Asthma, COPD, Respiratory, and Allergic Health Effects in an Adult Population Living near an Italian Refinery: A Cross-Sectional Study.

BACKGROUND AND AIM: Asthma and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality worldwide. Globally, 545 million people suffer from chronic respiratory diseases with a wide geographical variability. Risk factors for asthma are both genetic and related to several environmental factors (internal and external pollutants); these also have an important role in the occurrence of COPD. The aim of this study was to describe the prevalence of asthma, COPD, and asthma/COPD overlap (ACO) in an adult population living in two municipalities located in the Po Valley. METHODS: A standardized questionnaire on respiratory symptoms and sociodemographic characteristics was self-administered to a random sample of the adult population aged 20-64 years, living near a refinery in Northern Italy during the period between 2016 and 2019. Logistic and multinomial regression were implemented to explore factors associated with asthma, COPD, and ACO. RESULTS: In total, 1108 subjects filled out the questionnaire, the mean age was 48.02 ± 12.34 years (range 21-68), and 53% of the respondents/participants were female. Half of the responders were non-smokers, but the frequency of current and former smokers was significantly greater in men than in women (p < 0.001). The likelihood of being a probable case of asthma decreased with increasing age and increased for smokers. Tobacco smoke was associated with the presence of COPD and ACO. CONCLUSION: Respiratory diseases such as asthma and COPD are common in the general population, with differences among countries worldwide. Our findings show, on the basis of the main confirmed risk factor, namely smoking, that it is useful to plan target programs and actions in order to reduce smoking, thus improving the quality of life in public health.

Health status of petrochemical workers: a narrative review.

SUMMARY: Professional exposure to benzene has been extensively investigated by occupational medicine, leading to strict regulation of exposure threshold values. However, the petrochemical industry utilizes many chemical substances, whose exposure, without effective control and mitigation actions, could influence the health status over time. The aim of this narrative review is to describe health status of petrochemical workers related to occupational exposures, inquiring literature from 1980 to present. We used the PubMed and Web of Science search engines. As regards non-neoplastic diseases, despite heterogeneous prevalence estimates, we could say that standardized mortality rate (SMR) for hypertension, hypercholesterolemia and diabetes does not increase overall, compared to reference populations; a possible explanation may be the "healthy worker effect". Attention should be paid to color disperception and respiratory symptoms, due to toxic or irritating substances exposure. Studies concerning neoplastic pathology have mainly investigated mortality outcomes, finding no increase in cancer, except for melanoma or other skin cancers and leukemia. As regards the former, however, it is not excluded that other risk factors may contribute (e.g. UV rays in offshore workers), while for leukemia, only the most recent studies have analyzed various subtypes of hematopoietic tumors, highlighting a possible risk for the development of myelodysplastic syndrome. The risk of pleural mesothelioma was also increased, likely due to asbestos exposures, while the risk of death from prostate cancer remains controversial.

Multicentre study on resection margins in carcinoma of the oral cavity, oro-hypopharynx and larynx.

Objective: The prognostic significance of the resection margins is still subject of conflicting opinions. The purpose of this paper is to report the results of a study on the margins in carcinoma of the oral cavity, oro-hypopharynx and larynx. Methods: A multicentre prospective study was carried out between 2015 and 2018 with the participation of 10 Italian reference hospitals. The primary objective was to evaluate local control in patients with well-defined clinical characteristics and comprehensive histopathological information. Results: During the study period, 455 patients were enrolled; the minimum follow-up was 2 years. Previous treatment, grading and fresh specimen examination were identified as risk factors for local control in multivariate analysis. On the basis of these results, it seems possible to delineate "risk profiles" for different oncological outcomes. Discussion: The prognostic significance of the margins is reduced, and other risk factors emerge, which require diversified treatment and follow-up. Conclusions: Multidisciplinary treatment with adjuvant therapy, if indicated, reduces the prognostic importance of margins. Collaboration with a pathologist is an additional favourable prognostic factor and quality indicator.An appendix with literature review is present in the online version.

Effects of the COVID-19 Pandemic on Job Activity, Dietary Behaviours and Physical Activity Habits of University Population of Naples, Federico II-Italy.

Coronaviruses (CoVs) are a large family of respiratory viruses that can cause mild to moderate illness. The new variant COVID-19 has started to spread rapidly since December 2019, posing a new threat to global health. To counter the spread of the virus, the Italian government forced the population to close all activities starting from 9 March 2020 to 4 May 2020. In this scenario, we conducted a cross-sectional study on a heterogeneous sample (average age of 28 ± 12 years, 62.6% females) of the University of Naples Federico II (Italy). The aim of the study was to describe the lifestyle change in the university population during quarantine for the COVID 19 pandemic. Participants compiled an online survey consisting of 3 sections: socio-demographic data, dietary behaviours, physical activity habits and psychological aspects. The different results by gender are: 90.8% of females continued to work from home (81.9% were students); 34.8% increased their physical activity; and, only 0.8% prefer ready meals. Whereas, the same percentage of men continued to work from home (90%), but only 72.1% were students (p < 0.001 vs. females), only 23.9% increased physical activity (p < 0.001) and 1.7% favous ready meals. Our data shows that the male population was more affected by isolation and quarantine reporting more unfavourable behavioural changes.

Unraveling a new player in multiple sclerosis pathogenesis: The RNA-binding protein HuR.

BACKGROUND: ELAV-like proteins are a small family of RNA-binding proteins that are fundamental players in post-transcriptional mechanisms and are involved in the pathogenesis of neurologic and psychiatric disorders. HuR, the ubiquitously expressed member of the family, is also implicated in sustaining inflammation and inflammatory diseases, supporting the production of pro-inflammatory cytokines. Inflammation plays a central role in Multiple Sclerosis (MS), which represents the most common cause of permanent physical disability in young adults. MS is a chronic autoimmune disease affecting the Central Nervous System, with a complex aetiology involving genetic, environmental and epigenetic factors. No data are available on the potential entanglement of HuR in MS pathogenesis in patients. In the present work, we aimed at exploring HuR protein levels in peripheral blood mononuclear cells (PBMCs) from MS patients, compared to healthy controls. To further elucidate the possible involvement of HuR in MS, we also investigated the relationship between this specific RNA-binding protein and HSP70-2 protein, also considering the HSP70-2 rs1061581 polymorphism, given that HSP70-2 mRNA has been reported as a HuR target and this specific polymorphism to be associated with MS risk. METHODS: Alleles and genotypes for HSP70-2 rs1061581 polymorphism were assessed, by using a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism, followed by digestion with restriction enzyme, in MS patients and healthy controls. PBMCs from a subgroup of patients and controls were used to evaluate HuR and HSP70-2 protein content by Western blot. RESULTS: PBMCs from 52 MS patients had a lower HuR and higher HSP70-2 protein content compared to 43 healthy controls. An increase of 100 units of HuR significantly decreased the risk of developing MS by 9.8% (OR: 0.902, 95% CI: 0.83-0.98), controlling for HSP70-2 protein expression, HSP70-2 rs1061581 genotype, age and sex. Moreover, holding HuR levels, an increase of 100 units of HSP70-2 protein significantly increased the MS risk by 18.1% (OR: 1.181, 95% CI: 1.03-1.36) and the genetic susceptibility of developing MS for HSP70-2 rs1061581 GG carriers is confirmed. Of interest, MS patients with a moderate to severe form of MS (MSSS ≥ 3) showed a trend towards a reduction of HuR protein levels compared to patients with mild disease severity (MSSS < 3). CONCLUSIONS: HuR protein levels are reduced in MS patients compared to healthy subjects, and the protein amount may continue to decline with disease progression, suggesting a putative role of this RNA-binding protein. Moreover, our results suggest that MS pathology may have disrupted the link between HuR and its target transcript HSP70-2. It will be important to further explore the exact role of HuR in MS, considering the complex interplay with other RNA-binding factors and target mRNAs.

Effect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography.

BACKGROUND: Few studies, and with conflicting results, have evaluated the potential effects of iodinated contrast media on children's thyroid function. OBJECTIVE: To investigate the effects of iodinated contrast medium on thyroid function in neonates, infants and young children with congenital heart disease undergoing cardiac computed tomography (CT). MATERIALS AND METHODS: We retrospectively evaluated 10 neonates (group 1) and 23 infants and young children (group 2) without thyroid or renal disease for serum levels of thyroid-stimulating hormone, free triiodothyronine and free thyroxine before contrast-enhanced cardiac CT, 48 h after CT and at discharge from the hospital. Cardiac CT was performed with intravenous administration of 1.14±0.17 mL/kg of body weight of iopromide (containing 370 mg of iodine/mL). RESULTS: Group 1 had a reduction of thyroid-stimulating hormone from baseline to 48 h post injection (P=0.002). Group 2 had a reduction of thyroid-stimulating hormone median levels from baseline to 48 h post injection and an increase from 48 h to discharge (P=0.0005 and P=0.0001, respectively). CONCLUSION: Intravenous iodinated contrast medium in children with congenital heart disease caused transient thyroid-stimulating hormone decrease 48 h after CT, with thyroid-stimulating hormone returning to normal range at discharge.

Fluorescein-Guided Surgery for Resection of High-Grade Gliomas: A Multicentric Prospective Phase II Study (FLUOGLIO).

Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood-brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported.Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18).Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm3 (range, 1.3-87.8 cm3). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%.Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs. Clin Cancer Res; 24(1); 52-61. ©2017 AACR.

A propensity score analysis for comparison of T-3b and VATET in myasthenia gravis.

OBJECTIVE: We performed propensity score (PS) models to compare the outcome of patients with myasthenia gravis (MG) submitted to 2 different surgical approaches: extended transsternal (T-3b) or thoracoscopic extended thymectomy (VATET). METHODS: Patients' clinical data were retrieved from the MG database of the C. Besta Neurologic Institute Foundation. In the PS analysis, a matching ratio of 1:1 of the main clinical variables was obtained for the 2 groups of patients and treatment effect was estimated by comparing their outcome. RESULTS: A total of 210 patients met the inclusion criteria, by having a complete set of clinical data, and were included in the PS model; a matched dataset of 122 participants (61 per group) showed an adequate balance of all the covariates. Our analysis demonstrated that 68.9% of patients who had thymectomy by the VATET technique reached the pharmacologic remission/remission status at 2 years from thymectomy compared to 34.4% of those operated on by the T-3b technique (p < 0.001), had a lower INCB-MG score (p < 0.001), and had less muscle fatigability (p = 0.004). Similar results were found considering only nonthymomatous patients with MG. Results were also confirmed by paired statistical tests. CONCLUSIONS: Our PS matching analysis showed that VATET is a reliable and effective surgical approach alternative to T-3b in patients with MG who are candidates for thymectomy. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with MG, VATET is more effective than T-3b thymectomy.

Validation of the Besta Neurological Institute rating scale for myasthenia gravis.

INTRODUCTION: We validated the scale for myasthenia gravis (MG) developed at the Neurological Institute Foundation of Milan (INCB-MG scale). METHODS: A total of 174 patients were evaluated with the INCB-MG and compared with the MG Composite (MGC) as the gold standard. Dimensionality, reliability, and validity of the INCB-MG scale were studied by principal component factor analysis, Cronbach alpha, and Pearson correlation coefficients; interobserver reliability was calculated by the weighted Cohen K coefficient. RESULTS: Generalized and bulbar INCB-MG subscales were unidimensional with excellent consistency; the INCB-MG and MGC scales were strongly correlated. Fatigability assessment was correlated with the INCB-MG generalized, bulbar, and respiratory subscales. CONCLUSIONS: The INCB-MG scale is a reliable tool to assess MG and is strongly correlated with the MGC. The INCB-MG scale is a valid tool for every day practice and should be further investigated for its application in clinical trials.

Environmental factors and multiple sclerosis severity: a descriptive study.

Growing evidence suggests that environmental factors play a key role in the onset of multiple sclerosis (MS). This study was conducted to examine whether environmental factors may also be associated with the evolution of the disease. We collected data on smoking habits, sunlight exposure and diet (particularly consumption of vitamin D-rich foods) from a sample of 131 MS patients. We also measured their serum vitamin D concentration. The clinical impact of MS was quantified using the Multiple Sclerosis Severity Score (MSSS); MS was considered "severe" in patients with MSSS ≥ 6, and "mild" in patients with MSSS ≤ 1. The results showed a strong association between serum vitamin D concentration and both sunlight exposure (26.4 ± 11.9 ng/mL vs. 16.5 ± 12.1 ng/mL, p = 0.0004) and a fish-rich diet (23.5 ± 12.1 ng/mL vs. 16.1 ± 12.4 ng/mL, p = 0.005). Patients reporting frequent sunlight exposure had a lower MSSS (2.6 ± 2.4 h vs. 4.6 ± 2.6 h, p < 0.001). The mild MS patients reported much more frequent sunlight exposure (75% mild MS vs. 25% severe MS p = 0.004, Chi square test). A higher serum vitamin D concentration determined a lower risk of developing severe MS, adjusted for sunlight exposure (OR = 0.92 for one unit increase in vitamin D, 95% CI: 0.86-0.97, p = 0.005). A stronger inverse association emerged between frequent sunlight exposure and the risk of severe MS (OR = 0.26, 95% CI: 0.09-0.71, p = 0.009). Our data show that an appropriate diet and adequate expose to sunlight are associated with less aggressive MS.

Postinfectious neurologic syndromes: a prospective cohort study.

OBJECTIVES: Postinfectious neurologic syndromes (PINSs) of the CNS include heterogeneous disorders, sometimes relapsing. In this study, we aimed to a) describe the spectrum of PINSs; b) define predictors of outcome in PINSs; and c) assess the clinical/paraclinical features that help differentiate PINSs from multiple sclerosis (MS). METHODS: In this prospective cohort study, adult inpatients with PINSs underwent extensive diagnostic assessment and therapeutic protocols at inclusion and during a minimum 2-year follow-up. We compared them with newly diagnosed, treatment-naive patients with MS, also prospectively recruited. RESULTS: The study sample comprised 176 patients with PINSs aged 59.9 ± 17.25 years (range: 18-80 years) divided into 2 groups: group 1 (CNS syndromes, 64%)-encephalitis, encephalomyelitis, or myelitis; and group 2 (CNS + peripheral nervous system [PNS] syndromes, 36%)-encephalomyeloradiculoneuritis or myeloradiculoneuritis. We observed the patients for 24 to 170 months (median 69 months). Relapses, almost invariably involving the spinal cord, occurred in 30.5%. PNS involvement was an independent risk factor for relapses (hazard ratio 2.8). The outcome was poor in 43% of patients; risk factors included older age, greater neurologic disability at onset, higher serum-CSF albumin percentage transfer, myelitis, and PNS involvement. Steroid resistance occurred in 30% of the patients, half of whom responded favorably to IV immunoglobulins. Compared with MS, PINSs were characterized by older age, lower tendency to relapse, and distinct CSF findings. CONCLUSIONS: The category of PINSs should be revised: most of the clinical variants have a poor prognosis and are not readily classifiable on the basis of current knowledge. PNS involvement has a critical role in relapses, which seem to affect the spine only.

Complete stable remission and autoantibody specificity in myasthenia gravis.

OBJECTIVES: Patients with myasthenia gravis (MG) are subgrouped as acetylcholine receptor (AChR)-positive, muscle-specific kinase (MuSK)-positive, and AChR/MuSK-negative MG (or double negative [DN]) on the basis of autoantibody assay. We investigated the relationships between autoantibody specificity, main clinical features, and outcome of the disease, in particular the occurrence of complete stable remission (CSR), by means of a retrospective study on a cohort of 677 Italian patients with MG. METHODS: A total of 517 (76%) patients with AChR-positive MG, 55 (8%) patients with MuSK-positive MG, and 105 (16%) patients with DN MG were included in the study. Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate associations between baseline characteristics, antibody specificity, and CSR. RESULTS: Clinical stage at onset and at maximal worsening was more severe for MuSK-positive patients: bulbar impairment at maximal worsening was found in 83.6% of MuSK-positive patients compared with 58.6% of AChR-positive patients and 43.8% of DN patients (p < 0.001). Baseline characteristics of AChR-positive and DN patients were similar. CSR was observed in 3.6% of MuSK-positive patients compared with 22.2% of AChR-positive and 21.9% of DN patients. In the whole MG cohort, onset before age 40 (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.27-3.02, p = 0.002) and ocular and generalized clinical stages at maximal worsening were associated with CSR (ocular, HR = 8.05, 95% CI 1.88-34.53, p = 0.005; generalized, HR = 3.71, 95% CI 1.16-11.90, p = 0.023; bulbar, HR = 3.16, 95% CI 1.00-10.05, p = 0.051). CONCLUSIONS: MuSK antibodies identify a clinically distinguishable, more severe form of MG since the disease onset, with a lower occurrence of CSR. These features should be considered by the clinician in the management of this particular form of MG.

[Multiple sclerosis and occupational exposures: results of an explorative study]. / Sclerosi multipla e esposizioni occupazionali: risultati di uno studio preliminare.

OBJECTIVES: The aim of the study is to explore possible relationships between occupational exposures and Multiple Sclerosis (MS), whose etiology is not well defined yet. To date, only few literature data are available on this subject. METHODS: We carried out a case-control study, where cases were MS patients included in the MS Register of the Province of Pavia, Northern Italy, and controls, 1:4 matched by sex and age (5 years classes), were randomly selected from the National Health Service population files. The occupational histories were obtained from Italian Institute for Social Security (INPS) archives by automatic linkage using Italian Occupational Cancer Monitoring (OCCAM) method that estimates the risk of specific occupational cancers, by geographic area and industrial sector. OR adjusted for sex and age and corresponding 90% confidence intervals were used to estimate the association between exposure and disease. RESULTS: We included in the study 227 MS patients (130 (57.3%) female, 97 (42.7%) male) and 907 controls (514 (56.7%) female, 393 (43.3%) male). Our results suggest an increased risk for men in mechanical manufacturing industry (OR 1.71, 90% CI 1.03-2.85) and agriculture (OR 2.47, 90% CI 1.03-5.91). Women show an increased risk in mechanical manufacturing industry (OR 2.05, 90% CI 1.22-3.45), agriculture (OR 2.57, 90% CI 1.09-6.09) and leather/shoe industry (OR 2.34, 90% CI 1.06-5.20). CONCLUSIONS: Our preliminary findings indicate that solvent exposures could be related to the risk of MS, as both shoe/leather workers and mechanical manufacturing industry workers are exposed to organic solvents. Interestingly, a major risk of MS was also found among workers engaged in agriculture, suggesting a role of pesticides, whose neurotoxic effect is well known.

Epidemiology and geographical variation of myasthenia gravis in the province of Pavia, Italy.

BACKGROUND AND AIMS: Previous studies have reported a prevalence estimate of myasthenia gravis (MG) from 7.7 to 11.1 per 100,000 inhabitants in Europe. Moreover, the study of the geographical distribution of MG should be useful to generate specific hypotheses. The aims are to estimate MG prevalence and to investigate its geographical variation in a delimited area in Northern Italy. METHODS: The primary source of data was the MG database of the Neurological Institute of Pavia and all other sources of case collection in and outside the province. We adopted a Bayesian approach to analyze MG geographical variation within the finest geographical grid. RESULTS: We identified 119 live MG prevalent cases resident in the province of Pavia on December 31, 2008. The overall crude prevalence was 24 per 100,000 inhabitants. The Bayesian analysis identified a small cluster of higher MG prevalence in the northern area of the province. CONCLUSIONS: The estimated MG prevalence sets the province of Pavia among the high-risk areas. The identification of high/low MG risk areas deserves further investigation of genetic and environmental factors possibly related to a major risk of the disease in that area.

Melanoma in multiple sclerosis treated with natalizumab: causal association or coincidence?

We report a relapsing-remitting multiple sclerosis patient who received monthly intravenous natalizumab. After the fifth dose, the patient had a change in a long-standing mole. Ten months later, the mole became ulcerative and was ablated. Histological examination identified a spreading melanoma reaching the lower dermis (Clark level IV). Considering that at the moment the incidence of melanoma is estimable as about 5 per 100,000 multiple sclerosis person-years treated with natalizumab, and that, in the general population, the incidence of melanoma per 100,000 person-years is more than 10, we may speculate that the occurrence of melanoma during natalizumab treatment in multiple sclerosis is purely a coincidence.