In premenopausal women with PCOS, we evidenced an association of serum bisphenol A levels with HS and markers of low-grade inflammation, in particular with spleen size, unravelling the presence of the liver-spleen axis in this syndrome.

BackgroundPolycystic ovary syndrome (PCOS) is frequently associated with hypovitaminosis D. Vitamin D is endowed with pleiotropic effects, including insulin resistance (IR) and apoptotic pathway. Disruption of the complex mechanism that regulated ovarian apoptosis has been reported in PCOS. Phosphoprotein enriched in diabetes gene product (PED/PEA-15), an anti-apoptotic protein involved in type 2 diabetes mellitus (T2DM), is overexpressed in PCOS women, independently of obesity. Leptin-to-adiponectin ratio (L/A) is a biomarker of IR and low-grade inflammation in PCOS. The aim of the study was to investigate the levels of 25-hydroxy vitamin D (25(OH)D), and L/A, in association with PED/PEA-15 protein abundance, in both lean and overweight/obese (o/o) women with PCOS.Patients and MethodsPED/PEA-15 protein abundance and circulating levels of 25(OH)D, L/A, sex hormone-binding globulin, and testosterone were evaluated in 90 untreated PCOS patients (25 ± 4 yrs; range 18-34) and 40 healthy controls age and BMI comparable, from the same geographical area. FAI (free androgen index) and the homeostasis model assessment of insulin resistance (HoMA-IR) index were calculated.ResultsIn o/o PCOS, 25(OH)D levels were significantly lower, and L/A values were significantly higher than in lean PCOS (p < 0.001), while there were no differences in PED/PEA-15 protein abundance. An inverse correlation was observed between 25(OH)D and BMI, PED/PEA-15 protein abundance, insulin, HoMA-IR, FAI (p < 0.001), and L/A (p < 0.05). At the multivariate analysis, in o/o PCOS L/A, insulin and 25(OH)D were the major determinant of PED/PEA-15 protein abundance (β = 0.45, β = 0.41, and β = -0.25, respectively).ConclusionsLower 25(OH)D and higher L/A were associated to PED/PEA-15 protein abundance in PCOS, suggesting their involvement in the ovarian imbalance between pro-and anti-apoptotic mechanisms, with high L/A and insulin and low 25(OH)D levels as the main determinants of PED/PEA-15 protein variability. Further studies, involving also different apoptotic pathways or inflammatory cytokines and granulosa cells are mandatory to better define the possible bidirectional relationships between 25(OH)D, PED/PEA-15 protein abundance, leptin and adiponectin in PCOS pathogenesis.

The role of dynamic contrast-enhanced-MRI (DCE-MRI) for Prostate Imaging-Reporting and Data System (PI-RADS) scoring is a controversial topic. In this retrospective study, we aimed to measure the added value of DCE-MRI in combination with T2-weighted (T2W) and diffusion-weighted imaging (DWI) using PI-RADS v2.1, in terms of reproducibility and diagnostic accuracy, for detection of prostate cancer (PCa) and clinically significant PCa (CS-PCa, for Gleason Score ≥ 7). 117 lesions in 111 patients were identified as suspicion by multiparametric MRI (mpMRI) and addressed for biopsy. Three experienced readers independently assessed PI-RADS score, first using biparametric MRI (bpMRI, including DWI and T2W), and then multiparametric MRI (also including DCE). The inter-rater and inter-method agreement (bpMRI- vs. mpMRI-based scores) were assessed by Cohen’s kappa (κ). Receiver operating characteristics (ROC) analysis was performed to evaluate the diagnostic accuracy for PCa and CS-PCa detection among the two scores. Inter-rater agreement was excellent for the three pairs of readers (κ ≥ 0.83), while the inter-method agreement was good (κ ≥ 0.73). Areas under the ROC curve (AUC) showed similar high-values (0.8 ≤ AUC ≤ 0.85). The reproducibility of PI-RADS v2.1 scoring was comparable and high among readers, without relevant differences, depending on the MRI protocol used. The inclusion of DCE did not influence the diagnostic accuracy.

The importance of Diffusion Weighted Imaging (DWI) in prostate cancer (PCa) diagnosis have been widely handled in literature. In the last decade, due to the mono-exponential model limitations, several studies investigated non-Gaussian DWI models and their utility in PCa diagnosis. Since their results were often inconsistent and conflicting, we performed a systematic review of studies from 2012 examining the most commonly used Non-Gaussian DWI models for PCa detection and characterization. A meta-analysis was conducted to assess the ability of each Non-Gaussian model to detect PCa lesions and distinguish between low and intermediate/high grade lesions. Weighted mean differences and 95% confidence intervals were calculated and the heterogeneity was estimated using the I2 statistic. 29 studies were selected for the systematic review, whose results showed inconsistence and an unclear idea about the actual usefulness and the added value of the Non-Gaussian model parameters. 12 studies were considered in the meta-analyses, which showed statistical significance for several non-Gaussian parameters for PCa detection, and to a lesser extent for PCa characterization. Our findings showed that Non-Gaussian model parameters may potentially play a role in the detection and characterization of PCa but further studies are required to identify a standardized DWI acquisition protocol for PCa diagnosis.

Glioblastoma (GBM) is the most lethal primary brain tumor of the central nervous system in adults. Despite advances in surgical and medical neuro-oncology, the median survival is about 15 months. For this reason, initial diagnosis, prognosis, and targeted therapy of GBM represent very attractive areas of study. Aptamers are short three-dimensional structures of single-stranded nucleic acids (RNA or DNA), identified by an in vitro process, named systematic evolution of ligands by exponential enrichment (SELEX), starting from a partially random oligonucleotide library. They bind to a molecular target with high affinity and specificity and can be easily modified to optimize binding affinity and selectivity. Thanks to their properties (low immunogenicity and toxicity, long stability, and low production variability), a large number of aptamers have been selected against GBM biomarkers and provide specific imaging agents and therapeutics to improve the diagnosis and treatment of GBM. However, the use of aptamers in GBM diagnosis and treatment still represents an underdeveloped topic, mainly due to limited literature in the research world. On these bases, we performed a systematic review aimed at summarizing current knowledge on the new promising DNA and RNA aptamer-based molecules for GBM diagnosis and treatment. Thirty-eight studies from 2000 were included and investigated. Seventeen involved the use of aptamers for GBM diagnosis and 21 for GBM therapy. Our findings showed that a number of DNA and RNA aptamers are promising diagnostic and therapeutic tools for GBM management.

The importance of Diffusion Weighted Imaging (DWI) in hepatocellular carcinoma (HCC) has been widely handled in the literature. Due to the mono-exponential model limitations, several studies recently investigated the role of non-Gaussian DWI models in HCC. However, their results are variable and inconsistent. Therefore, the aim of this systematic review is to summarize current knowledge on non-Gaussian DWI techniques in HCC. A systematic search of the literature, including PubMed, Google Scholar, MEDLINE, and ScienceDirect databases, was performed to identify original articles since 2010 that evaluated the role of non-Gaussian DWI models for HCC diagnosis, grading, response to treatment, and prognosis. Studies were grouped and summarized according to the non-Gaussian DWI models investigated. We focused on the most used non-Gaussian DWI models (Intravoxel Incoherent Motion (IVIM), Diffusion Kurtosis Imaging (DKI), and Stretched Exponential—SE). The quality of included studies was evaluated by using QUADAS-2 and QUIPS tools. Forty-three articles were included, with IVIM and DKI being the most investigated models. Although the role of non-Gaussian DWI models in clinical settings has not fully been established, our findings showed that their parameters may potentially play a role in HCC. Further studies are required to identify a standardized DWI acquisition protocol for HCC diagnosis, grading, response to treatment, and prognosis.

Background: Roux-en-Y Gastric Bypass (RYGB) and Sleeve 30 Gastrectomy (SG) are performed in patients with obesity and type 2 diabetes mellitus (T2DM). Aim of this study is to evaluate retrospectively the clinical efficacy of RYGB and SG in two groups of obese T2DM patients. Methods: From the hospital database, we extracted the clinical records of 31 obese T2DM patients, of whom 15 (7F/8M) had undergone laparoscopic SG (LSG) and 16 (7F/9M) laparoscopic RYGB (LRYGB) in the period 2005-2008. The groups were comparable for age (range 33-59y) and BMI (range 38-57kg/m2). LRYGB alimentary limb was 150cm and biliopancreatic limb was 150cm from Treitz ligament. LSG vertical transection was calibrated on a 40F oro-gastric bougie. Data were analyzed at 6,12 and 18-24 months with reference to 40 weight loss and remission of comorbidities. Results: The reduction in body weight was comparable in the two groups. At 18-24 months the percent BMI reduction was 29±8 and 33±11% in LSG and LRYGB, respectively. Percent excess weight loss was 53±16 and 52±19% in LSG and LRYGB, respectively. Thirteen patients in LSG and 14 patients in LRYGB discontinued their hypoglycemic medications. Five (55%) patients in LSG and 8 (89%) in LRYGB discontinued antihypertensive drugs. Three out of 5 patients in LSG and one out of two patients in LRYGB withdrew lipid lowering agents. Conclusions: LSG and LRYGB are equally effective in terms of weight loss and remission of obesity-related comorbidities. Controlled long-term comparisons are needed to establish the optimal procedure in relation to patients’ characteristics.

IntroductionTreatment options for non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) are still a matter of debate. We compared the effects of a diet including different components versus a proven beneficial diet rich in monounsaturated fatty acids (MUFAs) on liver fat in T2D.Research design and methodsAccording to a parallel design, 49 individuals with T2D, overweight/obese, with high waist circumference, 35–75 years-old, in satisfactory blood glucose control with diet or drugs not affecting liver fat content, were randomly assigned to an 8-week isocaloric intervention with a MUFA diet (n=26) or a multifactorial diet rich in fiber, MUFA, n-6 and n-3 polyunsaturated fatty acids, polyphenols, and vitamins D, E, and C (n=23). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS complete data were available for n=21 (MUFA diet) and n=18 (multifactorial diet) participants.ResultsAdherence to dietary interventions was optimal. No significant differences between groups in body weight reduction, plasma glycated hemoglobin, insulin, glucose, lipids and liver enzymes were observed. Liver fat significantly decreased after both the multifactorial diet (9.18%±7.78% vs 5.22%±4.80%, p=0.003) and the MUFA diet (9.47%±8.89% vs 8.07%±8.52%, p=0.027) with a statistically significant difference between changes either in absolute terms (−4.0%±4.5% vs −1.4%±2.7%, p=0.035) or percent (−40%±33% vs −19%±25%, p=0.030).ConclusionsAn isocaloric multifactorial diet including several beneficial dietary components induced a clinically relevant reduction of liver fat in patients with T2D, more pronounced than that induced by simply replacing saturated fat with MUFA. This suggests that the ‘optimal diet’ for NAFLD treatment in T2D should be based on synergic actions of different dietary components on multiple pathophysiological pathways.Trial registration numberNCT03380416.