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To date, four vaccines have been authorised for emergency use and under conditional approval by the European Medicines Agency to prevent COVID-19: Comirnaty, COVID-19 Vaccine Janssen, Spikevax (previously COVID-19 Vaccine Moderna) and Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Although the benefit–risk profile of these vaccines was proven to be largely favourable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, children/adolescents, immunocompromised people and persons with a history of allergy or previous SARS-CoV-2 infection, is still limited. In this narrative review, we critically overview pre- and post-marketing evidence on the potential benefits and risks of marketed COVID-19 vaccines in the above-mentioned special cohorts. In addition, we summarise the recommendations of the scientific societies and regulatory agencies about COVID-19 primary prevention in the same vaccinee categories. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01131-6.

NION DISPONIBILE

Background Neonatal units’ volume of activity, and other quantitative and qualitative variables, such as staffing, workload, work environment, care organization and geographical location, may influence the outcome of high risk newborns. Data about the distribution of these variables and their relationships among Italian neonatal units are lacking. Methods Between March 2010-April 2011, 63 neonatal intensive care units adhering to the Italian Neonatal Network participated in the SONAR Nurse study. Their main features and work environment were investigated by questionnaires compiled by the chief and by physicians and nurses of each unit. Twelve cross-sectional monthly-repeated surveys on different shifts were performed, collecting data on number of nurses on duty and number and acuity of hospitalized infants. Results Six hundred forty five physicians and 1601 nurses compiled the questionnaires. In the cross-sectional surveys 702 reports were collected, with 11082 infant and 3226 nurse data points. A high variability was found for units’ size (4–50 total beds), daily number of patients (median 14.5, range 3.4-48.7), number of nurses per shift (median 4.2, range 0.7-10.8) and number of team meetings per month. Northern regions performed better than Central and Southern regions for frequency of training meetings, qualitative assessment of performance, motivation within the unit and nursing work environment; mean physicians’ and nurses’ age increased moving from North to South. After stratification by terciles of the mean daily number of patients, the median number of nurses per shift increased at increasing volume of activity, while the opposite was found for the nurse-to-patient ratio adjusted by patients’ acuity. On average, in units belonging to the lower tercile there was 1 nurse every 2.5 patients, while in those belonging to the higher tercile the ratio was 1 nurse every 5 patients. Conclusions In Italy, there is a high variability in organizational characteristics and work environment among neonatal units and an uneven distribution of human resources in relation to volume of activity, suggesting that the larger the unit the greater the workload for each nurse. Urgent modifications in planning and organization of services are needed in order to pursue more efficient, homogeneous and integrated regionalized neonatal care systems.

International audience; Recent studies have reported the potential clinical utility for metastatic breast cancer (MBC) patients of continuing trastuzumab beyond progression. Based on those results, here the authors have examined the benefits of trastuzumab-continuation by specifically evaluating RECIST responses upon first line trastuzumab-treatment as a potential predictive marker for therapeutic effect of trastuzumab-continuation beyond metastatic disease progression. The authors carried out a retrospective analysis of 272 HER2 positive MBC patients under trastuzumab treatment at 22 different oncology Italian centers during the years of 2000 and 2001 who progressed under first line trastuzumab-treatment. The primary end point of the study was the survival from the date of first documented progression upon first line trastuzumab treatment of disease. Data analysis involved the use of matching on propensity score to balance variables between treated and untreated subjects and to reduce bias. Of the 272 HER2-positive MBC patients, 154 (56.6%) continued treatment. 79 (51.3%) of those 154 patients showed responses based on RECIST criteria during first-line trastuzumab-treatment. Of the 118 patients that suspended trastuzumab, RECIST responses had been observed in 44 (37.3%). Cox proportional hazards analysis of progressed patients, matched using propensity score, showed that discontinuation of trastuzumab at metastatic disease progression was a risk factor for significantly reduced overall survival in both responder (HR = 2.23; 95% CI = 1.03-4.82) and non-responder groups (HR = 3.53, 95% CI = 1.73-7.21), with no significant differences in the two estimated HRs (-value of the likelihood-ratio test = 0.690). Continued trastuzumab treatment after disease progression has clinically and statistically significant effects in both RECIST responder and non-responder MBC patients.

At present, episcleral plaque brachytherapy and charged particle or photon irradiation are the most commonly employed methods in ocular and adnexal conservative treatments. In the near future, a different therapeutic approach to these malignancies could be represented by a new device based on electron beam emission. The equipment used consists of an electron accelerator originally developed for intraoperative radiotherapy, modified to fit ocular pathologies. Adequate collimators and an enhanced mechanical accuracy are required for this special practice. An operative planning for epibulbar, adnexal and intraocular tumors is described, discussing its rationale for possible applications. Experimental tests using phantoms and Gafchromic® films are in progress. As all conservative treatments, the main gaol of this activity is the maintenance of a good visual function.

Background: Vaccine hesitancy is a considerable issue in European countries and leads to low coverage rates. After a long debate, Italy has made vaccination mandatory for admission to its schools.Methods: In the NAVIDAD study (a cross-sectional multicentre study), a 63-item questionnaire was administered to 1820 pregnant women from 15 Italian cities. The questionnaire assessed the interviewee's opinion on mandatory vaccines, as well as their socioeconomic status, sources of information about vaccines, confidence in the Italian National Healthcare Service (NHS), and intention to vaccinate their newborn.Results: Information sources play a key role in determining the opinion on restoration of mandatory vaccines; in particular, women who obtained information from anti-vaccination movements are less likely to accept the vaccines (OR: 0.35, 95% CI: 0.21-0.58, p < 0.001). Women who had confidence in healthcare professional information agreed more on mandatory vaccination than did the other women (OR: 2.66, 95% CI: 1.62-4.36, p < 0.001); those who perceived that healthcare professionals have economic interest in child immunization and who declared that healthcare providers inform only on vaccinations benefits not on risks were less likely to agree on compulsory vaccination (OR: 0.66, CI 95%: 0.46-0.96, p = 0.03; OR: 0.66, CI 95%: 0.46-0.95, p = 0.03, respectively).Conclusion: Information sources and confidence towards health professionals are the main determinants of acceptance of mandatory vaccine restoration. To increase the acceptability of the restoration and reduce vaccine hesitancy, these aspects need to be strengthened.

Nephropathic subjects with impaired immune responses show dramatically high infection rates of coronavirus disease 2019 (COVID-19). This work evaluated the ability to acquire and maintain protective antibodies over time in 26 hemodialysis patients and 21 kidney transplant recipients. The subjects were followed-up through quantitative determination of circulating SARS-CoV-2 S1/S2 IgG and neutralizing antibodies in the 6-month period after clinical and laboratory recovery. A group of 143 healthcare workers with no underlying chronic pathologies or renal diseases recovered from COVID was also evaluated. In both dialysis and transplanted patients, antibody titers reached a zenith around the 3rd month, and then a decline occurred on average between the 270th and 300th day. Immunocompromised patients who lost antibodies around the 6th month were more common than non-renal subjects, although the difference was not significant (38.5% vs. 26.6%). Considering the decay of antibody levels below the positivity threshold (15 AU/mL) as “failure”, a progressive loss of immunisation was found in the overall population starting 6 months after recovery. A longer overall antibody persistence was observed in severe forms of COVID-19 (p = 0.0183), but within each group, given the small number of patients, the difference was not significant (dialysis: p = 0.0702, transplant: p = 0.1899). These data suggest that immunocompromised renal patients recovered from COVID-19 have weakened and heterogeneous humoral responses that tend to decay over time. Despite interindividual variability, an association emerged between antibody persistence and clinical severity, similar to the subjects with preserved immune function.

Aim The purpose of this study is to investigate the individual and contextual determinants of the perceived quality (PQ) of the telemedicine and teleassistance (TMTA) services and the willingness to continue (WC) with them among patients with diabetes using TMTA services during the COVID-19 pandemic in one large region of Italy. Methods A structured survey was administered to patients with type 1 and 2 diabetes who used TMTA during the first wave of the COVID-19 pandemic. The questionnaire contained questions on TMTA service experience and participants’ socio-demographic characteristics. Multiple regression models investigated the independent factors associated with PQ and WC. Results The final analysis included 569 patients with diabetes (54.7% female), with an average age of 58.1 years. TMTA services’ PQ and WC were high. A higher education and being unemployed were factors associated with an increased WC. Older age was negatively related to PQ. Perceived support from TMTA service was positively associated with PQ and WC. Perceived increase in disease self-management was positively associated with PQ and WC. Conclusions Our study identified several determinants of PQ and WC. These socio-demographic and TMTA-related factors should be considered in the implementation of care pathways integrating in-person visits with TMTA.

Background and AimsA similar course of COVID-19 in patients with inflammatory bowel diseases [IBD] and in the general population has been reported. However, disease prevalence in IBD patients is presently unknown. In this prospective observational study, we aimed at determining SARS-CoV2 infection prevalence in IBD patients treated with biologic therapy.MethodsFrom IBD patients under biologic therapy and recruited from three different locations in Italy and Germany, 354 sera were evaluated for antibody presence by RBD ELISA. Control groups were: i] age-matched healthy subjects tested in the same time period in Milan, Italy; ii] healthy subjects collected in the pre-COVID era; iii] IBD patients under biologic therapy collected in the pre-COVID era.ResultsEight out of 354 patients tested positive for the anti-RBD-SARS-CoV2 IgG antibody [prevalence 2.3%]. The percentage of IgG-positive patients among those recruited from Milan was significantly higher than among those recruited from other locations [prevalence 5.4% vs 0.4%, p ConclusionsSeroprevalence of SARS-CoV2 in IBD patients treated with biologic therapy reflects values measured in the local general population. Specific symptoms and contact history with SARS-CoV2-infected individuals strongly increase the likelihood of SARS-CoV2 seropositivity.

In most children, coronavirus disease 2019 (COVID-19) is a mild or moderate disease. Moreover, in a relevant number of cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains totally asymptomatic. All these findings seem to suggest that otherwise healthy children with suspected COVID-19 might be managed in the community in most cases, thus avoiding hospital admission and closely related medical, social and economic problems, including overwhelming hospitals. Unfortunately, home management of children with suspected COVID-19 rarely occurs, and many children with suspected or laboratory-confirmed SARS-CoV-2 infection are frequently hospitalized irrespective of the severity of disease. To evaluate the role of community health houses (CHHs) in the management of children with COVID-19, 1,009 children with suspected SARS-CoV-2 infection were studied in Emilia-Romagna Region, Italy. Among them, 194 (19.2%) resulted positive for SARS-CoV-2. The majority (583, 58%) were tested at home by CHHs, while 426 (42%) were brought to the hospital for testing. The patients who were managed in the hospital had a significantly lower median age than those who were managed at home (2 vs. 12 years, p < 0.001). Exposure to SARS-CoV-2 cases within the family was significantly more frequent among those who were managed at home (82 vs. 46%, p < 0.05). The clinical findings were similar between the children who were managed at home and those who were managed in the hospital. Only one of the children managed at home (0.7%) required hospitalization; in comparison, 26 (48%) of those whose swab samples were taken at the hospital were hospitalized. Our research shows for the first time the importance of CHHs in the management of COVID-19 in children; because of the high frequency of mild to moderate cases, management by CHHs can reduce the care load in hospitals, providing enormous advantages on the familial, medical, social, and economic levels. These findings could be useful for suggesting a territorial rather than hospital-based strategy in pediatrics in the case of a new wave of the epidemic.

Background The recent COVID-19 epidemic is showing how the response of the scientific literature is fundamental in the first days following the onset of a new epidemic. Quantifying which studies have a greatest impact can help researchers and policymakers in controlling the epidemic. The aim of this study is to describe the early scientific production in response to the COVID-19 epidemic through a scientometric analysis. Methods The study consisted of: 1) review of the scientific literature produced in the 30 days since the first paper related to COVID-19 has been published on Pubmed; 2) Identification of papers' Digital Object Identifiers (DOI) and analysis of related metrics with the construction of a 'Computed Impact Score' (CIS) that represents a unifying score over heterogeneous bibliometric indicators. The CIS takes into account all the bibliometric indicators both traditional (i.e. counting of citations) and alternative (i.e. altmetrics). In this study we use the altmetrics provided by Plum Analytics (PlumX). All bibliometric indicators for the selected papers have been collected by using their corresponding DOIs as the key for querying Scopus API, which integrates PlumX. On top of those indicators we compute the CIS. The papers with higher CIS are discussed and presented. Results 239 papers have been included in the study. A threshold for CIS of t = 1.04 (i.e.95% quantile) allowed us to record 8 papers as potentially impactful. The 8 papers are: 6 case reports, 1 methodological study, 1 editorial. First authors come from China (n = 6), USA (n = 1) and Germany (n = 1). The main topics are: case/s description (n = 5), outbreak investigation (n = 2) and 1 genomic study. Conclusions The early response of the scientific literature during an epidemic does not follow a pre-established pattern. Tracing the traditional and non-traditional metrics measures of papers can help to understand and evaluate the impact of literature on the scientific community and general population. Key messages The dynamic of the scientific community represents an important aspect of the early response to the onset of a new epidemic, which must be studied also to increase systems’ preparedness. In a connected digital world, tracing metrics measures of scientific papers can identify those with the greatest impact and help professionals to correctly inform the population.

Regulatory T cells represent a class of specialized T lymphocytes that suppress unwanted immune responses and size the activation of the immune system whereby limiting collateral damages in tissues involved by inflammation. In cancer, the accumulation of Tregs is generally associated with poor prognosis. Many lines of evidence indicate that Tregs accumulation in the tumor microenvironment (TME) suppresses the immune response against tumor-associated antigens (TAA), thus promoting tumor progression in non-small cell lung carcinoma (NSLC), breast carcinoma and melanoma. In colorectal cancer (CRC) the effect of Tregs accumulation is debated. Some reports describe the association of high number of Tregs in CRC stroma with a better prognosis while others failed to find any association. These discordant results stem from the heterogeneity of the immune environment generated in CRC in which anticancer immune response may coexists with tumor promoting inflammation. Moreover, different subsets of Tregs have been identified that may exert different effects on cancer progression depending on tumor stage and their location within the tumor mass. Finally, Tregs phenotypic plasticity may be induced by cytokines released in the TME by dysplastic and other tumor-infiltrating cells thus affecting their functional role in the tumor. Here, we reviewed the recent literature about the role of Tregs in CRC and in colitis-associated colorectal cancer (CAC), where inflammation is the main driver of tumor initiation and progression. We tried to explain when and how Tregs can be considered to be the “good” or the “bad” in the colon carcinogenesis process on the basis of the available data concluding that the final effect of Tregs on sporadic CRC and CAC depends on their localization within the tumor, the subtype of Tregs involved and their phenotypic plasticity.

Community-acquired pneumonia (CAP) is one of the major causes of morbidity, mortality and hospitalization, and S. pneumoniae is the most frequently isolated etiologic agent. The pneumococcal urinary antigen test (PUAT) is among the recommended methods to identify the causative agent in CAP patients. A novel PUAT (IMMUNOCATCHTMStreptococcus pneumoniae) was compared with the Uni-GoldTMS. pneumoniae assay routinely used in our laboratory and with the widely used BinaxNOW® S. pneumoniae antigen card. A total of 218 (183 freshly harvested and 35 frozen) urine samples (US) submitted for the detection of pneumococcal urinary antigen (PUAT) between December 2016 and November 2018 were evaluated. A number of 160 negative and 41 positive concordant results were scored for all the three assays. A total of 17 US gave discrepant results. The sensitivity and specificity of Immunocatch compared with Uni-Gold were 73.2% and 98.8%, respectively, and compared with BinaxNOW were 97.6% and 98.8%, respectively. The overall percent agreement (OPA) and the Cohen’s kappa coefficient between the Immunocatch and the Uni-Gold resulted 92.2% and 0.78%, respectively, and compared with BinaxNOW were 98.6% and 0.95%, respectively. These performances suggest that the novel Immunocatch S. pneumoniae test is a useful tool for qualitative detection of S. pneumoniae capsular antigen in US.

Background Vaccine hesitancy is an emerging phenomenon in European countries and leads to decreasing trends in infant vaccine coverage. The aim of this study was to analyze the level of confidence and correct awareness about immunizations, which are crucial for the success of vaccination programmes. Methods As part of the NAVIDAD multicentre study, we examined vaccination confidence and complacency among a sample of 1820 pregnant women from 14 Italian cities. The questionnaire assessed the interviewee's knowledge, beliefs and misconceptions, as well as their socioeconomic status, information sources about vaccines and confidence in the Italian National Healthcare Service. Results Only 9% of women completely believed to the efficacy, necessity and safety of vaccinations. Almost 20% of them had misconceptions on most of the themes. There was a significant difference in the level of knowledge considering educational level: women with a high educational level have less probability of obtaining a low knowledge score (odds ratio (OR) 0.43 [95% confidence interval (CI) 0.34–0.54]). The level of knowledge was also influenced by the sources of information: women who received information from their general practitioner (GP) and from institutional websites had a significantly lower chance of having misconceptions (OR 0.74 [95% CI 0.58–0.96]; OR 0.59 [95% CI 0.46–0.74]). Finally, the results underlined the influence of trust in healthcare professional information on the likelihood of having misconceptions (OR 0.49 [95% CI 0.27–0.89]). Conclusions The data suggest the efficacy of GPs and institutional websites as a source of information to contrast misconceptions and underline the importance of confidence in the healthcare system to increase complacency and confidence in vaccines.

Background Amenable mortality is an indicator that measures the extent to which health services contribute to the improvement of the health of a population. It can also highlight geographical and socioeconomic inequalities. Therefore, it is used to assess quality and performance of health care systems, both at national and subnational level. The Italian National Health Service sets the essential levels of care (Livelli Essenziali di Assistenza, LEA), a health-benefit package for all citizens. Because every region is responsible for providing the LEA and can offer additional health care, monitoring the performance of the Regional Health Services (RHSs) is of increasing interest. Methods We used Nolte and McKee's list of amenable conditions to analyze the temporal trend of the standardized mortality rate (per 100.000) in Italy from 2006 to 2015, overall and by gender. We also examined the standardized rate at regional level by comparing the two-year periods 2006/7 and 2014/5, overall and by gender. Results Between 2006 and 2015, the overall mortality rate decreased from 81 to 68 per 100.000 population; this reduction was more pronounced in men (91 to 76 per 100.000, -16.5%) than in women (72 to 62 per 100.000, -13.9%). The decreasing trend in amenable mortality affected Italian regions differently, with northern regions showing steeper reductions as compared to southern regions. As a result, 2014/5 was the first time men's mortality in North Italy (68 per 100.000) was lower than women's mortality in South Italy (72 per 100.000). Conclusions The overall reduction of amenable mortality shows that Italy's health care services keep contributing to the improvement of population health. Nevertheless, by analyzing RHS performance we saw that differences in organization of care lead to differences in health care quality and performance across regions. Deaths amenable to health care services contribute to inequalities between Northern and Southern Italy. Key messages Because universal health coverage is necessary but not sufficient to reduce health inequalities, investing into better-quality services should be recognized as a priority. Amenable mortality can highlight areas of intervention to reduce inequalities in the provision of health care services.

There is evidence that preterm infants of migrant mothers are at a higher risk of adverse perinatal outcomes than those of native-born mothers, and that human milk feeding is beneficial to infants&rsquo, neurodevelopment. Using the United Nations Human Development Index (HDI) to classify mother&rsquo, s country of origin, we investigated whether type of neonatal feeding (human milk vs. mixed milk vs. exclusive formula milk) affected preterm newborn neurodevelopment varying across different HDI categories (Italian native-born vs. high HDI migrant vs. low HDI migrant) up to 2 years of age. Neurodevelopment of 530 infants born in Italy at &le, 32 weeks of gestational age and/or weighing &lt, 1500 g was measured at 3-, 6-, 9-, 12-, 18-, and 24-months corrected age (CA) using the revised Griffiths Mental Development Scale 0&ndash, 2 years. The trajectories of the general developmental quotient and its five subscales were estimated using mixed models. At 24-months CA only preterm infants of low HDI migrant mothers and fed exclusive formula milk showed moderate neurodevelopment impairment, with lower developmental trajectories of eye-hand coordination, performance, and personal-social abilities. Migrant mothers from low HDI countries and their preterm infants should be targeted by specific programs supporting maternal environment, infant development, and human or mixed milk neonatal feeding. Future research should focus on a deeper understanding of the mechanisms through which type of feeding and mother migrant conditions interact in influencing preterm infants&rsquo, neurodevelopment.

Alterations of the gut microbiota may cause dysregulated mucosal immune responses leading to the onset of inflammatory bowel diseases (IBD) in genetically susceptible hosts. Restoring immune homeostasis through the normalization of the gut microbiota is now considered a valuable therapeutic approach to treat IBD patients. The customization of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics and faecal microbiota transplantation, is therefore considered to support current therapies in IBD management. In this review, we will discuss recent advancements in the understanding of host−microbe interactions in IBD and the basis to promote homeostatic immune responses through microbe-targeted therapies. By considering gut microbiota dysbiosis as a key feature for the establishment of chronic inflammatory events, in the near future it will be suitable to design new cost-effective, physiologic, and patient-oriented therapeutic strategies for the treatment of IBD that can be applied in a personalized manner.

The evolution of coastal and transitional environments depends upon the interplay of human activities and natural drivers, two factors that are strongly connected and many times conflicting. The urge for efficient tools for characterising and predicting the behaviour of such systems is nowadays particularly pressing, especially under the effects of a changing climate, and requires a deeper understanding of the connections among different drivers and different scales. To this aim, the present paper reviews the results of a set of interdisciplinary and coordinated experiences carried out in the Adriatic Sea (north-eastern Mediterranean region), discussing state-of-the art methods for coastal dynamics assessment and monitoring, and suggests strategies towards a more efficient coastal management. Coupled with detailed geomorphological information, the methodologies currently available for evaluating the different components of relative sea level rise facilitate a first identification of the flooding hazard in coastal areas, providing a fundamental element for the prioritization and identification of the sustainability of possible interventions and policies. In addition, hydro- and morpho-dynamic models are achieving significant advances in terms of spatial resolution and physical insight, also in a climatological context, improving the description of the interactions between meteo-oceanographic processes at the regional scale to coastal dynamics at the local scale. We point out that a coordinated use of the described tools should be promptly promoted in the design of survey and monitoring activities as well as in the exploitation of already collected data. Moreover, expected benefits from this strategy include the production of services and infrastructures for coastal protection with a focus on short-term forecast and rapid response, enabling the implementation of an event-oriented sampling strategy.

The spread of carbapenem-resistant Enterobacteriaceae (CRE) has been enabled by the lack of control measures directed at carriers of multidrug-resistant organisms in healthcare settings. Screening patients for asymptomatic colonization on the one hand, and implementation of contact precautions on the other hand, reduces patient-to-patient transmission. Screening plates represents a relatively low-cost method for isolating CRE from rectal swabs, however, molecular assays have become widely available. This study compared the performance of four commercial molecular platforms in detecting clinically significant carbapenemase genes versus routine screening for CRE. A total of 1015 non-duplicated rectal swabs were cultured on a chromogenic carbapenem-resistant selective medium. All growing Enterobacteriaceae strains were tested for carbapenemase-related genes. The same specimens were processed using the following molecular assays: Allplex&trade, Entero-DR, Amplidiag&reg, CarbaR + MCR, AusDiagnostics MT CRE EU, and EasyScreen&trade, ESBL/CPO. The prevalence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae detected by swab culture was 2.2%, while organisms producing oxacillinase (OXA)-48 and metallo-&beta, lactamases were infrequent. The cost of CRE-related infection control precautions, which must be kept in place while waiting for screening results, are significant, so the molecular tests could become cost-competitive, especially when the turnaround time is decreased dramatically. Molecular assays represent a powerful diagnostic tool as they allow the rapid detection of the most clinically relevant carbapenemases.

A feasibility study was performed in order to demonstrate the benefits of designing and manufacturing a customized foot orthosis by means of digital technologies, such as Reverse Engineering (RE), Generative Design (GD) and Additive Manufacturing (AM). The aim of this work was to define the complete design-manufacturing process, starting from the 3D scanning of the human foot anatomy to the direct fabricating of the customized foot orthosis. Moreover, this first methodological study tries to combine a user-friendly semi-automatic modelling approach with the use of low-cost devices for the 3D laser scanning and the 3D printing processes. Finally, the result of this approach, based on digital technologies, was also compared with that achieved by means of conventional manual techniques.

In this paper we report the application of CAD/CAM based technologies for the innovative development of customized surgical devices to assist the mandibular rehabilitation in both primary surgery (resection and reconstruction) and secondary surgery (only reconstruction). Design and manufacturing of such customized surgical device are conducted according to the virtual pre-operative planning of the surgeon and with the aim to transferring this planning into the operating theatre. In the case of primary surgery, a cutting guide is developed to assist the resection step while a bone plate is developed to assist the reconstruction step. Instead, in the case of secondary surgery, in addition to the bone plate to support the reconstruction, also a repositioning guide is designed to bring back to the original position the resected stumps according to the original shape of the mandible. Finally, the components of the surgical devices are manufactured by DMLS in alloys suitable for biomedical applications.

Idiopathic REM sleep behavior disorder is a parasomnia characterized by dream enactment and is commonly a prediagnostic sign of parkinsonism and dementia. Since risk factors have not been defined, we initiated a multicenter case-control study to assess environmental and lifestyle risk factors for REM sleep behavior disorder.Cases were patients with idiopathic REM sleep behavior disorder who were free of dementia and parkinsonism, recruited from 13 International REM Sleep Behavior Disorder Study Group centers. Controls were matched according to age and sex. Potential environmental and lifestyle risk factors were assessed via standardized questionnaire. Unconditional logistic regression adjusting for age, sex, and center was conducted to investigate the environmental factors.A total of 694 participants (347 patients, 347 controls) were recruited. Among cases, mean age was 67.7 ± 9.6 years and 81.0% were male. Cases were more likely to smoke (ever smokers = 64.0% vs 55.5%, adjusted odds ratio [OR] = 1.43, p = 0.028). Caffeine and alcohol use were not different between cases and controls. Cases were more likely to report previous head injury (19.3% vs 12.7%, OR = 1.59, p = 0.037). Cases had fewer years of formal schooling (11.1 ± 4.4 years vs 12.7 ± 4.3, p0.001), and were more likely to report having worked as farmers (19.7% vs 12.5% OR = 1.67, p = 0.022) with borderline increase in welding (17.8% vs 12.1%, OR = 1.53, p = 0.063). Previous occupational pesticide exposure was more prevalent in cases than controls (11.8% vs 6.1%, OR = 2.16, p = 0.008).Smoking, head injury, pesticide exposure, and farming are potential risk factors for idiopathic REM sleep behavior disorder.

This paper describes a new protocol for mandibular reconstruction. Computer-aided design/computer-aided manufacturing (CAD/CAM) technology was used to manufacture custom-made cutting guides for tumor ablation and reconstructive plates to support fibula free flaps. CT scan data from a patient with an odontogenic keratocyst on the left mandibular ramus were elaborated to produce a virtual surgical plan of mandibular osteotomy in safe tissue for complete ramus resection. The CAD/CAM procedure was used to construct a customized surgical device composed of a cutting guide and a titanium reconstructive bone plate. The cutting guide allowed the surgeon to precisely transfer the virtual planned osteotomy into the surgical environment. The bone plate, including a custom-made anatomical condylar prosthesis, was designed using the outer surface of the healthy side of the mandible to obtain an ideal contour and avoid the bone deformities present on the side affected by the tumor. Operation time was reduced in the demolition and reconstruction phases. Functional and aesthetic outcomes allowed patients to immediately recover their usual appearance and functionality. This new protocol for mandibular reconstruction using CAD/CAM to construct custom-made guides and plates may represent a viable way to reproduce the patient’s anatomical contour, give the surgeon better procedural control, and reduce operation time.

This report describes a novel protocol for the construction of surgical cutting guides and reconstructive titanium bone plates to guide osteotomies according to the preoperative plan and to position and fix an osseous free flap in mandibular reconstruction after cancer removal. Computed tomographic data of a mandible affected by an ameloblastoma were elaborated to produce a virtual surgical plan that included the osteotomy cuts, area of bone resection, and reconstruction. STLfiles were elaborated for use with direct metal laser sintering, and a cutting guide and custom-made bone fixation plate were rapidly prototyped. The operating time was reduced in both the demolition and reconstruction phases. The patient's usual appearance and functionality were restored immediately. The new protocol for mandibular reconstruction is a viable way of reproducing the patient's anatomical contour while giving the surgeon better procedural control and reducing operating time. The innovative technique presented here involves three steps: (1) surgery planning, (2) computer-aided design/computer-aided manufacture and rapid prototyping, and (3) the surgery. High-resolution computed tomographic images of the patient's craniofacial skeleton and soft tissues were acquired using a multidetector computed tomography scanner (HiSpeed CT scanning station; General Electric Company, Fairfield, Conn.). The Digital Imaging and Communications in Medicine–format data were processed by the surgeons using CMF 6.0 software (Materialise, Leuven, Belgium). Three projections of the bone cuts were made in the three spatial axes and imported in Rhino 4.0 software (Robert McNeel & Associates, Seattle, Wash.) to allow the perfect transfer of the surgical plan. The computer-aided design of the surgical device was obtained using Rhino 4.0 software. The first component was a customized cutting guide for use in mandibular resection and to maintain free space after tumor ablation (Fig. 1, above). The second component was a customized reconstructive bone plate to support the iliac free flap (Fig. 1, below). The plate was designed by thickening the outer surface of the mirrored healthy side of the mandible to obtain an ideal mandibular contour and to avoid bone deformities on the side affected by the tumor. Reference notches were also added to delimit the part that would support the free flap. The two components (cutting guide and bone plate) were projected so that the same holes for the screws to fix the guide were used to secure the bone plate that supported the free flap. The cutting guide and bone plate were manufactured directly using the EOSINT M270 system (Electro Optical Systems, Munich, Germany). EOS CobaltChrome MP1 (Electro Optical Systems) was used to produce the cutting guide. The bone plate was produced with EOS Titanium Ti64 (Electro Optical Systems). A man with an ameloblastoma of the left mandibular body underwent mandibular resection and reconstruction using an iliac free flap. The mandibular cutting guide was fixed to the mandible to reproduce the demolition plan (Fig. 2, above). After mandibular resection, the cutting guide was removed and the reconstructive plate was introduced and fixed using the same holes as for the cutting guide. The reconstructive bone plate supported the iliac free flap in the correct position to restore the patient's original mandibulofacial contour exactly (Fig. 2, below). The protocol presented here offers several benefits. First, the virtual environment permitted optimal preoperative planning for tumor ablation: the resection boundaries were chosen accurately in safe tissues. No operating time was consumed by modeling a plate to the native mandible.1–5 Second, the morphology of the opposite hemimandible was mirrored and the reconstruction bone plate was designed using the external healthy cortical bone as a template, reproducing the patient's ideal mandibular contour and avoiding potential bone deformities. Co...

In recent years, vast progress in basic science and technology has ramatically changed scientific perspectives by opening the new orizon of translational medicine. The term “translational” refers to he bench-to-bedside paradigm and addresses the process of applyng ideas, insights and discoveries generated through basic science chemistry, biology, genetics) to improve diagnosis, prevention and reatment of human diseases [1]. The bench-to-bedside process can be divided into several steps, rom basic inquiry into pathophysiology to the identification of otentially targetable pathways, up to the development of new rugs. The final track resides in clinical testing of therapeutic agents nd evaluation of their efficacy. Traditionally, these steps are perormed by independent experts, starting from the basic scientist, hrough the chemistry expert/drug developer, ending with the clincal scientist. These professionals most of the time are physically eparated, and very often use a different terminology with diffiulties in cooperation and communication. The identification of translational approach recognizes the strong need for a close nteraction between individuals in science. Furthermore, sharing nformation among players also favours feedback from the cliniian to the basic scientist, thus making research at least a two-way rocess, from bench-to-bedside and from bedside-to-bench [2]. In the last two decades, gastroenterology has become an area f dynamic translational research, with some targets already sucessfully translated into practice and policy, and some others still rogressing into clinically effective drugs in a number of different onditions (Supplementary Figure S1). Epitome of how bidirecional translation has been fruitful in this field is the discovery of he central role of the potent pro-inflammatory cytokine tumour

The protocol presented here is intended to minimise the intervention in bone reconstruction surgery when severe atrophy or deformity is present in the maxillary arches. A patient underwent augmentation of an atrophic maxillary arch using titanium mesh and particulate autogenous plus bovine demineralised bone. After computed tomography data elaboration, computer-aided design and computer-aided machining were used to plan the augmentation of bone volume to improve the implant position needed to support the final dental prosthesis. The augmented maxilla was rapidly prototyped in plastic, and the titanium mesh was tested on this model before the surgical intervention. Then, the preformed titanium mesh was implanted in the maxillary arch with bone grafting. The bone was augmented relative to the position of the implants for the definitive fixed implant-supported rehabilitation. The protocol presented here is a viable, reproducible way to determine the correct bone augmentation for the final implant-supported prosthetic rehabilitation.

A surgical guide is projected to aid the repositioning of the mandibular segments in their original locations, and a reconstruction bone plate is provided to support the fibula free flap. Computer-aided mandibular reconstruction involves three steps: virtual surgical planning, CAD/CAM and rapid-prototyping procedures for the design and manufacture of the customised surgical device and surgery. The duration of the reconstructive phase (

INTRODUCTION: The following is a summary of the official guidelines of the Italian Association for the Study of the Pancreas regarding the medical, endoscopic and surgical management of acute pancreatitis. STATEMENTS: Clinical features together with elevation of the plasma concentrations of pancreatic enzymes are the cornerstones of diagnosis (recommendation A). Contrast-enhanced computed tomography (CT) provides good evidence for the presence of pancreatiti (recommendation C) and it should be carried out 48-72 h after the onset of symptoms in patients with predicted severe pancreatitis. Severity assessment is essential for the selection of the proper initial treatment in the management of acute pancreatitis (recommendation A) and should be done using the APACHE II score, serum C-reactive protein and CT assessment (recommendation C). The etiology of acute pancreatitis should be able to be determined in at least 80% of cases (recommendation B). An adequate volume of intravenous fluid should be administered promptly to correct the volume deficit and maintain basal fluid requirements (recommendation A); analgesia is crucial for the correct treatment of the disease (recommendation A). Enteral feeding is indicated in severe necrotizing pancreatitis and it is better than total parenteral nutrition (recommendation A). The use of prophylactic broad-spectrum antibiotics reduces infection rates in CT-proven necrotizing pancreatitis (recommendation A). Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for intervention, including surgery and radiological drainage (recommendation B). CONCLUSIONS: The participants agreed to revise the guidelines every 3 years in order to re-evaluate each question on the management of acute pancreatitis patients according to the most recent literature.

PURPOSE: This study describes the workflow in a procedure to create a provisional facial prosthesis for cancer patients using digital and rapid prototyping technologies without the need for supporting craniofacial implants. MATERIALS AND METHODS: An integrated workflow procedure aimed at the construction of provisional silicone prosthesis was used to rehabilitate a facial disfigurement in a patient who had undergone ablative surgery of the midface. A laser scan of the defect was obtained, and a digital model of the patient's face was constructed using virtual mirroring of the healthy side and referencing the "Nose Digital Library." RESULTS: The missing volume of the face was reconstructed, and a rapid-prototyped mold was devised to process the silicone prosthesis. A provisional eyeglasses-supported prosthesis designed with a CAD/CAM-projected titanium substructure was connected using the micro-components of implant prosthetic devices. CONCLUSIONS: The workflow described herein offers a viable procedure for quickly restoring facial defects by means of provisional prosthetic rehabilitation.

BACKGROUND: Infant mortality rate (IMR) is used as a population health indicator. We provide an updated description of temporal and geographical trends of IMR in Italy. METHODS: Regional data on infant deaths and live births were available for France, Germany, England, Portugal (1999-2000), and Italy (1990-2001). Mortality rates including 95% CIs and time-trends were computed. RESULTS: IMR was 4.5 per 1000 live births in 1999-2001. Between 1999-2001 and 1990-1992 both neonatal and post-neonatal mortality rates declined (P < 0.05) but not the North/South ratio. In 1999-2000 the regional variability in IMR was higher in Italy than in other European countries. CONCLUSION: Despite progresses in reducing IMR, geographical disparities persist within Italy.