Search

Abstract Background Concomitant with the development of in vitro diagnostic multivariate index assays (IVDMIAs) to improve the diagnostic efficiency of ovarian cancer detection is the need to identify appropriate biostatistical approaches to assess improvements in risk predication. In this study, we assessed the utility of three different approaches for comparing diagnostic efficiency of an ovarian cancer multivariate assay in a retrospective case - control phase 2 biomarker trial. The control cohort included both disease-free women and women with benign gynecological conditions to more accurately reflect the target population of symptomatic women. Methods The study cohort comprised plasma samples from 244 healthy controls, 223 women with benign gynecological conditions, 53 borderline ovarian cancer cases and 222 women with malignant epithelial ovarian cancer. A multivariate classification model was developed that incorporated plasma concentrations of CA125, C-reactive protein (CRP), serum amyloid-A (SAA), interleukin-6 (IL6) and interleukin-8 (IL8) that were measured using in vitro diagnostics assays on medical device approved clinical analysers. The posterior probability values derived from the implemented algorithm were used for comparisons of the diagnostic performance between the multianalyte panel and CA125 using multiple methods; area under the curve (AUC) of the receiver operating characteristics curve, integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Results Each of the biomarkers displayed significantly elevated plasma concentrations in malignant ovarian cancer patients compared with either benign or control subjects. For the discrimination of borderline and malignant ovarian cancer from control and benign subjects, the multivariate classification model showed a significantly greater AUC than that for CA125 alone (88.4% versus 84.3%, respectively, p < 0.001). At a posterior probability threshold of 0.5, the IVDMIA delivered a specificity of 92.3% and a sensitivity of 76.4%. When set at a specificity of 95%, the multimarker diagnostic delivered a sensitivity of 69.5% compared with 62.5% for CA125. Enhanced diagnostic performance of the IVDMIA over the use of CA125 alone was confirmed statistically by alternative comparisons using IDI and NRI. Conclusions This study confirms in an independent sample set that a blood-based multianalyte assay has significant advantages over CA125 for distinguishing symptomatic women with borderline and malignant ovarian cancer from controls or those with benign disease.

Background: Nutrition exerts a fundamental role in the prevention of obesity (OB). The aim of this study was to assess the extent to which well recognized risk factors for early OB can be associated to overweight (OW) or OB under a standardized nutritional approach and surveillance in toddlers., Methods: The eligible population was represented by 676 toddlers aged 24-36 months, assigned to 18 primary care pediatricians trained on nutritional issues who shared a standardized nutritional approach. Six-hundred-twenty-nine children (333 boys), mean age 27.8 ± 4.2 months were effectively included in this observational study. Parents received nutritional advice with particular emphasis to proteins and sugar composition supported by leaflets and reinforced at each visit. Body mass index was assessed at the age of 24-36 months. The following individual and family risk factors were considered: gestational age, birth weight, eutocic/caesarean delivery, milk feeding history, household smoking or antibiotics exposure, parents' weight, height and educational level. Prevalence of OW/OB was compared to a group of 742 toddlers (373 boys) under usual care., Results: Under a standardized nutritional counselling, 28.1% toddlers were classified as OW/OB compared to 36.9% toddlers under usual care (p = 0.005). In unadjusted models, parental OW/OB was significantly associated to OW/OB in toddlers (p < 0.01), while high birth weight did not reach statistical significance (p = 0.07). In adjusted models, including all the explanatory variables studied, only paternal OW/OB vs. normal weight was significantly associated to OW/OB in toddlers (OR 2.035, 95% confidence interval 1.206-3.436). No protective effect of exclusive breast feeding during the first 6 months of age was demonstrated., Conclusions: Toddlers under a standardized nutrition counselling focused to limit protein and simple sugars, showed lower prevalence of OW/OB compared to usual care. Healthy promotion activities should take into account the influence of paternal BMI on the offspring adiposity., (© 2024. The Author(s).)

The pituitary-gonadal function was studied in 18 beta-thalassemic female adolescents, 8 with delayed puberty and 10 with primary amenorrhea,treated with repeated transfusions and long-term iron chelation therapy by subcutaneous infusion. A 100 micrograms gonadotropin-releasing hormone (GnRH) test, a double-bolus GnRH test after estradiol administration in non-responders, a 400 micrograms thyrotropin-releasing hormone (TRH) test and a 'high dose' human menopausal gonadotropin (hMG) test were performed. LH and FSH peak levels were significantly lower in thalassemic patients than in controls, both in the 100 micrograms GnRH test (LH was 4.3 +/- 0.7 mIU/ml vs 40.8 +/- 6.0 mIU/ml and FSH 3.3 +/- 0.5 mIU/ml vs 9.6 +/- 1.1 mIU/ml, respectively) and in the double-bolus GnRH test (LH was 2.3 +/- 0.2 mIU/ml vs 59.0 +/- 4.9 mIU/ml and FSH 1.8 +/- 0.3 mIU/ml vs 14.0 +/- 1.0 mIU/ml). The mean prolactin response to the TRH test was 27.8 +/- 3.2 ng/ml. After the 'high dose' hMG test 12 out of 14 admitted patients showed a poor response, lower than 250 pg/ml. Our data suggest that the hypogonadotropic condition of the thalassemic adolescents is due to pituitary hyporesponsiveness to GnRH and that most of these patients also have an impairment of ovarian function. Both conditions are a consequence of iron deposits in glands. Moreover, there is evidence that pituitary-gonadal function cannot be preserved by long-term iron chelation therapy.