Application of next-generation sequencing for the genomic characterization of patients with smoldering myeloma

Genomic analysis could contribute to a better understanding of the biological determinants of the evolution of multiple myeloma (MM) precursor disease and an improved definition of high-risk patients. To assess the feasibility and value of next-generation sequencing approaches in an asymptomatic setting, we performed a targeted gene mutation analysis and a genome-wide assessment of copy number alterations (CNAs) by ultra-low-pass whole genome sequencing (ULP-WGS) in six patients with monoclonal gammopathy of undetermined significance and 25 patients with smoldering MM (SMM). Our comprehensive genomic characterization highlighted heterogeneous but substantial values of the tumor fraction, especially in SMM; a rather high degree of genomic complexity, in terms of both mutations and CNAs, and inter-patient variability; a higher incidence of gene mutations and CNAs in SMM, confirming ongoing evolution; intraclonal heterogeneity; and instances of convergent evolution. ULP-WGS of these patients proved effective in revealing the marked genome-wide level of their CNAs, most of which are not routinely investigated. Finally, the analysis of our small SMM cohort suggested that chr(8p) deletions, the DNA tumor fraction, and the number of alterations may have clinical relevance in the progression to overt MM. Although validation in larger series is mandatory, these findings highlight the promising impact of genomic approaches in the clinical management of SMM

Moderate alcohol drinking and risk of preterm birth

Objective: We have analysed the association between alcohol drinking before and during the three trimesters of pregnancy and risk of preterm birth of babies with normal weight for gestational age or with low weight for gestational age (SGA). Design: Case-control study. Setting: General and university hospitals in Italy. Subjects: Cases were 502 women who delivered preterm births <37 weeks gestation. The controls included 1966 women who gave birth at term (&GE;37 weeks of gestation) to healthy infants of normal weight (ie between 10th and 90th centile according to the Italian standard) on randomly selected days at the hospitals where cases had been identified. Interventions: Interview. Results: No increased risk of preterm birth was observed in women drinking one or two drinks/die in pregnancy, but three or more drinks/die increased the risk (multivariate odds ratios (OR) 2.0 for &GE;3 drinks during the first trimester, 1.8 during the second and 1.9 during the third). When the analysis was conducted separately for preterm births with normal weight or SGA, the increased risk was observed in preterm SGA only (multivariate OR for &GE;3 drinks/die during the first trimester = 3.6, 95% confidence interval (CI) 1.3-11.1); the estimated multivariate OR for &GE;3 drinks/die during the first trimester of preterm babies with normal weight for gestational age was only slightly above unity and not statistically significant (multivariate OR 1.4, 95% CI 0.5-3.7). Conclusions: The study shows an increased risk in mothers who drink &GE;3 die units alcohol in pregnancy of preterm births

Risk factors for endometrial hyperplasia : results from a case-control study

We analyzed epidemiologic characteristics of women at risk for endometrial hyperplasia (EH), using data from a case-control study. One hundred twenty nine women aged 35\u201373 (median 51 years) with histologically confirmed complex endometrial hyperplasia without atypies identified at the University of Milan during the period 1990\u201399 were examined. Controls were 258 non hysterectomized women aged 36\u201374 (median 52 years), admitted to a network of hospitals covering the same area where cases had been identified for conditions other than gynecological, malignant, or hormone-related. Cases with EH were more educated than controls (OR > 12 years of education vs. < 7: 2.8, 95% CI 1.7\u20134.8), more frequently obese (OR 2.7, 95% CI 1.5\u20135.0) and diabetic (OR 2.4, 95% CI 0.8\u20136.9). Parous women (OR 1.8) and women reporting induced abortions (OR 1.6) showed an increased risk of EH, but the associations were not statistically significant. Compared to premenopausal women, the OR of EH was 0.2 (95% 0.1\u20130.5) for postmenopausal ones. Compared to women reporting menopause at age 50 or less, the OR of endometrial hyperplasia was 1.5 (95% CI 0.6\u20133.5) and 2.2 (95%CI 0.7\u20136.7), respectively, in women with menopause at age 50\u201352 and 65 53. Considering postmenopausal women only the OR was 3.1 (95% CI 1.1\u20139.3) for use of hormonal replacement therapy (HRT). We conclude that this study indicates that high education, obesity, diabetes, and HRT use increase the risk of endometrial hyperplasia

Oral contraceptives and risk of gestational trophoblastic disease

Clinical reports suggested that the use of oral contraceptives (OC) after a molar pregnancy may increase the risk of persistent throphoblastic disease. However, few epidemiologic studies have analyzed the effect of OC use on the risk of developing gestational trophoblastic disease (GTD). To give further information, we have analyzed data from a case-control study on risk factors for GTD. Cases were 268 women with a histologically confirmed diagnosis of complete or partial mole referred to the participating Trophoblastic Disease Centers. A total of 268 subjects were interviewed; 79 cases were classified as partial and 159 as complete mole. Controls were randomly selected women who gave birth to healthy infants at term on randomly selected days in the same network of hospitals in which cases had been identified. A total of 104 cases and 130 controls reported ever OC use, and the corresponding odds ratio (OR) was 1.5 (95% CI, 1.1-2.1). The risk of GTD increases with duration of OC use: the OR was 1.7 (95% CI 1.2-2.6) for ever-users reporting >or=12 months of use. No consistent pattern of risk was observed with time since last OC use. We have analyzed separately the association between OC use and risk of complete and partial moles: no statistically significant difference emerged, but the OR for partial moles was higher (OR 3.0, 95% CI 1.6-8.4) than for complete mole (OR 1.0, 95% CI 1.8). In conclusion, we observed a weak association between OC use and GTD; such a weak association could be explained by factors other than causality

Pregnancy outcomes and antiretroviral treatment in a national cohort of pregnant women with HIV: overall rates and differences according to nationality.

We used data from the main surveillance study of HIV and pregnancy in Italy to evaluate possible differences in pregnancy care and outcomes according to nationality. Among 960 women followed in 2001-06, 33.5% were of foreign nationality, mostly from African countries. Foreign women had lower rates of preconception counselling and planning of pregnancy. They had more frequently HIV diagnosed during pregnancy, with a later start of antiretroviral treatment and lower treatment rates at all trimesters but not when the entire pregnancy, including delivery, was considered. No differences were observed between the two groups in ultrasonography assessments, hospitalisations, AIDS events, intrauterine or neonatal deaths, and mode and complications of delivery. Foreign women had a slightly lower occurrence of preterm delivery and infants with low birthweight. The results indicate good standards of care and low rates of adverse outcomes in pregnant women with HIV in Italy, irrespective of nationality. Specific interventions, however, are needed to increase the rates of counselling and HIV testing before pregnancy in foreign women

Pregnancy outcomes and antiretroviral treatment in a national cohort of pregnant women with HIV : overall rates and differences according to nationality

We used data from the main surveillance study of HIV and pregnancy in Italy to evaluate possible differences in pregnancy care and outcomes according to nationality. Among 960 women followed in 2001-06, 33.5% were of foreign nationality, mostly from African countries. Foreign women had lower rates of preconception counselling and planning of pregnancy. They had more frequently HIV diagnosed during pregnancy, with a later start of antiretroviral treatment and lower treatment rates at all trimesters but not when the entire pregnancy, including delivery, was considered. No differences were observed between the two groups in ultrasonography assessments, hospitalisations, AIDS events, intrauterine or neonatal deaths, and mode and complications of delivery. Foreign women had a slightly lower occurrence of preterm delivery and infants with low birthweight. The results indicate good standards of care and low rates of adverse outcomes in pregnant women with HIV in Italy, irrespective of nationality. Specific interventions, however, are needed to increase the rates of counselling and HIV testing before pregnancy in foreign women.We used data from the main surveillance study of HIV and pregnancy in Italy to evaluate possible differences in pregnancy care and outcomes according to nationality. Among 960 women followed in 2001-06, 33.5% were of foreign nationality, mostly from African countries. Foreign women had lower rates of preconception counselling and planning of pregnancy. They had more frequently HIV diagnosed during pregnancy, with a later start of antiretroviral treatment and lower treatment rates at all trimesters but not when the entire pregnancy, including delivery, was considered. No differences were observed between the two groups in ultrasonography assessments, hospitalisations, AIDS events, intrauterine or neonatal deaths, and mode and complications of delivery. Foreign women had a slightly lower occurrence of preterm delivery and infants with low birthweight. The results indicate good standards of care and low rates of adverse outcomes in pregnant women with HIV in Italy, irrespective of nationality. Specific interventions, however, are needed to increase the rates of counselling and HIV testing before pregnancy in foreign women

Pregnancy outcomes and antiretroviral treatment in a national cohort of pregnant women with HIV: overall rates and differences according to nationality

We used data from the main surveillance study of HIV and pregnancy in Italy to evaluate possible differences in pregnancy care and outcomes according to nationality. Among 960 women followed in 2001–06, 33.5% were of foreign nationality, mostly from African countries. Foreign women had lower rates of preconception counselling and planning of pregnancy. They had more frequently HIV diagnosed during pregnancy, with a later start of antiretroviral treatment and lower treatment rates at all trimesters but not when the entire pregnancy, including delivery, was considered. No differences were observed between the two groups in ultrasonography assessments, hospitalisations, AIDS events, intrauterine or neonatal deaths, and mode and complications of delivery. Foreign women had a slightly lower occurrence of preterm delivery and infants with low birthweight. The results indicate good standards of care and low rates of adverse outcomes in pregnant women with HIV in Italy, irrespective of nationality. Specific interventions, however, are needed to increase the rates of counselling and HIV testing before pregnancy in foreign women

GADOBENATE DIMEGLUMINE-ENHANCED MRI OF THE BREAST: ANALYSIS OF DOSE RESPONSE AND COMPARISON WITH GADOPENTETATE DIMEGLUMINE

OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy and dose response relationship of three doses of gadobenate dimeglumine for MRI of the breast and to compare the results with those obtained after a dose of 0.1 mmol/kg of body weight of gadopentetate dimeglumine. SUBJECTS AND METHODS. Gadobenate dimeglumine at 0.05, 0.1, or 0.2 mmol/kg of body weight or gadopentetate dimeglumine at 0.1 mmol/kg of body weight was administered by IV bolus injection to 189 patients with known or suspected breast cancer. Coronal three-dimensional T1-weighted gradient-echo images were acquired before and at 0, 2, 4, 6, and 8 min after the administration of the dose. Images were evaluated for lesion presence, location, size, morphology, enhancement pattern, conspicuity, and type. Lesion signal intensity-time curves were acquired, and lesion matching with on-site final diagnosis was performed. A determination of global lesion detection from unenhanced to contrast-enhanced and combined images was performed, and evaluations were made of the diagnostic accuracy for lesion detection and characterization. A full safety evaluation was conducted. RESULTS: Significant dose-related increases in global lesion detection were noted for patients who received gadobenate dimeglumine (p < 0.04, all evaluations). The sensitivity for detection was comparable for 0.1 and 0.2 mmol/kg of gadobenate dimeglumine, and specificity was highest with the 0.1 mmol/kg dose. Higher detection scores and higher sensitivity values for lesion characterization were found for 0.1 mmol/kg of gadobenate dimeglumine compared with 0.1 mmol/kg of gadopentetate dimeglumine, although more variable specificity values were obtained. No differences in safety were observed, and no serious adverse events were reported. CONCLUSION: Gadobenate dimeglumine is a capable diagnostic agent for MRI of the breast. Although preliminary, our results suggest that 0.1 mmol/kg of gadobenate dimeglumine may offer advantages over doses of 0.05 and 0.2 mmol/kg of gadobenate dimeglumine and 0.1 mmol/kg of gadopentetate dimeglumine for breast lesion detection and characterization