Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).

BACKGROUND: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. METHODS: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. RESULTS: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. CONCLUSION: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

A 35-Year-Old Man With Fever, Cough, and Erythematous-Erosive Mucous Membrane Lesions Accompanied by a Generalized Cutaneous Rash.

CASE PRESENTATION: A 35-year-old man presented to the ED with a 7-day history of fever, asthenia, and cough. He had previously received a 3-day course of amoxicillin and clavulanic acid (1 g tid po) and then ceftriaxone (1 g IM once per day) prescribed by his general practitioner with no substantial benefit. He was an active smoker (11.2 pack/y), without known allergy-related syndromes and any important reports in his medical history.

A case of endobronchial actinomycosis as a challenging cause of lung atelectasis.

BACKGROUND: Primary endobronchial actinomycosis is exceptionally uncommon and can be misdiagnosed as unresolving pneumonia, endobronchial lipoma, bronchogenic carcinoma or foreign body. Predisposing factors are immunosuppressive conditions, chronic lung diseases, poor oral hygiene or foreign body aspiration. CASE PRESENTATION: We reported a case of 88-year old woman with a 4 days history of mild exertional dyspnea, productive cough with purulent sputum and fever up to 37.8 °C, who developed left sided endobronchial actinomycosis in absence of any pre-existent risk conditions; endobronchial de-obstruction and specific antibiotic treatment were performed with success, achieving a full resolution of the disease, with bronchoscopy playing a key role in the diagnosticand therapeutic pathways. CONCLUSIONS: This case raises the necessity for increased awareness in the management of endobronchial lesions and in cases of suspected endobronchial actinomycosis; bronchoscopy plays a key role in the diagnostic and therapeutic process; prompt recognition of this entity can expedite proper treatment and recovery.

Mediastinal lymph node enlargement in idiopathic pulmonary fibrosis: relationships with disease progression and pulmonary function trends.

BACKGROUND AND OBJECTIVES: Evidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients. METHODS: This retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models. RESULTS: The study population consisted of 152 IPF patients, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86-13.62, p ≤ 0.001) and significant disease progression (HR 2.99, 95% CI 1.22-7.33, p = 0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time. CONCLUSIONS: Diffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.

Are newly launched pharmacotherapies efficacious in treating idiopathic pulmonary fibrosis? Or is there still more work to be done?

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a challenging and multifactorial disease that has been thought for some time to lack effective treatments. The approval of two drugs, nintedanib and pirfenidone, has heralded a new era in its management. Areas covered: Currently, there is a growing interest on therapeutic strategies. Many studies have been designed and performed, although few of them turned out to be successful. Nowadays, nintedanib and pirfenidone are considered disease modifying drugs, recommended treatments by current evidence-based guidelines. A combined approach with more than one drug could be an effective strategy in IPF. However, data on combination therapy of the two approved drugs are still scarce, and ongoing trials are evaluating pharmacodynamic interactions and safety. The approved disease modifying drugs are also being assessed in combination with new molecules, showing promising results in preclinical models. Expert opinion: A deeper understanding of pathogenesis and key molecular mechanisms driving disease inception and progression will be key to identify novel agents to be tested both pre-clinically and clinically, possibly in combination with approved treatments. Looking at the near future, it is likely that clinical trials will adopt a phenotype-specific and pathway-specific approach, thus leading towards a personalized approach to IPF management.