High prevalence of adrenal cortical adenomas in patients with cerebral meningiomas.

PURPOSE: Adrenal cortical adenomas (ACAs) represent one of the most common endocrine neoplasms. Recently, a genetic syndrome, characterized by tumor-suppressor ARMC5-gene mutations and causing primary macronodular bilateral adrenal hyperplasia with concomitant meningiomas of the central nervous system, has been described. Apart from this rare disorder and despite the well-known influence of steroid hormones on meningiomas, no data are available about the association between ACAs and meningiomas. METHODS: We investigated the prevalence of ACAs in a group of patients with cerebral meningioma undergoing unenhanced chest CT scans before attending surgical treatment. Patients with meningioma were age- and sex-matched in a 1:3 ratio with hospitalized patients for COVID-19. RESULTS: Fifty-six patients with meningioma were included and matched with 168 control patients with COVID-19. One-hundred forty-four (66.1%) were female and the median age was 63 years. Twenty ACAs were detected in the overall population (8.9% of the subjects): 10 in patients with meningioma (18%) and the remaining 10 (6%) in the control group (p = 0.007). Multivariate analysis showed that age and presence of meningioma were statistically associated with the presence of ACAs (p = 0.01, p = 0.008). CONCLUSION: We report, for the first time, a higher prevalence of ACAs in patients with meningioma as compared to age- and sex-matched controls. Larger studies are needed to confirm our data and to clarify the characteristics of the ACAs in patients with meningioma. Whether the detection of ACAs should prompt a neuroimaging evaluation to exclude the presence of meningiomas needs also to be considered.

The role of chest ct in understanding interstitial lung disease (ILD): Systemic sclerosis (SSC). versus COVID-19

Background: COVID-19 pandemic is a global emergency which may overlap on the clinical and radiological scenario of ILD in SSc. In clinical practice, the striking similarities observed at computed tomography (CT) between the diseases make it difficult to distinguish a COVID-19 superinfection from a progression of SSc-ILD. Objectives: The aim of our study was to identify the main CT features that may help distinguishing SSc-ILD from COVID-19 pneumonia. Methods: 22 international readers were included and divided in the radiologist group (RAD) and non-radiologist group (nRAD). The RAD group included nonchest RAD and chest-RAD. A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. Results: Fibrosis inside focal ground glass opacities (GGO) in the upper lobes;fibrosis in the lower lobe GGO;reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT parameters most frequently associated with SSc-ILD. The CT parameters most frequently associated with COVID-19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p <0.0001) and signs of fibrosis in GGO in the lower lobes (p <0.0001) remained independently associated with COVID-19 pneumonia or SSc-ILD, respectively. These two variables were combined in a predictive score which resulted positively associated with the COVID-19 diagnosis, with 96.1% sensitivity and 83.3% specificity: 3 different risk class for COVID-19 pneumonia may be identified: high risk for COVID-19 pneumonia (5-9 points);probable overlap COVID-19 pneumonia in SSc-ILD (4 points);low risk for COVID-19 pneumonia (0-3 points). Conclusion: The CT differential diagnosis between COVID-19 Pneumonia and SSc-ILD is possible and may be fostered in practice by the use of a radiological score. In the case where an overlap of both diseases is suspected, the presence of consolidation in the lower lobes may suggest a COVID-19 pneumonia while the presence of fibrosis inside GGO may indicate a SSc-ILD.

Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy

Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3 ;IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL;IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 mug/m;IQR, 5.0-23.8 mug/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12;95% CI, 1.04-1.22;P = 0.004) and hypertension (OR, 6.15;95% CI, 1.75-29.11;P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. Trial registration: ClinicalTrials.gov identifier: NCT04318366.

Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy

Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 10(3) per mm(3);IQR, 0.58-1.00 x 10(3) per mm(3)), hyperinflammation with C-reactive protein (median, 184.5 mg/dL;IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 mu g/m;IQR, 5.0-23.8 mu g/m) were present. Median tidal volume was 6.7 mUkg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH(2)O (IQR, 10-14 cmH(2)O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median followup of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12;95% CI, 1.04-1.22;P= 0.004) and hypertension (OR, 6.15;95% CI, 1.75-29.11;P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (Pao(2) ) to fraction of inspired oxygen (Fio(2)) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors.

Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis

We suggest the use of MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) as a new name for severe pulmonary coronavirus disease 2019 (COVID-19). We hypothesise that, in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. This progressive endothelial thromboinflammatory syndrome may also involve the microvascular bed of the brain and other vital organs, leading to multiple organ failure and death. Future steps in the understanding of the disease and in the identification of treatments may benefit from this definition and hypothesised sequence of events.

MAVRILIMUMAB IMPROVES OUTCOMES IN SEVERE COVID-19 PNEUMONIA AND SYSTEMIC HYPER-INFLAMMATION

Background:Patients with severe COVID-19 pneumonia and hyperinflammation face increased mortality. There is an urgent need for effective treatments to reduce the burden of the COVID-19 pandemic.Objectives:Our protocol aimed at evaluating the potential improvement in clinical outcomes with mavrilimumab, an anti-Granulocyte/Macrophage Colony-Stimulating Factor Receptor alpha (GM-CSFRα) monoclonal antibody, in patients with COVID-19 pneumonia and systemic hyper-inflammation.Methods:Single-center, open-label, single active arm intervention;Adult patients with severe COVID-19 pneumonia (as evaluated by CT scanning), hypoxia (PaO2:FiO2 ratio ≤ 300 mmHg), and systemic hyper-inflammation (increased C-reactive protein [CRP] ≥ 100 mg/mL and/or ferritin ≥ 900 μg/L, increased lactate dehydrogenase [LDH]) received a single intravenous dose of mavrilimumab added to standard of care;follow-up 28 days. Main outcomes measure was time to clinical improvement (reduction ≥ 2 categories on the 7-point WHO clinical status scale, 1=discharge, 7=death);others included time to discharge from hospital;% of pts achieving a clinical improvement;survival;mechanical-ventilation free survival;time to fever resolution;CRP;PaO2:FiO2 ratio.Results:A mavrilimumab group (n=13 COVID-19 patients, non-mechanically ventilated, median age 57 [IQR, 52-58], males 12 [92%], febrile 11 [85%];PaO2:FiO2 195.5[166.7–215.0]) was compared to a cohort of 26 contemporaneous patients with similar baseline characteristics. Death occurred in 0% (n=0/13) of mavrilimumab recipients and 27% (n=7/26) of comparison-group patients (log rank p=0.046) during the 28-day follow-up. 100% (n=13) of mavrilimumab recipients and 65% (n=17) of comparison-group patients achieved clinical improvement (p=0.018) at Day 28, with earlier improvement (median 8.0 [IQR, 5.0–11.0] days vs 18.5 [11.0–NE] days) (p0.001) in mavrilimumab recipients. Fever had resolved in 91% (n=10/11 febrile patients) of mavrilimumab recipients by Day 14, compared to 61% (n=11/18 febrile) of patients in the comparison group (p=0.110);fever resolution was faster in mavrilimumab recipients versus controls (median 1.0 [IQR, 1.0–2.0] day vs 7.0 [3.0 - NE] days, respectively, p=0·009). Mavrilimumab was well tolerated in all patients.Conclusion:Patients with severe COVID-19 pneumonia and systemic hyper-inflammation who received treatment with mavrilimumab had better clinical outcomes compared to patients receiving routine care. Mavrilimumab was well-tolerated. Randomized controlled trials are warranted to confirm our findings.References:[1]Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62[2]Mehta P, McAuley DF, Brown M, et al. HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033-4Disclosure of Interests:Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Emanuel Della Torre: None declared, Piera Angelillo: None declared, Alessandro Tomelleri: None declared, nicola boffini: None declared, Stefano Tentori: None declared, Francesca Mette: None declared, Patrizia Rovere-Querini: None declared, Annalisa Ruggeri: None declared, Teresa D’Aliberti: None declared, Paolo Scarpelllini: None declared, Giovanni Landoni: None declared, Francesco De Cobelli: None declared, John F. Paolini Shareholder of: Kiniksa, Employee of: Kiniksa, Alberto Zangrillo: None declared, Moreno Tresoldi: None declared, Bruce C. Trapnell Consultant of: Kiniksa, Fabio Ciceri: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI