongly correlated with the long-term glycemic state and the risk of diabetes development. However, beyond its diagnostic role, its physiological functions remain poorly understood. To fill this gap, we investigated the intracellular distribution of HbA1C and its potential impact on red blood cell (RBC) functions. Specifically, the differences in cytosolic and membrane pools of HbA1C in RBCs from individuals with prediabetes, overt type 2 diabetes (T2D), and healthy controls were explored. Our cross-sectional findings confirmed the intracellular heterogeneity of HbA1C and revealed a strong correlation between fluctuations in HbA1C and those of other hemoglobin isoforms, specifically HbA2 and HbA0. This correlation was particularly evident in the context of diabetes or acute exposure to Ca²⁺-depleted environments. We also observed that short-term hyperglycemia does not significantly alter HbA1C intracellular localization. Furthermore, we found that the intracellular distribution of HbA1C is correlated with several physiological properties of RBCs, with these links varying according to the specific pathological abnormalities associated with pre- and overt diabetes. Further research is required to fully understand the mechanisms and implications of these observations. Full article

Contemporary diabetes management is progressively moving away from a glucocentric approach, with growing expectations that novel antidiabetic agents offer benefits beyond glycaemic control. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a cornerstone in the treatment of type 2 diabetes mellitus (T2DM). In addition to reducing blood glucose levels by promoting renal glucose excretion, these agents contribute significantly to cardio–renal–metabolic protection and are associated with improved cardiovascular outcomes and prolonged survival. Although SGLT2 inhibitors do not exhibit a class effect in all clinical aspects, growing evidence suggests their potential in a variety of additional therapeutic areas. We conducted an in-depth review of current scientific literature and clinical studies regarding this class of drugs. SGLT2 inhibitors demonstrate neuroprotective properties and may provide benefits in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, potentially through the improvement of mitochondrial function and attenuation of inflammatory responses. Their anti-inflammatory and antioxidative effects are closely linked to reductions in cardiac and renal fibrosis. Other observed benefits include weight loss, improved insulin sensitivity, normalization of serum uric acid, and a reduction in hepatic steatosis—each with important metabolic implications. Furthermore, SGLT2 inhibitors have been shown to positively influence iron metabolism and improve erythrocyte indices. Emerging data also indicate beneficial effects in women with polycystic ovary syndrome. Another promising area of investigation involves the modulation of Klotho protein expression and support of vascular homeostasis. In oncology, SGLT2 inhibitors are gaining attention, with encouraging preclinical results observed in malignancies such as pancreatic, thyroid, breast, and lung cancers. Based on a comprehensive evaluation of the existing body of evidence, it is anticipated that the clinical indications for SGLT2 inhibitors will expand beyond the cardio–renal–metabolic axis in the near future. Full article

Red blood cell (RBC), accounting for approximately 45% of total blood volume, are essential for oxygen delivery and carbon dioxide removal. Their unique biconcave morphology, high surface area-to-volume ratio, and remarkable deformability enable them to navigate microvessels narrower than their resting diameter, ensuring efficient microcirculation. RBC deformability is primarily determined by membrane viscoelasticity, cytoplasmic viscosity, and cell geometry, all of which can be altered under various physiological and pathological conditions. Reduced deformability is a hallmark of numerous diseases, including sickle cell disease, malaria, diabetes mellitus, sepsis, ischemia–reperfusion injury, and storage lesions in transfused blood. As these mechanical changes often precede overt clinical symptoms, RBC deformability is increasingly recognized as a sensitive biomarker for disease diagnosis, prognosis, and treatment monitoring. Over the past decades, diverse techniques have been developed to measure RBC deformability. These include single-cell methods such as micropipette aspiration, optical tweezers, atomic force microscopy, magnetic twisting cytometry, and quantitative phase imaging; bulk approaches like blood viscometry, ektacytometry, filtration assays, and erythrocyte sedimentation rate; and emerging microfluidic platforms capable of high-throughput, physiologically relevant measurements. Each method captures distinct aspects of RBC mechanics, offering unique advantages and limitations. This review synthesizes current knowledge on the pathophysiological significance of RBC deformability and the methods for its measurement. We discuss disease contexts in which deformability is altered, outline mechanical models describing RBC viscoelasticity, and provide a comparative analysis of measurement techniques. Our aim is to guide the selection of appropriate approaches for research and clinical applications, and to highlight opportunities for developing robust, clinically translatable diagnostic tools. Full article

Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies. Full article

Microfluidic methods are an important tool for studying the microrheology of blood and the mechanical properties of blood cells—erythrocytes, leukocytes, and platelets. In patients with diabetes, hypertension, obesity, sickle cell anemia, or cerebrovascular or peripheral vascular diseases, hemorheological alterations are commonly observed. These include increased blood viscosity and red blood cell (RBC) aggregation, along with reduced RBC deformability. Such disturbances significantly contribute to impaired microcirculation and microvascular perfusion. In blood vessels, abnormal hemorheological parameters can elevate resistance to blood flow, exert greater mechanical stress on the endothelial wall, and lead to microvascular complications. Among these parameters, erythrocyte deformability is a potential biomarker for diseases including diabetes, malaria, and cancer. This review highlights recent advances in microfluidic technologies for in vitro assays of RBC deformability and aggregation, as well as leukocyte aggregation and adhesion. It summarizes the core principles of microfluidic platforms and the experimental findings related to hemodynamic parameters. The advantages and limitations of each technique are discussed, and future directions for improving these devices are explored. Additionally, some aspects of the modeling of the microrheological properties of blood cells are considered. Overall, the described microfluidic systems represent promising tools for investigating erythrocyte mechanics and leukocyte behavior. Full article

Eryptosis is a programmed cellular death involving red blood cells (RBCs). It is a physiological mechanism that leads to the removal of defective erythrocytes, similarly to apoptosis. Its typical features are cell shrinkage, cell membrane blebbing, and membrane scrambling with the consequent exposure of the aminophospholipid phosphatidylserine on the outer surface of RBCs. Different mechanisms play a role in the pathogenesis of eryptosis, such as the increase in cytosolic calcium concentration, oxidative stress, inflammation, and uremic toxins. If erythrocyte synthesis does not compensate for the accelerated eryptosis, anemia may develop. Moreover, enhanced eryptosis contributes to the pathogenesis of different clinical diseases, such as diabetes, sepsis, metabolic syndrome, and uremia. In particular, in patients with chronic kidney disease (CKD), deficiencies of erythropoietin and iron may further reduce the lifespan of RBCs. In this review, we focused on eryptosis in CKD and end-stage renal disease on peritoneal dialysis (PD) and hemodialysis (HD). Full article

Background/Objectives: Dietary guidelines recommend limiting trans fatty acid (TFA) intake to avoid adverse health effects. However, the impact of TFA intake in type 1 diabetes mellitus (T1DM) remains unclear. The aim of the present study was to investigate the levels of TFAs in plasma and erythrocyte membrane lipids of young diabetic patients and healthy controls. Methods: Data were re-analyzed from three case-control studies including diabetic children (n = 40, mean age: 12.0 years), diabetic young adults (n = 34, mean age: 21.8 years), and children with diabetic ketoacidosis (DKA, n = 9, mean age: 16.0 years). In these studies, TFA data were quantified by gas chromatography, but data have not yet been published. Results: Diabetic young adults and diabetic children had significantly lower TFAs in plasma lipids compared to healthy controls (sum of TFA in plasma sterol esters: 0.54 [0.34] versus 0.64 [0.37] and 0.51 [0.13] versus 0.65 [0.29], %, median [interquartile range], p < 0.05). However, children with DKA had significantly higher TFA levels in almost all plasma lipid fractions than the other two diabetic groups. Several negative correlations were observed between TFA and n-3 and n-6 long-chain polyunsaturated fatty acid levels in all groups, especially in the erythrocyte membrane lipid fractions. However, in the plasma fractions the correlation was less clear; both positive and negative correlations were found in each of the groups studied. Conclusions: Lower TFA values in young adults and children with diabetes may be associated with dietary patterns lower in TFAs, while elevated TFA values in DKA may be linked to challenges in adherence to dietary guidelines. Full article

Background and Objectives: Gestational hydronephrosis (GH) is a physiological condition commonly observed during pregnancy, resulting from hormonal effects and mechanical compression of the ureters by the enlarging uterus. Although often asymptomatic, GH can cause urinary stasis, recurrent infections, and renal function impairment in symptomatic cases. The optimal management of such cases remains controversial, especially regarding the role of ureteral stent placement. This study aimed to compare clinical outcomes—including renal function, inflammatory markers, and obstetric parameters—in pregnant women with symptomatic GH who underwent ureteral stent placement versus those managed conservatively. Materials and Methods: We conducted a retrospective cohort study at Düzce University Hospital between 2020 and 2024, including 40 pregnant women diagnosed with symptomatic GH. The patients were divided into the following two groups: those who received a ureteral stent (n = 20) and those who were managed with conservative treatment (n = 20). Conservative management included hydration therapy, acetaminophen-based analgesia, and close clinical monitoring. The parameters assessed included serum creatinine, estimated glomerular filtration rate (GFR), inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count), urinary findings, obstetric outcomes, and postpartum complications. Statistical significance was set at p < 0.05. Results: Gestational age at diagnosis was significantly higher in the stent group (29.1 ± 3.2 weeks) than in the non-stent group (27.1 ± 3.5 weeks; p = 0.045), possibly reflecting increased mechanical compression in later pregnancy. Renal function parameters (serum creatinine and GFR), inflammatory markers (CRP, ESR, and WBC count), and obstetric outcomes (birth weight, Apgar scores) showed no significant differences between groups (p > 0.05). Interestingly, gestational diabetes mellitus (GDM) was more prevalent in the non-stent group (20% vs. 5%; p = 0.042), although no significant differences were found in fasting glucose levels. Conclusions: Ureteral stent placement in symptomatic GH does not appear to significantly improve renal function or obstetric outcomes. However, it may provide symptom relief in select patients with persistent or severe discomfort. Given the limitations of retrospective data and a small sample size, further prospective studies with larger cohorts and quality-of-life assessments are warranted to optimize management strategies and enhance patient-centered care. Full article

Background and Objectives: We conducted a retrospective observational study to evaluate the impact of elevated blood glucose levels in patients with SARS-CoV-2 infection and a prior diagnosis of diabetes mellitus (DM) or newly diagnosed hyperglycemia. Materials and Methods: This study analyzed 6065 patients admitted to the COVID-19 departments of the “Marius Nasta” National Institute of Pulmonology in Bucharest, Romania, between 26 October 2020 and 5 January 2023. Of these, 813 patients (13.40%) were selected for analysis due to either a pre-existing diagnosis of DM or hyperglycemia at the time of hospital admission. Results: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were elevated in patients with blood glucose levels exceeding 300 mg/dL. These elevations correlated with the presence of respiratory failure and increased mortality rates. Additionally, oxygen requirements were significantly higher at elevated blood glucose levels (p < 0.001), with a direct relationship between glycemia and oxygen demand. This was accompanied by lower oxygen saturation levels (p < 0.001). Maximum blood glucose levels were associated with the severity of respiratory failure (AUC 0.6, 95% CI: 0.56–0.63, p < 0.001). We identified cut-off values for blood glucose at admission (217.5 mg/dL) and maximum blood glucose during hospitalization (257.5 mg/dL), both of which were associated with disease severity and identified as risk factors for increased mortality. Conclusions: High blood glucose levels, both at admission and during hospitalization, were identified as risk factors for poor prognosis and increased mortality in patients with SARS-CoV-2 infection, regardless of whether the hyperglycemia was due to a prior diagnosis of DM or was newly developed during the hospital stay. These findings underscore the importance of glycemic control in the management of hospitalized COVID-19 patients. Full article

Objectives: Spondylodiscitis can be caused by various microorganisms and has shown a continuous rise in incidence and mortality. The purpose of our study was to analyze the demographic and laboratory data, as well as comorbidities of patients that were surgically treated for spondylodiscitis in our hospital. The causative pathogens involved in the etiology of spinal infections were also assessed. Methods: The study included 92 patients who underwent clinical, radiological, and microbiological analyses including bacterial isolation. According to their culture results, patients were divided into three groups: negative results (n = 29), positive results with Mycobacterium tuberculosis (M. tb.) (n = 26), and positive results with other pathological agents (n = 37). Results: Patients with M. tb. had a significantly lower body mass index (p = 0.022) and were significantly younger (p = 0.024) than the others. The analysis of the complete blood work showed significant differences between the groups regarding fibrinogen levels (p = 0.023), C-reactive protein (p = 0.009), and erythrocyte sedimentation rates (p = 0.042). Results also showed significant differences (p = 0.023) for patients with diabetes mellitus who were more prone to a tuberculosis etiology for their spondylodiscitis compared with patients without the disease. Conclusions: These findings have important implications for adopting individualized treatment strategies underlining the need for identification of patients at high risk for specific causative pathogens. Full article

Cardiovascular diseases (CVDs) are one of the most critical public health problems in the contemporary world because they are the leading cause of morbidity and mortality. Diabetes mellitus (DM) is one of the most substantial risk factors for developing CVDs. Glycated hemoglobin is a product of the non-enzymatic glycation of hemoglobin present in erythrocytes. The determination of the percentage of glycated hemoglobin (HbA1c) is commonly used in clinical practice to assess glycemic control in patients diagnosed with DM. This method is much more informative than repeated blood glucose tests, because the HbA1c value reflects the degree of glycemic control over the last three months. It is, therefore, not surprising that the HbA1c value correlates with the presence and severity of diabetes complications, including CVDs, in the population of diabetic patients. The purpose of this publication was to present the results of a literature review on the relationship between the HbA1c value in people without DM, the presence and severity of subclinical cardiovascular dysfunction, and the presence of clinically overt CVDs. The most important tools used to assess subclinical cardiovascular dysfunction included the measurement of intima-media thickness (IMT), especially carotid IMT (cIMT), arterial stiffness assessment by the measurement of pulse wave velocity (PWV), and ankle–brachial index (ABI). According to the results of the studies cited in this literature review, it can be concluded that there are certain relationships between HbA1c, the presence and severity of subclinical cardiovascular dysfunction, and the presence of clinically overt CVDs such as coronary heart disease, cerebrovascular disease, and chronic lower extremity ischemia in non-diabetic patients. It is worth noting, however, that the results of studies conducted so far in this area are not fully unambiguous. Further studies are needed to better understand the influence of additional factors on the relationship between HbA1c and cardiovascular dysfunction in non-diabetic patients. Full article