Most patients with newly diagnosed Graves' disease have no ocular involvement. Moderate-to-severe and active GO or sight-threatening GO are rare at presentation and rarely develop during ATD treatment. Most patients (>80%) with no GO at baseline do not develop GO after an 18-month follow-up period. Remission of mild GO occurs in the majority of cases.

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Similarities and differences exist between expert North American and European thyroidologists concerning the diagnosis and management of AIT. While differences reflect the frequent uncertainty of the underlying mechanism leading to AIT, similarities may represent the basis to refine the diagnostic criteria and to improve the therapeutic outcomes of this challenging clinical situation.

Autoimmune thyroid disorders (AITDs) are the result of a complex interplay between genetic and environmental factors, the former account for about 70-80% of liability to develop AITDs. However, at least 20-30% is contributed by environmental factors, which include certainly smoking (at least for Graves' disease and orbitopathy), probably stress, iodine and selenium intake, several drugs, irradiation, pollutants, viral and bacterial infections, allergy, pregnancy, and post-partum. Evidence for the intervention of these factors is often limited, and the mechanisms whereby environmental factors may concur to the onset of AITDs are in many instances unclear. Nevertheless, gene-environment interaction seems a fundamental process for the occurrence of AITDs.

The simultaneous finding of submandibular ectopic thyroid tissue and functional orthotopic thyroid gland is an extremely rare event. The present report describes the case of a woman presenting with a left submandibular mass, distant from a palpable multinodular goitre. Ultrasonography showed an ovoidal solid mass adjacent to the lower margin of the left submandibular gland. Cytological specimens showed colloid material and thyroid follicular cells with no malignant features. A preoperative CT scan demonstrated a very thin connection between the thyroid and the submandibular mass. The patient underwent total thyroidectomy and excision of the submandibular mass. The histopathological diagnosis of the thyroid tissue was multinodular goitre, and the submandibular mass was ectopic thyroid tissue showing a hyperplastic pattern. The main differential diagnosis of the submandibular mass was a metastasis from a well differentiated cancer. This case illustrates that an ectopic thyroid off the midline may not necessarily be a metastasis from a thyroid cancer.

The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation and antiviral drugs, steroids, and interleukin-6 pathway inhibitors. Clinical, laboratory, and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality. Univariate analyses showed prognostic significance for age greater than 70 years, the presence of two or more relevant comorbidities, a P/F ratio less than 200 at presentation, elevated LDH (lactate dehydrogenase) and CRP (C-reactive protein) values, intermediate- or therapeutic-dose anticoagulation, hydroxychloroquine, early antiviral therapy with lopinavir/ritonavir, short courses of steroids, and tocilizumab therapy. Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (−0.37), antiviral lopinavir/ritonavir (−1.22), or steroid (−0.59) therapy. In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia. Results from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia in terms of both clinical risk factors for in-hospital mortality and the effectiveness of the different therapies proposed for the management of COVID19 disease.

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged.For clarity, all collaborators are listed in this correction article.

Importance: With randomized clinical trials ongoing and vaccine still a long distance away, efforts to repurpose old medications used for other diseases provide hope for treatment of COVID−19. Objectives: To examine the risk factors for in−hospital mortality and describe the effectiveness of different treatment strategies in a real−life setting of patients with severe acute respiratory syndrome coronavirus 2 (SARS−CoV−2) pneumonia. Design: Real−life single−center study during the Lombardy COVID−19 outbreak. Setting: Valduce Hospital in Como, Lombardy Region, Italy. Participants: 205 laboratory−confirmed patients presenting with SARS−Cov−2 pneumonia requiring hospitalization. Interventions: All patients received best supportive care and, based on their clinical needs and comorbidities, specific interventions that included the main drugs being tested for repurposing to treat COVID−19, such as hydroxychloroquine, anticoagulation, antiviral drugs, steroids or interleukin−6 pathway inhibitors. Main outcomes and measures: Clinical, laboratory and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in−hospital mortality and compared with current literature data. Results: Univariate analyses for clinical variables showed prognostic significance for age equal or greater than 70 years (estimated 28−days survival: 21.4 vs 67.4%; p<0.0001), presence of 2 or more relevant comorbidities (35.3 vs 61.8%; p=0.0008), ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) less than 200 at presentation (21−days survival: 14.7 vs 52.4%;p<0.0001), high levels of lactate dehydrogenase (LDH) (26.4 vs 65.3%; p=0.0001), and elevated C−reactive protein (CRP) values (25.4 vs 74.9%; p=0.0001), while no statistical significance was found for all the other clinical variables tested. At univariate analysis for the different treatment scheduled, prognostic significance for survival was showed for intermediate or therapeutic-dose anticoagulation (estimated 28−days survival: 37.1 vs 23.4%; p=0.0001), hydroxychloroquine (35.7 vs 27.3%; p=0.0029), early antiviral therapy with lopinavir/ritonavir (60.1 vs 22.4%; p<0.0001), late short−course of steroids (47.9 vs 18.2%; p<0.0001) or tocilizumab therapy (69.4 vs 29.4%; p=0.0059). Multivariable regression confirmed increasing odds of in−hospital death associated with age older than 70 years (odds ratio 3.26, 95% CI 1.81 − 5.86; p<0.0001) and showed a reduction in mortality for patients treated with anticoagulant (−0.37, 0.49 − 0.95; p=0.0273), antiviral (−1.22, 0.16 − 0.54; p<0.0001), or steroids (−0.59, 0.35 − 0.87; p=0.0117) therapy.