The multicenter European Biological Variation Study (EuBIVAS): a new glance provided by the Principal Component Analysis (PCA), a machine learning unsupervised algorithms, based on the basic metabolic panel linked measurands

Abstract Objectives The European Biological Variation Study (EuBIVAS), which includes 91 healthy volunteers from five European countries, estimated high-quality biological variation (BV) data for several measurands. Previous EuBIVAS papers reported no significant differences among laboratories/population; however, they were focused on specific set of measurands, without a comprehensive general look. The aim of this paper is to evaluate the homogeneity of EuBIVAS data considering multivariate information applying the Principal Component Analysis (PCA), a machine learning unsupervised algorithm. Methods The EuBIVAS data for 13 basic metabolic panel linked measurands (glucose, albumin, total protein, electrolytes, urea, total bilirubin, creatinine, phosphatase alkaline, aminotransferases), age, sex, menopause, body mass index (BMI), country, alcohol, smoking habits, and physical activity, have been used to generate three databases developed using the traditional univariate and the multivariate Elliptic Envelope approaches to detect outliers, and different missing-value imputations. Two matrix of data for each database, reporting both mean values, and "within-person BV" (CVP) values for any measurand/subject, were analyzed using PCA. Results A clear clustering between males and females mean values has been identified, where the menopausal females are closer to the males. Data interpretations for the three databases are similar. No significant differences for both mean and CVPs values, for countries, alcohol, smoking habits, BMI and physical activity, have been found. Conclusions The absence of meaningful differences among countries confirms the EuBIVAS sample homogeneity and that the obtained data are widely applicable to deliver APS. Our data suggest that the use of PCA and the multivariate approach may be used to detect outliers, although further studies are required

False negativity to carbohydrate-deficient transferrin and drugs: a clinical case

Introduction: In this work we report on the possible effect of the medical therapy on CDT concentration in a chronic alcohol abuser, with known medical history (July 2007 – April 2012) and alcohol abuse confirmed by relatives. Case history: At the end of 2007, patient displayed the following laboratory results: AST 137 U/L, ALT 120 U/L, GGT 434 U/L, MCV 101 fL and CDT 3.3%. On December 2007, after double coronary artery bypass surgery, he began a pharmacological treatment with amlodipine, perindopril, atorvastatin, isosorbide mononitrate, carvedilol, ticlopidine and pantoprazole. In the next months, until may 2011, the patient resumed alcohol abuse, as confirmed by relatives; however, CDT values were repeatedly found negative (0.8% and 1.1%) despite elevated transaminases and GGT, concurrent elevated ethyl glucuronide concentration (> 50 mg/L) and blood alcohol concentration (> 1 g/L). Alcohol consumption still continued despite increasing disulfiram doses ordered by an Alcohol Rehab Center. On May 2011, the patient was transferred to a private medical center where he currently lives. Conclusions: This study suggests the possibility that a medical therapy including different drugs may hamper the identification of chronic alcohol abusers by CDT

Treating Persistent Ectopic Pregnancy by Methotrexate Using a Sliding Scale: Preliminary Experience

To assess the clinical utility of prescribing a sliding scale regimen for methotrexate administered in cases of persistent ectopic pregnancy, a prospectively designed clinical trial was performed. Patients (n = 37) previously operated on for ectopic pregnancy by laparoscopic salpingostomy and found to have persistent disease were enrolled into the study. Methotrexate was given intramuscularly at a dose of 1 mg/kg body weight, with the number of doses administered depending on the presenting level of serum beta-human chorionic gonadotropin (β-hCG). Group 1 (n = 27), levels of 10–1500 mIU/ml, received a single dose; group 2 (n = 5), levels of 1500–2500 mIU/ml, received two doses 3 days apart; group 3 (n = 5), levels > 2500 mIU/ml, received three doses 3 days apart. Patients were followed with weekly transvaginal ultrasound examinations, and serum β-hCG and progesterone measurements. Results noted resolution in all three treatment groups without the requirement of surgery or further treatment: group 1, 19.9 ± 1.7 days; group 2, 35.2 ± 4.5 days; group 3, 49.0 ± 1.0 days. All patients remained asymptomatic, and no adverse side effects from the drug were experienced. We conclude, although preliminary, that a sliding scale approach to prescribing methotrexate based on the initial serum titer of β-hCG to treat persistent ectopic pregnancy is easy to use, efficacious, and likely results in complete resolution of the condition. In most cases, even with presenting levels of β-hCG > 2500 mIU/ml, persistent disease will resolve within 50 days of initiating care

Development of a short-term canine full-thickness skin organ culture method under serum-free conditions

Full-thickness canine skin organ culture models could provide an entirely new opportunity for studying wound healing, keratinization disorders and allergic skin diseases, all of which have high prevalence and severe impact on canine quality of life. Here we present a canine organ culture method for the short-term maintenance of full-thickness, adult, canine skin in serum-free medium and investigate the possibility to induce mast cell degranulation ex vivo. General morphological features were maintained up to day 7. Epidermal thickness started to decrease from day 4 of culture. No changes were observed in epidermal pigmentation. Keratinocyte proliferation started to significantly decrease at day 7. Immunostaining for cytokeratin 10, cytokeratin 14 and loricrin was evident from day 1 to day 7. Compound 48/80 induced mast cell degranulation. This was the first attempt to establish a dog skin organ culture and document good preservation of most cutaneous structures till day 7. This method may help in dissecting canine skin biology in physiological and pathological conditions and to study drug mechanism of action in a biologically relevant environment

Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos

Background To preclude transfer of aneuploid embryos, current preimplantation genetic screening (PGS) usually involves one trophectoderm biopsy at blastocyst stage, assumed to represent embryo ploidy. Whether one such biopsy can correctly assess embryo ploidy has recently, however, been questioned. Methods This descriptive study investigated accuracy of PGS in two ways. Part I: Two infertile couples donated 11 embryos, previously diagnosed as aneuploid and, therefore, destined to be discarded. They were dissected into 37 anonymized specimens, and sent to another national laboratory for repeat analyses to assess (i) inter-laboratory congruity and (ii) intra-embryo congruity of multiple embryo biopsies in a single laboratory. Part II: Reports on human IVF cycle outcomes after transfer of allegedly aneuploid embryos into 8 infertile patients. Results Only 2/11 (18.2 %) embryos were identically assessed at two PGS laboratories; 4/11 (36.4 %), on repeat analysis were chromosomally normal, 2 mosaic normal/abnormal, and 5/11 (45.5 %) completely differed in reported aneuploidies. In intra-embryo analyses, 5/10 (50 %) differed between biopsy sites. Eight transfers of previously reported aneuploid embryos resulted in 5 chromosomally normal pregnancies, 4 delivered and 1 ongoing. Three patients did not conceive, though 1 among them experienced a chemical pregnancy. Conclusions Though populations of both study parts are too small to draw statistically adequately powered conclusions on specific degrees of inaccuracy of PGS, here presented results do raise concerns especially about false-positive diagnoses. While inter-laboratory variations may at least partially be explained by different diagnostic platforms utilized, they cannot explain observed intra-embryo variations, suggesting more frequent trophectoderm mosiaicsm than previously reported. Together with recentl published mouse studies of lineages-specific degrees of survival of aneuploid cells in early stage embryos, these results call into question the biological basis of PGS, based on the assumption that a single trophectoderm biopsy can reliably determine embryo ploidy

Gestione delle pazienti con tumore fillode della mammella: esperienza triestina nel periodo 2006-2014

La diagnosi e la gestione dei tumori fillodi della mammella \ue8 complessa a causa del basso tasso di incidenza e dell\u2019imprevedibilit\ue0 del comportamento di questo tipo di neoplasie (meno dell\u20191% tra tutti i tumori della mammella [1]). L\u2019obiettivo di questo studio \ue8 analizzare i casi di tumori filloidi diagnosticati a Trieste nel periodo 2006-2014 al fine di contestualizzare il comportamento particolarmente aggressivo di un tumore fillode maligno insorto in una paziente con pregressi fillodi benigni