Justifiability of amniocentesis on the basis of positive findings of triple test, ultrasound scan and advanced maternal age

Objective. To assess the effectiveness of antenatal screening for chromosomal abnormalities based on maternal age (≥35 years), positive ultrasound findings or a positive triple test. Materials and methods. Retrospective six-year study. The pregnant women routinely underwent established clinical and laboratory practice at the Department of Medical Genetics between 1997 and 2003. The women's case notes were examined to identify indications for karyotyping, gestation period and the outcome of karyotyping and pregnancy. Results. Invasive antenatal tests were performed on 1440 cases, 1168 (81.11%) age 35(a), 72 (5.00%) positive triple test (b), 24 (1.67%) positive ultrasound scanning (c) and 176 (12.2%) other (psychological, personal reasons, etc) (d). The overall positive predictive value was 1.67% (1.6%(a), 1.4% (b), 12.5% (c), 0.0% (d). The constructed model of logistic regression gave an odds-ratio of 8.647 for the "positive ultrasound result vs. maternal age ≥35" indication, while the odds-ratio for the triple test vs. maternal age ≥35 was 0.854. Conclusions. Amniocentesis and cytogenetic analysis of foetal karyotype should be presented as a diagnostic possibility to all women over 35 years. The application of biochemical markers was far from the expected results. If we compare results for indication positive ultrasound scanning vs. maternal age, an oddsratio of ~9 was obtained. These results demonstrate that the likelihood of obtaining positive results (i.e. the presence of chromosome alterations) from an amniocentesis having this indication is almost 9 times higher than from having an amniocentesis performed solely for advanced maternal age

Satisfaction with online teaching of medical statistics during the COVID-19 pandemic: A survey by the Education Committee of the Italian Society of Medical Statistics and Clinical Epidemiology

: On May 2020, after 2 months of online teaching with no face-to-face lectures, the Education Committee of the Italian scientific Society of Medical Statistics and Clinical Epidemiology conceived an online survey to assess satisfaction of Italian academics of medical statistics with online teaching and remote exams. This survey highlighted teachers' perceptions as well as opportunities and limitations of online teaching of medical statistics, biostatistics, and epidemiology. Although 61% of Italian academics of medical statistics declared to be favorable to provide online teaching of medical statistics, biostatistics, and epidemiology in the future, we recognize that distance education cannot substitute the unique value of teaching and knowledge exchange that could only be transmitted through a personal interaction between students and teachers. These indications may be useful to improve the quality of the teaching process in the future

18F-FDG PET/CT role in staging of gastric carcinomas: comparison with conventional contrast enhancement computed tomography

The purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in staging gastric cancer comparing it with contrast enhancement computed tomography (CECT).This retrospective study included 45 patients who underwent performed whole body CECT and F-FDG PET/CT before any treatment. We calculated CECT and F-FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) for gastric, lymphnode, and distant localizations; furthermore, we compared the 2 techniques by McNemar test. The role of F-FDG PET/CT semiquantitative parameters in relation to histotype, grading, and site of gastric lesions were evaluated by ANOVA test.Sensitivity, specificity, accuracy, PPV and NPV of CECT, and F-FDG PET/CT for gastric lesion were, respectively, 92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%, 46.15%. No differences were identified between the 2 techniques about sensitivity and specificity. No statistical differences were observed between PET parameters and histotype, grading, and site of gastric lesion. The results of CECT and F-FDG PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and 58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and F-FDG PET/CT about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%, 88.57%, 82.22%, 60%, 88.57%. FDG PET/CT specificity was significantly higher both for lymphnode and distant metastases.The F-FDG PET/CT is a useful tool for the evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant metastases using 1 single image whole-body technique. Integration of CECT with F-FDG PET/CT permits a more valid staging in these patients

In Vitro and In Vivo Effects of Melatonin-Containing Combinations in Human Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rates. Therefore, it is necessary to identify new targets and therapeutic strategies to improve the prognosis of patients with PDAC. Integrative therapies are increasingly being used to boost the efficacy of the known anticancer therapeutic approaches. Hence, this study aimed to evaluate the effects of a novel combination of different potential anticancer molecules, melatonin (MLT), cannabidiol (CBD), and oxygen-ozone (O2/O3) to treat PDAC using in vitro and in vivo models of human PDAC. The effect of this combination was investigated in combination with gemcitabine (GEM), the most common chemotherapeutic drug used for PDAC treatment. The combination of MLT + CBD + O2/O3 was more effective than the individual treatments in inhibiting PDAC cell viability and proliferation, inducing cell death, and modulating the RAS pathway protein levels. Moreover, different combinations of treatments reduced tumor mass in the PDAC mouse model, thus promoting the effect of GEM. In conclusion, a mixture of MLT + CBD + O2/O3 could serve as a potential adjuvant therapeutic strategy for PDAC

Pediatric Hodgkin Lymphoma: Predictive value of interim 18F-FDG PET/CT in therapy response assessment

We investigated the prognostic value of interim 18F-FDG PET/CT (PET-2) in pediatric Hodgkin lymphoma (pHL), evaluating both visual and semiquantitative analysis. Thirty pHL patients (age ⠤16) underwent serial 18F-FDG PET/CT: At baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of first-line chemotherapy (PET-T). PET response assessment was carried out visually according to the Deauville Score (DS), as well as semiquantitatively by using the semiquantitative parameters reduction from PET-0 to PET-2 (ΠΣSUVmax0-2, ΠΣSUVmean0-2). Final clinical response assessment (outcome) at the end of first-line chemotherapy was the criterion standard, considering patients as responders (R) or nonresponders (NR). Disease status was followed identifying patients with absence or relapsed/progression disease (mean follow-up: 24 months, range 3-78). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of visual and semiquantitative assessment were calculated; furthermore, Fisher exact test was performed to evaluate the association between both visual and semiquantitative assessment and outcome at the end of the first-line chemotherapy. The prognostic capability of PET-2 semiquantitative parameters was calculated by ROC analysis and expressed as area under curve (AUC). Finally, progression-free survival (PFS) was analyzed according to PET-2 results based on the 5-point scale and semiquantitative criteria, using the Kaplan-Meier method. Based on the outcome at the end of first-line chemotherapy, 5 of 30 patients were NR, the remnant 25 of 30 were R. Sensitivity, specificity, PPV, NPV, and accuracy of visual analysis were 60%,72%,30%,90%,70%; conversely, sensitivity, specificity, PPV, NPV, and accuracy of semiquantitative assessment were 80%, 92%, 66.7%, 95.8%, 90%. The highest AUC resulted for ΠΣSUVmax0-2 (0.836; cut-off <12.5; sensitivity 80%; specificity 91%). The association between ΠΣSUVmax0-2 and outcome at the end of first-line chemotherapy resulted to have a strong statistical significance (P=0.0026). Both methods demonstrated to influence PFS, even if the semiquantitative assessment allowed a more accurate identification of patients with a high risk of treatment failure (P=0.005). Our preliminary results showed that PET-2 visual assessment, by using Deauville criteria, can be improved by using the semiquantitative analysis. The SUV max reduction (ΠΣSUVmax0-2) evaluation might provide a support for the interpretation of intermediate scores, predicting with good confidence those patients who will have a poor outcome and require alternative therapies

Hydrolyzed protein formula for allergy prevention in preterm infants: follow-up analysis of a randomized, triple-blind, placebo-controlled study

Background: Allergic diseases are a major public health burden worldwide. Evidence suggests that early nutrition might play a key role in the future development of allergies and the use of hydrolyzed protein formulas have been proposed to prevent allergic disease, mainly in term infants with risk factors. Aim: To evaluate the preventive effect of a hydrolyzed protein formula vs. an intact protein formula on allergy development in preterm infants with or without risk factors. Methods: We performed a 3-year follow-up study of a previous triple-blind, placebo-controlled randomized trial. Evidence of atopic dermatitis, asthma and IgE-mediated food allergies were evaluated according to a validated parental questionnaire (Comprehensive Early Childhood Allergy Questionnaire). Food sensitization was also investigated by skin prick test at 3 years of chronological age. Results: Of the 30 subjects in the intact protein formula group and 30 in the extensively hydrolyzed formula group, respectively 18 and 16 completed the 3-year follow-up and entered the final analysis. No group differences in the incidence of atopic dermatitis, asthma, IgE-mediated food allergies, and food sensitization were found. Conclusion: Despite the small number of cases, extensively hydrolyzed protein formula seems to be ineffective in allergic diseases prevention in preterm neonates. Further adequately powered, randomized controlled trials evaluating hydrolyzed protein formula administration to prevent allergic diseases in preterm neonates are needed

A pilot study employing hepatic intra-arterial irinotecan injection of drug-eluting beads as salvage therapy in liver metastatic colorectal cancer patients without extrahepatic involvement: The first southern Italy experience

Background: The main aim of this prospective study was to evaluate the efficacy of drug-eluting beads with irinotecan (DEBIRI) for liver metastases from colorectal cancer. Secondary aims were to evaluate survival and toxicity. Methods: Twenty-five patients with metastases in <50% of the liver and without extrahepatic involvement were enrolled. Treatment response assessment was performed by multidetector contrast enhancement computed tomography (MDCT) with evaluation of the enhancement pattern of the target lesion and tumor response rates according to modified Response Evaluation Criteria in Solid Tumors (mRECIST, Version 1.1). All adverse events were recorded by the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events, Version 3.0. Associations of tumor response and variables were calculated using the chi-squared test. Overall survival (OS) was calculated using the Kaplan–Meier method. Comparisons were made using the log-rank test. Results: According to mRECIST, complete response (CR) was observed in 21.8% of patients, partial response (PR) in 13%, stable disease (SD) in 52.2% and progressive disease (PD) in 13% of patients. Response rate (RR = CR + PR) was 34.8%. No associations between treatment response and variables such as Dukes’ classification, grading and Kras status were found (P>0.05). The median OS was 37 months (95% CI: 13.881 to 60.119). Cox regression model showed that neither site, Dukes’ classification, grading, Kras status nor number of chemotherapy treatments pre-DEBIRI influenced the OS. The log-rank test showed no statistically significant difference in OS among patients who underwent 1, 2 or 3 DEBIRI treatments (χ2=2.831, P=0.09). In our study, the main toxicities included postembolization syndrome (PES), hypertransaminasemia and fever. Conclusion: The favorable tumor response and the favorable toxicity profile make DEBIRI treatment a potential third-line therapy. Although further larger studies are needed to confirm these data, we can state that DEBIRI is an attractive emerging treatment in these patients

Altered Gene Expression Encoding Cytochines, Grow Factors and Cell Cycle Regulators in the Endometrium of Women with Chronic Endometritis

To evaluate the expression of genes encoding cytokines, grow factors and cell cycle regulators in the proliferative endometrium of women with chronic endometritis (CE) compared to controls. We performed a case-control study on seven women with CE as diagnosed by hysteroscopy and histology (Cases) compared to six women without CE (Controls). All women underwent diagnostic hysteroscopy plus endometrial biopsy during the mid-proliferative phase of the menstrual cycle. Endometrial samples were divided into two different aliquots for histological and molecular analyses. The endometrial expression profile of 16 genes encoding proteins involved in the inflammatory process, proliferation and cell cycle regulation/apoptosis was assessed by using high-throughput qPCR. Study endpoints were between-group differences in the expression of VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1, BAX and IL12. RESULTS: VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1 were significantly overexpressed in women with CE compared to controls, while BAX and IL12 had similar expression between groups. In women with CE, we found an altered endometrial expression of genes involved in inflammatory, cell proliferation, and apoptosis processes. The dominance of proliferative and anti-apoptotic activity in CE may potentially promote the development of polyps and hyperplastic lesions

Shorter androgen receptor polyQ alleles protect against life-threatening COVID-19 disease in European males

Background: While SARS-CoV-2 similarly infects men and women, COVID-19 outcome is less favorable in men. Variability in COVID-19 severity may be explained by differences in the host genome. Methods: We compared poly-amino acids variability from WES data in severely affected COVID-19 patients versus SARS-CoV-2 PCR-positive oligo-asymptomatic subjects. Findings: Shorter polyQ alleles (≤22) in the androgen receptor (AR) conferred protection against severe outcome in COVID-19 in the first tested cohort (both males and females) of 638 Italian subjects. The association between long polyQ alleles (≥23) and severe clinical outcome (p = 0.024) was also validated in an independent cohort of Spanish men <60 years of age (p = 0.014). Testosterone was higher in subjects with AR long-polyQ, possibly indicating receptor resistance (p = 0.042 Mann-Whitney U test). Inappropriately low serum testosterone level among carriers of the long-polyQ alleles (p = 0.0004 Mann-Whitney U test) predicted the need for intensive care in COVID-19 infected men. In agreement with the known anti-inflammatory action of testosterone, patients with long-polyQ and age ≥60 years had increased levels of CRP (p = 0.018, not accounting for multiple testing). Interpretation: We identify the first genetic polymorphism that appears to predispose some men to develop more severe disease. Failure of the endocrine feedback to overcome AR signaling defects by increasing testosterone levels during the infection leads to the polyQ tract becoming dominant to serum testosterone levels for the clinical outcome. These results may contribute to designing reliable clinical and public health measures and provide a rationale to test testosterone as adjuvant therapy in men with COVID-19 expressing long AR polyQ repeats. Funding: MIUR project "Dipartimenti di Eccellenza 2018-2020" to Department of Medical Biotechnologies University of Siena, Italy (Italian D.L. n.18 March 17, 2020) and "Bando Ricerca COVID-19 Toscana" project to Azienda Ospedaliero-Universitaria Senese. Private donors for COVID-19 research and charity funds from Intesa San Paolo