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.

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.

Sodium nitroprusside for advanced heart failure. A metanalysis of literature data.

Advanced heart failure (HF) is associated with a very poor prognosis and places a big burden on health-care services. The gold standard treatment, i.e. long-term mechanical circulatory support or heart transplantation, is precluded in many patients but observational studies suggest that the use of SNP might be associated with favourable long-term clinical outcomes. We performed a metanalysis of published studies that compared sodium nitroprusside (SNP) with optimal medical therapy to examine the safety and efficacy of SNP as part of the treatment regimen of patients hospitalized for advanced heart failure (HF). We searched PUBMED, EMBASE and WEB OF SCIENCE for studies that compared SNP with optimal medical therapy in advanced HF on July 2022. After screening 700 full-text articles, data from two original articles were included in a combined analysis. The analysis demonstrated a 66% reduction in the odds of death in advanced HF patients treated with SNP. The results show the potential importance of the inclusion of SNP in the treatment regimen of patients hospitalized because of advanced HF and underlines that controlled, randomized studies are still required in this condition.

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.

Does the Motor Cortex Want the Full Story? The Influence of Sentence Context on Corticospinal Excitability in Action Language Processing.

The reading of action verbs has been shown to activate motor areas, whereby sentence context may serve to either globally strengthen this activation or to selectively sharpen it. To investigate this issue, we manipulated the presence of manual actions and sentence context, assessing the level of corticospinal excitability by means of transcranial magnetic stimulation. We hypothesized that context would serve to sharpen the neural representation of the described actions in the motor cortex, reflected in context-specific modulation of corticospinal excitability. Participants silently read manual action verbs and non-manual verbs, preceded by a full sentence (rich context) or not (minimal context). Transcranial magnetic stimulation pulses were delivered at rest or shortly after verb presentation. The coil was positioned over the cortical representation of the right first dorsal interosseous (pointer finger). We observed a general increase of corticospinal excitability while reading both manual action and non-manual verbs in minimal context, whereas the modulation was action-specific in rich context: corticospinal excitability increased while reading manual verbs, but did not differ from baseline for non-manual verbs. These findings suggest that sentence context sharpens motor representations, activating the motor cortex when relevant and eliminating any residual motor activation when no action is present.

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.

Hemithyroidectomy versus total thyroidectomy in the intermediate-risk differentiated thyroid cancer: the Italian Societies of Endocrine Surgeons and Surgical Oncology Multicentric Study.

The surgical treatment of the intermediate-risk DTC (1-4 cm) remains still controversial. We analyzed the current practice in Italy regarding the surgical management of intermediate-risk unilateral DTC to evaluate risk factors for recurrence and to identify a group of patients to whom propose a total thyroidectomy (TT) vs. hemithyroidectomy (HT). Among 1896 patients operated for thyroid cancer between January 2017 and December 2019, we evaluated 564 (29.7%) patients with unilateral intermediate-risk DTC (1-4 cm) without contralateral nodular lesions on the preoperative exams, chronic autoimmune thyroiditis, familiarity or radiance exposure. Data were collected retrospectively from the clinical register from 16 referral centers. The patients were followed for at least 14 months (median time 29.21 months). In our cohort 499 patients (88.4%) underwent total thyroidectomy whereas 65 patients (11.6%) underwent hemithyroidectomy. 151 (26.8%) patients had a multifocal DTC of whom 57 (10.1%) were bilateral. 21/66 (32.3%) patients were reoperated within 2 months from the first intervention (completion thyroidectomy). Three patients (3/564) developed regional lymph node recurrence 2 years after surgery and required a lymph nodal neck dissection. The single factor related to the risk of reoperation was the histological diameter (HR = 1.05 (1.00-1-09), p = 0.026). Risk stratification is the key to differentiating treatment options and achieving better outcomes. According to the present study, tumor diameter is a strong predictive risk factor to proper choose initial surgical management for intermediate-risk DTC.

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.

Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes.

INTRODUCTION: Hypercortisolism requires a prompt therapeutic management to reduce the risk of development of a potential fatal emergency. A synchronous bilateral adrenalectomy (SBA) is effective in recovering hypercortisolism. However, specific indications for an SBA are not available. We aimed to evaluate the outcome of patients who underwent an SBA and to identify biomarkers able to predict the requirements of an SBA. PATIENTS AND METHODS: A mono-centric and longitudinal study was conducted on 19 consecutive patients who underwent SBA for ACTH-dependent hypercortisolism between December 2003 and December 2017. This study population was compared to two control groups composed of patients cured after the resection of the ACTH secreting pituitary adenoma (Group A: 44 patients) and of the ACTH-secreting neuroendocrine tumours (Group B: 8 patients). RESULTS: Short- or long-term SBA complications or the recurrence of hypercortisolism did not occur. A single patient experienced Nelson syndrome. Clinical features after SBA showed improvement in the glico-metabolic assessment, hypertension, bone metabolism and the occurrence of hypokalaemia and infections. The younger the age at the time of Cushing's disease diagnosis, the longer the duration of active hypercortisolism, higher values of plasmatic ACTH and Cortisol (1 month after pituitary neurosurgery) and higher values of Ki67 in pituitary adenomas were detected in this study population as compared to Group A. CONCLUSIONS: SBA is an effective and safe treatment for patients with unmanageable ACTH-dependent hypercortisolism. A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing.

Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

Obstructive sleep apnea syndrome and autonomic dysfunction.

Autonomic nervous system (ANS) has been extensively explored in obstructive sleep apnea (OSA). Autonomic alterations in these patients have been described by means of several methods, evaluating ANS function both directly with microneurography and indirectly through baroreflex sensitivity (BRS, by the sequence method or the cross-spectral approach), heart rate variability analysis (HRV, both in the time and frequency domain) during sleep and wake, or conventional laboratory tests, including cold pressor test, hand grip test or measurement of urinary cathecolamine excretion. Several studies in OSA patients have shown ANS alterations, in particular sympathetic overactivity, both acutely during apnea events and chronically during the daytime, being both also involved in cardiovascular consequences of sleep disordered breathing. The association between OSA and sympathetic dysregulation suggests a dose response relationship between OSA severity and the degree of sympathetic overactivity and this association seems to be reversible as the treatment of OSA is implemented. Additionally ANS is involved in regulating visceral and humoral functions to maintain the body homeostasis and in reaction and adaptation to external and internal stressor stimuli. However, the vast majority of studies have focussed on cardiovascular alterations, which are easier to measure, somewhat neglecting the other functions regulated by ANS. More evidence is therefore needed to better characterize the impact that sleep disorder breathing may have on ANS both in the short and long term.

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.