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).

Objectives To investigate the etiology of transient loss of consciousness (T‐LOC) suspected to be syncope and unexplained falls in elderly adults with dementia. Design Prospective, observational, multicenter study. Setting Acute care wards, syncope units or centers for the diagnosis of dementia. Participants Individuals aged 65 and older with a diagnosis of dementia and one or more episodes of T‐LOC of a suspected syncopal nature or unexplained falls during the previous 3 months were enrolled. Measurements The causes of T‐LOC suspected to be syncope and unexplained falls were evaluated using a simplified protocol based on European Society of Cardiology guidelines. Results Of 357 individuals enrolled, 181 (50.7%) had been referred for T‐LOC suspected to be syncope, 166 (46.5%) for unexplained falls, and 10 (2.8%) for both. An initially suspected diagnosis of syncope was confirmed in 158 (87.3%), and syncope was identified as the cause of the event in 75 (45.2%) of those referred for unexplained falls. Orthostatic hypotension was the cause of the event in 117 of 242 (48.3%) participants with a final diagnosis of syncope. Conclusion The simplified syncope diagnostic protocol can be used in elderly people with dementia referred for suspected syncope or unexplained falls. Unexplained falls may mask a diagnosis of syncope or pseudosyncope in almost 50% of cases. Given the high prevalence of orthostatic syncope in participants (~50%), a systematic reappraisal of drugs potentially responsible for orthostatic hypotension is warranted.

Introduction: During this long COVID-19 pandemic outbreak, continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) are being widely used to treat patients with moderate to severe acute respiratory failure (ARF). As for now, data on the efficacy of NIV in COVID-19 acute respiratory distress syndrome (ARDS) are lacking, and for this reason it is extremely important to accurately determine the outcomes of this strategy. This study aimed to evaluate clinical data and outcomes of NIV in patients with COVID-19 ARDS. Matherials and methods: Seventy-nine consecutive patients with sudden worsening of respiratory failure were evaluated. All patients (71% male) had a confirmed SARS-CoV-2 infection and signs, symptoms and radiological findings compatible with COVID-19 pneumonia and all of them underwent a trial of NIV. Primary outcomes were NIV success and failure defined by intubation and mortality rate.Secondary outcome was the duration of NIV. Results: NIV was successful in 38 (48.1%) patients (Table 1). EOT was necessary in 21 patients (26.6%). Death occurred in 20 patients (25.3%). In the group of patients having failed a trial with NIV and then being intubated, compared to those who continued NIV, there was no higher mortality rate. By evaluating the ICU survival outcome of the subgroup of patients intubated after NIV, 57% of the patients were discharged and 43% died. Conclusion: Previous studies conducted on patients undergoing invasive mechanical ventilation showed higher mortality rate than the present study. Our data showed that NIV can avoid intubation in almost half of the patients. Therefore, this data could reassure clinicians who would consider using NIV in COVID-19 ARDS-related treatment.

Background The severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is extremely variable, ranging from asymptomatic patients to those who develop severe acute respiratory distress syndrome (ARDS). As for now, there are still no really effective therapies for coronavirus disease 2019 (COVID-19). Some evidences suggest that tocilizumab (TCZ) may avoid the progression of severe COVID-19. The aim of this retrospective case-control study was to analyze the efficacy and safety of TCZ in patients with COVID-19 ARDS undergoing noninvasive mechanical ventilation (NIV). Methods Seventy-nine consecutive patients with severe COVID-19 pneumonia and worsening acute respiratory failure (ARF) were admitted to the Pulmonology Unit of Azienda USL of Reggio Emilia-IRCCS. All patients were inflamed (elevated CRP and IL-6 levels) and received NIV at admission according to the presence of a pO2/FiO2 ratio ≤ 200 mmHg. The possibility of being treated with TCZ depended on the drug availability. The primary outcome was the in-hospital mortality rate. A secondary composite outcome of worsening was represented by the patients who died in the pulmonology unit or were intubated. Results Out of 79 patients, 41 were treated with TCZ. Twenty-eight patients received intravenous (IV) TCZ and 13 patients received subcutaneous (SC) TCZ. In-hospital overall mortality rate was 38% (30/79 patients). The probabilities of dying and being intubated during the follow-up using Kaplan-Meier method were significantly lower in total patients treated with TCZ compared to those of patients not treated with TCZ (log-rank p value = 0.006 and 0.036, respectively). However, using Cox multivariate analyses adjusted for age and Charlson comorbidity index only the association with the reduced risk of being intubated or dying maintained the significance (HR 0.44, 95%CI 0.22–0.89, p = 0.022). Two patients treated with TCZ developed cavitating lung lesions during the follow-up. Conclusions This study shows that TCZ treatment may be effective in COVID-19 patients with severe respiratory impairment receiving NIV. More data on safety are required. Randomized controlled trials are needed to confirm these results.

Streptococcus pneumoniae related diseases are a leading cause of morbidity and mortality, especially in children and in the elderly population. It is transmitted to other individuals through droplets and it can spread to other parts of the human host, causing a wide spectrum of clinical syndromes, affecting between 10 and 100 cases per 100,000 people in Europe and the USA. In order to reduce morbidity and mortality caused by this agent, pneumococcal vaccines have been developed over the years and have shown incredible effectiveness in reducing the spread of this bacterium and the development of related diseases, obtaining a significant reduction in mortality, especially in developing countries. However, considerable problems are emerging mainly due to the replacement phenomenon, multi-drug resistance, and the high production costs of conjugated vaccines. There is still a debate about the indications given by various countries to different age groups; this is one of the reasons for the diffusion of different serotypes. To cope with these problems, significant efforts have been made in the research field to further improve vaccination serotypes coverage. On the other hand, an equally important commitment by health care systems to all age group populations is needed to improve vaccination coverage.