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 1999-2014. 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.

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.

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.

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.

[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.

The Association of Self-Reported Birthweight with Lung Function and Respiratory Diseases: Results from a Multi-Centre, Multi-Case Control Study in Italy.

Early life conditions are associated with lung function and the development of respiratory and non-respiratory illnesses. The relationship with birthweight (BW), however, is conflicting. We examined associations of self-reported BW with lung function and the development of respiratory and also non-respiratory diseases within the GEIRD (Gene-Environment Interaction in Respiratory Diseases) project, an Italian multi-centre, multi-case control study involving cases of COPD, asthma, allergic rhinitis and controls. Multinomial logistic regression was performed with case/control status as response variable; BW as main determinant; and adjusting for sex, age and smoking status. Of the 2287 participants reporting BW, 6.4% (n = 147) had low BW (<2500 g), and this proportion was greater in women than men (7.8% vs. 5.1%; p = 0.006). Both men and women with low BW were shorter than those with normal BW (mean ± SD: 160.2 ± 5.5 vs. 162.6 ± 6.5 cm in women, p = 0.009; 172.4 ± 6.1 vs. 174.8 ± 7.2 cm in men, p < 0.001). Although FEV1 and FVC were reduced in individuals with low BW, this was explained by associations with sex and height. In multivariable analysis, BW was not associated with respiratory diseases in adulthood. However, those with low BW had a higher risk of self-reported hospitalisation for lung disease before the age of two (10.3% vs. 4.1%; p < 0.001), severe respiratory infection before the age of five (16.9% vs. 8.8%; p = 0.001) and hypertension in adulthood (29.9% vs. 23.7%; p = 0.001); however, they had a lower risk of arrhythmia (2.7% vs. 5.8%; p = 0.027).

Characterisation of lung function trajectories and associated early-life predictors in an Australian birth cohort study.

Background: There is growing evidence that lung function in early-life predicts later lung function. Adverse events over the lifespan might influence an individual's lung function trajectory, resulting in poor respiratory health. The aim of this study is to identify early-life risk factors and their impact on lung function trajectories to prevent long-term lung impairments. Methods: Our study included participants from the Raine Study, a prospective pregnancy cohort, with at least two spirometry measurements. Lung function trajectories from the 6- to 22-year follow-ups were characterised using finite mixture modelling. Multinomial logistic regression analyses were used to evaluate the association between early-life predictors and lung function trajectories. Main results: A total of 1512 participants (768 males, 744 females), representing 53% of the whole cohort, were included in this analysis. Four lung function trajectories of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC (z-scores) were identified. FEV1 and FVC trajectories were categorised as: "very low", "low", "average" and "above average", respectively. Based on their shape, lung function trajectories of FEV1/FVC were categorised as "very low", "low-average", "average-low" and "average". Asthma and maternal smoking were identified as risk factors for low lung function trajectories in this cohort, as well as early-life exposure to PM2.5Absorbance. Conclusions: Early-life risk factors may influence lung function trajectories over time. Nonetheless, identifying children with a high risk of having low lung function trajectories should be prioritised to prevent deficits in later life.

Weekend Mortality in an Italian Hospital: Immediate versus Delayed Bedside Critical Care Treatment.

BACKGROUND: a number of studies highlighted increased mortality associated with hospital admissions during weekends and holidays, the so-call "weekend effect". In this retrospective study of mortality in an acute care public hospital in Italy between 2009 and 2015, we compared inpatient mortality before and after a major organizational change in 2012. The new model (Model 2) implied that the intensivist was available on call from outside the hospital during nighttime, weekends, and holidays. The previous model (Model 1) ensured the presence of the intensivist coordinating a Medical Emergency Team (MET) inside the hospital 24 h a day, 7 days a week. METHODS: life status at discharge after 9298 and 8223 hospital admissions that occurred during two consecutive periods of 1185 days each (organizational Model 1 and 2), respectively, were classified into "discharged alive", "deceased during nighttime-weekends-holidays" and "deceased during daytime-weekdays". We estimated Relative Risk Ratios (RRR) for the associations between the organizational model and life status at discharge using multinomial logistic regression models adjusted for demographic and case-mix indicators, and timing of admission (nighttime-weekends-holidays vs. daytime-weekdays). RESULTS: there were 802 and 840 deaths under Models 1 and 2, respectively. Total mortality was higher for hospital admissions under Model 2 compared to Model 1. Model 2 was associated with a significantly higher risk of death during nighttime-weekends-holidays (IRR: 1.38, 95% CI 1.20-1.59) compared to daytime-weekdays (RRR: 1.12, 95% CI 0.97-1.31) (p = 0.04). Respiratory diagnoses, in particular, acute and chronic respiratory failure (ICD 9 codes 510-519) were the leading causes of the mortality excess under Model 2. CONCLUSIONS: our data suggest that the immediate availability of an intensivist coordinating a MET 24 h, 7 days a week can result in a better prognosis of in-hospital emergencies compared to delayed consultation.

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.

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.).

The use of Grauer classification in the management of type II odontoid fracture in elderly: Prognostic factors and outcome analysis in a single centre patient series.

OBJECTIVE: To evaluate the results of Type II odontoid fractures management in the elderly, according to the Grauer classification. METHODS: Consecutive patients with type II odontoid fracture, age > 65 years and follow-up longer than 3 months were included. Fracture management was proposed according to Grauer classification. Peri-surgical risk factors, NDI, VAS and rate of fusion were evaluated according to the treatment modality and compared between conservative and surgical groups. RESULTS: Thirty-four patients were considered eligible for the study; 2 patients showed a Type IIa fracture, 30 patients a type IIb, and 2 patients a type IIc. Type IIa patients underwent conservative treatment that resulted in failure. A conservative management was adopted in 9 cases with type IIb due to patient preference or anaesthesiologic reasons with a treatment success at 6 months of 11%. Trans-odontoid stabilization was adopted in 21 type IIb cases with an evidence of bony or fibrous union at 6 months of 95% and a median NDI of 20%. A posterior approach was reserved for 2 type IIc fracture patients and in 6 cases as rescue surgery (bony union at 6 months of 100%; median NDI 37%). Higher Lakshmanan grade, gap and displacement of the fracture were found as significant risk factor for fracture non-union (p < 0.05). CONCLUSIONS: The surgical group presented better clinical and radiological outcome and the anterior approach proved to achieve the best results in type IIb fractures. The presence of osteoporosis and fracture spatial features should be duly considered in the decision-making process.

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.

Stellate cell computational modeling predicts signal filtering in the molecular layer circuit of cerebellum.

The functional properties of cerebellar stellate cells and the way they regulate molecular layer activity are still unclear. We have measured stellate cells electroresponsiveness and their activation by parallel fiber bursts. Stellate cells showed intrinsic pacemaking, along with characteristic responses to depolarization and hyperpolarization, and showed a marked short-term facilitation during repetitive parallel fiber transmission. Spikes were emitted after a lag and only at high frequency, making stellate cells to operate as delay-high-pass filters. A detailed computational model summarizing these physiological properties allowed to explore different functional configurations of the parallel fiber-stellate cell-Purkinje cell circuit. Simulations showed that, following parallel fiber stimulation, Purkinje cells almost linearly increased their response with input frequency, but such an increase was inhibited by stellate cells, which leveled the Purkinje cell gain curve to its 4 Hz value. When reciprocal inhibitory connections between stellate cells were activated, the control of stellate cells over Purkinje cell discharge was maintained only at very high frequencies. These simulations thus predict a new role for stellate cells, which could endow the molecular layer with low-pass and band-pass filtering properties regulating Purkinje cell gain and, along with this, also burst delay and the burst-pause responses pattern.

Spatial variability of nitrogen dioxide and formaldehyde and residential exposure of children in the industrial area of Viadana, Northern Italy.

Chipboard production is a source of ambient air pollution. We assessed the spatial variability of outdoor pollutants and residential exposure of children living in proximity to the largest chipboard industry in Italy and evaluated the reliability of exposure estimates obtained from a number of available models. We obtained passive sampling data on NO2 and formaldehyde collected by the Environmental Protection Agency of Lombardy region at 25 sites in the municipality of Viadana during 10 weeks (2017-2018) and compared NO2 measurements with average weekly concentrations from continuous monitors. We compared interpolated NO2 and formaldehyde surfaces with previous maps for 2010. We assessed the relationship between residential proximity to the industry and pollutant exposures assigned using these maps, as well as other available countrywide/continental models based on routine data on NO2, PM10, and PM2.5. The correlation between NO2 concentrations from continuous and passive sampling was high (Pearson's r = 0.89), although passive sampling underestimated NO2 especially during winter. For both 2010 and 2017-2018, we observed higher NO2 and formaldehyde concentrations in the south of Viadana, with hot-spots in proximity to the industry. PM10 and PM2.5 exposures were higher for children at < 1 km compared to the children living at > 3.5 km to the industry, whereas NO2 exposure was higher at 1-1.7 km to the industry. Road and population densities were also higher close to the industry. Findings from a variety of exposure models suggest that children living in proximity to the chipboard industry in Viadana are more exposed to air pollution and that exposure gradients are relatively stable over time.

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.

Effects of Respiratory Disorders on Smoking Cessation and Re-Initiation in an Italian Cohort Study.

The present study aims to prospectively assess the influence of respiratory disorders on smoking cessation and re-initiation. Three population-based Italian cohorts answered a questionnaire on respiratory health and smoking habits during 1998-2001 and after a mean follow-up (SD) of 9.1 (0.8) years. Out of 1874 current smokers and 1166 ex-smokers at baseline, 965 (51.5%) and 735 (63.0%) reported their smoking status at follow-up. From current smokers, 312 had stopped smoking at follow-up, while 86 ex-smokers had resumed smoking. People reporting asthma at baseline were more likely to stop smoking than the other subjects (48.6% vs. 31.7%), while people reporting allergic rhinitis or chronic cough/phlegm had a higher probability to resume smoking (16.7% vs. 10.5% and 20.7% vs. 10.4%, respectively). In the multivariable logistic model, smoking relapse strongly decreased with increasing abstinence duration in people without chronic cough/phlegm (OR for ≥7.5 years vs. <7.5 years = 0.23, 95% CI 0.20-0.27), while no effect was detected in people with chronic cough/phlegm (p for interaction = 0.039). Smoking cessation was enhanced in asthmatic subjects, while people with allergic rhinitis or chronic cough/phlegm were at higher risk to resume smoking. Chronic cough/phlegm blunted the decrease in smoking resumption associated with longer abstinence duration.

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.).

Autochthonous Cases of Mucosal Leishmaniasis in Northeastern Italy: Clinical Management and Novel Treatment Approaches.

Mucosal leishmaniasis (ML) is a rare clinical variant of tegumentary leishmaniasis in Mediterranean Europe. Here we report on three autochthonous cases of head and neck ML in patients living in Northeastern Italy. Patients presented with non-specific, long-standing symptoms of upper respiratory tract involvement, mimicking other diseases. Parasitological diagnosis was reached by histopathology, immunohistochemistry and molecular biology on tissue specimens. Leishmania infantum was identified by molecular typing in all three cases. All patients reached a complete remission with protracted multivalent antileishmanial drugs; in one case, a novel approach of combined medical and endoscopic surgical treatment was carried out. High clinical suspicion led to a prompt diagnosis and deployment of a multivalent treatment. ML should be considered in the differential diagnosis of nasal, oral, and pharyngolaryngeal lesions in endemic areas. A prompt diagnosis is mandatory to establish a correct management; different antileishmanial medications as well as endoscopic surgical options may be required to reach a complete remission.