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Introduction: Experiences related to pediatric oncology diagnosis cause great imbalances within the family structure. Assessing the frailties and needs of families and children with cancer from a psychosocial perspective is an important step in providing appropriate pediatric psychology care., Methods: The aim of this study was to develop an Italian translation of the last version of the Psychosocial Assessment Tool questionnaire (PAT 3.1) and to pilot-test it among pediatric oncological families. The guidelines for cross-cultural adaptation of health-related quality of life measures were followed. Specifically, two independent forward translations were produced, followed by a reconciliation step by a multidisciplinary expert committee and back-translation. Revision of the original text and all translations were performed by the expert committee leading to a final version, which was pilot-tested by cognitive debriefing on five families. Subsequently, the final Italian PAT 3.1 version was approved., Results: The Italian version of the PAT 3.1 generated in the present study is a useful instrument to examine the psychosocial risk of the families with a child with cancer., Conclusions: This instrument will be a valuable tool for future clinical trials and it will help clinicians to target specific pediatric psychology support intervention. The questionnaire will be further validated through a multicenter Italian study on psychosocial screening of pediatric oncology and pediatric general diseases., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Group B Streptococcus (GBS) is a major cause of sepsis and meningitis in newborns. The Centers for Disease Control and Prevention (CDC) recommends to pregnant women, between 35 and 37 weeks of gestation, universal vaginal-rectal screening for GBS colonization, aimed at intrapartum antibiotic prophylaxis (IAP). The latter is the only currently available and highly effective method against early onset GBS neonatal infections. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the preventive measures implemented to mitigate the effects of SARS-CoV-2 infection led to the reduction in the access to many health facilities and services, including the obstetric and perinatal ones. The purpose of the present study was to evaluate the prevalence of maternal GBS colonization, as well as use of IAP and incidence of episodes of neonatal GBS infection when antibiotic prophylaxis has not been carried out in colonized and/or at risk subjects, in a population of pregnant women during (years 2020-2021) and after (year 2022) the COVID-19 pandemic, also with the aim to establish possible epidemiological and clinical differences in the two subjects' groups., Methods: We retrospectively analyzed the clinical data of pregnant women admitted to, and delivering, at the Gynaecology and Obstetrics Unit, Department of Sciences for Health Promotion and Mother and Child Care, of the University Hospital of Palermo, Italy, from 01.01.2020 to 31.12.2022. For each of them, we recorded pertinent socio-demographic information, clinical data related to pregnancy, delivery and peripartum, and specifically execution and status of vaginal and rectal swab test for GBS detection, along with eventual administration and modality of IAP. The neonatal outcome was investigated in all cases at risk (positive maternal swabs status for GBS, either vaginal or rectal, with or without/incomplete IAP, preterm labor and/or delivery, premature rupture of membranes ≥ 18 h, previous pregnancy ended with neonatal early onset GBS disease [EOD], urine culture positive for GBS in any trimester of current gestation, intrapartum temperature ≥ 38 °C and/or any clinical/laboratory signs of suspected chorioamnionitis). The data concerning mothers and neonates at risk, observed during the pandemic (years 2020-2021), were compared with those of both subjects' groups with overlapping risk factors recorded in the following period (year 2022). The chi squared test has been applied in order to find out the relationship between pregnant women with GBS colonization receiving IAP and outcome of their neonates., Results: The total source population of the study consisted of 2109 pregnant women, in addition to their 2144 newborns. Our analysis, however, focused on women and neonates with risk factors. The vaginal-rectal swab for GBS was performed in 1559 (73.92%) individuals. The test resulted positive in 178 cases overall (11.42% of those undergoing the screening). Amongst our whole sample of 2109 subjects, 298 women had an indication for IAP (vaginal and/or rectal GBS colonization, previous pregnancy ended with neonatal GBS EOD, urine culture positive for GBS in any trimester of current gestation, and unknown GBS status at labor onset with at least any among delivery at < 37 weeks' gestation, amniotic membranes rupture ≥ 18 h and/or intrapartum temperature ≥ 38.0 °C), and 64 (21.48%) received adequate treatment; for 23 (7.72%) it was inadequate/incomplete, while 211 (70.8%) did not receive IAP despite maternal GBS colonization and/or the presence of any of the above mentioned risk factors. Comparing the frequency of performing vaginal-rectal swabs in the women admitted in the two time periods, the quote of those screened out of the total in the pandemic period (years 2020-2021) was higher than that of those undergoing GBS screening out of the total admitted in the year 2022 (75.65% vs. 70.38%, p = 0.009), while a greater number (not statistically significant, p = 0.12) of adequate and complete IAP was conducted in 2022, than in the previous biennium (26.36 vs. 18.62%). During the whole 3 years study period, as expected, none of the newborns of mothers with GBS colonization and/or risk factors receiving IAP developed EOD. Conversely, 13 neonates with EOD, out of 179 (7.3%) born to mothers with risk factors, were observed: 3 among these patients' mothers performed incomplete IAP, while the other 10 did not receive IAP. Neither cases of neonatal meningitis, nor deaths were observed. The incidence rate in the full triennium under investigation, estimated as the ratio between the number of babies developing the disease out of the total of 2144 newborns, was 6.06‰; among those born to mothers with risk factors, if comparing the two time periods, the incidence was 8.06% in the pandemic biennium, while 5.45% in the following year, evidencing thus no statistical significance (p = 0.53)., Conclusions: The present study revealed in our Department an increased prevalence of pregnant women screened for, and colonized by GBS, in the last decade. However, an overall still low frequency of vaginal-rectal swabs performed for GBS, and low number of adequate and complete IAP despite the presence of risk factors have been found, which did not notably change during the two time periods. Moreover, significant EOD incidence rates have been reported among children of mothers carrying risk factors, although also in this case no statistically significant differences have been observed during and after the pandemic. Such data seem to be in contrast to those reported during the COVID-19, showing a decrease in the access to health facilities and increased mortality/morbidity rates also due to the restrictive measures adopted to mitigate the effects of the pandemic. These findings might be explained by the presence within the same metropolitan area of our Department of a COVID hospital and birthing center, which all the patients with SARS-CoV-2 infection referred to, and likely leading to a weaker concern of getting sick perceived by our patients. Although IAP is an easy procedure to implement, however adherence and uniformity in the management protocols are still not optimal. Therefore, the prophylactic measures adopted to date cannot be considered fully satisfactory, and should be improved. Better skills integration and obstetrical-neonatological collaboration, in addition to new effective preventive tools, like vaccines able to prevent invasive disease, may allow further reduction in morbidity and mortality rates related to GBS perinatal infection., (© 2024. The Author(s).)

Context: In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM)., Objective: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS)., Methods: We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset., Results: Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, P = .034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin., Conclusion: NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS)., Materials and Methods: The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS. As per protocol, patients were considered responders if the GMI was >1.33, non-responders if <0.75 and neither if 0.76-1.32., Results: Overall 91 patients were assessable for the primary endpoint (32 patients with LMS and 59 patients with LPS): the median number of cycles received was 6.0 (Q1-Q3 3.0-12.0), and the main reason for treatment discontinuation was disease progression in 72% of patients. The median PFS was 6.0 months, while the median TTP1 was 7.5 months (8.1 and 6.4 months for LMS and LPS, respectively). Thirty-three patients [52%, 95% confidence interval (CI) 36% to 58%, P = 0.674, odds of response 1.1] had a GMI >1.33 (LMS 46%, 95% CI 26% to 67%, odds of response 0.85; LPS 56%, 95% CI 40% to 72%, odds of response 1.3). Overall, in LPS we observed 15/47 patients with a GMI <0.5 and 15/47 patients with a GMI >2. Among LMS patients, 9/26 had a GMI <0.5 and 10/26 had a GMI >2. Overall, ORR (complete response + partial response) was 16% (24% for LMS and 12% for LPS)., Conclusions: While the primary endpoint of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with trabectedin in comparison to previous therapy (GMI <0.5 or >2, the latter including some patients with a long TTP with trabectedin). A mismatch between PFS and overall survival was observed, possibly due to the natural history of the two different histologies and the availability of further lines in LMS., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Ministerial Decrete 77 (DM 77) promotes dehospitalization for chronic patients and defines out-of-hospital health facilities at this purpose. It has never been investigated how much patients with cancer know and judge this decree law., Material and Methods: The Collegio italiano dei primari oncologi medici ospedalieri (Cipomo) carried out a survey with a dedicated questionnaire on oncological patients attending public hospital to investigate the liking of DM 77., Results: Anonymous responses were obtained from 1.443 patients. Median age 64ys, 42% males, 21% live alone, 70% have a companion. 19% thinks that oral chemotherapy could be managed outside the hospital, 26.68% carried out follow-up (FU),19.15% parenteral therapy, 32.16% basic examinations. Home is preferred by 21.8%, a health facility close to home by 36.3%, hospital by 37.54%. 59.67% would like FU in hospital by their personal oncologist, 5.47% by GP, 35.41% by both together and 9.45% by oncologist outside the hospital. Asked what they might feel about being followed out of the hospital, 29.94% say of not being treated at its best, 12.68% of not being able to be visited in hospital anymore, 5.27% of being abandoned, 30.7% of being freer and 10.88% of feeling less sick. Regarding the use of new technical tools to favor dehospitalisation, 44.15% answered yes, 15.88% no and 30.07% did not know. About the distance or traveling time from home to the therapy administration side, 20.26% answered this should be no more than 15 km or 30 mins, 9.91% no more than 30 km or 45 mins, 5.47% no more than 50 km or 60 mins but 39.5% say that the distance does not matter to them but only the continuity of care. The question related to the inconveniences with going to hospital for therapy: 40.81% waiting time, 20.47% lack of parking, 17.02% rotation of doctors,12.76% travel time and 5.62% bureaucracy., Conclusions: The patients' answers suggest that dehospitalization could improve their quality of life, but at the condition of being able to maintain a close relationship with the personal oncologist.

Purpose: Despite extensive research on cancer and work-related outcomes, evidence from longitudinal cohort studies is limited, especially in young women with breast cancer (BC). We aimed to investigate employment trajectories in young BC survivors and to identify potential factors associated with changes in work activity., Methods: The HOHO European prospective multicenter cohort study enrolled 300 young women (≤ 40 years) with newly diagnosed BC. Women completed surveys at baseline and every 6 months for 3 years, then yearly for up to 10 years to assess, among other variables, employment status, sociodemographic, medical, and treatment data. Symptoms were assessed by the Breast Cancer Prevention Trial symptom scales and single items from the Cancer Rehabilitation Evaluation System. Univariable and multivariable multinomial logistic regression analyses identified factors associated with changes in employment status., Results: Among the 245 women included in this analysis, 85% were employed at the last individual post-baseline assessment (1 to 10 years). At 5 years, women had a 29.4% probability (95% CI: 23.6-35.5) of experiencing any reduction and a 14.9% probability (95% CI: 10.6-19.9) of experiencing any increase in work activities. Being enrolled in Switzerland (vs. Italy) and reporting more trouble in performing daily activities were significantly associated with work reduction., Conclusion: Our results suggest that most young BC survivors remain employed in the long-term., Implications for Cancer Survivors: Regular evaluation of symptoms which may interfere with daily life and identification of financial discomfort is critical in providing timely and individually tailored interventions and in limiting unwanted reductions in work activities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This article aims to present the results of a national, cross-sectional, voluntary, online survey on the presence and roles of associations of breast cancer patients and volunteers in Italian specialist breast centres. The survey was developed according to standard methods. The questionnaire was pre-tested by a random sample of three breast centres, loaded onto the SurveyMonkey platform, and piloted by one volunteer breast centre. The breast centre clinical leads were invited to participate via email. A link to the online instrument was provided. No financial incentives were offered. The results were reported using standard descriptive statistics. The response rate was 82/128 (65%). Members of associations were routinely present in 70% Italian breast centres. Breast centres most often reporting their presence were those certified by the European Society of Breast Cancer Specialists. Patient support (reception and information, listening, identification of needs, and psychological support) was the primary area where associations were reported to offer services. The magnitude of this phenomenon warrants a study to investigate the impact of the activities of associations on the quality of life of patients and on the cost-benefit ratio of the service, and the modes of their interactions with the nursing staff and the medical staff.

Background: Despite recommendations, mammography screening is often insufficiently integrated into specialist breast centres. A national, cross-sectional, voluntary, online survey on this issue was carried out among the Italian breast centres associated with Senonetwork, the Italian network of breast cancer services., Methods: A 73-item questionnaire was created, pre-tested and piloted. Centres integrating and not integrating a screening programme were compared using the unified theory of acceptance and use of technology (UTAUT) model. Centres' clustering was performed using the Gower's distance metric. Groups and clusters were compared with the equality-of-means test., Results: The response rate was 82/128 (65%). Overall, 84% (69/82) breast centres reported a collaboration with a screening programme in performing and/or reading mammograms and in the diagnostic work-up of women with abnormal screening results. The same proportion was observed among those centres responding to all questions (62/74). Performance expectancies (or the perceived usefulness of integration in terms of clinical quality, patient convenience, ease of job, and professional growth), satisfaction and motivation were higher in those centres collaborating with the screening programme. Effort expectancy indicators (or the degree to which the respondents believe that the integration is easy to implement) and those concerning the existence of facilitating conditions were lower both in centres collaborating and not collaborating with the screening programme. Among the former, six clusters of centres, distributed from 'no integration' to 'high', were identified. In cluster analysis, the highest level of integration was associated with higher agreement that integration eases the job, offers better opportunities for professional growth, and makes the working environment more satisfactory. The least integrated cluster assigned the lowest score to the statement that local health authority made available the resources needed., Conclusions: While confirming the positive effects of integrating screening programmes into breast centres, this survey has brought to light specific difficulties that must be faced. The results provide insights into the importance of integration focusing on the perspectives of professional career and motivation. The deficiency of facilitating conditions to integration is modifiable. Screening professionals' societies may have a role as initiators of the integration. Other supporting actions may be included in health laws at the national and regional level., (© 2022. The Author(s).)

Many coronavirus disease 2019 (Covid-19) survivors show symptoms months after acute illness. The aim of this work is to describe the clinical evolution of Covid-19, one year after discharge. We performed a prospective cohort study on 238 patients previously hospitalized for Covid-19 pneumonia in 2020 who already underwent clinical follow-up 4 months post-Covid-19. 200 consented to participate to a 12-months clinical assessment, including: pulmonary function tests with diffusing lung capacity for carbon monoxide (DLCO); post-traumatic stress (PTS) symptoms evaluation by the Impact of Event Scale (IES); motor function evaluation (by Short Physical Performance Battery and 2 min walking test); chest Computed Tomography (CT). After 366 [363-369] days, 79 patients (39.5%) reported at least one symptom. A DLCO < 80% was observed in 96 patients (49.0%). Severe DLCO impairment (< 60%) was reported in 20 patients (10.2%), related to extent of CT scan abnormalities. Some degree of motor impairment was observed in 25.8% of subjects. 37/200 patients (18.5%) showed moderate-to-severe PTS symptoms. In the time elapsed from 4 to 12 months after hospital discharge, motor function improves, while respiratory function does not, being accompanied by evidence of lung structural damage. Symptoms remain highly prevalent one year after acute illness., (© 2021. The Author(s).)

Background and Aims: Beyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort., Methods and Results: In this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19-34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148-1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44-53.95; p = 0.016)., Conclusions: HCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Metagenomics is a powerful tool to study and understand the microbial dynamics that occur during food fermentation and allows to close the link between microbial diversity and final sensory characteristics. Each food matrix can be colonized by different microbes, but also by different strains of the same species. In this study, using an innovative integrated approach combining culture-dependent method with a shotgun sequencing, we were able to show how strain-level biodiversity could influence the quality characteristics of the final product. The attention was placed on a model food fermentation process: Salame Piemonte, a Protected Geographical Indication (PGI) Italian fermented sausage. Three independent batches produced in February, March and May 2018 were analysed. The sausages were manufactured, following the production specification, in a local meat factory in the area of Turin (Italy) without the use of starter cultures. A pangenomic approach was applied in order to identify and evaluate the lactic acid bacteria (LAB) population driving the fermentation process. It was observed that all batches were characterized by the presence of few LAB species, namely Pediococcus pentosaceus, Latilactobacillus curvatus and Latilactobacillus sakei. Sausages from the different batches were different when the volatilome was taken into consideration, and a strong association between quality attributes and strains present was determined. In particular, different strains of L. sakei, showing heterogeneity at genomic level, colonized the meat at the beginning of each production and deeply influenced the fermentation process by distinctive metabolic pathways that affected the fermentation process and the final sensory aspects., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Although many studies emphasize the importance of using oxygen saturation (SpO 2 ) targets in the NICUs, there is a wide variability in used saturation ranges among centers. Primary aim was to draw a representative picture on how the management of oxygen monitoring is performed in the Italian NICUs. Second aim was to identify healthcare-professionals related factors associated with oxygen targeting in the preterm population., Methods: Cross-sectional study with data collection via an electronic survey form. A questionnaire containing pre-piloted and open questions on monitoring and management of the SpO 2 was administered to neonatologists across the network of the Italian Society of Neonatology. The questions focused on: the infrastructure, specific training, healthcare professionals and patients-related factors. The results of the survey were anonymously collected, summarized and analyzed., Results: Out of 378 questionnaires, 93 were correctly filled. Thirty-six different SpO 2 ranges were observed. Centers using written standard operating procedures on oxygen management and SpO 2 monitoring maintained a correct average range of SpO 2 90-95%, avoided hyperoxia and reconsidered saturation targets in relation to comorbidities. 39.8% of responders disabled alarms during neonatal care. One center used biomarkers for complete monitoring of neonatal oxygenation status., Conclusions: There is considerable variation in SpO 2 targets for preterm infants in the Italian NICUs. Standard operating procedures and specific training for health care personnel are the main factors playing a role for the correct maintenance of the recommended oxygen targets in preterms.

The novel coronavirus disease 2019 (COVID-19) pandemic has been an overwhelming challenge for worldwide health systems. Since the beginning of year 2020, COVID-19 has represented a potential harm for cancer patients and has often hindered oncology care. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. During the second wave of COVID-19 pandemic, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on oncologists' clinical activity and what changes have been made compared with the Italian situation during the first wave of the pandemic. Overall, 138 heads of medical oncology departments participated in this survey: 75 (54%) from the North, 24 (17%) from the Centre and 39 (28%) from the South of Italy and islands. This survey provides an overview of Italian oncologists facing the second wave of COVID-19 pandemic. The lesson learned during the first wave of COVID-19 pandemic has led to a better organisation of clinical activities, and regular testing among healthcare practitioners, with better chances to grant patients' protection. However, the lack of standardised informatic platforms results in serious challenges in replacing frontal visits, often making a concrete reduction of patients' hospital accesses unfeasible. Oncologists need to keep preserving the continuum of care of patients. Standardisation of safety measures, together with the implementation of informatic platforms, can significantly improve oncology pathways during this second wave of COVID-19 pandemic., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: evaluation of technical skills of the operators during the obstetrical device application for operative vaginal delivery, named kiwi-cup in a simulation training program., Methods: Thirty-five residents in obstetrics and gynecology of the University of Pisa, Italy were recruited and evaluated with an assessment scale on technical skills from 0 to 55 points. They performed various operative vaginal delivery simulations with kiwi-cup and were evaluated at time 0 by a tutor. After 8 weeks, simulation training was repeated and trainees were re-evaluated by the same tutor., Results: after 8 weeks from the first simulation session, trainees have been shown to increase technical skills (46.27 ± 4.6 with p-value < 0.0001), the successful application rate (85.71% with p-value 0.0161).) and to reduce the time to complete the procedure (86.2 ± 29.9 s with p-value < 0.0001)., Conclusion: simulation training on operational vaginal delivery significantly increases technical skills, improves successful rate, and reduces the time taken to complete the procedure., Clinical Trial Registration: Not applicable.

This is a reply to the paper by Miroslav Variny [...].

Background: Sociocultural issues play a key role in children needing kidney replacement therapy (KRT)., Methods: Data of incident patients < 18 years treated with chronic dialysis or preemptive kidney transplantation (pTx) between 2007 and 2016 were retrospectively collected from the Italian Pediatric Dialysis Registry; KRT modality and outcome were compared between patients with at least one non-Italian parent ("resident foreign patients," RFPs) and those from native parents ("domestic patients," DPs) and between the quinquennium 2007-2011 (period 1) and 2012-2016 (period 2)., Results: We included 448 children (26.8% RFPs). The percentage of RFPs increased from 23 to 30.3% (p = 0.08) from periods 1 to 2. They were younger (6.7 vs. 9.4 years, p = 0.025) and less often treated with pTx (3.3 vs. 13.4%, p = 0.009) than DPs. The percentage of pTx increased from period 1 to 2 in RFPs only (8.4-18.6%, p = 0.006). Independent predictors of a lower probability of pTx were lower age, belonging to RFPs group, starting KRT in period 1 and focal segmental glomerulosclerosis or glomerulopathy as primary kidney disease. Peritoneal dialysis was the preferred dialysis modality in both groups. Age, primary kidney disease, and center size were independently associated with dialysis modality choice. Patient survival, waiting time to Tx, and dialysis modality survival were not different between the two groups., Conclusions: The proportion of patients receiving KRT born from immigrant families increased in recent years in Italy. They were younger and less often treated with pTx than domestic patients. In case of dialysis, the outcome was not different between the two groups. Graphical abstract.

Background: Reproducible, high-quality surgery is a key point in the management of cancer patients. Quality indicators for surgical treatment of melanoma has been presented with benchmarks but data on morbidity are still limited. This study presents the quality indicators on morbidity after surgical treatment for non-metastatic skin melanoma in an Italian registry., Methods: Data were extracted from the Central National Melanoma Registry (CNMR) promoted by the Italian Melanoma Intergroup (IMI). All surgical procedures (WE, SNLB or LFND) for non-metastatic skin melanoma between January 2011 and February 2017 were evaluated for inclusion in the study. Only centers with adequate completeness of information (> 80%) were included in the study. Short-term complications (wound infection, dehiscence, skin graft failure and seroma) were investigated., Results: Wound infection rate was 1.1% (0.4 to 2.7%) in WE, 1.3% (0.7 to 2.5%) in SLNB and 4.1% (2.1 to 8.0%) in LFND. Wound dehiscence rate was 2.0% (0.8 to 5.1%) in WE, 0.9% (0.2 to 3.0%) in SLNB and 2.8% (0.9 to 8.6%) in LFND. Seroma rate was 4.2% (1.5 to 11.1%) in SLNB and 15.1% (4.6 to 39.9%) in LFND. Unreliable information was found on skin graft failure., Conclusions: Our findings contribute to available literature in setting up the recommended standards for melanoma centers, thus improving the quality of surgery offered to patients. A consensus on the core issues around surgical morbidity is needed to provide practical guidance on morbidity prevention and management.

Background: In parallel with the progress in neurosurgery, improvements in residents' training strategies have been reported. Increasing focus has been placed on residents' participation in research. Previous studies analyzed neurosurgery residents' contributions to research activities, time dedicated to research, and outcomes. However, few studies investigating these aspects outside the United States are present in the literature., Methods: A 3-section survey was sent to neurosurgery residents in Italy to determine the current opinion, perceptions, and experiences in the research field. A review of the pertinent literature was carried out., Results: Ninety-seven responding residents (response rate of 41.5%) self-reported an average time spent on research of 9.7 ± 11.4 hours/week. In decreasing frequency, residents were working on retrospective cohort studies (27.5%), case reports (21.7%), case series (15.5%), prospective cohort studies (13.4%), and others (16.4%). The most commonly reported factors promoting interest in research were interaction with peers (76.3%), mentorship (70.1%), and conference exposure (52.6%). Reported strategies of program support were heterogeneous with a prevalence for established collaborative agreements (59.8%) and the presence of a study coordinator (37.1%). The most frequently cited limiting factors were regulatory paperwork (70.1%), call schedule (60.8%), and lack of participating students/residents (57.7%)., Conclusions: By describing the current status of Italian residents' participation in research, we provide additional insight into factors supporting research involvement and existing barriers. Strategies for improvement at national and departmental levels are suggested. We encourage further investigations in other countries, to provide useful information in a worldwide framework., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite recent technical advances, interventional cardiac catheterization is still challenging in neonatal age and no specific data concerning early outcome are so far published in literature., Methods: Neonatal trans-catheter cardiac interventions performed in high-volume Italian referral centers were retrospectively analyzed. Primary outcomes were procedural major adverse events, in-hospital mortality and procedural failure. Secondary outcomes were minor adverse events and need for blood transfusion., Results: From January 2000 to December 2017, 1423 newborns (mean weight 3.0 ± 0.6 kg, range 1.0-5.8; median age 2.0 days) underwent interventional cardiac catheterization. Overall, global procedure adverse event rate and in-hospital mortality were 10.2% and 5.2%, respectively. At multi-variable analysis, primary composite outcome was significantly related to low-weight (<2.5 kg) (p < 0.01) and younger age (≤7 days) (p < 0.01) at the procedure, prematurity (p < 0.01), uni-ventricular physiology (p < 0.01), associated genetic syndromes (p < 0.01) and procedure risk category (p < 0.01). No relationship between volume of activity of any single center and procedure outcome was found. Over time, a trend toward an increased number of procedures and their complexity was recorded. Trans-catheter management of cardiac malformations with critical, duct-dependent pulmonary blood flow by arterial duct stenting or right ventricular outflow tract stenting showed the highest increase., Conclusions: Interventional cardiac catheterization is relatively safe and feasible in neonatal age. Peri-natal age, low weight, uni-ventricular physiology and genetic syndromes still significantly contribute to procedural morbidity and in-hospital mortality of this approach., Competing Interests: Declaration of competing interest None of the authors declares any conflict of interest regarding this paper, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Adjuvant treatment decisions in early breast cancer (eBC) have traditionally been driven by risk stratification based on clinical and pathological risk factors. The 21-gene Oncotype DX® assay has been validated as a predictive test for benefit from adjuvant chemotherapy (CT), hence assessing its impact in clinical decisions is of high interest. The objective of this study was to estimate the rate of adjuvant treatment decision modification impacted by the Recurrence Score® result, and the consequent budget impact., Methods: The study was a multicentre, prospective, real-life experience in Lombardy (Italy) including consecutive patients with T1-T3, N0-N1a, and ER+/HER2-eBC with clinical-pathologic "intermediate risk" of relapse. The change in treatment recommendations was assessed before and after availability of Recurrence Score result. A budget model evaluated the implications of 21-gene testing in the study population., Results: The overall proportion of CT recommendations was reduced from 24.6% to 15.2% after 21-gene testing, with a major impact in patients initially considered for CT plus hormone therapy (CHT). In these patients, the total budget was reduced, leading to a net saving of -€81,017. The greater the physician propensity to prescribe CHT, the higher the potential savings for the health system from sparing CT in most tested patients., Conclusions: Our real-life experience suggests that all intermediate-risk ER+/HER2-eBC patients who are initially deemed candidates for CHT should be tested with the 21-gene test. The potential to spare CT in at least half of them offers relevant advantages for patients and national health services., Competing Interests: Declaration of competing interest Alberto Zambelli and Carlo Tondini: Genomic Health (RF/CA); Giorgio Colombo: Genomic Health (H). The other authors indicated no financial relationships. (C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment (ET); Expert testimony; (H) Honoraria received (OI); Ownership interests; (IP) Intellectual property rights/inventor/patent holder (SAB); Scientific advisory board., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Quality of life (QoL) patient-reported outcomes (PROs) data from pivotal first-line trials in metastatic colorectal cancer (mCRC) are poor. The Valentino study showed that de-escalation to single-agent panitumumab after 4-month induction with panitumumab-FOLFOX is inferior to panitumumab-5-FU/LV in patients with RAS wild-type mCRC, although slightly reducing toxicity. We report QoL, a secondary end-point., Methods: PROs were assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30), EORTC QLQ-CR29, EuroQol EQ-5D questionnaires, at baseline and every 8 weeks until disease progression. First two evaluations correspond to induction treatment (identical in both arms), while subsequent to maintenance. To describe QoL changes over time, mean changes from baseline at each time point were calculated in overall population. To compare maintenance between two arms, mean changes and proportion of improved/stable/worse patients versus baseline were compared for each item., Results: In arm A/B, 91.5%/92.0% of enrolled patients completed questionnaires at baseline. No significant differences in the two arms were reported in compliance, baseline scores and mean changes versus baseline for the three questionnaires during maintenance (24/32/40 weeks). Overall, mean changes versus baseline showed an early deterioration during induction with partial recovering during maintenance for global QoL, functional scales and several symptoms/items of QLQ-C30 (fatigue, nausea/vomiting, appetite loss, diarrhoea) and QLQ-CR29 (body image, dry mouth, hair loss, taste, faecal incontinence, sore skin), and EQ-5D Visual Analogue Scale (VAS) score., Conclusion: In patients with RAS wild-type mCRC, induction with oxaliplatin-containing chemotherapy plus anti-EGFRs induces a transient significant QoL deterioration. After induction phase, treatment deintensification determines an overall recovery of health-related QoL, besides the expected prevention of oxaliplatin-related neurotoxicity., Competing Interests: Conflict of interest statement F.P. reports receiving honoraria for speaker activities and participation in advisory boards from Sanofi SA, Amgen, Inc, Bayer AG, Merck-Serono, Roche, and Servier Laboratories. A.S.-B. reports participation in advisory boards for Amgen, Bayer and Sanofi. L.R. reports being related to this manuscript as a member of the advisory board and for panitumumab supply from Amgen; unrelated to this manuscript as consulting or advisory role from Lilly, Bayer, Baxter, Sirtex Medical, Italfarmaco, Sanofi, ArQule, Incyte, Ipsen, Exelixis, Celgene, Eisai, Hengrui, MSD; has also received lecture fees from AstraZeneca, AbbVie, Gilead, Roche; has received travel expenses from ArQule, Ipsen. A.Z. reports receiving honoraria for speaker activities and participation in advisory boards from Sanofi SA, Amgen, Inc, Bayer AG, Merck-Serono, and Roche. M.D.B. reports receiving honoraria for speaker activities and participation in advisory boards from Amgen, Inc, Roche, Eli Lilly and Company, Servier Laboratories. Incyte Corp, and Celgene Corporation. F.d.B. reports receiving honoraria for speaker activities and participation in advisory boards from Amgen, Inc, Roche, and Novartis International AG. No other disclosures were reported., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Shiga toxin-producing Escherichia coli (STEC) infections result in a significant public health impact because of the severity of the disease that, in young children especially, can lead to hemolytic-uremic syndrome (HUS). A rise in the number of HUS cases was observed in the Apulia region of Italy from 2013 to 2017, and so, in 2018, a symptom-based surveillance system for children with bloody diarrhea (BD) was initiated in order to detect and manage STEC infections. The objective of the study was to describe the epidemiology of STEC infections in children from June 2018 to August 2019. Children <15 years old with BD were hospitalized and tested for STEC. Real-time PCR for virulence genes ( stx1 , stx2 , eae ) and serogroup identification tests were performed on stool samples/rectal swabs of cases. STEC infection was detected in 87 (10.6%) BD cases. The median age of STEC cases was 2.7 years, and 60 (68.9%) were <4. Of these 87 cases, 12 (13.8%) came from households with diarrhea. The reporting rate was 14.2/100,000, with the highest incidence in cases from the province of Bari (24.2/100,000). Serogroups O26 and O111 were both detected in 22/87 (25.3%) cases. Co-infections occurred in 12.6% of cases (11/87). Twenty-nine STEC were positive for stx1 , stx2 , and eae . Five cases (5.7%) caused by O26 (n = 2), O111 (n = 2), and O45 (n = 1) developed into HUS. A risk-oriented approach based on the testing of children with BD during the summer may represent a potentially beneficial option to improve the sensitivity of STEC surveillance, not only in Italy but also in the context of Europe as a whole.

The European Union 2050 climate neutrality goal and the climate crisis require coordinated efforts to reduce energy consumption in all sectors, and mainly in buildings greatly affected by the increasing temperature, with relevant CO 2 emissions due to inefficient end-use technologies. Moreover, the old building stock of most countries requires suited policies to support renovation programs aimed at improving energy performances and optimize energy uses. A toolbox was developed in the framework of the PrioritEE project to provide policy makers and technicians with a wide set of tools to support energy efficiency in Municipal Public Buildings. The toolbox, available for free, was tested in the partners' communities, proving its effectiveness. The paper illustrates its application to the Potenza Municipality case study in which the online calculator DSTool (the core instrument of the toolbox) was utilized to select and prioritize the energy efficiency interventions in public buildings implementable in a three-year action plan in terms of costs, energy savings, CO 2 emissions' reduction and return on investments. The results highlight that improvements in the building envelopes (walls and roofs), heating and lighting and photovoltaic systems allow reducing CO 2 emission approximately 644 t/year and saving about 2050 MWh/year with a total three-year investment of 1,728,823 EUR.

The novel severe acute respiratory syndrome coronavirus-2 pandemic is a global health problem, which started to affect China by the end of 2019. In Europe, Italy has faced this novel disease entity (named novel coronavirus disease [COVID-19]) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during the pandemic., Competing Interests: Conflict of interest statement The authors they have no conflicts of interest to declare for the present article., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Objective: The aim of this study was to assess the role of lung ultrasound (LUS) in a diagnostic algorithm of respiratory diseases, and to establish the accuracy of LUS compared with chest radiography (CXR)., Methods: Over a period of 2 years, 509 consecutive patients admitted for respiratory-related symptoms to both emergency and general medicine wards were enrolled and evaluated using LUS and CXR. LUS was conducted by expert operators who were blinded to the medical history and laboratory data. Computed tomography (CT) of the chest was performed in case of discordance between the CXR and LUS, suspected lung cancer and an inconclusive diagnosis. Diagnosis made by CT was considered the gold standard., Results: The difference in sensitivity and specificity between LUS and CXR as demonstrated by ROC curve analyses (LUS-AUROC: 0.853; specificity: 81.6%; sensitivity: 93.9% vs CXR-AUROC: 0.763; specificity: 57.4%; sensitivity: 96.3%) was significant (P = 0.001). Final diagnosis included 240 cases (47.2%) of pneumonia, 44 patients with cancer (8.6%), 20 patients with chronic obstructive pulmonary disease (COPD, 3.9%), 24 patients with heart failure (4.7%) and others (6.1%). In 108 patients (21.2%) with any lung pathology, a CT scan was performed with a positive diagnosis in 96 cases (88.9%); we found that CXR and LUS detected no abnormality in 24 (25%) and 5 (5.2%) cases, respectively. LUS was concordant with the final diagnosis (P < 0.0001), and in healthy patients, there was a low percentage of false positives (5.9%)., Conclusion: The results support the routine use of LUS in the clinical context., (© 2019 Asian Pacific Society of Respirology.)

Complement deficiencies are rare and often underdiagnosed primary immunodeficiencies that may be associated with invasive bacterial diseases. Serious infections with encapsulated organisms (mainly Streptococcus pneumoniae, but also Neisseria meningitides and Haemophilus influenzae type B) are frequent in patients with a deficiency of the second component of complement (C2), but no data are available on long-term follow-up. This study aimed to evaluate the long-term clinical outcome and the importance of an early diagnosis and subsequent infection prophylaxis in C2 deficiency. Here, we report the 21-year follow-up of a whole family which was tested for complement parameters, genetic analysis and biochemical measurements, due to recurrent pneumococcal meningitis in the elder brother. The two sons were diagnosed with homozygous type 1 C2 deficiency, while their parents were heterozygous with normal complement parameters. For the two brothers, a recommended vaccination program and antibiotic prophylaxis were prescribed. During the long-term follow-up, no severe/invasive infections were observed in either patient. At the age of 16, the younger brother developed progressive hypogammaglobulinemia of all three classes, IgA, IgM and IgG. A next generation sequencing panel excluded the presence of gene defects related to primary antibody deficiencies. Our data show that early diagnosis, use of vaccinations and antibiotic prophylaxis may allow a normal life in hereditary C2 deficiency, which can be characterized using functional and genetic methods. Moreover, a periodical check of immunoglobulin serum levels could be useful to detect a possible hypogammaglobulinemia.

To describe an operating protocol for bloody diarrhea (BD) in a pediatric population as a rapid response to a public health threat represented by an excess of pediatric HUS cases in the Apulia region (Southern Italy) starting from 2013. The protocol was set up with the goal of correct clinical management of Shiga toxin-producing Escherichia coli (STEC) infections, reductions in subsequent cases of hemolytic uremic syndrome (HUS), and improved short- and long-term disease outcomes. The protocol consisted of rapid hospitalization of children with bloody diarrhea (BD), hematochemical laboratory tests every 12-24 hours, and prompt laboratory diagnosis of STEC. No antibiotics were recommended until diagnosis. Children positive for STEC infections underwent early vigorous volume expansion. In June-December 2018, 438 children with BD were hospitalized, of which 53 (12.1%) had a STEC infection. The most common serogroups were O26 (36.1%), O111 (23.0%), and O157 (14.8%). Thirty-one samples carried the stx2 gene. Four cases evolved into HUS (7.5%), all with favorable outcome despite neurological involvement in two cases. Prompt and accurate laboratory diagnosis of STEC infections is of the utmost importance in patients with BD for correct clinical management. The strict adherence to the protocol could reduce the progression rate of STEC infections to HUS and prevents complications. Enhanced BD surveillance may help reduce cases of pediatric HUS in Southern Italy.

Background and Aims: HCV is associated with an increased risk of cardiovascular events (CV). Whether HCV clearance by direct-acting antivirals (DAA) reduces incident CV disease is poorly understood. We investigate whether HCV eradication reduces CV events., Methods: In a prospective multicentre study, 2204 HCV patients (F0-F2:29.5%, F3-F4: 70.5%) were enrolled. Males were 48%, median age was 68 (59-74) years and BMI 25.9 (23.1-28); 24.7% were smokers, 18% had diabetes, 13.2% had cholesterol levels >200 mg/dl and 9.1% took statins, 44% had hypertension. During an overall median follow-up of 28 (24-39) months, incident CV events, such as ischemic heart disease (IHD) and ischemic cerebral stroke (ICS), were recorded. An overall of 2204 patients were evaluated as control group and 1668 patients after HCV elimination were followed as a case group. Factors associated with CV events were evaluated by uni- and multi-variate analyses., Results: Incident CV rates per 100 patient years in pre-treatment and untreated controls and treated cases were 1.12, 1.14 and 0.44 (p = 0.0001 vs. controls), respectively, and a decreased of relative risk (RR = 0.379; p = 0.0002) was observed. CV risk was 2.0-3.5 times lower then in controls (HR 3.671; 95%C.I.:1.871-7.201; p < 0.001). The calculated number of patients to be treated to get a benefit in a patient was 55.26. The annual incidence reduction of CV events was 0.68%. HCV clearance was independently associated with CV events reduction (OR, 4.716; 95% C.I.:1.832-12.138; p = 0.001)., Conclusions: HCV clearance by DAA reduces CV events (IHD and ICS) with both clinical and socio-economic benefits., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Neonatal acidaemia at birth can increase neonatal morbidity and mortality and it is predictive of neonatal asphyxia. The umbilical blood gas analysis is a valid tool for the evaluation of neonatal acidaemia. However, umbilical cord blood gas analysis is commonly performed in high-risk situations or in the setting of Apgar scores < 7 at 5 min., Methods: A retrospective cohort study was conducted from June to December 2018 at the Department of mother's and child's health, Poliambulanza Foundation Hospital Institute. Inclusion criteria were: full term newborns with body weight appropriate for gestational age, born by vaginal delivery or caesarean section, reassuring Apgar Score > 7 at 5 min, arterial cord blood gas analysis showing pH < 7.4 or BE <-8 mmol/l or lactate > 6 mmol/l. The aim was to evaluate the predictive role of blood gas analysis for respiratory distress syndrome in newborns with reassuring Apgar Score., Results: 352 full term newborns were enrolled. Umbilical cord blood artery pH showed an association with respiratory distress syndrome (χ 2 (1) = 10,084, OR (95% CI): 3,9 × 10 - 4 (2,9 × 10 - 6 - 0,048); p < 0,05). ROC curve revealed that the cut-off point of pH was 7.12, with a sensibility and specificity of 68 and 63%, respectively., Conclusions: Umbilical cord blood artery pH < 7.12 at birth is associated to respiratory distress syndrome in newborns. Blood gas analysis is an important instrument to help health care providers during assistance in the delivery room, but also to early identify newborns at high risk for respiratory distress syndrome and better manage the care of these newborns after birth.

Objectives: Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns., Materials and Methods: Patient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern., Results: Among 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (p = 0.021) and sexual difficulties (p = 0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (p = 0.039)., Conclusions: Young women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: High volume haemodiafiltration (HDF) is associated with better survival than conventional haemodialysis (HD) in adults, but data concerning its use in children are lacking. The aim of this study was to assess the prevalence of paediatric HDF use and its associated factors in recent years in Italy., Methods: We retrospectively reviewed the files of patients from the Italian Pediatric Dialysis Registry's database who were registered between January 1, 2004 and December 31, 2016 and treated with extracorporeal dialysis for at least 6 months, looking in particular at modality and its associated factors., Results: One hundred forty-one out of 198 patients were treated exclusively with bicarbonate HD (71.2%), 57 with HDF (28.8%). Patients treated with HDF were younger (median 9.7 vs 13.2 years, p = 0.0008), were less often incident patients (52.6% vs 75.9%, p = 0.0031), had longer duration of the HD cycle (26.9 vs 20.8 months, p = 0.0036) and had a longer time to renal transplantation (32 vs 25 months, p = 0.0029) than those treated with bicarbonate HD only. The percentage of patients treated with HDF increased with dialysis vintage (16.9% at 6 months, 38.1% after more than 2 years of dialysis). The use of HDF was stable over time and was more common in the largest centres., Conclusions: Over the observation period, HDF use in Italy has been limited to roughly a quarter of patients on extracorporeal dialysis, in particular to those with high dialysis vintage, younger age or a long expected waiting time to renal transplantation.

Although several procedures for treating scoliosis have been developed, the most effective treatment is still based on early detection. For early diagnosis of idiopathic scoliosis, many authors have proposed methods of school screening; however, there is still no standardized screening program. The aim of this study was to evaluate a school screening method and the prevalence and distribution of scoliosis in Italian school children, aged 9-14 years, and to determine if the screening method can reduce morbidity in an Italian territory. The screening program consisted of three steps: the first step was a clinical examination carried out by the school physician and two specialists. In the second step, doubtful cases (presence of a hump between the two sides of the torso, in the thoracic or thoracolumbar region, measured using a hump meter) were evaluated by an orthopedic specialist and subsequently controlled every 6 months either clinically or by radiographic examination. The third step was the classification of the scoliosis and procedures for treatment. All patients were scheduled for a follow-up program and were evaluated during the subsequent 3 years. Statistical analyses were performed with GraphPad Prism 6. A total of 8995 children were screened for scoliosis. Of these, 487 showed clinical signs of scoliosis, and 181 were referred for anteroposterior radiographs because of a positive result on the forward-bending test (hump>5 mm). No significant statistical difference was observed by the three clinical examiners. Of the 181 patients who were referred, 69 were radiographed, and the clinical diagnosis was confirmed in 94.2% of the cases. The prevalence of scoliosis (defined as a curve of ≥10°) was 0.76% (65 of 8995 children), and most of the curves (44; prevalence 67.69%) were small (<20°). The overall ratio of boys to girls was 1 : 3.3, but varied according to the magnitude of the curve (1 : 3 for curves of <20°, 1 : 3.25 for curves of 20-29°, and 1 : 4 for curves of ≥30°). Double curves were the most common type identified, followed by thoracolumbar curves; specifically, of the 65 children who had a curve, 21 (32.30%) had a double curve, 18 (27.6%) had a thoracolumbar curve, 17 (26.1%) had a lumbar curve, and nine (13.84%) had a thoracic curve. In the following 3 years, only four patients were found to have curves more than 20° and none more than 30°. Our results show that the school screening program was accurate and repeatable. Moreover, screening children for scoliosis using a simple test appears to be an effective means of early detection. Above all, the screening process effectively decreased morbidity in the territory at a negligible cost.

Background: Maternal and child health are internationally considered to be among the best measures for assessing health-care quality. The study was carried out with the following aims: 1) to assess the quality of perinatal care (PC) by measuring the frequencies of the five PC indicators developed by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and comparing results with international standards; 2) to examine whether maternal, pregnancy care and neonatal characteristics could be factors associated with the quality of perinatal care hospital performance, measured through these indicators., Methods: We retrospectively reviewed medical charts of women over the age of 18 who experienced delivery in Gynecology/obstetrics wards between January-December 2016, and those of their newborns hospitalized in the Neonatology or Neonatal Intensive Care Unit (NICU) of a public non-teaching hospital in Catanzaro (Italy). Indicators were calculated according to the methodology specified in the manual for JCAHO measures. Univariate and multivariate analyses were performed to test the independent association of maternal, pregnancy care and neonatal characteristics on the adherence to JCAHO PC indicators., Results: The records of 1943 women and 1974 newborns were identified and reviewed in order to be included in at least one of the PC indicators. Elective/early-term delivery, was performed in 27.6% of eligible women, far from the recommended goal (0%); cesarean section in nulliparous women with a term, singleton baby in a vertex position exceeded the suggested target of < 24% and the adherence to antenatal steroids administration was suboptimal (87%). Results of the exclusive breastfeeding indicator achieved a better performance (81%) and compliance with the PC-04 indicator was satisfactory with only 0.4% healthcare-associated bloodstream infection developed in eligible newborns., Conclusions: This is the first study performed in Italy that has evaluated the quality of PC by using all the five JCAHO indicators. The application of this feasible set of indicators allowed us to measure several aspects of PC for which there is no standardized monitoring system in Italy. Our findings revealed significant deficiencies in the adherence to recommended processes of PC and suggest that there is still substantial work required to improve care.

Background: The recent literature showed positive results for bracing of patients with idiopathic scoliosis above 45° who refused surgery. However, no one has investigated whether other parameters can affect the results., Aim: The aim of this study was to evaluate the effectiveness of bracing in idiopathic scoliosis with curves above 40° and to verify the mechanical and biological parameters which go beyond the simple bend value expressed in Cobb degrees., Design: This is an observational controlled cohort study nested in a prospective clinical on-going database including 1,238 patients with idiopathic scoliosis., Setting: Inpatients and outpatients in Rome., Population: The study enrolled 160 patients with idiopathic scoliosis with curves above 40°., Methods: This is a prospective study based on an ongoing database including 1,238 patients with idiopathic scoliosis. The patients studied had idiopathic scoliosis with curves of 40° or more, Risser grade 0-4, and had refused any surgical treatment. 160 patients met the inclusion criteria. Of these, 104 patients had a definite outcome, 28 abandoned treatment and 28 are currently under treatment. The minimum duration of follow-up was 24 months. X-rays were used to obtain Cobb degrees and torsion of the apical vertebrae (Perdriolle's method). Three outcomes were distinguished according to SRS-SOSORT criteria: correction, stabilization and progression. To achieve the second aim, we divided the sample into subgroups according to Cobb degrees (<45°; ≥45°), Risser (0-2; 3-4) and rotation (<20; ≥20). Furthermore, logistic regression was applied by Stepwise Regression., Results: The results of our study showed that in 104 patients with a definite outcome the Cobb mean value was initially 47±5.25 SD and 34.19 ±8.45 SD at follow-up. Perdriolle was initially 20.04±5.53 SD and 16.76±7.04 at follow-up. Overall, 81 patients (78%) obtained a curve correction, and stabilization was achieved in 14 cases (13%). Nine patients experienced curve progression (9%), 16 patients were recommended for surgery because the curve at follow up was over 45°. The analysis of subgroups shows that with Cobb <45° at baseline, the average reduction was 11.46° Cobb, while in cases with Cobb ≥45 at baseline, the mean correction was 13.74° Cobb. In subgroups with Perdriolle <20° at baseline, the average reduction was 16.02° Cobb, while in cases with Perdriolle ≥20° at baseline, the mean correction was 8.4° Cobb. In subgroups with Risser 0-2 at baseline, the average reduction was 14.7° Cobb, while in cases with Risser 3-4 at baseline, the mean correction was 6.7° Cobb. The logistic regression model shows significance for the initial value of Perdriolle and Risser., Conclusions: Our results indicate that an adequate conservative treatment must definitely be considered for patients with scoliotic curves who refuse surgery; the results will be better particularly if the rotation is lower than 20 and Risser is between 0-2., Clinical Rehabilitation Impact: With the simultaneous evaluation of the Cobb angle, the vertebral rotation and the potential vertebral growth, it was possible to predict the final results at the start of treatment.

Background: Thrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC)., Methods: TMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with eculizumab., Results: The great clinical variability of brain injury in our cohort has led us to retrospectively build a "neurological score" useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI)., Conclusions: A "neurological score" may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach.

Background: Cane-cut on-vine withering is a grape dehydration technique used for dry and sweet wine production. The aim of this work was to study the influence of the cane-cut technique applied at harvest to Moscato bianco grapes during the on-vine withering process to produce dehydrated berries with a different chemical composition and a volatile profile., Results: After 24 days of dehydration, an on-vine withering system using the cane-cut technique induced an increase in the total volatile content compared with grapes produced with a normal on-vine withering process. This increase was greater in glycosidically bound volatile compounds than in the free fraction. Bound linalool showed a significant increase of 52% when the cane-cut withering system was applied but the grapes that were normally withered appeared to be less prone to the loss of free linalool. A significant increase in the glycosylated forms of nerol and geraniol was also observed in the two on-vine withering systems on the 24th day compared with the control (fresh grapes at harvest date)., Conclusion: A cane-cut, on-vine withering system applied at harvest induced changes in the volatile composition of Moscato bianco grapes increasing total volatile content, consisting mainly of bound compounds, by the 24th day of dehydration. The grapes dehydrated on-vine using this new system also showed significantly greater content of most of the free volatile compounds detected. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Gentile F, Martino M, Santangelo L, Giordano P, Torres DD, Carbone V, Di Palma AM, Rossini M, Gesualdo L, Giordano P, Giordano M. From Uganda to Italy: a case of nephrotic syndrome secondary to Plasmodium infection, Quartan malarial nephropathy and kidney failure. Turk J Pediatr 2019; 61: 776-779. Malaria (M), the first parasitic infection, is sometimes associated with nephrotic syndrome (NS) in tropical areas. Kidney involvement during quartan malaria is represented by immune-complex mediated glomerulonephritis (GN). Generally, NS develops several weeks after onset of quartan fever and its clinical course proceeds slowly to end-stage kidney disease (ESKD) even after eradication of the infection. We describe a case of Plasmodium malariaeassociated nephrotic syndrome and chronic proliferative glomerulopathy in a boy from Uganda. Renal biopsy revealed chronic proliferative GN with capillary wall thickening producing a double contour, segmental sclerosis and tubular atrophy. Blood Giemsa smear contained rare ring-form trophozoites and gametocytes of Plasmodium spp. This case highlights the importance of obtaining remote travel histories from immigrants presenting with nephrotic syndrome especially due to the current immigration crisis in Europe. Malaria has low prevalence or less known in our continent and requires more medical attention by European doctors.

Whether antithrombotic treatment is safe and/or affects the risk of intracranial bleeding in subjects with sporadic brain arteriovenous malformations (AVMs) is unknown. We conducted a retrospective analysis on the use of antithrombotics among patients affected by brain AVMs in follow-up at our institution. Attention was paid to the type of antithrombotic drug (either antiplatelets or anticoagulants), current or past use, dosage, and duration of treatment. Several clinical and angioarchitectural features of brain AVMs were also taken into consideration. The association between the use of antithrombotics and haemorrhagic onset was analyzed. A total of 77 patients were included in this study. Among them, ten patients were taking antithrombotic drugs at the time of AVM diagnosis. The rate of haemorrhagic onset was not significantly different between subjects who were and were not taking antithrombotic drugs (40 vs 55.2%, p = ns). Among the many clinical and angioarchitectural features analyzed, the only parameter that showed a statistically significant association with haemorrhagic onset was the size of the nidus. Patients who took antithrombotic treatments after being diagnosed with a brain AVM did not show an increased rate of intracranial haemorrhage over time considering a mean follow-up 4 years. In our study, antithrombotic treatment was not associated with increased intracranial bleeding among subjects with brain AVMs. In the presence of a strong clinical indication, antiplatelet and anticoagulant medications should not be denied a priori to patients with brain AVMs. Studies on larger populations are necessary to confirm these data.

Background and Aims: The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF., Methods and Results: We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP>600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p < 0.001), WBC count (p < 0.001), immobilization syndrome (p < 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP>600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p < 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP>600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p < 0.001) and anamnestic HF (p = 0.002)., Conclusions: Our study shows that BNP>600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP>600 pg/ml and anamnestic HF., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Acinetobacter baumannii is an opportunistic pathogen that has become a major cause of concern, since it is a frequent cause of healthcare-associated infections (HAIs). The aim of the study was to describe the occurrence, the management and the control of an outbreak that occurred in an intensive care unit (ICU) of a teaching hospital in Southern Italy caused by multiple strains of extensively drug-resistant A. baumannii (XDRAB)., Methods: Case-patient was defined as a patient with an healthcare-associated infection caused by an XDRAB isolate identified in a clinically significant culture. Environmental samples were collected from different surfaces. The isolates were identified by typical Gram stain morphology, using the Vitek 2 system (bioMérieux, France) and by MALDI-TOF MS mass spectrometry (bioMèrieux, France). Genotyping was performed through rep-PCR analysis., Results: A patient presented an XDRAB ventilator-associated pneumonia at admission and was managed with strict isolation precautions until discharge. Five patients had a ventilator-associated pneumonia and two had a central line-associated bloodstream infection. Of the environmental samples, 1 sample obtained from the side of the bed of an infected patient yielded growth of XDRAB. Infection control measures were adopted. Rep-PCR analysis identified four patterns., Conclusions: The integration of epidemiological and microbiological data and the application of infection control measures were crucial to bring such an outbreak to a rapid halt. The distinctive characteristic of this study was the complex molecular pattern of the outbreak, which subsided in a short period of time due to adherence to infection-control measures, confirming the fundamental role of molecular typing in the comprehension of outbreaks dynamics and of integrated control interventions for the interruption of epidemic events.

In summer 2013, an excess of paediatric cases of haemolytic uraemic syndrome (HUS) in a southern region of Italy prompted the investigation of a community-wide outbreak of Shiga toxin 2-producing Escherichia coli (STEC) O26:H11 infections. Case finding was based on testing patients with HUS or bloody diarrhoea for STEC infection by microbiological and serological methods. A case-control study was conducted to identify the source of the outbreak. STEC O26 infection was identified in 20 children (median age 17 months) with HUS, two of whom reported severe neurological sequelae. No cases in adults were detected. Molecular typing showed that two distinct STEC O26:H11 strains were involved. The case-control study showed an association between STEC O26 infection and consumption of dairy products from two local plants, but not with specific ready-to-eat products. E.coli O26:H11 strains lacking the stx genes were isolated from bulk milk and curd samples, but their PFGE profiles did not match those of the outbreak isolates. This outbreak supports the view that infections with Stx2-producing E. coli O26 in children have a high probability of progressing to HUS and represent an emerging public health problem in Europe., Competing Interests: Conflicts of Interest: None declared., (This article is copyright of The Authors, 2016.)

This study was aimed at developing and piloting a school-based intervention on severe illness-induced bereavement through a project focused on spreading knowledge of palliative care among high school students (phases 0-II Medical Research Council Framework). The intervention entailed the screening of a topic-related movie and a classroom meeting. Eight classes from 2 high schools participated, and a before-after evaluation was used to assess intervention feasibility and impact. Valid questionnaires, including 2 open-ended questions focusing on bereavement and strategies for coping with loss, were filled in by 89% (before) and 84% (after) of the 159 students. In the after evaluation, content analysis on the "strategies" question showed that answers concerning closeness and sharing were reported more frequently. Positive feedback was collected as regards the overall experience., (© The Author(s) 2013.)

Background: HNF1B gene mutations might be an underdiagnosed cause of nephropathy in adult patients mainly because of their pleomorphic clinical presentations. As most studies are based on paediatric populations, it is difficult to assess the likelihood of finding HNF1B mutations in adult patients and consequently define clinical settings in which genetic analysis is indicated. The aim of this study was the search for mutations in the HNF1B gene in a cohort of unrelated adult patients with nephropathy of unknown aetiology., Methods: Patients were tested for the HNF1B gene if they had chronic kidney disease of unknown origin and renal structure abnormalities (RSA) or a positive family history of nephropathy. The HNF1B coding sequence and intron-exon boundaries were analysed by direct sequencing. The search for gene deletions was performed by Multiple Ligation Probe Analysis (MLPA)., Results: Heterozygous mutations were identified in 6 out of 67 screened patients (9.0%) and included two whole gene deletions, one nonsense (p.Gln136Stop), two missense (p.Gly76Cys and p.Ala314Thr) mutations and a frameshift microdeletion (c.384&#95;390 delCATGCAG), the latter two (c.384&#95;390 del and p.Ala314Thr) not ever being reported to date. Mean age of the mutated patients at screening was 48.5 years with a M/F ratio of 2/4. The clinical manifestations of affected patients were extremely pleomorphic, including several urological and extra-renal manifestations., Conclusions: Mutations of HNF1B could explain chronic kidney disease in up to 9% of adult patients with a nephropathy of unknown aetiology and RSA: therefore an HNF1B mutation analysis should be considered in this group of patients., (© 2014 Asian Pacific Society of Nephrology.)

Febrile neutropenia (FN) is a severe dose-limiting side effect of myelosuppressive chemotherapy in patients with solid tumors. Clinical practice guidelines recommend primary prophylaxis with G-CSF in patients with an overall ≥ 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72 h after chemotherapy; for daily G-CSF, administration should continue until the absolute neutrophil count (ANC) is 1 × 10(9)/L post-nadir and should not be terminated after ANC increase in the early days of administration. The aim of this study was to assess guideline adherence in oncology practice in Italy. In this multicenter, prospective, observational study, patients were enrolled at the first G-CSF use in any cycle and were followed for two subsequent cycles (or until the end of chemotherapy if less than two additional cycles). Primary objective was to explore G-CSF use in Italian clinical practice; therefore, data were collected on the G-CSF type, timing of administration, and number of doses. 512 eligible patients were enrolled (median age, 62). The most common tumor types were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was administered later than 72 h after chemotherapy in 42 % of cycles, and the median [range] number of doses was four [1, 10]. Pegfilgrastim was administered later than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered in a manner which is not supported by evidence-based guidelines. As this practice may lead to poor outcomes, educational initiatives are recommended.

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.

Judging a person's ability to engage in competitive sports is the task of the sports physician. However, in the presence of chronic kidney disease (CKD) or urinary abnormalities such as hematuria or microproteinuria, or in the event of Cakut-type congenital abnormalities a second, qualified opinion by a nephrologist may be needed. A group of pediatric nephrologists belonging to the Italian Society of Pediatric Nephrology were asked to fill in a questionnaire regarding their attitude towards noncompetitive sports and their opinion on whether it is appropriate for them to express their judgment on the suitability/unsuitability of competitive sports activities in children and adolescents with CKD. Regarding noncompetitive sports the nephrologists' attitude was mostly positive, with the only exception of severe CKD. There were some reservations regarding unilateral renal agenesis and kidney transplant recipients. The situation with regard to competitive sports is more complex, as the expression of a favorable opinion often depends on the outcome of a series of instrumental examinations. There are no guidelines and no evidence-based positions on this issue. In order to make the opinions more uniform, the assessment methods should be standardized so that young people with CKD will be able to benefit from sports activities not only in terms of physical performance but also socialization and personal well-being.

Many epidemiological studies have shown that parents, siblings and offspring of long-lived subjects have a significant survival advantage when compared with the general population. However, how much of this reported advantage is due to common genetic factors or to a shared environment remains to be resolved.We reconstructed 202 families of nonagenarians from a population of southern Italy. To estimate the familiarity of human longevity, we compared survival data of parents and siblings of long-lived subjects to that of appropriate Italian birth cohorts. Then, to estimate the genetic component of longevity while minimizing the variability due to environment factors, we compared the survival functions of nonagenarians' siblings with those of their spouses (intrafamily control group).We found that both parents and siblings of the probands had a significant survival advantage over their Italian birth cohort counterparts. On the other hand, although a substantial survival advantage was observed in male siblings of probands with respect to the male intrafamily control group, female siblings did not show a similar advantage. In addition, we observed that the presence of a male nonagenarians in a family significantly decreased the instant mortality rate throughout lifetime for all the siblings; in the case of a female nonagenarians such an advantage persisted only for her male siblings.The methodological approach used here allowed us to distinguish the effects of environmental and genetic factors on human longevity. Our results suggest that genetic factors in males have a higher impact than in females on attaining longevity.

Background: The study of ancient skeletal pathologies can be adopted as a key tool in assessing and tracing several diseases from past to present times. Skeletal fluorosis, a chronic metabolic bone and joint disease causing excessive ossification and joint ankylosis, has been only rarely considered in differential diagnoses of palaeopathological lesions. Even today its early stages are misdiagnosed in endemic areas., Methodology/principal Findings: Endemic fluorosis induced by high concentrations of fluoride in water and soils is a major health problem in several countries, particularly in volcanic areas. Here we describe for the first time the features of endemic fluorosis in the Herculaneum victims of the 79 AD eruption, resulting from long-term exposure to high levels of environmental fluoride which still occur today., Conclusions/significance: Our observations on morphological, radiological, histological and chemical skeletal and dental features of this ancient population now suggest that in this area fluorosis was already endemic in Roman times. This evidence merged with currently available epidemiologic data reveal for the Vesuvius area population a permanent fluoride health hazard, whose public health and socio-economic impact is currently underestimated. The present guidelines for fluoridated tap water might be reconsidered accordingly, particularly around Mt Vesuvius and in other fluoride hazard areas with high natural fluoride levels.

Background: Albeit several studies pointed out the pivotal role that CD4+T cells have in Multiple Sclerosis, the CD8+ T cells involvement in the pathology is still in its early phases of investigation. Proteasome degradation is the key step in the production of MHC class I-restricted epitopes and therefore its activity could be an important element in the activation and regulation of autoreactive CD8+ T cells in Multiple Sclerosis., Methodology/principal Findings: Immunoproteasomes and PA28-alphabeta regulator are present in MS affected brain area and accumulated in plaques. They are expressed in cell types supposed to be involved in MS development such as neurons, endothelial cells, oligodendrocytes, macrophages/macroglia and lymphocytes. Furthermore, in a genetic study on 1262 Italian MS cases and 845 controls we observed that HLA-A*02+ female subjects carrying the immunoproteasome LMP2 codon 60HH variant have a reduced risk to develop MS. Accordingly, immunoproteasomes carrying the LMP2 60H allele produce in vitro a lower amount of the HLA-A*0201 restricted immunodominant epitope MBP(111-119)., Conclusion/significance: The immunoproteasome LMP2 60HH variant reduces the risk to develop MS amongst Italian HLA-A*02+ females. We propose that such an effect is mediated by the altered proteasome-dependent production of a specific MBP epitope presented on the MHC class I. Our observations thereby support the hypothesis of an involvement of immunoproteasome in the MS pathogenesis.