Residential exposure to air pollution and incidence of leukaemia in the industrial area of Viadana, Northern Italy.

BACKGROUND: Exposure to air pollution has been proposed as one of the potential risk factors for leukaemia. Work-related formaldehyde exposure is suspected to cause leukaemia. METHODS: We conducted a nested register-based case-control study on leukaemia incidence in the Viadana district, an industrial area for particleboard production in Northern Italy. We recruited 115 cases and 496 controls, frequency-matched by age, between 1999 and 2014. We assigned estimated exposures to particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and formaldehyde at residential addresses, averaged over the susceptibility window 3rd to 10th year prior to the index date. We considered potential confounding by sex, age, nationality, socio-economic status, occupational exposures to benzene and formaldehyde, and prior cancer diagnoses. RESULTS: There was no association of exposures to PM10, PM2.5, and NO2 with leukaemia incidence. However, an indication of increased risk emerged for formaldehyde, despite wide statistical uncertainty (OR 1.46, 95%CI 0.65-3.25 per IQR-difference of 1.2 µg/m3). Estimated associations for formaldehyde were higher for acute (OR 2.07, 95%CI 0.70-6.12) and myeloid subtypes (OR 1.79, 95%CI 0.64-5.01), and in the 4-km buffer around the industrial facilities (OR 2.78, 95%CI 0.48-16.13), although they remained uncertain. CONCLUSIONS: This was the first study investigating the link between ambient formaldehyde exposure and leukaemia incidence in the general population. The evidence presented suggests an association, although it remains inconclusive, and a potential significance of emissions related to industrial activities in the district. Further research is warranted in larger populations incorporating data on other potential risk factors.

[The role of exposure to airborne pollutants in the workplace on the prevalence and severity of chronic respiratory disease in Italy]. / Il ruolo dell'esposizione a inquinanti aerodispersi nel luogo di lavoro sulla prevalenza e gravità della malattia respiratoria cronica in Italia.

OBJECTIVES: occupational exposure to vapours, gases, dusts and fumes (VGDF) plays an important role in the development and exacerbation of respiratory diseases. The aim of this study is to evaluate the possible association of occupational exposure to airborne pollutants and chronic respiratory diseases. DESIGN: multicase-control study. SETTING AND PARTICIPANTS: cases of chronic respiratory diseases and controls from the Italian multicentric study Gene Environment Interaction in Respiratory Diseases (GEIRD). MAIN OUTCOME MEASURES: the occurrence of rhinitis, asthma, chronic bronchitis/chronic obstructive pulmonary disease (COPD), asthma severity, spirometry data, exhaled nitric oxide (FeNO) were examined in relation to chronic and acute occupational exposures to airborne pollutants using multiple regression models. RESULTS: 2,943 subjects were enrolled in the study. Regularm exposure to VGDF was associated with a higher prevalence of chronic bronchitis/COPD (OR 1.40, 95%CI 0.98-1.99), especially in those also having asthma (OR 1.80, 95%CI 1.14-2.85), a lower prevalence of remittent asthma (OR 0.53, 95%CI 0.29-0.96) and, in those with asthma, an increased activity of the disease (severity score) (OR 1.77, 95%CI 1.20-2.60). No associations were observed between occupational exposure and prevalence of rhinitis, spirometry and FeNO data. Finally, an association was found between acute exposure to airborne pollutants (occupational and non-occupational) and the respiratory diseases investigated, in particular active asthma and asthma associated chronic bronchitis/BPCO. CONCLUSIONS: these data confirm a significant role of occupational exposure to airborne pollutants on respiratory health, underlying the importance of workplace exposure prevention, in particular for more susceptible subjects, as those with respiratory diseases.

Endoscopic Ultrasound-guided Fine-needle Biopsy With or Without Rapid On-site Evaluation for Diagnosis of Solid Pancreatic Lesions: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND AND AIMS: The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE. METHODS: A noninferiority study (noninferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy, and secondary endpoints were safety, tissue core procurement, specimen quality, and sampling procedural time. RESULTS: Eight hundred patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, P = .396). Noninferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1% to 3.1%; noninferiority P < .001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, P = .021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs 11.7 ± 6.0 minutes, P < .0001). CONCLUSIONS: EUS-FNB demonstrated high diagnostic accuracy in evaluating SPLs independently on execution of ROSE. When new-generation FNB needles are used, ROSE should not be routinely recommended. (ClinicalTrial.gov number NCT03322592.).

Ultrastructural and Immunohistochemical Diagnosis of a Neonatal Herpes Simplex Virus Infection Presenting as Fulminant Hepatitis: A Case Report.

TORCH (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes Simplex Virus and Syphilis) infections are a major cause of intrauterine and perinatal infections with associated morbidity and mortality. Neonatal Herpes Simplex Virus infection caused by an enveloped, double-stranded DNA virus of the Herpesviridae family is devastating and fatal. Herpes Viruses are not hepatotropic but may rarely cause hepatitis. Most cases of HSV hepatitis rapidly progress to fulminant hepatic failure and often fatal before the diagnosis or transplantation. Nowadays, despite the availability of antiviral treatment (acyclovir), the outcome remains poor because of late identification of hepatic Herpes Simplex Virus (HSV) infection. We report a male neonate suspected with a metabolic/mitochondrial disease and multi-organ involvement but who developed a fulminant hepatic failure and disseminated coagulopathy secondary to HSV type 1 (HSV-1) infection. The postmortem diagnosis was performed demonstrating HSV-1 in liver tissue by transmission electron microscopy and by retrospective detection of HSV specific antigens by immunohistochemistry.

The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories.

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.

Gastritis and gastroesophageal reflux disease are strongly associated with non-allergic nasal disorders.

BACKGROUND: Gastroesophageal reflux disease (GERD) has been reported to be significantly associated with chronic rhinosinusitis, but the strength of the association is still debated. AIMS: To evaluate the strength of the association between gastritis/GERD and non-allergic rhinitis (NAR)/allergic rhinitis (AR)/sinusitis. METHODS: We investigated 2887 subjects aged 20-84 years, who underwent a clinical visit in seven Italian centres (Ancona, Palermo, Pavia, Terni, Sassari, Torino, Verona) within the study on Gene Environment Interactions in Respiratory Diseases, a population-based multicase-control study between 2008 and 2014. Subjects were asked if they had doctor-diagnosed "gastritis or stomach ulcer (confirmed by gastroscopy)" or "gastroesophageal reflux disease, hiatal hernia or esophagitis". The association between NAR/AR/sinusitis and either gastritis or GERD was evaluated through relative risk ratios (RRR) by multinomial logistic regression. RESULTS: The prevalence of gastritis/GERD increased from subjects without nasal disturbances (22.8% = 323/1414) to subjects with AR (25.8% = 152/590) and further to subjects with NAR (36.7% = 69/188) or sinusitis (39.9% = 276/691). When adjusting for centre, sex, age, education level, BMI, smoking habits and alcohol intake, the combination of gastritis and GERD was associated with a four-fold increase in the risk of NAR (RRR = 3.80, 95% CI 2.56-5.62) and sinusitis (RRR = 3.70, 2.62-5.23) with respect to controls, and with a much smaller increase in the risk of AR (RRR = 1.79, 1.37-2.35).. CONCLUSION: The study confirmed the association between gastritis/GERD and nasal disturbances, which is stronger for NAR and sinusitis than for AR.

Hyperexcitability and Hyperplasticity Disrupt Cerebellar Signal Transfer in the IB2 KO Mouse Model of Autism.

Autism spectrum disorders (ASDs) are pervasive neurodevelopmental conditions that often involve mutations affecting synaptic mechanisms. Recently, the involvement of cerebellum in ASDs has been suggested, but the underlying functional alterations remained obscure. We investigated single-neuron and microcircuit properties in IB2 (Islet Brain-2) KO mice of either sex. The IB2 gene (chr22q13.3 terminal region) deletion occurs in virtually all cases of Phelan-McDermid syndrome, causing autistic symptoms and a severe delay in motor skill acquisition. IB2 KO granule cells showed a larger NMDA receptor-mediated current and enhanced intrinsic excitability, raising the excitatory/inhibitory balance. Furthermore, the spatial organization of granular layer responses to mossy fibers shifted from a "Mexican hat" to a "stovepipe hat" profile, with stronger excitation in the core and weaker inhibition in the surround. Finally, the size and extension of long-term synaptic plasticity were remarkably increased. These results show for the first time that hyperexcitability and hyperplasticity disrupt signal transfer in the granular layer of IB2 KO mice, supporting cerebellar involvement in the pathogenesis of ASD.SIGNIFICANCE STATEMENT This article shows for the first time a complex set of alterations in the cerebellum granular layer of a mouse model [IB2 (Islet Brain-2) KO] of autism spectrum disorders. The IB2 KO in mice mimics the deletion of the corresponding gene in the Phelan-McDermid syndrome in humans. The changes reported here are centered on NMDA receptor hyperactivity, hyperplasticity, and hyperexcitability. These, in turn, increase the excitatory/inhibitory balance and alter the shape of center/surround structures that emerge in the granular layer in response to mossy fiber activity. These results support recent theories suggesting the involvement of cerebellum in autism spectrum disorders.

Randomized trial comparing fork-tip and side-fenestrated needles for EUS-guided fine-needle biopsy of solid pancreatic lesions.

BACKGROUND AND AIMS: The aim of this study was to compare the performance of EUS-guided fine-needle biopsy using fork-tip or side-fenestrated needles in patients with solid pancreatic lesions. METHODS: A randomized controlled study was conducted in a single academic center on patients who underwent sampling with fork-tip or side-fenestrated 22-gauge or 25-gauge needles. Three passes were performed, each independently evaluated by a blinded pathologist and by endosonographers for macroscopic on-site evaluation (MOSE). The primary outcome was histologic yield; secondary aims were safety, diagnostic yield, sample quality, number of needle passes required to establish a diagnosis, and reliability of MOSE. RESULTS: One hundred ninety-two patients were enrolled. Both 22-gauge and 25-gauge fork-tip needles retrieved significantly higher rates of histologic samples than side-fenestrated needles (P < .013). Safety and diagnostic accuracy were comparable in the 2 arms, whereas sample quality (tissue integrity and blood contamination) was significantly better in the fork-tip group (P < .0001). The median number of diagnostic passes was lower using fork-tip needles (P = .054). The agreement between MOSE and pathologic evaluation was almost perfect in the fork-tip group and fair in the side-fenestrated group. CONCLUSIONS: Both needles showed equivalent safety and diagnostic accuracy. However, fork-tip needles provided a higher rate of extremely good-quality histologic samples and required fewer needle passes to reach a diagnosis. MOSE is a highly reliable tool when fork-tip needles are used compared with side-fenestrated needles. (Clinical trial registration number: NCT03622229.).

Long-term follow-up after surgical removal of meningioma of the inner third of the sphenoidal wing: outcome determinants and different strategies.

Meningioma arising in the inner third of the sphenoidal wing has been well recognized since the origin of neurosurgery, yet it still poses a formidable challenge for the surgeon. Treatment strategies can be optimized through a tailored approach to surgical timing and use of a non-surgical armamentarium. The aim of this study was to evaluate the long-term effect of different strategies on progression-free survival and overall survival. We examined the clinical records of brain tumor patients to assess determinants for surgery (extent of tumor removal, postoperative complications) and for progression-free survival and overall survival in relation to timing of surgery eventually followed by stereotactic radiosurgery (SRS). The records of 60 patients were retrospectively reviewed, from preoperative assessment to a median follow-up of 104 months. All were symptomatic with prevalently visual symptoms (42.2%), large tumors (median diameter 3.44 cm), extension into the cavernous sinus (38.3%), and severe vascular involvement of one or more encased or narrowed vessels (50%). Subtotal removal was achieved in 40% of cases, mainly determined by cavernous sinus and vascular involvement; neurological complications occurred in 18.3% (persistent in 6.7% due to oculomotor and vascular injury). The overall rate of symptom improvement was 32.3% at 3 months and 49.5% at 12 months. Radiological monitoring prevented clinical progression; tumor progression occurred in 11.7% of cases. There were significant differences in progression-free survival between patients with (median 46 months) and those without (median 104 months) recurrence (p = 0.002): 12.5% after total removal, 6.2% after subtotal removal and adjuvant SRS, and 28.5% after subtotal removal and observation. The related Kaplan-Meier survival curve showed no significant difference between the three strategies. Further, disease progression after recurrence was noted in 28.6% of cases, but overall survival was not influenced by either tumor recurrence or type of treatment. Treatment failure was recorded in four cases (6.7%): one perioperative death and three later on. Surgery is the mainstay for the treatment of symptomatic meningioma and to restore neurological function; however, resectability is limited by vascular and cavernous sinus involvement. Careful postoperative monitoring prevented clinical progression and adjuvant or adjunctive SRS proved effective in tumor control. A low surgical complication rate and excellent long-term outcomes were achieved with this strategy.

Cerebellar Learning Properties Are Modulated by the CRF Receptor.

Corticotropin-releasing factor (CRF) and its type 1 receptor (CRFR1) play an important role in the responses to stressful challenges. Despite the well established expression of CRFR1 in granular cells (GrCs), its role in procedural motor performance and memory formation remains elusive. To investigate the role of CRFR1 expression in cerebellar GrCs, we used a mouse model depleted of CRFR1 in these cells. We detected changes in the cellular learning mechanisms in GrCs depleted of CRFR1 in that they showed changes in intrinsic excitability and long-term synaptic plasticity. Analysis of cerebella transcriptome obtained from KO and control mice detected prominent alterations in the expression of calcium signaling pathways components. Moreover, male mice depleted of CRFR1 specifically in GrCs showed accelerated Pavlovian associative eye-blink conditioning, but no differences in baseline motor performance, locomotion, or fear and anxiety-related behaviors. Our findings shed light on the interplay between stress-related central mechanisms and cerebellar motor conditioning, highlighting the role of the CRF system in regulating particular forms of cerebellar learning.SIGNIFICANCE STATEMENT Although it is known that the corticotropin-releasing factor type 1 receptor (CRFR1) is highly expressed in the cerebellum, little attention has been given to its role in cerebellar functions in the behaving animal. Moreover, most of the attention was directed at the effect of CRF on Purkinje cells at the cellular level and, to this date, almost no data exist on the role of this stress-related receptor in other cerebellar structures. Here, we explored the behavioral and cellular effect of granular cell-specific ablation of CRFR1 We found a profound effect on learning both at the cellular and behavioral levels without an effect on baseline motor skills.

Hebbian Spike-Timing Dependent Plasticity at the Cerebellar Input Stage.

Spike-timing-dependent plasticity (STDP) is a form of long-term synaptic plasticity exploiting the time relationship between postsynaptic action potentials (APs) and EPSPs. Surprisingly enough, very little was known about STDP in the cerebellum, although it is thought to play a critical role for learning appropriate timing of actions. We speculated that low-frequency oscillations observed in the granular layer may provide a reference for repetitive EPSP/AP phase coupling. Here we show that EPSP-spike pairing at 6 Hz can optimally induce STDP at the mossy fiber-granule cell synapse in rats. Spike timing-dependent long-term potentiation and depression (st-LTP and st-LTD) were confined to a ±25 ms time-window. Because EPSPs led APs in st-LTP while APs led EPSPs in st-LTD, STDP was Hebbian in nature. STDP occurred at 6-10 Hz but vanished >50 Hz or <1 Hz (where only LTP or LTD occurred). STDP disappeared with randomized EPSP/AP pairing or high intracellular Ca2+ buffering, and its sign was inverted by GABA-A receptor activation. Both st-LTP and st-LTD required NMDA receptors, but st-LTP also required reinforcing signals mediated by mGluRs and intracellular calcium stores. Importantly, st-LTP and st-LTD were significantly larger than LTP and LTD obtained by modulating the frequency and duration of mossy fiber bursts, probably because STDP expression involved postsynaptic in addition to presynaptic mechanisms. These results thus show that a Hebbian form of STDP occurs at the cerebellum input stage, providing the substrate for phase-dependent binding of mossy fiber spikes to repetitive theta-frequency cycles of granule cell activity.SIGNIFICANCE STATEMENT Long-term synaptic plasticity is a fundamental property of the brain, causing persistent modifications of neuronal communication thought to provide the cellular basis of learning and memory. The cerebellum is critical for learning the appropriate timing of sensorimotor behaviors, but whether and how appropriate spike patterns could drive long-term synaptic plasticity remained unknown. Here, we show that this can actually occur through a form of spike-timing-dependent plasticity (STDP) at the cerebellar inputs stage. Pairing presynaptic and postsynaptic spikes at 6-10 Hz reliably induced STDP at the mossy fiber-granule cell synapse, with potentiation and depression symmetrically distributed within a ±25 ms time window. Thus, STDP can bind plasticity to the mossy fiber burst phase with high temporal precision.

Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study.

BACKGROUND: It has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk. OBJECTIVE: We studied prospectively whether airway responsiveness is associated with the risk of developing COPD. METHODS: We pooled data from two multicentre cohort studies that collected data from three time points using similar methods (European Community Respiratory Health Survey and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We classified subjects (median age 37 years, 1st-3rd quartiles: 29-44) by their level of airway responsiveness using quintiles of methacholine dose-response slope at the first examination (1991-1994). Then, we excluded subjects with airflow obstruction at the second examination (1999-2003) and analysed incidence of COPD (postbronchodilator FEV1/FVC below the lower limit of normal) at the third examination (2010-2014) as a function of responsiveness, adjusting for sex, age, education, body mass index, history of asthma, smoking, occupational exposures and indicators of airway calibre. RESULTS: We observed 108 new cases of COPD among 4205 subjects during a median time of 9 years. Compared with the least responsive group (incidence rate 0.6 per 1000/year), adjusted incidence rate ratios for COPD ranged from 1.79 (95% CI 0.52 to 6.13) to 8.91 (95% CI 3.67 to 21.66) for increasing airway responsiveness. Similar dose-response associations were observed between smokers and non-smokers, and stronger associations were found among subjects without a history of asthma or asthma-like symptoms. CONCLUSIONS: Our study suggests that increased airway responsiveness is an independent risk factor for COPD. Further research should clarify whether early treatment in patients with high responsiveness can slow down disease progression.

Surgical management of syringomyelia unrelated to Chiari malformation or spinal cord injury.

PURPOSE: Syringomyelia is a misleading disease since the problem always lies elsewhere. Arachnoiditis, because it is radiographically difficult to discern, is an especially insidious cause. To better guide selection from among surgical treatment options for syringomyelia, we reviewed our case series of patients without Chiari malformation or spinal injury. METHODS: Excluding syringomyelia due to Chiari malformation, spinal cord injury, and tumors, 32 patients (mean age 44 years) were operated on between 1995 and 2013 and followed up for a mean of 53.8 months. Presumed causes at diagnosis, clinical and radiological findings, type of operation, clinical and radiological outcome were reviewed. RESULTS: Duration of clinical history varied widely (range 6-164 months). Clinical assessment was based on the McCormick classification (15 independent, 17 dependent). Causes included birth trauma, pyogenic meningitis, tuberculous meningitis, postoperative scarring, dysraphism, and basilar impression. Treatment was local decompression with arachnoid lysis and shunts. Hindbrain-related syringomyelia was differentiated from non hindbrain-related syringomyelia. Hindbrain arachnoiditis was significantly associated with radiological findings at the foramen magnum (p = 0.01) and craniocervical decompression (p < 0.03), with good clinical and radiological outcome at 6 months and later follow-up controls (p = 0.02), whereas uneven results were observed in cases of non-hindbrain arachnoiditis. CONCLUSIONS: To remove the cause of syringomyelia, surgical planning will rely on thorough clinical history and accurate imaging to determine the site of cerebrospinal fluid obstruction. Craniocervical decompression to dissect basal arachnoiditis in the posterior fossa can be recommended in hindbrain syringomyelia. Treatment of non-hindbrain arachnoiditis is more controversial, probably owing to uncertainties about the extent of adhesions.

Hereditary angioedema: current therapeutic management and future approaches.

PURPOSE OF REVIEW: The aim of this review is to provide an account of the focus of therapeutic strategies for hereditary angioedema (HAE), give a brief overview of those used in the past and set aside and toughly discuss those currently available as first line. Further research is ongoing and the future therapeutic approaches that are still in different phases of study will be reviewed as well. RECENT FINDINGS: In the last two decades, major research advancements on HAE pathophysiology and management were made and numerous novel therapeutic options are now available. Compared to the past, drugs available nowadays are more effective, well tolerated, and possibly have a more convenient administration route. Moreover, numerous other drugs with innovative mechanisms of action are under development. SUMMARY: HAE is a rare genetic disease that if not promptly treated, it can lead to death from asphyxiation. Furthermore, due to its disfiguring and painful manifestations, HAE implies an important burden on the quality of life. Recently, following great research progresses on HAE therapy, evidence-based guidelines on HAE management were released. The therapeutic landscape of HAE is still under florid development, and it is possible novel treatments will remarkably revolutionize HAE management in the future.

Mild asthma and chronic bronchitis seem to influence functional exercise capacity: a multi-case control study.

BACKGROUND: In the Genes Environment Interaction in Respiratory Diseases population-based multi-case control study, we investigated whether asthma, chronic bronchitis (CB) and rhinitis were associated with a reduced 6-minute walk distance (6MWD), and whether the 6MWD determinants were similar for subjects with/without respiratory diseases. METHODS: Cases of asthma (n = 360), CB (n = 120), rhinitis (n = 203) and controls (no respiratory diseases: n = 302) were recruited. The variation in the 6MWD across the groups was analyzed by ANCOVA, adjusting for gender, age, height, weight and comorbidity. The 6MWD determinants were studied by linear regression, and heterogeneity across the cases and controls was investigated. RESULTS: The 6MWD differed across cases and controls (p = 0.01). It was shorter for cases of asthma (-17.1, 95% CI -28.3 to -5.8 m) and CB (-20.7, 95% CI: -36.6 to -4.8 m) than for controls (604 ± 68 m on average), but not for cases of rhinitis. The negative association between age and the 6MWD was significant for cases of CB, but not for the other groups (p = 0.001). CONCLUSIONS: Even at the level of severity found in the general population, asthma and CB could influence the 6MWD, which seems to reflect the functional exercise level for daily physical activities. The negative association between ageing and the 6MWD was particularly strong in subjects with CB. Our report adds to the mounting evidence that CB is not a trivial condition, especially in the ageing adult population, and it supports the importance of monitoring functional capacity and of physical reconditioning in mild asthma.

Pleomorphic xanthoastrocytoma: long-term results of surgical treatment and analysis of prognostic factors.

BACKGROUND: Pleomorphic Xanthoastrocytoma (PXA) is a rare brain tumour, most commonly affecting children and young adults. To date, only few data regarding the long-term follow-up of these patients after surgery are available. The aim of this study is to describe our single-institution experience in the surgical management of this particular glioma over a period of over 18 years. METHODS: We performed a retrospective review of all cases of PXA (40 patients) operated upon at the Department of Neurosurgery of Verona, Italy, between 1990 and 2008. The impact of clinical, radiological, surgical and histological factors on overall survival (OS) and progression-free survival (PFS) was analysed by means of univariate and multivariate models. FINDINGS: We achieved a gross total resection (GTR) in 65% of patients. Histological diagnosis was of grade II in 80%; anaplastic features were present in the remaining 20%. Adjuvant treatment, radiotherapy or chemo-radiotherapy, was administered in 40% of the cases. Median follow-up was 74 months. OS at 5- and 10 years was 76.32% and 68.24%, respectively. PFS at 5- and 10 years was 71% and 58%, respectively. In the multivariate model, histological grade, extent of resection and age at diagnosis (≤ 30 years vs > 30 years) were the only independent prognostic factors for both OS and PFS. CONCLUSIONS: Our retrospective long-term study confirms the relatively favourable prognosis associated with PXA. Young patients with a low-grade tumour (WHO grade II) who underwent GTR carry the longest OS and PFS.

Residential exposure to air pollution and adverse respiratory and allergic outcomes in children and adolescents living in a chipboard industrial area of Northern Italy.

BACKGROUND: Chipboard production is a source of wood dust, formaldehyde, and combustion-related pollutants such as nitrogen dioxide (NO2) and particulate matter (PM). In this cohort study, we assessed whether exposures to NO2, formaldehyde, PM10, PM2.5, and black carbon were associated with adverse respiratory and allergic outcomes among all 7525 people aged 0-21 years residing in the Viadana district, an area in Northern Italy including the largest chipboard industrial park in the country. METHODS: Data on hospitalizations, emergency room (ER) admissions, and specialist visits in pneumology, allergology, ophthalmology, and otorhinolaryngology were obtained from the Local Health Unit. Residential air pollution concentrations in 2013 (baseline) were derived using local (Viadana II), national (EPISAT), and continental (ELAPSE) exposure models. Associations were estimated using negative binomial regression models for counts of events occurred during 2013-2017, with follow-up time as an offset term and adjustment for sex, age, nationality, and a census-block socio-economic indicator. RESULTS: Median annual exposures to NO2, PM10, and PM2.5 were below the European Union annual air quality standards (40, 40, and 25 µg/m3) but above the World Health Organization 2021 air quality guideline levels (10, 15, and 5 µg/m3). Exposures to NO2 and PM2.5 were significantly associated with higher rates of ER pneumology admissions (13 to 30 % higher rates per interquartile range exposure differences, all p < 0.01). Higher rates of allergology and ophthalmology visits were found for participants exposed to higher pollutants' concentrations. When considering the 4-km buffer around the industries, associations with respiratory hospitalizations became significant, and associations with ER pneumology admissions, allergology and ophthalmology visits became stronger. Formaldehyde was not associated with the outcomes considered. CONCLUSION: Using administrative indicators of health effects a priori attributable to air pollution, we documented the adverse impact of long-term air pollution exposure in residential areas close to the largest chipboard industries in Italy. These findings, combined with evidence from previous studies, call for an action to improve air quality through preventive measures especially targeting emissions related to the industrial activities.

Long-term residential exposure to air pollution and risk of chronic respiratory diseases in Italy: The BIGEPI study.

Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and summer ozone (O3) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean ± SD exposures were 28.7 ± 6.0 µg/m3 (PM10), 20.1 ± 5.6 µg/m3 (PM2.5), 27.2 ± 9.7 µg/m3 (NO2), and 70.8 ± 4.2 µg/m3 (summer O3). The concentrations of PM10, PM2.5, and NO2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM10: OR 1.62, 95%CI: 1.19-2.20 and PM2.5: OR 1.80, 95%CI: 1.16-2.81, per 10 µg/m3) and between NO2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 µg/m3), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO2, a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD.