Fine particulate matter and sleep-disordered breathing severity in a large Italian cohort.

BACKGROUND: Air pollution and obstructive sleep apnea (OSA) are both linked with cardiovascular co-morbidities and share similar pathophysiological mechanisms. A causal association between the two has been postulated. However, the results of the studies on this topic are conflicting mainly because of the lack of adjustment for important confounders such as seasonality and temperature. We aimed to evaluate if such an association exists in a highly polluted area like Lombardy region (Italy) when accounting for all confounders. METHODS: Data of adult patients seen at the Sleep Disorder Centre in Milan from 2010 to 2020 were analysed and the main polygraphic data were retrieved. Air pollutant concentrations of the following pollutants NO2, O3, PM2.5, and PM10 were collected through monitoring stations. RESULTS: A total of 3493 patients were included: males (2358, 67.5%) mean age 60.1 (SD = 14.3) years, BMI 29.2 (6.2) kg/m2, mean AHI 16.5 (18.1) events/h. After adjusting for all confounders, in the multivariable analysis, the only associations that remained significant were long-term exposure to O3 with indexes of OSA severity (AHI and ODI) but only in spring. Furthermore, a positive association was seen between long-term exposure to PM10 and ODI but in springtime only. CONCLUSION: The findings of the current study does not support an association between fine particulate matter and OSA severity.

Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Combined pre- and post-capillary pulmonary hypertension in left heart disease.

Patients with heart failure (HF) often have pulmonary hypertension (PH), which is mainly post-capillary; however, some of them also develop a pre-capillary component. The exact mechanisms leading to combined pre- and post-capillary PH are not yet clear, but the phenomenon seems to start from a passive transmission of increased pressure from the left heart to the lungs, and then continues with the remodeling of both the alveolar and vascular components through different pathways. More importantly, it is not yet clear which patients are predisposed to develop the disease. These patients have some characteristics similar to those with idiopathic pulmonary arterial hypertension (e.g., young age and frequent incidence in female gender), but they share cardiovascular risk factors with patients with HF (e.g., obesity and diabetes), with both reduced and preserved ejection fraction. Thanks to echocardiography parameters and newly introduced scores, more tools are available to distinguish between idiopathic pulmonary arterial hypertension and combined PH and to guide patients' management. It may be hypothesized to treat patients in whom the pre-capillary component is predominant with specific therapies such as those for idiopathic pulmonary arterial hypertension; however, no adequately powered trials of PH-specific treatment are available in combined PH. Early evidence of clinical benefit has been proven in some trials on phosphodiesterase type 5 inhibitors, while data on prostacyclin analogues, endothelin-1 receptor antagonists, and soluble guanylate cyclase stimulators are still controversial.

Allergic rhinitis and COVID-19: friends or foes?

Summary: Allergic rhinitis (AR) is a common disease affecting up to 40% of the general population worldwide. In the Coronavirus 2019 (COVID-19) pandemic era, many observational studies analysing the effect of asthma and chronic obstructive pulmonary disease on the risk of developing COVID-19 were conducted, while data on AR are limited.In this paper, we review the risk of developing SARS-Cov-2 infection carried by AR patients, the outcomes of those with COVID-19 disease, and the COVID-19 influence on the allergic and nasal symptoms and the psychological status of AR patients, in both adult and paediatric populations.AR patients seem to be protected from COVID 19 infection. Even if data about the influence of AR on the severity of COVID-19 disease are still not conclusive, it seems that being an AR patient does not increase the risk of poor COVID-19 prognoses. The clinical manifestation of AR can be distinguished by COVID-19 symptoms. Treating AR adequately is also strongly recommended, especially during pandemic.

Thyroid hormones modulate irisin concentrations in patients with recently onset hypothyroidism following total thyroidectomy.

PURPOSE: Irisin is a newly discovered adipo-myokine known for having significant effects on body metabolism. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This study was designed to evaluate the influential role of levothyroxine replacement therapy on circulating levels of irisin in patients with recently onset hypothyroidism following total thyroidectomy. METHODS: Circulating levels of thyroid hormones, irisin and other metabolic parameters, were assessed in 40 recently thyroidectomized patients (34 females, mean age 50.1 ± 15.2 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine. RESULTS: At baseline, circulating levels of thyroid hormones were indicative of hypothyroidism (TSH 12.7 ± 5.0 µU/mL, FT3 1.9 ± 0.7 pg/mL, FT4 8.7 ± 3.6 pg/mL). Mean serum irisin concentrations significantly increased after 2 months under replacement therapy with levothyroxine (from 2.2 ± 0.6 to 2.9 ± 0.6 µg/mL, p < 0.0001). Variations of circulating levels of irisin under levothyroxine replacement therapy were directly correlated with those of FT3 (Rho = 0.454, p = 0.0033) and FT4 (Rho = 0.451, p = 0.0035). Multivariate regression analysis revealed that changes in thyroid hormones concentrations explained up to 10% of the variations of serum irisin levels under levothyroxine replacement therapy (FT3 R2 = 0.098, FT4 R2 = 0.103). CONCLUSION: Our study suggests that levothyroxine replacement therapy mildly influences irisin metabolism in patients with recently onset hypothyroidism following total thyroidectomy.

Use of complementary medicine among patients with allergic rhinitis: an Italian nationwide survey.

BACKGROUND: A growing use of complementary alternative medicine (CAM) has been found in Europe as well in Italy for chronic diseases, including the allergic rhinitis. The study aims at investigating the prevalence and the pattern of use of CAM amongst patient with allergic rhinitis. METHODS: A 12-item questionnaire was developed by a panel of experts and administered to patients with moderate/severe allergic rhinitis consecutively referring during the study time-frame to seven allergy clinics placed all around Italy. The items covered several topics including reason for choosing CAM, its clinical efficacy, schedule of treatment, costs, type of therapy. RESULTS: Overall 359 questionnaires were analysed. 20% of patients declared CAM use. A significant correlation between the use of CAM and female sex (p < 0.01) and with a higher level of education (p < 0.01) was observed. CAM users were adults (36% in the range between 20 and 40 years and 32% between 41 and 60 years). Youngsters (< 20 years) (7%) and elderly (> 60) (25%) less frequently used CAM.The most used type of CAM was homoeopathy (77% of patients). 60% of users would recommend CAM despite a poor clinical efficacy according to 67% of them. CONCLUSIONS: Although no evidence supports CAM efficacy and safety, the number of patients who relies on it is not negligible. As allergic rhinitis is not a trivial disease, the use of CAM as the only treatment for it should be discouraged at any level, but by general practitioner and specialist in particular.

Migrants and allergy: a new view of the atopic march.

Summary: Atopy is the result of the influence of environmental factors on genetically predisposed individuals. Migration flows represent an interesting model to study the possible reciprocal roles of genes and environment. In this review the following issues influencing the development of allergic sensitization and/or atopic disorders in migrants will be rooted out: 1) ethnicity, genetic polymorphisms and risk of atopy; 2) double faceted effects of parasitic infestations; 3) biodiversity loss and industrial progress. Moreover, an extensive revision of the literature about the relationship between the migratory status and allergy development is provided.

Beyond the word and image: II- Structural and functional connectivity of a common semantic system.

Understanding events requires interplaying cognitive processes arising in neural networks whose organisation and connectivity remain subjects of controversy in humans. In the present study, by combining diffusion tensor imaging and functional interaction analysis, we aim to provide new insights on the organisation of the structural and functional pathways connecting the multiple nodes of the identified semantic system -shared by vision and language (Jouen et al., 2015). We investigated a group of 19 healthy human subjects during experimental tasks of reading sentences or seeing pictures. The structural connectivity was realised by deterministic tractography using an algorithm to extract white matter fibers terminating in the selected regions of interest (ROIs) and the functional connectivity by independent component analysis to measure correlated activities among these ROIs. The major connections link ventral neural stuctures including the parietal and temporal cortices through inferior and middle longitudinal fasciculi, the retrosplenial and parahippocampal cortices through the cingulate bundle, and the temporal and prefrontal structures through the uncinate fasciculus. The imageability score provided when the subject was reading a sentence was significantly correlated with the factor of anisotropy of the left parieto-temporal connections of the middle longitudinal fasciculus. A large part of this ventrally localised structural connectivity corresponds to functional interactions between the main parietal, temporal and frontal nodes. More precisely, the strong coactivation both in the anterior temporal pole and in the region of the temporo-parietal cortex suggests dual and cooperating roles for these areas within the semantic system. These findings are discussed in terms of two semantics-related sub-systems responsible for conceptual representation.

Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies.

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. METHODS: Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. OBJECTIVE: The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Morphology combined with ancillary techniques: An algorithm approach for thyroid nodules.

INTRODUCTION: Several authors have underlined the limits of morphological analysis mostly in the diagnosis of follicular neoplasms (FN). The application of ancillary techniques, including immunocytochemistry (ICC) and molecular testing, contributes to a better definition of the risk of malignancy (ROM) and management of FN. According to literature, the application of models, including the evaluation of ICC, somatic mutations (ie, BRAFV600E ), micro RNA analysis is proposed for FNs. This study discusses the validation of a diagnostic algorithm in FN with a special focus on the role of morphology then followed by ancillary techniques. METHODS: From June 2014 to January 2016, we enrolled 37 FNs with histological follow-up. In the same reference period, 20 benign nodules and 20 positive for malignancy were selected as control. ICC, BRAFV600E mutation and miR-375 were carried out on LBC. RESULTS: The 37 FNs included 14 atypia of undetermined significance/follicular lesion of undetermined significance and 23 FN. Specifically, atypia of undetermined significance/follicular lesion of undetermined significance resulted in three goitres, 10 follicular adenomas and one NIFTP whereas FN/suspicious for FN by seven follicular adenomas and 16 malignancies (nine non-invasive follicular thyroid neoplasms with papillary-like nuclear features, two invasive follicular variant of papillary thyroid carcinoma [PTC] and five PTC). The 20 positive for malignancy samples included two invasive follicular variant of PTC, 16 PTCs and two medullary carcinomas. The morphological features of BRAFV600E mutation (nuclear features of PTC and moderate/abundant eosinophilic cytoplasms) were associated with 100% ROM. In the wild type cases, ROM was 83.3% in presence of a concordant positive ICC panel whilst significantly lower (10.5%) in a negative concordant ICC. High expression values of MirR-375 provided 100% ROM. CONCLUSIONS: The adoption of an algorithm might represent the best choice for the correct diagnosis of FNs. The morphological detection of BRAFV600E represents the first step for the identification of malignant FNs. A significant reduction of unnecessary thyroidectomies is the goal of this application.

The role of mobile apps in allergic respiratory diseases: an Italian multicentre survey report.

Summary: We performed a multicentre survey about the role of mobile apps in allergic respiratory diseases. The main objective was to investigate the current use and usefulness of mobile phone apps in the management of allergic respiratory disease. An original questionnaire including 12 multiple-choice questions was administered to 360 participants (153 male and 207 female subjects). Of notice, 290 subjects owned a smartphone, 120 a personal computer and 68 a tablet (multiple answers were possible). 123 subjects reported to be regular mobile-apps users, 209 were occasional users and 76 has never downloaded an app. Indeed, 259 subjects have never dealt with a medical or healthcare app, with only 8 subjects answering to often take advantage of such supportive tools. Data were even more discouraging when asking whether subjects had ever downloaded an app directly related to their own medical condition (allergy, asthma and rhinitis). 87.2% provided a negative answer. Among the few individuals who reported a previous experience with allergy/asthma apps only 2 subjects reported to regularly use the apps they had downloaded, even after months. The majority of subjects believed the apps would provide a relevant support, but only 25/360 participants found that the apps are "truly helpful", while 44 considered them of "help but not essential". Our data seem to show that the apps in the medical field, especially for allergic respiratory diseases, are welcome by patients, but their continued use and utility wane with the passage of time from the date of the download. In the future it will therefore be important to focus on the quality of the apps themselves and on the careful selection of the most suitable patients to use them. Finally, it will be important to make use of the fundamental contribution of healthcare professionals for the development of the apps.

Replacement therapy with levothyroxine modulates platelet activation in recent-onset post-thyroidectomy subclinical hypothyroidism.

BACKGROUND AND AIM: Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF2α in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy. METHODS AND RESULTS: Circulating levels of thyroid hormones, sCD40L, and 8-iso-PGF2α were assessed in 40 recently thyroidectomized patients (33 females, mean age 52.0 ± 11.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine (LT-4). At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 7.7 ± 3.9 µU/mL, FT3 1.8 ± 0.6 pg/mL, and FT3 8.9 ± 3.0 pg/mL). Circulating levels of sCD40L and 8-iso-PGF2α were directly correlated with each other (r = 0.360, p = 0.023) and with TSH levels (r = 0.322, p = 0.043 and r = 0.329 p = 0.038, respectively). After 2 months under the replacement therapy with LT-4 circulating levels of TSH (from 7.7 ± 3.9 to 2.7 ± 2.8 µU/mL, p < 0.0001), sCD40L (from 6.11 ± 2.41 to 2.43 ± 2.00 ng/mL, p < 0.0001) and 8-iso-PGF2α (from 45.33 ± 6.94 to 40.36 ± 6.20, p < 0.0001) significantly decreased. Changes in circulating levels of sCD40L and 8-iso-PGF2α were directly correlated with each other (r = 0.349 p = 0.028) and with changes in TSH levels (r = 0.367 p = 0.020 and r = 0.339 p = 0.032, respectively). CONCLUSION: Our study suggests an influential role of TSH on proatherogenic activation of platelets, probably through enhanced lipid peroxidation. These findings could partially explain the increased susceptibility of patients with subclinical hypothyroidism to develop atherosclerotic disease.

Incidence, malignancy rates of diagnoses and cyto-histological correlations in the new Italian Reporting System for Thyroid Cytology: An institutional experience.

OBJECTIVE: FNA biopsy is considered as the most accurate method for the selection of patients with thyroid nodules that need for surgery or for the wait and see management. The aim of the present study is to clarify the risk of malignancy for the cytological data classified according to the 2014 Italian reporting system. METHODS: We report a retrospective analysis of 4043 patients in our institution's experience during the period April 2014 through December 2016 with the Italian reporting system for thyroid cytology. RESULTS: The diagnostic incidences of the 4043 cases were as follows: 9.8% TIR1; 1.3% TIR1C; 70% TIR2; 6.6% TIR3A; 4.5% TIR3B; 2.4% TIR4; 5.2% TIR5. A repeated aspiration was carried out in 68 out of 269 cases (25%) classified as TIR3A. A total of 407 cases with cytology underwent surgical resection. A malignant neoplasm was detected in 261 out of 407 (64%) cases. Regarding TIR3B, surgical excision was undertaken in 109 cases, which included 42 high-risk lesions and 67 Hürthle cell neoplasms. The risk of malignancy was significantly higher in the former compared to the latter (50% vs 9%; P<.05). CONCLUSIONS: This investigation emphasises the reliability of the 2014 Italian Reporting System concerning the mutual frequency of the diagnostic categories. The risk of malignancy is perfectly within the range of the estimated values.

Eosinophil fungal rhinosinusitis caused by Fusarium infection secondary to odontogenic maxillary sinus disease: when collaboration between otolaryngologist and allergologist leads to the correct diagnosis and therapy.

SUMMARY: Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now "rhinosinusitis". On the basis of numerous causative factors, often co-existing in the same patient, the diagnosis of rhinosinusitis is also made by a wide variety of practitioners (allergologists, otolaryngologists, pulmonologists, primary care physicians, paediatricians, and many others). Approximately 5-15% of the population suffers from chronic rhinosinusitis, and in 10-12% of them, it is of dental origin. The treatment of odontogenic maxillary sinus disease is directed to the management of the rhinosinusitis and of the odontogenic source. The widespread use of dental implants and reconstructive procedures for dental implant placement has led to new types of complication, as in this case report, due to chronic eosinophilic rhinosinusitis secondary to Fusarium infection in the maxillary sinus. The patient was initially evaluated by the allergologist, and subsequently successfully treated by the otolaryngologist with Functional Endoscopic Sinus Surgery. The advantages of endoscopic sinus surgery include more accurate visualization, no external incision, reduced soft tissue dissection, and reduced hospital stay. Chronic maxillary sinusitis of dental origin is a common disease that requires treatment of the sinusitis as well as of the odontogenic source.

Vitamin D levels and allergic diseases. An italian cross-sectional multicenter survey.

SUMMARY: Background. During the two last decades, the interest in the role of Vitamin D (VD) in allergic disease has increased. Apart from the well-known actions of VD in bone metabolism, recent studies suggested its possible role as an immune-modulator in allergy. Objective. This study, conducted over the Italian territory, evaluated the possible correlations between VD serum level and diagnosed allergic diseases (rhinitis / asthma, food allergy, atopic dermatitis). Thus, VD was assessed in patients with physician-diagnosed allergic diseases. Methods. The study was carried out in hospital- and private practice-based setting between October 2012 and March 2013, and 18 Centers participated. Only adult patients, with at least one positive skin prick test were included. The diagnostic procedures and the data collection were standardized among the centers. VD levels were assayed by the same laboratory test. Results. Three hundred and nine patients were enrolled (132 male, mean age 37.5 ± 17 years). Of them, 40% reported a positive family history for allergies (asthma / rhinitis). Rhinitis plus asthma was present in 47% of patients, atopic dermatitis in 15%, and a consistent clinical history of food allergy associated with positive skin tests was present in 25% of subjects. There was no significant association between VD level and age, sex, family history, rhinitis, or food allergy. VD levels were overall lower in patients with asthma and rhinitis, but without statistical significance. A significant difference in VD levels was detected between patient with or without atopic dermatitis. VD was not related to seasonal allergens, whereas a significant negative correlation was seen for house dust mite and dog dander. Conclusion. Our data, derived from a cross-sectional study involving only allergic patients, agree partially with the current literature. Nonetheless, the association between VD levels and allergies appeared weak. Studies involving larger samples would be required to better define the association between VD and allergies.

Clinical utility of postmortem microcomputed tomography of the fetal heart: diagnostic imaging vs macroscopic dissection.

OBJECTIVES: Congenital cardiac malformations are commonly identified at perinatal autopsy, which can be challenging in fetuses of early gestation and in macerated fetuses. Our objective was to examine fetal complex congenital heart disease by microcomputed tomography (micro-CT), using standard autopsy as the gold standard. METHODS: In this ethically approved study, ex-vivo isolated fetal heart and fetal heart-lung blocks underwent iodine preparation prior to micro-CT, and were fixed in formalin after the micro-CT examination. Images were acquired using a microfocus-CT scanner with individual specimen image optimization. Twenty-one indices assessed normally at autopsy were evaluated for each dataset. Cardiac dissection was performed using a dissecting microscope within 24 h of the micro-CT examination. RESULTS: We examined six fetal hearts, comprising five with complex congenital cardiac malformations at a gestational age of 17-23 weeks and an anatomically normal heart of 23 weeks' gestation for reference. All specimens demonstrated excellent internal contrast at micro-CT examination, and the correct overall diagnosis was made in all cases. There was agreement for 114/126 indices assessed on micro-CT and at autopsy dissection (overall concordance of 95.8% (95% CI, 90.5-98.2%)). Micro-CT was particularly useful in the assessment of ventricular morphology in macerated fetuses. CONCLUSIONS: Micro-CT of small ex-vivo fetal specimens can provide highly accurate three-dimensional rendering of complex congenital fetal heart disease. This approach represents a significant advance in postmortem imaging and confirms the potential of this technology for non-invasive examination of small fetuses and organs.