A Sensitive Electrochemical Sensor Based on Sonogel-Carbon Material Enriched with Gold Nanoparticles for Melatonin Determination.

In this work, the development of an electrochemical sensor for melatonin determination is presented. The sensor was based on Sonogel-Carbon electrode material (SNGCE) and Au nanoparticles (AuNPs). The low-cost and environmentally friendly SNGCE material was prepared by the ultrasound-assisted sonogel method. AuNPs were prepared by a chemical route and narrow size distribution was obtained. The electrochemical characterization of the SNGCE/AuNP sensor was carried out by cyclic voltammetry in the presence of a redox probe. The analytical performance of the SNGCE/AuNP sensor in terms of linear response range, repeatability, selectivity, and limit of detection was investigated. The optimized SNGCE/AuNP sensor displayed a low detection limit of 8.4 nM melatonin in synthetic samples assessed by means of the amperometry technique. The potential use of the proposed sensor in real sample analysis and the anti-matrix capability were assessed by a recovery study of melatonin detection in human peripheral blood serum with good accuracy.

Systematic Differences Between Total and Free Prostate-Specific Antigen Immunoassays: Comparison Using Passing and Bablok Regression.

Recent studies have shown that there are systematic differences among total and free prostate-specificantigen (PSA) immunoassays. In this study we analyzedintermethod differences in total PSA (tPSA) and free PSA(fPSA) measurement using ARCHITECT i2000SR (Abbott Diagnostics) and COBAS E601 (Roche Diagnostics). A number of 160 blood samples were tested for tPSA and 50 samples for fPSA (selecting only sampleswith tPSA: 4.1-10.0 µg/L). Passing-Bablok regression analysis was used to compare the two analytical methods fortPSA, fPSA and percentage of fPSA (%fPSA). A strong correlation was noticed between ARCHITECT i2000SR and COBAS E601 for tPSA, fPSA and %fPSA (r between 0.94 and 0.99). Concentrations of tPSA and fPSA measured by COBAS E601 were higher thanthose measured by ARCHITECT i2000SR with a bias of 0.8 µg/L for tPSA and 0.14 µg/L for fPSA. Analyzing therelative difference between methods for fPSA and %fPSA, COBAS E601 exceed a 10% relative difference limit. Our study confirms that there are differences in measured concentrations of tPSA and fPSA byvarious commercial methods. Because clinical judgment on subsequent diagnostic procedures, such as prostatebiopsy, is based on tPSA and fPSA results, tests harmonization should be a priority.

NT-proBNP and CA 125 levels are associated with increased pro-inflammatory cytokines in coronary sinus serum of patients with chronic heart failure.

PURPOSE: Heart failure (HF) is considered to be a complex syndrome associated with neurohormonal and cytokine activation, that contribute to its progression. There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor marker widely used for ovarian cancer therapy monitoring, was significantly elevated in HF patients. We hypothesized that inflammatory stimuli may be responsible for amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and CA-125 production and release in chronic HF (CHF). We aimed to measure the levels of NT-proBNP, CA 125, pro-anti-inflammatory cytokines (IL-6, IL-1ß, IL-8, TNF-α and IL-4), from peripheral venous (PV) and coronary sinus (CS) blood samples, in patients with CHF and to assess their correlation with echocardiographic indices. METHODS: We enrolled 32 subjects (20M/12F) with CHF (III-IV NYHA functional class) who were to undergo cardiac resynchronization therapy (CRT) device implantation and 30 healthy controls (18M/12F). Two blood samples, from PV and CS, were collected at the time of CRT for each CHF patient. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. RESULTS: All investigated biomarkers were significantly higher in CHF patients than in non-CHF controls (P < 0.001). There were positive correlations between biomarkers concentrations in PV and CS (r between 0.54 and 0.98, all P < 0.003). NT-proBNP, IL-6 and IL-1ß levels were 17%, 86% and 36% higher in CS than in PV, these increases being very well correlated each other, while CA 125 levels were 86% higher in PV than in CS. Moreover, CS NT-proBNP, CS IL-6 and CS IL-1ß serum concentrations were inversely related to the echocardiographically determined left ventricular ejection fraction (LVEF) (r = -0.61, P < 0.001; r = -0.71, P < 0.001 and r = -0.48, P = 0.005, respectively). A positive relationship was found between CA 125 and IL-1ß (r = 0.51, P = 0.003) in CS serum and between CA 125 and IL-6 (r = 0.43, P = 0.015), TNF-α (r = 0.46, P = 0.008) in PV serum. CA 125 concentrations were closely related to NT-proBNP both in CS (r = 0.46, P = 0.008) and PV (r = 0.52, P = 0.002). CONCLUSIONS: CS sampling of NT-proBNP, CA 125 and pro-anti-inflammatory cytokines provides an additional insight into the possible mechanisms by which these biomarkers lead to left ventricular remodeling. Our results clearly suggest that serum NT-proBNP and CA 125 levels not only in PV, but also in CS of patients with CHF, may be dependent on inflammation as a consequence of cytokine network activation.

The role of pro-fibrotic biomarkers in paroxysmal and persistent atrial fibrillation.

PURPOSE: Signaling pathways involved in electrical, structural and contractile remodeling processes behind development and progression of atrial fibrillation (AF) have not been completely elucidated, but it seems to be related to complex interactions among neurohormonal and cellular mediators. We aimed to investigate interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-ß1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), as biomarkers of atrial remodeling, in patients with paroxysmal and persistent AF, and their correlation with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and left atrial (LA) diameter. METHODS: Thirty-seven patients (22M/15F) with paroxysmal AF, 32 patients (22M/10F) with persistent AF and 30 healthy control subjects (18M/12F) were enrolled in the study. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. RESULTS: IL-6 levels and MMP-9/TIMP-1 ratio were significantly higher in AF patients than in non-AF controls (P < .001), and in persistent than in paroxysmal AF (P < .001), in line with NT-proBNP and LA diameter. In contrast, TGF-ß1levels declined with increasing AF duration (from 51.2 pg/mL, IQR: 38.9-87.9 pg/mL in paroxysmal to 23.9 pg/mL, IQR: 16.9-43.6 pg/mL in persistent AF). TGF-ß1 was negatively correlated with NT-proBNP (r = -0.53, P = .001 in paroxysmal AF and r = -0.71, P < .001 in persistent AF) and LA diameter (r = -0.44, P = .006 in paroxysmal AF and r = -0.51, P = .003 in persistent AF). CONCLUSIONS: Our results demonstrate that AF development and progression (from paroxysmal to persistent) is associated with a gradual increase in serum levels of NT-proBNP, IL-6 and MMP-9/TIMP-1 ratio. Moreover, this study suggests that the relationship between TGF-ß1, NT-proBNP and LA diameter allows for the progression of atrial remodeling during AF, despite compensatory changes in the TGF-ß1 signaling pathway.

A rare case of polyglandular autoimmune syndrome type IIIc with primary antibody failure.

Primary antibody deficiency syndromes are a rare group of disorders present at any age, with complex polygenic disorders. We report the forth case of polyglandular autoimmune syndrome (PAS) type IIIc worldwide with complex clinical features and no family history of endocrine disorders or primary immunodeficiencies. Our patient, a 44-year-old Caucasian female was diagnosed with PAS type IIIc due to the presence of autoimmune thyroiditis, autoimmune alopecia diffusa and primary ovarian insufficiency, associated with lymphoproliferative disease and primary antibody failure. Treatment included lifelong intravenous immunoglobulin, supplements and antibiotics. The clinical complexity and rare occurrence made it challenging to determine diagnosis and provide better treatment for the patient. The current case provides an insight of the challenges to determine primary antibody failure signs in the presence of PAS which will further help to determine diagnosis and therapeutic treatment for PAS patients.

Effects of thyroid hormone withdrawal on natriuretic peptides during radioactive iodine therapy in female patients with differentiated thyroid cancer.

OBJECTIVE: We aimed to investigate the effects of thyroid hormone withdrawal on N-terminal prohormone forms of atrial natriuretic peptide (NT-proANP) and brain natriuretic peptide (NT-proBNP) during radioiodine therapy in female patients with differentiated thyroid cancer (DTC). METHODS: Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), NT-proANP and NT-proBNP were measured in 51 female patients with DTC (48.7 ± 4.2 years) at three time-points: day of radioiodine therapy (t1 - under acute hypothyroidism), 5 days after radioiodine (t2 - under acute hypothyroidism) and 3 months after radioiodine (t3 - under TSH suppression). Thirty healthy euthyroid women served as controls (42.8 ± 5.6 years). RESULTS: At t1/t2/t3, median NT-proANP was 5.2/1.7/487 pmol/L vs. 297.7 pmol/L in control group (p < 0.001), median NT-proBNP was 50.1/36.5/79.5 pmol/L vs. 64.5 pmol/L (p < 0.001) and median NT-proANP/NT-proBNP ratios was 0.20/0.18/4.81 vs. 4.14 (p < 0.001). In acute hypothyroidism, FT3 levels were positively correlated with NT-proANP (r = 0.38, p = 0.005), NT-proANP/NT-proBNP ratios (r = 0.47, p = 0.001), heart rate (r = 0.39, p = 0.005), and negatively with mean arterial blood pressure (r = -0.58, p < 0.001). CONCLUSIONS: Our results indicate that NT-proANP reflects more accurately direct thyroid hormone effects than NT-proBNP. Thyroid hormone-dependent hemodynamic effects seem to be overlapped on the direct stimulatory effect of thyroid hormones on NT-proANP secretion by cardiac myocytes.

Comparison of Architect i2000 for determination of Scc with IMX determination of SCC with different methods.

BACKGROUND: SCC (squamous cell carcinoma) antigen (SSCA), a tumor marker, is already used for the diagnosis and follow-up of carcinoma of the cervix and lungs. The aim of our study was the determination of SCCA concentration in 96 serum samples using CMIA (chemiluminesecent microparticle immnoassay) on an Architect i2000 (Abbott Diagnostics) and MEIA (microparticle enzyme immnoassay) on an IMx Chemistry Analyzer (Abbott Diagnostics). METHODS: In our investigation we used a CMIA (chemiluminesecent microparticle immnoassay) Architect i2000 and MEIA (microparticle enzyme immnoassay) Imx Chemistry Analyzer for SCCA determination. RESULTS: All patients were hospitalized at the Department of Gynecologic Oncology and Department for Oncology at the University Clinics Center of Sarajevo. The normal serum range of SCCA should be < 0.1 microg/L. The quality control, precision and accuracy of the Architect i2000 were assessed. The quality control was done using quality control serums for low (X = 2.17 microg/L), medium (X = 10.23 microg/L), and high (X = 48.99 microg/L) range. The precision for the Architect i2000 has a CV of 3.44% to 4.44%. We established that the main difference between Architect i2000 and IMx was statistically significant at p < 0.05 according to Student's t-test. The correlation coefficient was r = 0.990. The some samples have higher concentrations on the Architect than on the IMx because the sensitivity of the Architect assay is high (< 0.1 microg/L). CONCLUSIONS: The CMIA Architect technology is an applicable method significant in diagnostic of SCCA.

Eustachian Tube Teratoma: A Rare Entity.

Introduction: Teratomas, tumors derived from all 3 fetal germ cell layers, are rarely located in the head and neck region and extremely rare in the Eustachian tube area. Case report: The authors present the case of a 2 years old child with chronic ear discharge. Referral diagnosis was tumor or cyst of the temporal bone. Intraoperatively, a solid, hairy tumor located inside the Eustachain tube, with extension into the middle ear space was discovered and removed. Histology revealed a mature teratoma. Review of the literature showed reports of rare similar cases of Eustachian tube teratomas, differentiating themfrom hairy polyps of the rhynopharynx. The imaging of our patient, the surgical techique for removal of the tumor and long term follow-up are detailed. Conclusions: Teratomas located inside the Eustachian tube are exceptional. Their removal should be carefully planned in view of their long term anatomical sequelae and in order to avoid long term postoperative morbidity.

Quantitative Assessment of Treatment Response in Metastatic Breast Cancer Patients by SPECT-CT Bone Imaging-Getting Closer to PET-CT.

BACKGROUND: Cancer represents the major cause of death mainly through its ability to spread to other organs, highlighting the importance of metastatic disease diagnosis and accurate follow up for treatment management purposes. Although until recently the main method for imaging interpretation was represented by qualitative methods, quantitative analysis of SPECT-CT data represents a viable, objective option. METHODS: Seventy-five breast cancer patients presenting metastatic bone disease underwent at least two Bone SPECT-CT studies using [99mTc]-HDP between November 2019 to October 2022. RESULTS: Our findings show a good positive relationship between the qualitative methods of imaging interpretation and quantitative analysis, with a correlation coefficient of 0.608 between qualitative whole body scintigraphy and quantitative SPECT-CT, and a correlation coefficient of 0.711 between the qualitative and quantitative interpretation of SPECT-CT data; nevertheless, there is a need for accurate, objective and reproducible methods for imaging interpretation, especially for research purposes. CONCLUSIONS: Quantitative evaluation of the SPECT-CT data has the potential to be the first choice of imaging interpretation for patient follow up and treatment response evaluation, especially for research purposes, because of its objectivity and expression of uptake changes in absolute units.

Portrait of the Inflammatory Response to Radioiodine Therapy in Female Patients with Differentiated Thyroid Cancer with/without Type 2 Diabetes Mellitus.

No clinical studies have investigated the effect of radioiodine (131I)-targeted therapy on the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as inflammatory response markers in patients with differentiated thyroid cancer (DTC) associated with type 2 diabetes mellitus (T2DM) and obesity. This study aimed to assess the relationship between blood radioactivity, body mass index (BMI), and peripheral blood cells three days after 131I intake in 56 female patients without T2DM (DTC/-T2DM) vs. 24 female patients with T2DM (DTC/+T2DM). Blood radioactivity, measured three days after 131I intake, was significantly lower in the DTC/+T2DM than in the DTC/-T2DM patients (0.7 mCi vs. 1.5 mCi, p < 0.001). The relationship between blood radioactivity and BMI (r = 0.83, p < 0.001), blood radioactivity and NLR (r = 0.53, p = 0.008), and BMI and NLR (r = 0.58, p = 0.003) indicates a possible connection between the bloodstream 131I uptake and T2DM-specific chronic inflammation. In patients without T2DM, 131I therapy has immunosuppressive effects, leading to increased NLR (19.6%, p = 0.009) and PLR (39.1%, p = 0.002). On the contrary, in the chronic inflammation context of T2DM, 131I therapy amplifies immune metabolism, leading to a drop in NLR (10%, p = 0.032) and PLR (13.4%, p = 0.021). Our results show that, in DTC/+T2DM, the bidirectional crosstalk between neutrophils and obesity may limit 131I uptake in the bloodstream. Considering the immune response to 131I therapy, the two groups of patients can be seen as a synchronous portrait of two sides. The explanation could lie in the different radiosensitivity of T and B lymphocytes, with T lymphocytes being predominant in patients with DTC/-T2DM and, most likely, B lymphocytes being predominant in T2DM.

Correlation Studies between S100 Protein Level and Soluble MIA or Tissue MelanA and gp100 (HMB45) Expression in Cutaneous Melanoma.

(1) Background: Cutaneous melanoma (CM) originates from melanocytes and causes 90% of skin cancer deaths; therefore, the comparison of different soluble and tissue markers could be valuable in the detection of melanoma progression and therapy monitoring. The present study is focused on the potential correlations between soluble S100B and MIA protein levels in different melanoma stages or with tissue expression of S100, gp100 (HMB45), and MelanA biomarkers. (2) Methods: Soluble S100B and MIA levels were evaluated by means of immunoassay methods in blood samples from 176 patients with CM, while tissue expressions of S100, MelanA, and gp100 (HMB45) were detected by means of immunohistochemistry in 76 melanomas. (3) Results: Soluble S100B correlated with MIA in stages III (r = 0.677, p < 0.001) and IV (r = 0.662, p < 0.001) but not in stages I and II; however, 22.22% and 31.98% of stage I and II patients, respectively, had high values for at least one of the two soluble markers. S100 tissue expression correlated with both MelanA (r = 0.610, p < 0.001) and HMB45 (r = 0.476, p < 0.01), while HMB45 and MelanA also significantly positively correlated (r = 0.623, p < 0.001). (4) Conclusions: Blood levels of S100B and MIA corroborated with melanoma tissue markers expression could help to improve the stratification process for patients with a high risk of tumor progression.

Cardiovascular Effects of Cumulative Doses of Radioiodine in Differentiated Thyroid Cancer Patients with Type 2 Diabetes Mellitus.

Radioiodine (131I) therapy for differentiated thyroid cancer (DTC) involves exposure of the whole body, including the heart, to ionizing radiation. This exposure to the subsequent risk of heart disease is uncertain, especially in patients with DTC associated with type 2 diabetes mellitus (DTC/+T2DM). The current study aimed to assess the relationship between left ventricular ejection fraction (LVEF), high cumulative 131I dose, and peripheral blood parameters in patients with DTC/−T2DM and DTC/+T2DM. The study enrolled 72 female patients with DTC/−T2DM and 24 with DTC/+T2DM who received cumulative 131I doses above 150 mCi (5.55 GBq). LVEF was lower in patients with concomitant T2DM than those without (p < 0.001). The cumulative 131I dosage was inversely correlated with LVEF only in DTC/−T2DM patients (r = −0.57, p < 0.001). In the DTC/+T2DM group, LVEF was negatively associated with absolute platelet count (r = −0.67, p < 0.001) and platelet-to-lymphocyte ratio (r = −0.76, p < 0.001). Our results demonstrate that exposure to high cumulative 131I doses has different cardiovascular effects in DTC/−T2DM and DTC/+T2DM.

Analysis of the Correlation between the Radioactive Iodine Activity and Neutrophil-to-Lymphocyte Ratio in Patients with Differentiated Thyroid Cancer.

Publications investigating the effect of radioactive iodine (131I) therapy on the circulating peripheral blood cells in patients with differentiated thyroid cancer (DTC) are limited to blood samples collected more than 92 h after 131I. Studies conducted on blood samples collected up to 92 h are rare due to the radioactive contamination risk. This research aimed to assess the relationship between the prescribed 131I activity, human whole blood activity, and peripheral blood cells at many time points (6, 22, 46, 69, and 92 h after 131I). The study enrolled 50 female patients with DTC who received a 131I median activity of 90.54 mCi (3.35 GBq). The neutrophil-to-lymphocyte ratio (NLR) was measured as an inflammatory marker. 131I uptake in the residual thyroid tissue peaked after 46 h. Blood activity decreased in the first 46 h and increased 69 h after the 131I intake. Blood activity was associated with the absolute lymphocyte count and the NLR at 69 h (r = −0.49 and r = 0.52, p < 0.001). Our results demonstrate that the time interval between 46 and 69 h should be associated with the release of hematological inflammatory mediators, such as neutrophils and lymphocytes, to eradicate tumor cells in response to 131I therapy.

Radiomics Analysis of [18F]FDG PET/CT Thyroid Incidentalomas: How Can It Improve Patients' Clinical Management? A Systematic Review from the Literature.

BACKGROUND: We performed a systematic review of the literature to provide an overview of the application of PET-based radiomics of [18F]FDG-avid thyroid incidentalomas and to discuss the additional value of PET volumetric parameters and radiomic features over clinical data. METHODS: The most relevant databases were explored using an algorithm constructed based on a combination of terms related to our subject and English-language articles published until October 2021 were considered. Among the 247 identified articles, 19 studies were screened for eligibility and 11 met the criteria, with 4 studies including radiomics analyses. RESULTS: We summarized the available literature based on a study of PET volumetric parameters and radiomics. Ten articles provided accurate details about volumetric parameters and their prospective value in tumour assessment. We included the data provided by these articles in a sub-analysis, but could not obtain statistically relevant results. Four publications analyzed the diagnostic potential of radiomics and the possibility of creating precise predictive models, their corresponding quality score being assessed. CONCLUSIONS: The use of PET volumetric parameters and radiomics analysis in patients with [18F]FDG-avid thyroid incidentalomas outlines a great prospect in diagnosis and stratification of patients with malignant nodules and may represent a way of limiting the need for unnecessary invasive procedures; however, further studies need to be performed for a standardization of the method.

The New Radiolabeled Peptide 99mTcEDDA/HYNIC-TOC: Is It a Feasible Choice for Diagnosing Gastroenteropancreatic NETs?

(1) Background: The aim of our study is to reveal the advantages and limitations of the use of 99mTcEDDA/HYNIC-TOC (Tektrotyd®, Polatom) in the diagnosis of gastroenteropancreatic neuroendocrine tumors and to compare our results with the values obtained for 111In-pentetreotide and 68Ga-DOTA-peptides, routinely used in medical practice. (2) Methods: This retrospective monocentric study included 173 patients with gastroenteropancreatic neuroendocrine tumors who underwent 99mTcEDDA/HYNIC-TOC scans as part of their clinical management. The examination protocol included a whole-body scan acquired 2 h after the radiotracer's administration, with the SPECT/CT performed 4 h post-injection. Physiological and abnormal uptake were established by two experienced physicians and, based on the obtained results, sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated. (3) Results: Our method presented a sensitivity of 90.5%, a specificity of 71.9%, and an accuracy of 84.3%, with a positive predictive value of 86.7% and a negative predictive value of 78.8%. (4) Conclusions: 99mTc-EDDA/HYNIC-TOC, a receptor-based radiopharmaceutical, could represent a competitor for 68Ga-labeled peptides in the diagnosis and management of patients with gastroenteropancreatic neuroendocrine tumors. Our results show a lower sensitivity (90.5%) than 68Ga-DOTA-peptides, but with great specificity, accuracy, positive, and negative predictive values.

Quantitative Analysis of SPECT-CT Data in Metastatic Breast Cancer Patients-The Clinical Significance.

PURPOSE: To assess the potential added value of the SPECT-CT quantitative analysis in metastatic breast cancer lesions detection and differentiation from degenerative lesions. METHODS: This prospective monocentric study was conducted on 70 female patients who underwent SPECT-CT bone scans using 99mTc-HDP that identified the presence of metastatic bone lesions and degenerative lesions in each patient. Once the lesions were identified, a quantitative analysis of radiotracer uptake was conducted. The highest one to five SUVmax values for both metastatic and degenerative bone lesions were identified in each patient and the data were then statistically analyzed. RESULTS: The SUVmax value was significantly higher in metastatic bone lesions than in degenerative lesions (p < 0.001). The diagnostic accuracy of SPECT-CT quantitative data analysis revealed a sensitivity of 91.5% and a specificity of 93.3% at a cut-off value of the SUVmax of 16.6 g/mL. CONCLUSION: Quantitative analysis performed using SPECT-CT data can improve the diagnostic accuracy in differentiating between metastatic bone lesions and degenerative lesions, thus leading to appropriate treatment and better follow-up in metastatic breast cancer patients.

Evaluating Cardiotoxicity in Breast Cancer Patients Treated with HER2 Inhibitors: Could a Combination of Radionuclide Ventriculography and Cardiac Biomarkers Predict the Cardiac Impact?

(1) Background: The aim of our study was to determine whether monitoring cardiac function through RNV and cardiac biomarkers could predict the cardiac impact of combined therapy with trastuzumab, pertuzumab and docetaxel, which are regularly used nowadays to treat HER2-positive breast cancer. (2) Methods: This prospective monocentric study included 22 patients, diagnosed with HER2-positive breast cancer, who had their LVEFs and cardiac biomarkers evaluated both at the beginning of their treatment and after 6 months. Among all of the enrolled patients, two blood specimens were collected to assess circulating cardiac biomarkers. RNV was performed in each patient after "in vivo" radiolabeling of the erythrocytes. The obtained results were then statistically correlated. (3) Results: The average LVEF decrease between the two time points was approximately 4%. Of the five biomarkers we considered in this paper, only NT-proBNP correlated with the LVEF values obtained both in the baseline study and after 6 months of follow-up (r = -0.615 for T0 and r = -0.751 for T1, respectively). ST2/IL-33R proved statistically significant at the T1 time point (r = -0.547). (4) Conclusions: A combination of LVEF, NT-proBNP and ST2/IL-33R assessment may be useful for early detection of cardiac impairment in breast cancer patients treated with trastuzumab, pertuzumab and docetaxel.

TNF-α May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) may impair radioiodine (131I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of 131I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after 131I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after 131I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after 131I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = -0.62, p < 0.001 and r = -0.58, p < 0.001). Our results demonstrate that TNF-α may exert different antitumor effects in response to 131I therapy depending on the patient's immune profile.

Clinical significance of serum matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in the first phase of burn trauma evolution.

No prospective study has specifically examined the serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the early shock phase of burn-injured patients. Thus, we aimed to detect early changes, activity dynamics, and the predictive value of MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio to better understand the early repair mechanisms for the development of future therapies for patients with thermal burns. Twenty-five patients with a total body surface area (TBSA) affected by burn <25%, and 30 healthy subjects were enrolled in the study. Serum levels of MMP-9 and TIMP-1 were determined by the ELISA method. Our results showed that MMP-9 concentrations increased immediately after injury and remained on a plateau. In contrast, TIMP-1 showed an upward trend throughout the 7-day study period, and the time course of the MMP-9/TIMP-1 ratio followed the inverse dynamics of TIMP-1. Analysis of the areas under the receiver operating characteristic (ROC) curves (AUC) showed that patients with burn wounds tended to have a MMP-9 value higher than 421.5 ng/ml (AUC=0.979), TIMP-1 value higher than 231.6 ng/ml (AUC=0.908), and MMP-9/TIMP-1 ratio higher than 2.31 (AUC=0.959) (P<0.001). Our findings suggest that although the variations in the two biomarkers were different regarding the time of the initial insult, their ratio is a specific and sensitive indicator of burn evolutivity in patients with a TBSA affected by a burn <25%.

Role and dynamics of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in burn patients.

Burn injuries can trigger tissue changes that can explain the variation in the level of different biochemical markers that can be recorded both locally or systemically. Some events observed in burn wounds such as vascular hyperpermeability have been associated with the release of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after trauma. Because it is unknown whether the serum levels of MMP-9 and TIMP-1 are a consequence of these destructions or a local response to thermal damage, we decided to follow their dynamics. Twenty-five patients (mean age 49.40±17.55 years) with a total body surface area (TBSA) affected by a thermal burn of <25% and 30 healthy subjects (mean age 49.70±8.04 years) were enrolled in the present study. Enzyme immunoassays were used to measure the serum levels of MMP-9 and TIMP-1. Our results showed that MMP-9 was increased 6.25-fold immediately after injury compared to the controls and remained on a plateau throughout the 7-day monitoring period. TIMP-1 showed an upward trend with an increase of 49.52% on the seventh day after triggering insult. The time-course of the MMP-9/TIMP-1 ratio followed the inverse dynamics of TIMP-1 starting from a ratio value measured at admission 3.82-fold higher than the one observed in the healthy volunteers and a highly statistically significant correlation between the values measured at different time-points during the monitoring period (P<0.001). The results of this retrospective study indicate that the MMP-9/TIMP-1 ratio may provide information on local changes over time, starting from the triggering insult, and may be considered as a predictive biomarker of burn evolutivity.