The prevention of congenital toxoplasmosis using a combination of Spiramycin and Cotrimoxazole: The long-time experience of a tertiary referral centre.

BACKGROUND: Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans-placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection. OBJECTIVES: We report our long-standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin-Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection. METHODS: We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin-Cotrimoxazole. RESULTS: Of 1364 women referred to our centre, postnatal follow-up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin-Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin-Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin-Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin-Cotrimoxazole therapy was significantly lower than the expected rate reported in literature. CONCLUSIONS: A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in-utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity.

Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).

OBJECTIVE: In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. METHOD: Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. RESULTS: One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. CONCLUSION: The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

The Development and Validation of a Questionnaire to Investigate the Association Between Maternal Food Insecurity and Fetal Structural Anomalies: Delphi Procedure and Pilot Study.

INTRODUCTION: Food insecurity represents a public health issue that has been associated with poor birth outcomes. We describe the methodological steps followed to structure and validate a questionnaire, which has the potential to contribute to the planning and conduction of future studies investigating the possible association between maternal food insecurity and fetal structural anomalies. METHODS: We first conducted a literature review to structure and validate the questionnaire. Subsequently, we drafted the questionnaire based on the results of this review, further refined through two focus groups. Afterward, the questionnaire was submitted using the Delphi Method to a panel of experts for validation. We conducted a pilot study prior to recruiting the final sample. RESULTS: The questionnaire consisted of sections covering information about socio-demographic characteristics, women's health and lifestyle, pregnancy, and food security status. After the first Delphi round, the Content Validity Index (CVI) for each section ranged 0.81-0.85, while after the second round all items had a CVI of 1. The final version of the questionnaire, consisting of 87 items, was pilot tested among 20 participants. Cronbach's Alpha for each section resulted in values higher than 0.6. The response rate ranged from 78 to 100%. A situation of food security was present in 85% of the participants, while 5% were in a situation of mild food insecurity and 10% of moderate food insecurity. CONCLUSION: The questionnaire has appropriate measurement properties, and is an adequate instrument to evaluate the association between maternal food insecurity and fetal structural anomalies.

Fetal MRI prior to intrauterine surgery of open neural tube defects: What does the radiologist need to know.

The management of myelomeningocele study trial showed significant prognostic improvement in fetal repair before 26 weeks of gestation. Hence, surgery in utero represents the best treatment option for open-neural tube defects (NTDs). Fetal surgery of open-NTDs has specific inclusion and exclusion criteria, which can be adequately studied with fetal MRI. The main concern: the spine (spinal defects other than Myelomeningocele and Myeloschisis, the level of the lesion higher than T1 or lower than S1 and the degree of kyphosis ≥ 30°), the skull/brain (no cerebellum herniation and Chiari II malformation and the presence of any intracranial abnormality unrelated to open NTDs), the uterus (cervix length less than 2 cm, multiple gestations and placental and uterine abnormalities) and any other fetal abnormality not attributed to spinal defect. In this review, we describe the fundamental role of fetal MRI in supporting therapeutic decisions in pre-surgery intrauterine planning through the accurate and comprehensive description of findings, providing a proposal of a structured report. In addition, we describe how post-surgical MRI is important in investigating the effectiveness of surgery and detecting repairing complications.

[SENTIERI Project: air pollution and health impact of population living in industrial areas in Italy]. / Valutazione dell'impatto dell'inquinamento atmosferico sulla salute della popolazione residente nelle aree industriali italiane incluse nel Progetto SENTIERI.

OBJECTIVES: to estimate the impact of PM2.5 and PM10 in the Italian industrial areas included in the SENTIERI project characterized by industrial plants with combustion processes deriving from point emissions. DESIGN: using satellite data, the Population Weighted Exposure (PWE) to PM2.5 and PM10 for 2011 and 2015 was estimated. The concentration-response functions available were used to estimate the number of premature deaths attributable to exposure to industrial emissions. The counterfactual levels recommended by the new WHO Air Quality Guidelines were used. SETTING AND PARTICIPANTS: for the selection of industrial plants, the European database on emissions of the European Pollutant Release and Transfer Register was used. Residents in areas of 1 km x 1 km and 4 km x 4 km around the selected industrial plants were considered. MAIN OUTCOME MEASURES: the number of premature deaths from non-accidental causes, cardiovascular and respiratory diseases, and lung cancer was estimated. RESULTS: residents were exposed to PM2.5 values of 17.3 µg/m3 (Northern Italy: 23.3) and to 24.3 µg/m3 (Northern Italy: 30.3) of PM10. PWE for both pollutants tends to increase as the size of the area under study is reduced and it is generally higher everywhere in 2011 than in 2015, with values that are always higher than the average (overall) in the Norther Italy. In 2011, 1,709 (IC95% 1,309-1,903) and 1,611 (IC95% 1,225-2,353) non accidental premature deaths were estimated attributable to PM2.5 and PM10, respectively, in residents close to the industrial plants (1 km x 1 km). Deaths attributable to exposure to PM2.5 and PM10 tend to follow a North-Central-South&Islands gradient for all observed causes and for both years of analysis. CONCLUSIONS: although exposure assessment of the population by using random-forest model does not allow to disentangle the contribution of the industrial component, the results of the study are suggestive of an impact on health from PM exposure in the industrial areas considered, with a greater impact in the vicinity of the plants, recommending the implementation of urgent impact reduction actions.

[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report]. / SENTIERI - Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Sesto Rapporto.

INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest. METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources. RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males: pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered. LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources. CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.

Association of maternal food insecurity before and during pregnancy with fetal structural anomalies: A multicenter case-control study protocol.

BACKGROUND: Food insecurity, an issue also affecting developed countries, is associated with different negative outcomes. Particularly in pregnant women, a vulnerable population group, it has a double burden, as it affects both the woman and her child. Food insecurity has been associated with low birth weight and shorter gestational age, but there is less evidence on the association with fetal structural anomalies. AIM: To fill this gap, a study will be conducted to examine if pregnant women in a condition of food insecurity have a higher risk for fetal structural anomalies. METHODS: A case-control study will be conducted in three centers. Cases will be pregnant women (>18 years old) diagnosed with a fetal structural anomaly during the prenatal ultrasound examination of the II-III trimester, while controls will be pregnant women (>18 years old) with a negative result for fetal structural anomaly at the II-III trimester prenatal ultrasound examination. The exposure of interest will be food insecurity during the last 12 months, measured using the validated Household Food Insecurity Access Scale. A dedicated questionnaire will be given to women after they sign the informed consent form. SUMMARY: Finding a positive association between food insecurity in pregnant women and fetal structural anomalies could be the first step towards screening for it among pregnant women and designing policies that could mitigate this condition. Lowering food insecurity could prevent a certain number of fetal structural anomalies, leading to fewer negative pregnancy outcomes and health problems during childhood and adulthood.

Occupational cohort study of asbestos-cement workers in a contaminated site in Sicily (Italy).

OBJECTIVES: to analyse the asbestos-related diseases risk among the former workers of Sacelit asbestos-cement plant, operating in San Filippo del Mela (Sicily: 1958- 1993). DESIGN: cohort study. SETTING AND PARTICIPANTS: 228 subjects were employed in Sacelit from 1958 to 1993. Due to the available observation periods, the analyses of the different outcomes were performed for the subjects alive at the beginning of the respective follow up periods: mortality (1986-2018) was analysed for 204 subjects (177 men, 27 women), hospitalization (2001-2016) for 164 workers (139 men, 25 women) and the incidence of mesothelioma (1998-2016) was estimated for 178 subjects (153 men, 25 women). MAIN OUTCOMES MEASURES: mortality (Standardized Mortality Ratio: SMR) and hospitalization (Standardized Hospitalization Ratio: SHR) from specific diseases were analysed. Incidence (Standardized Incidence Ratio: SIR) of mesothelioma cases was detected, also. SMR (1986-2014), SHR (2001-2016) and SIR (1998-2016), with 95% Confidence Intervals, were computed with respect to the regional rates, with STATA11. RESULTS: in the men cohort, mortality from lung (17 cases, SMR 2.83) and pleural cancers (5 cases, SMR 30) and from asbestosis (15 cases, SMR 1,930) was in excess. The risk of hospitalization was in excess, in both genders, from lung cancer (men: 6 cases, SHR 4.1; women: 2 cases, SHR 8.6) and asbestosis (men: 17 cases, SHR 1,304; women: 6 cases, SHR 2,455). The incidence of mesothelioma was in excess in men (5 cases, SIR 23.9); no female cases of mesothelioma were observed. CONCLUSIONS: a high occurrence of asbestos-related diseases in the cohort, particularly among men, was observed. The excess of hospitalization from asbestosis and lung cancer was highlighted also in women. The prosecution of the on-going health surveillance plan is particularly appropriated.

Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses.

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10-4 ) and transforming growth factor alpha (TGF-α, p = 6.5 × 10-5 ) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p = 7.8 × 10-7 ), TGF-α (p = 4.08 × 10-5 ), fractalkine (p = 1.12 × 10-3 ), monocyte chemotactic protein-3 (p = 1.36 × 10-4 ), macrophage inflammatory protein 1-alpha (p = 4.6 × 10-4 ) and vascular endothelial growth factor (p = 4.23 × 10-5 ). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that Granulocyte-macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth-factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL.

Pregnancy outcomes in women on metformin for diabetes or other indications among those seeking teratology information services.

AIMS: Metformin is used to treat type 2 diabetes, polycystic ovary syndrome associated infertility, and gestational diabetes. This study aims to evaluate the safety of metformin in early pregnancy. METHOD: We evaluated the risk of major birth defects and pregnancy losses in a cohort of pregnant women exposed to metformin during the first trimester for different indications relative to a matched unexposed reference group. RESULTS: The risk of major birth defects was 5.1% (20/392) in pregnancies exposed to metformin during the first trimester and 2.1% (9/431) in the reference group [adjusted odds ratio (OR) 1.70; 95% CI 0.70-4.38]. Among metformin users, this risk was 7.8% (17/219) in patients with pre-gestational diabetes and 1.7% (3/173) in those without this diagnosis. Compared to the unexposed reference, the OR for metformin user with diabetes was 3.95 (95% CI 1.77-9.41) and for metformin with other indications it was 0.83 (95% CI 0.18-2.81). The risk of pregnancy losses (spontaneous abortions and stillbirths) was 20.8% in women on metformin during the first trimester and 10.8% in the reference group [adjusted hazard ratio (HR) 1.57; 95% CI 0.90-2.74]. The risks for women on metformin with and without pre-gestational diabetes were 24.0% and 16.8% respectively, with adjusted HR of 2.51 (95% CI 1.44-4.36) and 1.38 (95% CI 0.74-2.59) when compared to the reference. CONCLUSION: Pregnant women with pre-gestational diabetes on metformin are at a higher risk for adverse pregnancy outcomes than the general population. This appears to be due to the underlying diabetes since women on metformin for other indications do not present meaningfully increased risks.

[Health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy)]. / Impatto sulla salute delle fibre di amianto presenti in affioramenti naturali nell'area del Pollino (Basilicata).

OBJECTIVES: to estimate the health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy). DESIGN: geographic mortality, hospitalization, and incidence study. Setting and participant s: population resident in 12 Municipalities of Mount Pollino area with naturally occurring asbestos fibres. MAIN OUTCOME MEASURES: standardized mortality ratio (SMR) and standardized hospitalization rate (SHR) for asbestos-related diseases; standardized incidence ratio (SIR) for mesotheliomas. Result s: in the area of Mount Pollino, where asbestos fibres naturally occur, especially in the sub-area in which fibres are close to dwellings and settlements, it was observed: • a significant excess of mesothelioma incidence (SIR: 208; CI95% 111-355; 13 observed); • a non-significant excess of hospitalization for malignant pleural neoplasms (SHR: 176; CI95% 93-335; 9 observed); • a significant excess for mortality and hospitalization for pneumoconiosis (SMR: 534; CI95% 345-824; 20 observed - SHR: 245; CI95% 149-405; 15 observed); • a significant excess for hospitalization (SHR: 852; CI95% 290-2,506; 3 observed) for asbestosis. CONCLUSION: it is necessary to continue environmental monitoring and environmental remediation in the area with higher asbestos exposure. It is suggested to implement a permanent process of epidemiological surveillance in this same area. A communication plan with local administrators, general practitioners, school teachers, media, and the resident population at large should be realized.

Spatial distribution of kidney disease in the contaminated site of Taranto (Italy).

BACKGROUND: Exposure to heavy metals has been associated with kidney disease. We investigated the spatial distribution of kidney disease in the industrially contaminated site of Taranto. METHODS: Cases were subjects with a first hospital discharge diagnosis of kidney disease. Cases affected by specific comorbidities were excluded. Standardized Hospitalization Ratios (SHRs) were computed for low/high exposure area and for modeled spatial distribution of cadmium and fine particulate matter. RESULT: Using the high/low exposure approach, in subjects aged 20-59 years residing in the high exposure area a significant excess of hospitalization was observed in males and a non-significant excess in females. No excesses were observed in subjects aged 60 years and over. The analysis by the modeling approach did not show a significant association with the greatest pollution impact area. CONCLUSION: Due to the excesses of hospitalization observed in the high/low exposure approach, a continuing epidemiological surveillance of residents and occupational groups is warranted.

[Evaluation of the use of the socioeconomic deprivation index at area level in ecological studies on environment and health]. / La valutazione dell'uso dell'indice di deprivazione socioeconomica a livello di area negli studi ecologici su ambiente e salute.

BACKGROUND: in SENTIERI surveillance system, the health risk assessment in the contaminated sites (CSs) was carried out considering the socioeconomic deprivation index (ID-SENTIERI) at the municipal level as a confounder. Pasetto et al. discussed the use of IDs in ecological studies and proposed to examine the role of ID-SENTIERI as a confounder. OBJECTIVES: to evaluate the initial conditions necessary for the role of confounding, i.e., the verification of an association of the ID-SENTIERI with the risk of some of the diseases for which evidence of a relationship with the socioeconomic state (SES) is documented in the literature. DESIGN: the methodological approach is to exploit ecological correlations in order to assess the relationship between ID and the occurrence of mortality or congenital malformations (CMs). SETTING AND PARTICIPANTS: mortality and CM data from municipalities in the regions of Emilia-Romagna (Northern Italy), Tuscany (Central Italy), and Campania (Southern Italy) were used. Mortality for all causes, all tumours, and lung cancers were analysed for the period 1995-2008. For the CMs, data from the regional registries of Emilia-Romagna, Tuscany, and Campania in the periods 1995-2011, 1992-2011, 2004-2010, respectively, were used. Analyses of the relationship between mortality/CMs and ID-SENTIERI were carried out according to cause, region, gender, and demographic amplitude classes using a GAM-Poisson regression model. RESULTS: the mortality analyses show that, for the male population of the three regions under study, the relationship between ID and mortality is increasing for each outcome for municipalities with less than 50,000 inhabitants; while results for female population differ from region to region. The results of the CMs show growing associations, considering only municipalities under 10,000 inhabitants. CONCLUSIONS: the results of the study suggest that scientific evidence of an association between SES and health should be evaluated taking into account the gender, the study area, and the demographic size of the municipalities. For ID to be used as a confounding variable, it must be associated with the outcomes for which the influence of socioeconomic factors in the reference areas has been ascertained. If there is no such association, the ID cannot be used as a confounder, as it could lead to distortions of estimates and such distortions are difficult to predict. In these cases, ad hoc IDs should be produced.

[Environmental justice in the epidemiological surveillance system of residents in Italian National Priority Contaminated Sites (SENTIERI Project)]. / Environmental justice nel sistema di sorveglianza epidemiologica SENTIER.

OBJECTIVES: descriptive evaluation of distributional justice in the epidemiological surveillance system of populations residing in Italian National priority Contaminated Sites (NPCSs) of SENTIERI project. Analysis of the feasibility of monitoring different Environmental Justice dimensions in SENTIERI. DESIGN: descriptive study and ecological meta-analysis. SETTING AN PARTICIPANTS: residents in 298 municipalities included in 44 NPCSs in SENTIERI. Description of their level of deprivation and mortality analysis by deprivation level in the first period evaluated in SENTIERI, years 1995-2002. MAIN OUTCOME MEASURES: an index of multiple deprivation at municipality level DI-SENTIERI, built using 4 indicators based on variables from the Italian 2001 Census, was used to describe deprivation in communities living in NPCSs. The risk of mortality for all causes and all tumors in the pool of NPCSs municipalities by deprivation level was assessed using meta-Standardized Mortality Ratios (meta-SMRs). RESULTS: sixty percent of municipalities (No. 179) in NPCSs belong to the two more deprived quintiles. The socioeconomic disadvantage of communities resident in NPCS has a North-South gradient: the proportion of municipalities belonging to the two more deprived quintiles is 29% in the North, 68% in the Centre, 92% in the South. Meta-SMRs for all causes in less deprived municipalities were 98 (90%CI 95-100) in men e 101 (90%CI 97-104) in women, the values for all cancers were 99 (90%CI 94-103) in men and 100 (90%CI 95-105) in women. The corresponding estimates in more deprived municipalities were, respectively in men and women, 103 (90%CI 101- 104) and 102 (90%CI 100-104) for all causes, 104 (90%CI 102-106) and 102 (90%CI 100-104) for all cancers. CONCLUSIONS: residents in NPCSs are exposed to environmental stressors and are generally more deprived. The socioeconomic disadvantage is mostly affecting Central and Southern Italy populations. Furthermore, in these deprived communities the risk of mortality for all diseases and all cancers is higher. Populations living in NPCSs are affected by distributional injustice. To monitor the different dimensions of Environmental Justice, the DI-SENTIERI should be developed and other socioeconomic indicators implemented.

Reference rates for cohort studies in Italy: an essential tool in occupational and residential cohort studies. / Aggiornamento dei tassi di mortalità in Italia, strumento fondamentale per la conduzione di studi di coorte occupazionali e residenziali.

The cohort study aims to test the hypothesis of an association between specific exposure/s and adverse health outcomes. The cohorts include the subjects who experience the exposure/s and are followed up over time to ascertain the health outcomes. This contribution presents the database for the analysis of mortality studies which is made available for public institutions carrying out cohort studies in Italy. The rates were computed from official mortality data from ISTAT. The database contains 141 causes or groups of causes for the years 1970-2012 ensuring correspondence with subsequent editions of ICD (International Classification of Diseases) VIII, IX and X.

[Emotional Leadership: a survey on the emotional skills expressed by nursing management]. / La leadership emozionale: indagine conoscitiva sulle competenze emozionali espresse dai ruoli manageriali infermieristici.

INTRODUCTION: The emotional leadership applied to nursing management is a new topic in the Italian nursing literature, but of great interest internationally. There is a close correlation between nursing leaders with a well-developed emotional intelligence and nurses working well-being. SCOPE: This study investigates knowledge about the emotional leadership and emotional competence in nursing management. METHODS: The survey was conducted using a questionnaire devised for the purpose, validated and administered to 130 managers, head nurses and nurses in a hospital in Rome. RESULTS: Analysis of data shows a great interest in the subject. 90% of the sample showed that it is essential for managerial roles, be aware and able to manage their own and others' emotions to generate wellbeing at work. Emotional competencies are considered important just as theoretical, technical and social skills to a effective leadership on nursing. CONCLUSIONS: This study is one of the first Italian survey on the importance of the development of emotional intelligence in nursing leadership to improve wellbeing at work. Results of the survey should be confirmed by further studies. The emotional skills could be improved in nursing education programs and used as a yardstick for the nursing managers selection.

Cardiovascular Effects of a Thoracoamniotic Shunt in a Fetus Affected by Isolated Right Congenital Diaphragmatic Hernia and Hydrops.

A thoracoamniotic shunt was placed in a fetus affected by a right congenital diaphragmatic hernia (RCDH) complicated by voluminous nonimmune hydrops (NIH) at 30 weeks of gestation. The fetus showed congestive cardiac failure with a combined cardiac output (CCO) of 460.7 ml/min (Z-score: -1.2). After seven days, no edema, ascites, or pleural effusion was present. CCO increased significantly, reaching a Z-score of -0.2, as well as right and left cardiac output (Z-scores: -0.3 and -0.8, respectively). Two weeks later, the cardiac function and the ascites got worse despite the correct shunt placement, suggesting a possible occlusion. At 33 weeks, a C-section was performed due to labor in breech presentation. Despite the intensive care provided, the newborn died due to pulmonary hypertension and respiratory insufficiency. The thoracoamniotic shunt's effect on fetal circulation and the mechanisms of NIH in the event of RCDH are still unclear. Due to the high mortality rate of this condition and its poorer outcomes compared to left-sided defects, shunting cannot be considered an efficient attempt to improve fetal and neonatal survival rates to date. A close relationship between the amount of lymphatic effacement and cardiac function is clear, but further studies are needed to provide more information about this severe condition and its treatment.

Mortality in an Italian cohort of former asbestos cement workers.

BACKGROUND: A pooled study on Italian asbestos cement plant cohorts observed mortality risk for asbestos-related diseases. This study analysed the mortality of workers cohort of an asbestos cement plant in Syracuse, Italy. METHODS: Workers' vital status and causes of death, during 1970-2018, were identified in regional health databases. Standardized mortality ratios (SMRs) by sex and temporal variables were calculated. RESULTS: Of the 900 cohort's subjects (636 men, 259 women, 5 unknown sex), for 867 the vital ascertainment was possible: 505 died during study period. All-cause mortality is similarly to the expected among men and lower among women. Pleural and lung malignant neoplasms (MN) exceeded in men (SMR=27.1, SMR=1.95), retroperitoneal and peritoneal MN in both sexes, no cases of larynx MN were observed. Mortality excess for ovarian MN (SMR=1.5) and asbestosis in both sexes (men: SMR=431.9, women: SMR=116.6) were found. CONCLUSIONS: Exceeding mortality from asbestos-related diseases, particularly in men was highlighted.

Effect of acute histologic chorioamnionitis on bronchopulmonary dysplasia and mortality rate among extremely low gestational age neonates: A retrospective case-control study.

OBJECTIVE: To evaluate whether acute histologic chorioamnionitis (HCA) diagnosed in the placenta may be associated with an increased occurrence of bronchopulmonary dysplasia (BPD) or death among extremely low gestational age neonates (ELGAN). METHODS: This Italian single-center case-control retrospective study involved ELGAN admitted to the neonatal intensive care unit between January 2019 and June 2022. Infants born from pregnant women with acute and severe HCA, identified as stage ≥2 and grade 2 HCA, (HCA-infants) were compared with infants of pregnant women without chorioamnionitis or with stage 1, grade 1 chorioamnionitis (no-HCA-infants). RESULTS: Among 101 eligible ELGAN, 63 infants had complete clinical and histologic data relevant to the study: thirty infants were included in the HCA-infants group and 33 in the no-HCA-infants group. Neonatal and maternal demographic and clinical characteristics were similar between the two groups. Infants born from mothers with acute and severe HCA had significantly higher occurrence of composite BPD or death (18 [60%] vs. 9 [27%]; P = 0.012), as well as higher incidence of severe forms of BPD (6 [30%] vs. 2 [6%]; P = 0.045). In multiple logistic regression analysis, after adjustment for confounding covariates, HCA was an independent risk factor for BPD or death (OR, 4.49; 95% CI: 1.47-13.71). CONCLUSIONS: This is the first study showing that in utero exposure to acute and severe HCA is an independent risk factor for the occurrence of composite BPD or death among ELGAN.