Purpose:
The primary objective was to compare T2-FRFSE and T2-PROPELLER sequences for image quality. The secondary objective was to compare the ability to detect prostate lesions at MRI in the ...presence and absence of motion artefact using the 2 sequences.
Methods:
99 patients underwent 3 T MRI examination of the prostate, including T2-FRFSE and T2-PROPELLER sequences. All patients underwent prostate biopsy. Two independent readers rated overall image quality, presence of motion artefact, and blurring for both sequences using a 5-point Likert scale. Scores were compared for the whole group and for subgroups with and without significant motion artefact. Outcome for lesion detection at an MRI threshold of PI-RADS score ≥3 was compared between T2-FRFSE and T2-PROPELLER.
Results:
The overall image quality was not significantly different between T2-FRFSE and T2-PROPELLER sequences (3.74 vs. 3.93, p = 0.275). T2-PROPELLER recorded a lesser degree of motion artefact (score 4.53 vs. 3.78, p <0.0001), but demonstrated greater image blurring (score 3.29 vs. 3.73, p <0.001). However, in a subgroup of patients with significant motion artefact on T2-FRFSE, the T2-PROPELLER sequence demonstrated significantly higher image quality (3.46 vs. 2.49, p <0.001). T2-FRFSE and T2-PROPELLER showed comparable positive predictive values for lesion detection at 93.2% and 97.7%, respectively.
Conclusions:
T2-PROPELLER provides higher quality imaging in the presence of motion artefact, but T2-FRFSE is preferred in the absence of motion. T2-PROPELLER is therefore recommended as a secondary T2 sequence when imaging requires repeat acquisition due to motion artefact.
Owing to advances in treatment modalities and supportive care, overall survival rates have reached up to 90% among children with acute lymphoblastic leukemia (ALL). However, due to the underlying ...illness and therapy, they are at a greater risk of developing lifestyle diseases. Hence, special attention is paid to early detection of the components of metabolic syndrome (MetS). This study aimed at investigating the association of plasma levels of nine diabetes markers with being overweight and components of MetS in ALL survivors. The study included 56 subjects with mean age of 12.36 ± 5.15 years. The commercially available Bio-Plex Pro Human Diabetes 10-Plex Panel kit was used to evaluate levels of diabetes biomarkers. ALL survivors presented statistically higher concentrations of GIP (p = 0.026), glucagon (p = 0.001), leptin (p = 0.022), and PAI-1 (p = 0.047), whereas the concentration of ghrelin was lower (p < 0.001) compared to the control group. Moreover, subjects within normal BMI range showed higher GIP (p = 0.005) and lower ghrelin concentration (p < 0.001) compared to healthy peers. At least one risk factor of MetS was present in 58.9% of participants, who showed significantly higher levels of C-peptide (p = 0.028), leptin (p = 0.003), and PAI-1 (p = 0.034) than survivors who did not meet any MetS criteria. In conclusion, ALL survivors are at greater risk of disturbances in carbohydrate metabolism. Understanding the pathogenesis and applicability of diabetes markers is crucial for developing strategies to prevent metabolic syndrome in ALL survivors.
Patients suffering from childhood acute lymphoblastic leukemia (ALL) are at risk of late adverse treatment-related effects. The examination of targeted biomarkers could be used to improve the ...diagnosis and prediction of life-threatening ALL sequelae. The purpose of this cross-sectional study was to search for treatment-related alterations in apolipoprotein (Apo) levels as potential markers of the occurrence of obesity in subjects treated for ALL, and to assess the relationships between weight, gender, anticancer treatment, and Apo concentrations. Fifty-eight ALL survivors were included in the study. The mean time of follow-up after treatment cessation was 5.41 ± 4.29 years. Serum levels of apolipoproteins were measured using a multiplex assay kit. Among ALL survivors, we observed a significant correlation of Apo-C1, Apo-C3, Apo-H, and Apo-J levels, depending on body mass index (BMI). Marked differences were observed in the area under the curve of Apo-A1, Apo-A2, Apo-C1, Apo-D. In our study, patients with a history of childhood ALL developed alterations in their Apo profile. Furthermore, this is the first study revealing that some apolipoproteins may act as valuable biomarkers useful in the prognosis of metabolic imbalance. We believe that this paper, at least partially, will highlight the importance of long-term prognosis of metabolic complications associated with the anticancer chemotherapy used to treat hematological malignancies in children.
Introduction
Nephrotoxicity is a potential adverse effect of anticancer treatment in childhood. Cytostatics, abdominal radiotherapy, total body irradiation (TBI) and some agents used in supportive ...care may induce acute kidney injury (AKI) or lead to chronic kidney disease (CKD). The aim of this study was to test the hypothesis whether urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are increased in acute lymphoblastic leukemia (ALL) survivors.
Method
The study cohort consisted of 86 patients (42 females) previously treated for ALL. The median time after cessation of treatment was 6.55 (IQR: 1.96–9.93) years and median age at the time of study: 12 (IQR: 6.76–16.00). The control group included 53 healthy peers. Immunoenzymatic ELISA commercial kits were used to measure urine KIM-1 and NGAL levels.
Results
The median levels of urine uNGAL (p < 0.05), uNGAL/creatinine (cr.) ratio (
p
< 0.0001) and uKIM-1/creatinine ratio (
p
< 0.0001) were significantly higher in ALL survivors in comparison with healthy controls. Female patients had significantly higher levels of NGAL and NGAL/cr. than males (mean 8.42 ± 7.1 vs. 4.59 ± 4.5 ng/mL and 86.57 ± 77 vs. 37.7 ± 37 ng/mg, respectively; p < 0.01). Of all the study participants, 11 (13%) presented eGFR below 90 mL/min/1.73 m
2
. The NGAL/cr. ratio seemed to be the best predictor of decreased eGFR (AUC = 0.65). The cumulative dose of methotrexate and cyclophosphamide did not predict the values of the urine NGAL, NGAL/cr., KIM-1/cr. and eGFR.
Five years after the end of treatment, the patients had higher levels of uKIM-1 (1.02 ± 0.8 vs. 0.62 ± 0.6 ng/mL,
p
< 0.01), uNGAL (7.9 ± 6.7 vs. 4.6 ± 5 ng/mL,
p
< 0.01) and lower eGFR (114 ± 29 vs. 134 ± 35 mL/min/1.73 m
2
,
p
< 0.01) in comparison with ALL survivors with the observation period of less than 5 years.
Conclusion
We demonstrated that ALL survivors have higher levels of urine NGAL
,
NGAL/cr. and uKIM-1/cr. ratio as compared to the control group. Further long-term follow-up studies are necessary to assess the significance of the NGAL and KIM-1 and their relationship to kidney damage after anticancer treatment in childhood.
Acute lymphoblastic leukemia (ALL) and glioma are some of the most common malignancies, with ALL most often affecting children and glioma affecting adult men. Proangiogenic cytokines and growth ...factors play an important role in the development of both of these tumors. Glioma is characterized by an extremely extensive network of blood vessels, which continues to expand mainly in the process of neoangiogenesis, the direct inducers of which are cytokines from the family of vascular endothelial growth factors, i.e., vascular endothelial growth factor (VEGF-A) and its receptor vascular endothelial growth factor receptor 2 (VEGF-R2), as well as a cytokine from the fibroblast growth factor family, fibroblast growth factor 2 (FGF-2 or bFGF). Growth factors are known primarily for their involvement in the progression and development of solid tumors, but there is evidence that local bone marrow angiogenesis and increased blood vessel density are also present in hematological malignancies, including leukemias. The aim of this study was to examine changes in the concentrations of VEGF-A, VEGF-R2, and FGF-2 (with a molecular weight of 17 kDa) in a group of patients divided into specific grades of malignancy (glioma) and a control group; changes of VEGF-A and FGF-2 concentrations in childhood acute lymphoblastic leukemia and a control group; and to determine correlations between the individual proteins as well as the influence of the patient's age, diet, and other conditions that may place the patient in the risk group. During the statistical analysis, significant differences in concentrations were found between the patient and control groups in samples from people with diagnosed glioma and from children with acute lymphoblastic leukemia, but in general, there are no significant differences in the concentrations of VEGF-A, VEGF-R2, and FGF-2 between different grades of glioma malignancy. Among individuals treated for glioma, there was no significant impact from the patient's gender and age, consumption of food from plastic packaging, frequency of eating vegetables and fruit, smoking of tobacco products, the intensity of physical exercise, or the general condition of the body (Karnofsky score) on the concentrations of the determined cytokines and receptor. The listed factors do not bring about an actual increase in the risk of developing brain glioma.
Childhood acute lymphoblastic leukemia (ALL) survivors are at higher risk of developing many late effects later in life. They experience multiple health problems that have significant public health ...implications, such as frailty, premature onset of lifestyle diseases, and second tumors. There is some evidence that chronic inflammation causes accelerated aging in childhood cancer survivors; however, the available data are very limited. The aim of the study was to evaluate the broad panel of cytokines among asymptomatic ALL survivors after anticancer treatment. The study included 56 subjects with a mean age of 16.11 ± 3.98 years. The commercially available Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay and Bio-Plex TGF-β Assay were used for simultaneous determination of 48 cytokines and 3 isoforms of TGF-β. Among 51 tested cytokines, the levels of 33 were statistically significantly higher in ALL survivors than in the control group (p < 0.05). Increased levels of pro-inflammatory cytokines, including the IL-1 family (IL-1 β, IL-1Ra; p < 0.0001), IL-6 (p < 0.001), IL-17 (p < 0.001), IL-18 (p < 0.05), TNFα (p < 0.01), IFNα2 (p < 0.05), and IFNγ (p < 0.01), were found elevated in the entire study group, compared with the controls. Subjects treated previously according to the high-risk protocol had higher IL-18 levels than low- and intermediate-risk groups (p < 0.05). Elevated levels of IL-1ra, IL-6, IL-12 (p70), IL-17, LIF, M-CSF, CSF, and VEGF were found in ALL survivors treated before the age of 5, compared with subjects treated over 5 years of age (p < 0.05). Moreover, individuals who received radiotherapy presented elevated levels of both IL-18 (p < 0.05) and MIG (p < 0.05). In conclusion, we found that young asymptomatic survivors after ALL treatment demonstrated a biological profile of complex low-grade chronic inflammation.
Childhood cancer survivors (CCS) are predisposed to developing numerous late effects of anticancer treatment later in life. The existing literature suggests that vitamin D deficiency (VDD) may ...influence cardiovascular abnormalities and metabolic diseases. The objectives of this study were to investigate the prevalence of VDD among childhood cancer survivors and examine the association of vitamin D deficiency and carotid intima-media thickness (IMT). The study comprised 111 childhood cancer survivors (62 males, 49 females) with a median follow-up time of 6.14 years. Vitamin D status was determined by measuring serum 25(OH)D levels using the automatic immunoenzymatic method. Ultrasonography of the common carotid artery (CCA), the carotid bulb, and the proximal part of the internal carotid artery (ICA) was conducted. Vitamin D deficiency (<20 ng/mL) was detected in 69.4% of CCS. A higher parathormone level and increased BMI were observed among VDD survivors. No effects of type of diagnosis, radiotherapy or hematopoietic stem cell transplantation on vitamin D status were observed. Our findings reveal that survivors with VDD exhibited significantly greater thickness in the CCA and carotid bulb. In conclusion, the results of our study of childhood cancer survivors demonstrate that vitamin D deficiency is prevalent in up to 70% of individuals. We did not confirm the hypothesis that factors related to anticancer treatment used during childhood contributed to the higher prevalence of VDD. Additionally, we did not verify the contribution of vitamin D deficiency to the increase in IMT thickness.
A new method was developed for the simultaneous determination of vascular endothelial growth factor (VEGF-A) and fibroblast growth factor-2 (FGF-2) in blood serum, using biosensors with array Surface ...Plasmon Resonance imaging (SPRi) detection. It can be applied as a single method for simultaneous VEGF-A and FGF-2 determination or as two separate methods for testing only one selected protein in each case. Validation was carried out for each method. Limit of detection (LOD) and limit of quantification (LOQ) values were determined and were found not to differ significantly from the parameters obtained in comparisons with commercial enzyme-linked immunosorbent assay (ELISA) tests. Tests were carried out to check the robustness of the method. The results indicate a lack of robustness of the analytical method to elevated temperature and pH values other than those recommended by the manufacturers of the reagents (recommended pH = 7.40). The values of recoveries were determined and confirmed the reliability of the results obtained with the use of the newly developed method. The selectivity studies showed no negative influence of other proteins present in the matrix of the tested samples on the results of the VEGF-A and FGF-2 concentration measurements. The developed method is also characterized by high reproducibility of the results obtained and agreement with the VEGF-A and FGF-2 concentration values obtained with commercial ELISA tests. The proposed method offers fast, reproducible, and accurate simultaneous quantification of VEGF-A and FGF-2 in human body fluids. Only 4 µL of test sample are required for simultaneous analysis. The total time for simultaneous analysis of both biomarkers does not exceed 20 min. The developed analytical method is superior to ELISA in terms of analysis time and sample volume for analysis, and it offers lower LOD and LOQ values and allows for the simultaneous analysis of two biomarkers. There is also no need to collect a large number of samples. Standard ELISAs usually have 96 reaction wells. The proposed biosensor can be used to analyse only one sample, without the need to waste reagents on unused reaction sites. In addition, it is possible to regenerate the biosensor and reuse it.
Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline ...metabolism in the brain are somewhat historical. This study aims to investigate alterations of proline metabolism in gliomas of WHO grade 4 (GG4) in the context of the brain. A total of 20 pairs of samples were studied, consisting of excised tumor and unaffected brain tissue, obtained when partial brain resection was required to reach deep-seated lesions. Levels of proline oxidase/proline dehydrogenase (POX/PRODH), Δ
-pyrroline-5-carboxylate reductases (PYCR1/2/3), prolidase (PEPD), and metalloproteinases (MMP-2, MMP-9) were assessed, along with the concentration of proline and proline-related metabolites. In comparison to normal brain tissue, POX/PRODH expression in GG4 was found to be suppressed, while PYCR1 expression and activity of PEPD, MMP-2, and -9 were upregulated. The GG4 proline concentration was 358% higher. Hence, rewiring of the proline metabolism in GG4 was confirmed for the first time, with a low-POX/PRODH/high-PYCR profile. High PEPD and MMPs activity is in keeping with GG4-increased collagen turnover and local aggressiveness. Further studies on the mechanisms of the interplay between altered proline metabolism and the GG4 microenvironment are warranted.
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