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Background The start-up of the Turin municipal solid waste incineration plant (2013) was accompanied by surveillance of health effects, which included a human biomonitoring campaign. Here we present the results of the risk perception survey of local residents before the plant went into operation. Methods The survey sample was 394 local residents: 198 residing near the plant (exposed group) and 196 residing in an area distant from the plant site (unexposed group). The survey questionnaire investigated awareness of environmental and health issues, including a section on the perception of environmental health risks. Multivariate Poisson regressions were performed to determine the differences in risk perception between the two groups (exposed vs. unexposed). Results The exposed group was more concerned about natural hazards (prevalence ratio [PR] 1.61; 95% confidence interval [CI] 0.99–2.61), anthropogenic hazards (PR 1.35; 95% CI 1.03–1.77), and waste management (PR 1.19; 95% CI 0.94–1.50). There were no significant differences in opinions about environmental pollution-related diseases between the two groups, though the exposed considered themselves to be at risk for developing these diseases. The survey population placed its trust more in health care providers than in any other category. Conclusions The risk perception survey questionnaire yielded data that enabled a better understanding and interpretation of the social context: residents living near the incineration plant were more concerned than those living distant from it, especially about anthropogenic hazards. This information was subsequently incorporated into the design the communication tools.

When the Turin incinerator went into operation in 2013, it was accompanied by surveillance of health effects that included a human biomonitoring survey of 394 residents. They responded to items investigating their awareness of environmental and health issues and perception of environmental health risks. In this study, we compared the questionnaire responses before plant startup and at 3 years of operation. To accomplish this, we investigated changes in perceived risk and evaluated the efficacy of communication strategies. A total of 344 participants equally distributed in an exposed and an unexposed group responded to the follow-up questionnaire. Survey items investigated the perception of a relationship between illness and exposure to environmental pollution, feeling at risk of developing an illness, and concern about natural and anthropogenic hazards. The proportion of ‘certain’ and ‘very probable’ responses was compared to the total using the difference-in-differences method. Analyses showed an overall decrease in the differences between the two groups, which suggests that the communication actions undertaken for the exposed group were effective. Future communication plans should also include initiatives targeting the unexposed group.

Only few studies on the health effect of waste incinerators were focused on human biomonitoring (HBM). Our aim is to describe a protocol for assessing early variation of selected items in a population group living close to a waste incinerator in Turin, Italy. A cohort of 394 subjects was randomly selected, among residents near the incinerator and residents far from it. To achieve this sample size, 765 subjects were contacted. The cohort was monitored before the start-up of the plant and will be followed up 1 and 3 years after, with measurements of respiratory function, selected blood and urine parameters including 19 metals, 17 congeners of PCDDs/Fs, 12 congeners of DL-PCBs, 30 congeners of NDL-PCBs, 11 OH-PAHs, specific hormones (T3, T4, TSH, cortisol and ACTH) and common health parameters. The same protocol is applied for plant workers and breeders living near the plant. Individual exposure to urban pollution and waste incinerator fallout were assessed through the use of mathematical models. Information on individual habits was assessed using a specific questionnaire. SPoTT is the first Italian study that adopts a longitudinal design of appropriate statistical power to assess health impacts of waste incinerator plants’ emission. The initial results comparing the baseline to the first follow-up are due at the end of 2016.

Inflammation is a biological response involving immune cells, blood vessels and mediators induced by endogenous and exogenous stimuli, such as pathogens, damaged cells or chemicals. Unresolved (chronic) inflammation is characterized by the secretion of cytokines that maintain inflammation and redox stress. Mitochondrial or nuclear redox imbalance induces DNA damage, which triggers the DNA damage response (DDR) that is orchestrated by ATM and ATR kinases, which modify gene expression and metabolism and, eventually, establish the senescent phenotype. DDR-mediated senescence is induced by the signalling proteins p53, p16 and p21, which arrest the cell cycle in G1 or G2 and promote cytokine secretion, producing the senescence-associated secretory phenotype. Senescence and inflammation phenotypes are intimately associated, but highly heterogeneous because they vary according to the cell type that is involved. The vicious cycle of inflammation, DNA damage and DDR-mediated senescence, along with the constitutive activation of the immune system, is the core of an evolutionarily conserved circuitry, which arrests the cell cycle to reduce the accumulation of mutations generated by DNA replication during redox stress caused by infection or inflammation. Evidence suggests that specific organ dysfunctions in apparently unrelated diseases of autoimmune, rheumatic, degenerative and vascular origins are caused by inflammation resulting from DNA damage-induced senescence.In this Review, the authors describe the relationships between persistent DNA damage, inflammation and cellular senescence, which represent a common pathway that contributes to the pathology of many conditions, including rheumatic diseases.

Bone metastases (BM) are still the main cause of morbidity in cancer patients because of skeletal-related events (SREs) that reduce quality of life. They have also led to increased social and healthcare costs. At present, data available on BM are insufficient. This was a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 months’ follow-up. Information on patients at the first diagnosis of BM, including demographics and characteristics of the primary tumor and BM. Data were periodically updated by participating centres and reviewed by the coordinator centre. From October 2014 to July 2019, 618 patients with BM from solid tumors were enrolled and 220 were eligible for the present study. Median age was 62 years (range 26–86). Median follow-up was 34 months (range 6–149). At the time of enrolment, 109 (50%) had only BM (BOM) and 109 (50%) had concomitant visceral lesions and BM (BVM). Median time-to-first BM was 47 months (range 0–312) in BOM and 78.6 months in BVM patients. Disease-free interval differed on the basis of BC molecular subtype and stage. Ninety-eight BM patients had at least on SRE. Zoledronate was used in 69.1% of cases and denosumab in 28.3%. First-line treatment was hormone-based (50.7%), chemotherapy-based (38.7%) or chemotherapy- + hormone therapy-based (9.7%). Median progression-free and overall survival were 15.1 months (95% CI 12.6–18.4) and 66.8 months (95% CI 52.1–79.2), respectively. Our prospective study could substantially help to better understand the natural history of BM from BC.

Background The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7–6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3–4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p  = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p  = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p  = 0.003) and multivariable (HR 0.57, p  = 0.02) analysis. Conclusions The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab.

BackgroundAngiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy.ObjectiveTo describe the outcome of cabozantinib in patients previously treated with immunotherapy.Patients and methodsPatients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity.ResultsEighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4 months, median overall survival was 17.3 months. According to the IMDC criteria, the rates of patients alive at 12 months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p < 0.001). The median progression-free survival (PFS) was 11.5 months (95% CI 8.3–14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up.ConclusionsCabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies.

Background Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with primary or secondary dysfunction of mitochondrial oxidative phosphorylation and is the most common mitochondrial disease in childhood. Numerous reports on the biochemical and molecular profiles of LS have been published, but there are limited studies on genetically confirmed large series. We reviewed the clinical, imaging, biochemical and molecular data of 122 patients with a diagnosis of LS collected in the Italian Collaborative Network of Mitochondrial Diseases database. Results Clinical picture was characterized by early onset of several neurological signs dominated by central nervous system involvement associated with both supra- and sub-tentorial grey matter at MRI in the majority of cases. Extraneurological organ involvement is less frequent in LS than expected for a mitochondrial disorder. Complex I and IV deficiencies were the most common biochemical diagnoses, mostly associated with mutations in SURF1 or mitochondrial-DNA genes encoding complex I subunits. Our data showed SURF1 as the genotype with the most unfavorable prognosis, differently from other cohorts reported to date. Conclusion We report on a large genetically defined LS cohort, adding new data on phenotype-genotype correlation, prognostic factors and possible suggestions to diagnostic workup.

Since December 2019, coronavirus disease 2019 (COVID-19) pandemic has spread from China all over the world and many COVID-19 outbreaks have been reported in long-term care facilities (LCTF). However, data on clinical characteristics and prognostic factors in such settings are scarce. We conducted a retrospective, observational cohort study to assess clinical characteristics and baseline predictors of mortality of COVID-19 patients hospitalized after an outbreak of SARS-CoV-2 infection in a LTCF. A total of 50 patients were included. Mean age was 80 years (SD, 12 years), and 24/50 (57.1%) patients were males. The overall in-hospital mortality rate was 32%. At Cox regression analysis, significant predictors of in-hospital mortality were: hypernatremia (HR 9.12), lymphocyte count < 1000 cells/µL (HR 7.45), cardiovascular diseases other than hypertension (HR 6.41), and higher levels of serum interleukin-6 (IL-6, pg/mL) (HR 1.005). Our study shows a high in-hospital mortality rate in a cohort of elderly patients with COVID-19 and hypernatremia, lymphopenia, CVD other than hypertension, and higher IL-6 serum levels were identified as independent predictors of in-hospital mortality. Given the small population size as major limitation of our study, further investigations are necessary to better understand and confirm our findings in elderly patients.