[99mTc]Sestamibi SPECT can predict proliferation Index, angiogenesis, and vascular invasion in parathyroid patients: a retrospective study

The aim of this study was to evaluate the possible association among sestamibi uptake and the main histopathological characteristics of parathyroid lesions related to aggressiveness such as the proliferation index (Ki67 expression and mitosis), angiogenesis (number of vessels), and vascular invasion in hyperparathyroidism patients. To this end, 26 patients affected by primary hyperparathyroidism subjected to both scintigraphy with [(99)mTc]Sestamibi and surgery/bioptic procedure were retrospectively enrolled. Hyperfunctioning of the parathyroid was detected in 19 patients. Our data showed a significant positive association among the sestamibi uptake and the proliferation index histologically evaluated both in terms of the number of Ki67 positive cells and mitosis. According to these data, lesions with a higher valuer of L/N (lesion to nonlesion ratio) frequently showed several vessels in tumor areas and histological evidence of vascular invasion. It is noteworthy that among patients with negative scintigraphy, 2 patients showed a neoplastic lesion after surgery (histological analysis). However, it is important to highlight that these lesions displayed very low proliferation indexes, which was evaluated in terms of number of both mitosis and Ki67-positive cells, some/rare vessels in the main lesion, and no evidence of vascular invasion. In conclusion, data obtained on patients with positive or negative scintigraphy support the hypothesis that sestamibi can be a tracer that is capable of predicting some biological characteristics of parathyroid tumors such as angiogenesis, proliferation indexes, and the invasion of surrounding tissues or vessels

Human serum albumin-bound selenium (Se-HSA) in serum and its correlation with other selenium species

Introduction: Selenium (Se) is a trace element with different toxicological and nutritional properties according to its chemical forms. Among the wide range of selenium species, human serum albumin-bound selenium (Se-HSA) has still uncertain composition in terms of organic or inorganic selenium species. This study aimed at investigating the relation between Se-HSA levels with total selenium and the specific organic and inorganic selenium species. Methods: We determined levels of total selenium and selenium species in serum of participants enrolled in two populations of the Emilia-Romagna region, in Northern Italy. Anion exchange chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry was used as quantification method. Correlations between Se-HSA and the other selenium compounds were analyzed using linear regression and restricted cubic spline regression models, adjusted for potential confounders. Results: The first cohort comprised 50 participants (men/women: 26/24) with median (interquartile range, IQR) age 50 (55-62) years, while the second was composed of 104 participants (M/W: 50/54), median (IQR) age 48 (44-53) years. Median (IQR) levels of total selenium were 118.5 (109-136) µg/L and 116.5 (106-128) µg/L, respectively, while Se-HSA was 25.5 µg/L (16.2-51.5) and 1.1 (0.03-3.1) µg/L, respectively. In both populations, Se-HSA was positively associated with inorganic selenium species. Conversely, Se-HSA was inversely associated with organic selenium, especially with selenoprotein P-bound-Se (Se-SELENOP) and less strongly with selenomethionine-bound-Se (Se-Met), while the relation was null or even positive with other organic species. Evaluation of non-linear trends showed a substantially positive association with inorganic selenium, particularly selenite, until a concentration of 30 µg/L, above which a plateau was reached. The association with Se-SELENOP was inverse and strong until 100 µg/L, while it was almost null at higher levels. Conclusions: Our findings seem to indicate that Se-HSA incorporates more selenium when circulating levels of inorganic compounds are higher, thus supporting its mainly inorganic nature, particularly at high circulating levels of selenite

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

This study aims to investigate the possible different roles of the BMP-2 variants, cytoplasmic and nuclear variant, in both epithelial to mesenchymal transition and in microcalcifications origin in human breast cancers. To this end, the in situ expression of cytoplasmic and nuclear BMP-2 was associated with the expression of the main epithelial to mesenchymal transition biomarkers (e-cadherin and vimentin) and molecules involved in bone metabolisms (RUNX2, RANKL, SDF-1) by immunohistochemistry. In addition, the expression of cytoplasmic and nuclear BMP-2 was associated with the presence of microcalcifications. Our data showed a significant association among the number of cytoplasmic BMP-2-positive cells and the number of both vimentin (positive association) and e-cadherin (negative association) positive breast cells. Conversely, no associations were found concerning the nuclear BMP-2-positive breast cells. Surprisingly, the opposite result was obtained by analyzing the variants of BMP-2 and both the expression of RANKL and SDF-1 and the presence of microcalcifications. Specifically, the presence of microcalcifications was related to the expression of nuclear BMP-2 variant rather than the cytoplasmic one, as well as a strong association between the number of nuclear BMP-2 and the expression of the main breast osteoblast-like cells (BOLCs) biomarkers. To further corroborate these data, an in vitro experiment for demonstrating the co-expression of nBMP-2 and RANKL or vimentin or SDF-1 in breast cancer cells that acquire the capability to produce microcalcifications was developed. These investigations confirmed the association between the nBMP-2 expression and both RANKL and SDF-1. The data supports the idea that whilst cytoplasmic BMP-2 can be involved in epithelial to mesenchymal transition phenomenon, the nuclear variant is related to the essential mechanisms for the formation of breast microcalcifications. In conclusion, from these experimental and translational perspectives, the complexity of BMP-2 signaling will require a detailed understanding of the involvement of specific BMP-2 variants in breast cancers

Influence of dietary patterns on urinary excretion of cadmium in an Italian population: A cross-sectional study

Introduction: Cadmium is a toxic heavy metal with detrimental effects on human health. Apart from smoking and occupational factors, diet is the main source of cadmium. However, the relation between adherence to so-called "healthy" dietary patterns and cadmium exposure has not been investigated in detail. In this study, we aimed at assessing such association in a Northern Italian population. Methods: Using a cross-sectional study design, we investigated a population of non-smokers aged 30-60 years in the period 2017-2019. Each subject completed a validated food frequency questionnaire (FFQ) in order to estimate adherence to four dietary patterns, namely the Dietary Approach to Stopping Hypertension-DASH diet, Greek Mediterranean Index-GMI, the Italian Mediterranean Index-IMI, and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. We collected a fasting morning urinary sample to measure urinary levels of cadmium and cotinine. The association between increasing adherence to dietary patterns and cadmium exposure was evaluated using a cubic spline regression non-linear model and adjusting for relevant confounders (age, sex, body mass index, urinary cotinine levels, intake of fiber, and alcohol). Results: We recruited 137 participants (males/females: 62/75) with median (interquartile range-IQR) age of 47 (IQR: 43-53) years. Median scores for the investigated dietary patterns were 24 (IQR: 21-28), 4 (IQR: 3-6), 4 (IQR: 3-5), and 7.5 (IQR: 6.5-8.5) for DASH, GMI, IMI and MIND diets, respectively. The median urinary cadmium level was 0.21 μg/L (IQR: 0.11-0.34 μg/L). Spline regression analysis showed an inverse linear association between increasing adherence to the DASH and MIND diets and urinary cadmium levels, reaching a plateau at high adherence scores, approximately > 25 and > 9 for DASH and MIND diets, respectively. An increase of cadmium exposure with increasing MIND score also emerged. Conversely, the association was almost null for IMI, and slightly positive for GMI. Conclusions: The present findings suggest that increasing adherence to the DASH and MIND diets are associated with decreased cadmium levels only at moderate level. Overall, these results indicate that public health strategies, including the decrease of cadmium contamination in healthy foods should be implemented

The ETS Homologous Factor (EHF) Represents a Useful Immunohistochemical Marker for Predicting Prostate Cancer Metastasis.

The main aim of this study was to investigate the risk of prostate cancer metastasis formation associated with the expression of ETS homologous factor (EHF) in a cohort of bioptic samples. To this end, the expression of EHF was evaluated in a cohort of 152 prostate biopsies including primary prostate cancers that developed metastatic lesions, primary prostate cancers that did not develop metastasis, and benign lesions. Data here reported EHF as a candidate immunohistochemical prognostic biomarker for prostate cancer metastasis formation regardless of the Gleason scoring system. Indeed, our data clearly show that primary lesions with EHF positive cells ≥40% had a great risk of developing metastasis within five years from the first diagnosis. Patients with these lesions had about a 40-fold increased risk of developing metastasis as compared with patients with prostate lesions characterized by a percentage of EHF positive cells ≤30%. In conclusion, the immunohistochemical evaluation of EHF could significantly improve the management of prostate cancer patients by optimizing the diagnostic and therapeutic health procedures and, more important, ameliorating the patient's quality of life

High Sensitivity C-Reactive Protein Increases the Risk of Carotid Plaque Instability in Male Dyslipidemic Patients

Background: The aim of this study was to evaluate how the high sensitivity C-reactive protein (hs-CRP) values influence the risk of carotid plaque instability in association with other cardiovascular risk factors. Methods: One hundred and fifty-six carotid plaques from both symptomatic and asymptomatic patients requiring surgical carotid endarterectomy were retrospectively collected. According to the modified American Heart Association, atherosclerosis plaques have been histologically distinguished into unstable and stable. The following anamnestic and hematochemical data were also considered: age, gender, hypertension, diabetes mellitus, smoking habit, therapy, low-density lipoprotein (LDL)-C, kidney failure and hs-CRP. Results: The results of our study clearly show that high levels of hs-CRP significantly increase the carotid plaque instability in dyslipidemic patients. Specifically, a 67% increase of the risk of carotid plaque instability was observed in patients with high LDL-C. Therefore, the highest risk was observed in male dyslipidemic patients 2333 (95% CI 0.73–7.48) and in aged female patients 2713 (95% CI 0.14–53.27). Discussion: These data strongly suggest a biological relationship between the hs-CRP values and the alteration of lipidic metabolism mostly in male patients affected by carotid atherosclerosis. The measurement of hs-CRP might be useful as a potential screening tool in the prevention of atheroscletotic disease

Immunotherapy for colorectal cancer: where are we heading?

Introduction: In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy. Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment. Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response

Functional Imaging in Musculoskeletal Disorders in Menopause

: Menopause-related musculoskeletal (MSK) disorders include osteoporosis, osteoarthritis (OA), sarcopenia and sarco-obesity. This review focuses on the applications of nuclear medicine for the functional imaging of the aforementioned clinical conditions. Bone Scan (BS) with 99mTc-labeled phosphonates, alone or in combination with MRI, can identify "fresh" vertebral collapse due to age-associated osteoporosis and provides quantitative parameters characterized by a good correlation with radiological indices in patients with OA. 18F-NaF PET, particularly when performed by dynamic scan, has given encouraging results for measuring bone turnover in osteoporosis and allows the evaluation of subchondral bone metabolic activity in OA. FDG PET can help discriminate between pathological and nonpathological vertebral fractures, especially by applying appropriate SUV-based thresholds. In OA, it can effectively image inflamed joints and support appropriate clinical management. Preliminary evidences suggest a possible application of FDG in sarco-obesity for the detection and quantification of visceral adipose tissue (VAT). Further studies are needed to better define the role of nuclear medicine in menopause-related MSK disease, especially as regards the possible impact of new radiopharmaceuticals (ie, FAPI and RGD peptides) and recent technological advances (eg, total-body PET/CT scanners)