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Background: Thanks to the availability of rich surname, linguistic and genetic information, together with its geographic and cultural complexity, Trentino (North-Eastern Italy) is an ideal place to test the relationships between genetic and cultural traits. Aim: We provide a comprehensive study of population structures based on surname and dialect variability and evaluate their relationships with genetic diversity in Trentino. Subjects and methods: Surname data were collected for 363 parishes, linguistic data for 57 dialects and genetic data for different sets of molecular markers (Y-chromosome, mtDNA, autosomal) in 10 populations. Analyses relied on different multivariate methods and correlation tests. Results: Besides the expected isolation-by-distance-like patterns (with few local exceptions, likely related to sociocultural instances), we detected a significant and geography-independent association between dialects and surnames. As for molecular markers, only Y-chromosomal STRs seem to be associated with the dialects, although no significant result was obtained. No evidence for correlation between molecular markers and surnames was observed. Conclusion: Surnames act as cultural markers as do other words, although in this context they cannot be used as reliable proxies for genetic variability at a local scale.

Aims We aimed at investigating the relationship between particulate matter (PM) and daily admissions for cardiovascular diseases (CVDs) at national level in Italy. Methods and results Daily numbers of cardiovascular hospitalizations were collected for all 8084 municipalities of Italy, in the period 2013–2015. A satellite-based spatiotemporal model was used to estimate daily PM10 (inhalable particles) and PM2.5 (fine particles) concentrations at 1-km2 resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and cardiovascular admissions. Flexible functions were estimated to explore the shape of the associations at low PM concentrations, also in non-urban areas. We analysed 2 154 810 acute hospitalizations for CVDs (25% stroke, 24% ischaemic heart diseases, 22% heart failure, and 5% atrial fibrillation). Relative increases of total cardiovascular admissions, per 10 µg/m3 variation in PM10 and PM2.5 at lag 0–5 (average of last 6 days since admission), were 0.55% (95% confidence intervals: 0.32%, 0.77%) and 0.97% (0.67%, 1.27%), respectively. The corresponding estimates for heart failure were 1.70% (1.28%, 2.13%) and 2.66% (2.09%, 3.23%). We estimated significant effects of PM10 and PM2.5 also on ischaemic heart diseases, myocardial infarction, atrial fibrillation, and ischaemic stroke. Associations were similar between less and more urbanized areas, and persisted even at low concentrations, e.g. below WHO guidelines. Conclusion PM was robustly associated with peaks in daily cardiovascular admissions, especially for heart failure, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health.

To assess if patients with type 2 diabetes mellitus (DM2) are: a) at excess risk of undergoing testing, contracting, and dying from SARS-CoV-2 infection compared to the general population; b) whether cardiovascular diseases (CAVDs) contribute to COVID-19-related death; and c) what is the effect of DM2 duration and control on COVID-19-related death.This population-based study involved all 449,440 adult residents of the Reggio Emilia province, Italy. DM2 patients were divided in groups by COVID testing, presence of CAVDs and COVID death. Several mediation analyses were performed.Patients with DM2 had an increased likelihood of being tested (Odds ratio, OR 1.27 95 %CI 1.23-1.30), testing positive (OR 1.21 95 %CI 1.16-1.26) and dying from COVID-19 (OR 1.75 95 %CI 1.54-2.00). COVID-19-related death was almost three times higher among obese vs non-obese patients with DM2 (OR 4.3 vs 1.6, respectively). For COVID-19 death, CAVDs mediated a) just 5.1 % of the total effect of DM2, b) 40 % of the effect of DM2 duration, and c) did not mediate the effect of glycemic control.For COVID-19-related deaths in DM2 patients, the effect is mostly direct, obesity amplifies it, DM2 control and duration are important predictors, while CAVDs only slightly mediates it.

To evaluate the impact of low skeletal muscle mass in patients with COVID-19 on relevant outcomes like 30-day mortality, need for intubation and need for intensive care unit admission.For this study, data from six centers were acquired. The acquired sample comprises 1138 patients. There were 547 women (48.1%) and 591 men (51.9%) with a mean age of 54.5 ± 18.8 years; median age, 55 years; range, 18-84 years). In every case, thoracic CT without intravenous application of contrast medium was performed. The following parameters of the pectoralis muscles were estimated: muscle area as a sum of the bilateral areas of the pectoralis major and minor muscles, muscle density, muscle index (PMI) (pectoralis muscle area divided by the patient's body height square) as a ratio pectoralis major and minor muscles divided by the patient's body heightOverall, 220 patients (19.33%) were admitted to the intensive care unit. In 171 patients (15.03%), mechanical lung ventilation was performed. Finally, 154 patients (13.53%) died within the observation time of 30-day. All investigated parameters of pectoralis muscle were lower in the patients with unfavorable courses of Covid-19. All pectoralis muscle parameters were associated with 30-day mortality in multivariate analyses adjusted for age and sex: pectoralis muscle area, HR = 0.93 CI 95% (0.91-0.95) p0.001; pectoralis muscle density, HR = 0.94 CI 95% (0.93-0.96) p0.001; pectoralis muscle index, HR = 0.79 CI 95% (0.75-0.85) p0.001, pectoralis muscle gauge, HR = 0.995 CI 95% (0.99-0.996) p0.001.in COVID-19, survivors have larger areas and higher index, gauge and density of the pectoralis muscles in comparison to nonsurvivors. However, the analyzed muscle parameters cannot be used for prediction of disease courses.

Prior studies variably reported residual chest CT abnormalities after COVID-19. This study evaluates the CT patterns of residual abnormalities in severe COVID-19 pneumonia survivors. All consecutive COVID-19 survivors who received a CT scan 5–7 months after severe pneumonia in two Italian hospitals (Reggio Emilia and Parma) were enrolled. Individual CT findings were retrospectively collected and follow-up CT scans were categorized as: resolution, residual non-fibrotic abnormalities, or residual fibrotic abnormalities according to CT patterns classified following standard definitions and international guidelines. In 225/405 (55.6%) patients, follow-up CT scans were normal or barely normal, whereas in 152/405 (37.5%) and 18/405 (4.4%) patients, non-fibrotic and fibrotic abnormalities were respectively found, and 10/405 (2.5%) had post-ventilatory changes (cicatricial emphysema and bronchiectasis in the anterior regions of upper lobes). Among non-fibrotic changes, either barely visible (n = 110/152) or overt (n = 20/152) ground-glass opacities (GGO), resembling non-fibrotic nonspecific interstitial pneumonia (NSIP) with or without organizing pneumonia features, represented the most common findings. The most frequent fibrotic abnormalities were subpleural reticulation (15/18), traction bronchiectasis (16/18) and GGO (14/18), resembling a fibrotic NSIP pattern. When multiple timepoints were available until 12 months (n = 65), residual abnormalities extension decreased over time. NSIP, more frequently without fibrotic features, represents the most common CT appearance of post-severe COVID-19 pneumonia.

ObjectiveWe aimed at identifying baseline predictive factors for emergency department (ED) readmission, with hospitalisation/death, in patients with COVID-19 previously discharged from the ED. We also developed a disease progression velocity index.Design and settingRetrospective cohort study of prospectively collected data. The charts of consecutive patients with COVID-19 discharged from the Reggio Emilia (Italy) ED (2 March 2 to 31 March 2020) were retrospectively examined. Clinical, laboratory and CT findings at first ED admission were tested as predictive factors using multivariable logistic models. We divided CT extension by days from symptom onset to build a synthetic velocity index.Participants450 patients discharged from the ED with diagnosis of COVID-19.Main outcome measureED readmission within 14 days, followed by hospitalisation/death.ResultsOf the discharged patients, 84 (18.7%) were readmitted to the ED, 61 (13.6%) were hospitalised and 10 (2.2%) died. Age (OR=1.05; 95% CI 1.03 to 1.08), Charlson Comorbidity Index 3 versus 0 (OR=11.61; 95% CI 1.76 to 76.58), days from symptom onset (OR for 1-day increase=0.81; 95% CI 0.73 to 0.90) and CT extension (OR for 1% increase=1.03; 95% CI 1.01 to 1.06) were associated in a multivariable model for readmission with hospitalisation/death. A 2-day lag velocity index was a strong predictor (OR for unit increase=1.21, 95% CI 1.08 to 1.36); the model including this index resulted in less information loss.ConclusionsA velocity index combining CT extension and days from symptom onset predicts disease progression in patients with COVID-19. For example, a 20% CT extension 3 days after symptom onset has the same risk as does 50% after 10 days.

Background COVID-19 prognostic factors include age, sex, comorbidities, laboratory and imaging findings, and time from symptom onset to seeking care. Purpose The study aim was to evaluate indices combining disease severity measures and time from disease onset to predict mortality of COVID-19 patients admitted to the emergency department (ED). Materials and methods All consecutive COVID-19 patients who underwent both computed tomography (CT) and chest X-ray (CXR) at ED presentation between 27/02/2020 and 13/03/2020 were included. CT visual score of disease extension and CXR Radiographic Assessment of Lung Edema (RALE) score were collected. The CT- and CXR-based scores, C-reactive protein (CRP), and oxygen saturation levels (sO2) were separately combined with time from symptom onset to ED presentation to obtain severity/time indices. Multivariable regression age- and sex-adjusted models without and with severity/time indices were compared. For CXR-RALE, the models were tested in a validation cohort. Results Of the 308 included patients, 55 (17.9%) died. In multivariable logistic age- and sex-adjusted models for death at 30 days, severity/time indices showed good discrimination ability, higher for imaging than for laboratory measures (AUCCT = 0.92, AUCCXR = 0.90, AUCCRP = 0.88, AUCsO2 = 0.88). AUCCXR was lower in the validation cohort (0.79). The models including severity/time indices performed slightly better than models including measures of disease severity not combined with time and those including the Charlson Comorbidity Index, except for CRP-based models. Conclusion Time from symptom onset to ED admission is a strong prognostic factor and provides added value to the interpretation of imaging and laboratory findings at ED presentation.

Daily air pollution has been linked with mortality from urban studies. Associations in rural areas are still unclear and there is growing interest in testing the role that air pollution has on other causes of death. This study aims to evaluate the association between daily air pollution and cause-specific mortality in all 8092 Italian municipalities.Natural, cardiovascular, cardiac, ischemic, cerebrovascular, respiratory, metabolic, diabetes, nervous and psychiatric causes of death occurred in Italy were extracted during 2013-2015. Daily ambient PMWe estimated a positive association between PMShort-term exposure to particulate matter was associated with mortality from nervous diseases. Mortality from metabolic diseases was associated with NO

Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2–3 and 6–7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2-3 and 6-7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase=1.79; 95% confidence interval [CI]=1.23-2.62) at 2-3 months and CRP integral (OR for one SD increase=2.24; 95%CI=1.53-3.28) at 6-7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.

We aimed to describe body composition changes up to 6–7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2–3 months (T1), and 6–7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) −1.11 (−1.72; −0.51) cm2] and in body fat areas were observed [−3.13 (−10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [−3.55 (−4.94; −2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6–7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.

Background/aim The relationship between air pollution and respiratory morbidity has been widely addressed in urban and metropolitan areas but little is known about the effects in non-urban settings. Our aim was to assess the short-term effects of PM10 and PM2.5 on respiratory admissions in the whole country of Italy during 2006–2015. Methods We estimated daily PM concentrations at the municipality level using satellite data and spatiotemporal predictors. We collected daily counts of respiratory hospital admissions for each Italian municipality. We considered five different outcomes: all respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), lower and upper respiratory tract infections (LRTI and URTI). Meta-analysis of province-specific estimates obtained by time-series models, adjusting for temperature, humidity and other confounders, was applied to extrapolate national estimates for each outcome. At last, we tested for effect modification by sex, age, period, and urbanization score. Analyses for PM2.5 were restricted to 2013–2015 cause the goodness of fit of exposure estimation. Results A total of 4,154,887 respiratory admission were registered during 2006–2015, of which 29% for LRTI, 12% for COPD, 6% for URTI, and 3% for asthma. Daily mean PM10 and PM2.5 concentrations over the study period were 23.3 and 17 μg/m3, respectively. For each 10 μg/m3 increases in PM10 and PM2.5 at lag 0–5 days, we found excess risks of total respiratory diseases equal to 1.20% (95% confidence intervals, 0.92, 1.49) and 1.22% (0.76, 1.68), respectively. The effects for the specific diseases were similar, with the strongest ones for asthma and COPD. Higher effects were found in the elderly and in less urbanized areas. Conclusions Short-term exposure to PM is harmful for the respiratory system throughout an entire country, especially in elderly patients. Strong effects can be found also in less urbanized areas.

Background Right-sided colorectal cancer (CRC) has worse survival than does left-sided CRC. The objective of this study was to further assess the impact of right-side location on survival and the role of the extent of lymphadenectomy. Methods All CRCs diagnosed between 2000 and 2012 in Emilia-Romagna Region, Italy, were included. Data for stage, grade, histology, screening history, and number of removed lymph nodes (LN) were collected. Multivariable Cox regression models were used to estimate hazard ratios (HR), with relative 95% confidence intervals (95%CI), of right vs. left colon and of removing 21 lymph nodes by cancer site. Results During the study period, 29,358 patients were registered (8828 right colon, 18,852 left colon, 1678 transverse). Patients with right cancer were more often older, females, with advanced stage and high grade, and higher number of removed LNs. Five-year survival was lower in the right than in the left colon (55.2% vs 59.7%). In multivariable analysis, right colon showed a lower survival when adjusting for age, sex, and screening status (HR 1.12, 95%CI 1.04–1.21). Stratification by number of lymph nodes removed (12–21 or > 21) was associated with better survival in right colon (HR 0.54, 95%CI 0.40–0.72 and HR 0.40, 95%CI 0.30–0.55, respectively) compared to left colon (HR 0.89, 95%CI 0.76–1.06 and HR 0.83, 95%CI 0.69–1.01, respectively). Conclusions This study confirms that right CRC has worse survival; the association is not due to screening status. An adequate removal of lymph nodes is associated with better survival, although the direction of the association in terms of causal links is not clear.

Background Inappropriate prescribing of diagnostic procedures leads to overdiagnosis, overtreatment and resource waste in healthcare systems. Effective strategies to measure and to overcome inappropriateness are essential to increasing the value and sustainability of care. We aimed to describe the determinants of inappropriate reporting of the clinical question and of inappropriate imaging and endoscopy referrals through an analysis of general practitioners’ (GP) referral forms in the province of Reggio Emilia, Italy. Methods A clinical audit was conducted on routinely collected referral forms of all GPs of Reggio Emilia province. All prescriptions for gastroscopy, colonoscopy, neurological and musculoskeletal computerised tomography (CT) and magnetic resonance imaging (MRI) from 2012 to 2017 were included. The appropriateness of referral forms was assessed using Clinika VAP software, which combines semantic analysis of clinical questions and available metadata. Local protocols agreed on by all physicians defined criteria of appropriateness. Two multilevel logistic models were used to identify multiple predictors of inappropriateness of referral forms and to analyse variability among GPs, primary care subdistricts and healthcare districts. Results Overall, 37% of referral forms were classified as inappropriate, gastroscopy and CT showed higher proportions of inappropriate referrals compared to colonoscopy and MRI. Inappropriateness increased with patient age for CT and MRI; for gastroscopy, it was lower for patients aged 65–84 compared to those younger, and for colonoscopy, it was higher for older patients. Fee exemptions were associated with inappropriateness in MRI referral forms. The effect of GPs’ practice organization was consistent across all tests, showing higher inappropriateness for primary care medical networks than in primary care medical groups. Male GPs were associated with inappropriateness in endoscopy, and older GPs were associated with inappropriateness in musculoskeletal CT. While there was moderate variability in the inappropriate prescribing among GPs, there was not among the healthcare districts or primary care subdistricts. Conclusions Routinely collected data and IT tools can be useful to identify and monitor diagnostic procedures at high risk of inappropriate prescribing. Assessing determinants of inappropriate referral makes it possible to tailor educational and organizational interventions to those who need them.

Basal cell carcinoma (BCC) is one of the most common skin cancers. Photodynamic therapy (PDT) is a first line therapy option for superficial BCCs, providing good response and low side effects. The aim of current study is to evaluate the clinicopathological features associated with partial responses or recurrences of BCCs treated with one cycle-PDT (two sessions, one week apart).Superficial BCCs treated with PDT between 2016 and 2019 were analyzed. At the 6-month follow-up visit, BCCs were subdivided in "high clearance" or "partial response", based on clinical and/or dermoscopic examination. "High clearance" lesions underwent 24-month follow-up visit and were assigned to "sustained clearance" or "recurrence" groups. Information about age, sex, site, size of lesions, skin biopsy and multiple lesions were collected and the association with the outcomes were estimated with multivariable logistic models.234 superficial BCCs from 216 patients were analyzed. At the 6-month follow-up visit, 171 out of 234 BCCs (73%) presented a "high clearance", while 63 lesions (27%) showed a "partial response". 28 out of 171 high clearance BCCs (16%) presented a recurrence within 24 months. When "partial response" is compared with the "high clearance" or "sustained clearance" group, a significant difference in mean superficial size of lesions is detected, with higher values in "partial response". Head and neck BCCs have a double risk of recurrence within 24 months.PDT is a good therapeutic option for superficial BCCs, even though BCCs of head and neck have a higher risk of recurrences and larger BCCs could need a supplementary treatment.

Carbon monoxide (CO) poisoning is the primary cause for access to emergency department (ED) services for more than 50,000 persons in Europe and the USA every year. CO poisoning diagnosis is based on multiple factors and is usually confirmed by high carboxyhemoglobin (COHb) levels in the blood. We conducted a systematic evaluation of literature to investigate the usefulness of COHb as a biomarker of environmental CO exposure. We conducted an electronic search in Medline, Embase, and the Cochrane Library databases. We selected studies reporting high or low environmental CO concentrations, as well as COHb levels in exposed subjects presenting in ED or staying at home. We included 19 studies, but only 7 studies reported environmental CO concentration and proved a correlation between COHb and CO exposure in healthy and non-smoker subjects only. However, confounding factors were often incompletely assessed. The main symptoms reported were headache, nausea, vertigo and vomiting. COHb data stored in healthcare databases were used in six studies and provided useful information about symptoms, CO sources and patient characteristics. Most studies were classified at risk of bias. This review indicates that COHb is the most commonly used biomarker to assess CO exposure and seems to be useful. Further studies are needed to establish the reliability of COHb as a biomarker and/or explore other possible biomarkers. Surveillance systems of the general population, correlated with geographical locations and other confounding factors, could be important for CO exposure monitoring and the development of focused prevention programs.

It has been hypothesized that bacille Calmette-Guerin (BCG), the anti-tuberculosis vaccine, can be protective against Covid-19. Using data of performed swabs and RT-PCR results for SARS-CoV-2 in the Reggio Emilia province (Emilia-Romagna Region, Northern Italy) from March 6th to March 26th, 2020, we computed age, gender, and place of birth (Italy or abroad) specific risk of being tested, prevalence of positive tests, and probability of testing positive given that a swab has been taken during the epidemic peak. We report that immigrants resident in Reggio Emilia province, mostly coming from Countries with high BCG vaccination coverage, and Italians had a similar prevalence of infection (odds ratio - OR 0.99; 95%CI 0.82-1.20) and similar probability of being tested (OR 0.93; 95%CI 0.81-1.10). Our data do not support the hypothesis that immigrants from Countries where BCG vaccination is recommended have a lower risk of Covid-19 infection.

Lockdowns to contain the spread of the SARS-CoV-2 have disrupted routines and behaviors, which could lead to a worsening of lifestyle and an increase in the burden of non-communicable diseases. This study aimed to describe the changes in physical activity, diet, alcohol drinking, and cigarette smoking during lockdown. A self-administered online survey addressing adults living in a province in northern Italy was advertised through websites and social media. Citizens could access the survey in anonymity from 4 May until 15 June 2020. A total of 1826 adults completed the survey, with a worsening of physical activity (35.1%), diet (17.6%), alcohol drinking (12.5%), and cigarette smoking (7.7%) reported. In contrast, 33.5% reported an improvement in diet, 12.6% in alcohol drinking, 5.3% in physical activity and 4.1% in cigarette smoking. Female sex, young adult age, suspension of work activity, and symptoms of psychological distress were the factors associated with a greater likelihood of change, which was frequently for the worse. Lockdown had an impact on lifestyle, with some net beneficial effects on diet and mostly negative effects on physical activity. Public health measures should be implemented to avoid long-term negative effects of the lockdown, supporting individuals more prone to change for the worse.

Background/aim The aim of the present study was to assess the association between PM2.5, its sources, and preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) in a large open residential cohort (Supersito Project in the Emilia-Romagna Region – Northern Italy). Methods We collected 2012–2014 pregnancy and childbirth data from Birth Assistance Certificates and selected the pregnancies of interest. PTBs (gestational age Results The study included 23,708 neonates born to 23,415 women, among whom 1,311 PTB, 424 LBW, and 1,354 SGA occurred. PTB was the only outcome associated with PM2.5 mass (OR 1.03, 95% CI 1.002-1.058 per 1 μg/m3). Traffic, oil combustion and secondary sulfates and organics showed independent effects on PTB. Exposure to secondary nitrates was associated with a lower risk of PTB. There was no association between LBW or SGA and source-specific PM2.5 components or the residual PM2.5 related to all other sources. Conclusion This study found an association between PTB and PM2.5. Traffic, secondary sulfates, and organic and oil combustion were the sources with most consistent association.

"OBJECTIVES: to identify groups of people in relation to the perception of environmental risk and to assess the main characteristics using data collected in the environmental module of the surveillance network Italian Behavioral Risk Factor Surveillance System (PASSI).perceptive profiles were identified using a latent class analysis; later they were included as outcome in multinomial logistic regression models to assess the association between environmental risk perception and demographic, health, socio-economic and behavioural variables.the latent class analysis allowed to split the sample in "worried", "indifferent", and "positive" people. The multinomial logistic regression model showed that the "worried" profile typically includes people of Italian nationality, living in highly urbanized areas, with a high level of education, and with economic difficulties; they pay special attention to their own health and fitness, but they have a negative perception of their own psychophysical state.the application of advanced statistical analysis enable to appraise PASSI data in order to characterize the perception of environmental risk, making the planning of interventions related to risk communication possible. ".

We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long-term (>5years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973-2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose-response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04-1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01-1.77), but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99-4.88), particularly for latencies ≥10years (HR 3.28, 95% CI 1.14-9.43). A competing risks analysis revealed that the clinical impact of radiation-induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose-response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited.

Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 months after metastasectomy is around of 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy for patients who underwent surgical resection of CRC metastases, despite the lower level of evidence (based on the quality of studies in this setting). Actually, up to now there is no standard treatment encoded and the effective role of an adjuvant therapy remains still controversial. The aim of this review is to report the state-of-art about the role of systemic chemotherapy with hepatic arterial infusion (HAI) in the management of patients after resection of metastases from CRC, with literature revision and a meta-analysis of the randomized-controlled trials.