Predictors of Mortality in Tocilizumab-Treated Severe COVID-19.

Purpose: Tocilizumab is associated with positive outcomes in severe COVID-19. We wanted to describe the characteristics of nonresponders to treatment. Methods: This was a retrospective multicenter study in two respiratory departments investigating adverse outcomes at 90 days from diagnosis in subjects treated with tocilizumab (8 mg/kg intravenously single dose) for severe progressive COVID-19. Results: Of 121 subjects, 62% were males, and 9% were fully vaccinated. Ninety-six (79.4%) survived, and 25 died (20.6%). Compared to survivors (S), nonsurvivors (NS) were older (median 57 versus 75 years of age), had more comorbidities (Charlson comorbidity index 2 versus 5) and had higher rates of intubation/mechanical ventilation (p < 0.05). On admission, NS had a lower PO2/FiO2 ratio, higher blood ferritin, and higher troponin, and on clinical progression (day of tocilizumab treatment), NS had a lower PO2/FiO2 ratio, decreased lymphocytes, increased neutrophil to lymphocyte ratio, increased ferritin and lactate dehydrogenase (LDH), disease located centrally on computed tomography scan, and increased late c-reactive protein. Cox proportional hazards regression analysis identified age and LDH on deterioration as predictors of death; admission PO2/FiO2 ratio and LDH as predictors of intubation; PO2/FiO2 ratios, LDH, and central lung disease on radiology as predictors of noninvasive ventilation (NIV) (a < 0.05). The log-rank test of mortality yielded the same results (p < 0.001). ROC analysis of the above predictors in a separate validation cohort yielded significant results. Conclusions: Older age and high serum LDH levels are predictors of mortality in tocilizumab-treated severe COVID-19 patients. Hypoxia levels, LDH, and central pulmonary involvement radiologically are associated with intubation and NIV.

SARS-Cov-2 Infection in Severe Asthma Patients Treated With Biologics.

BACKGROUND: At the beginning of the pandemic, there have been considerable concerns regarding coronavirus disease 2019 (COVID-19) severity and outcomes in patients with severe asthma treated with biologics. OBJECTIVE: To prospectively observe a cohort of severe asthmatics treated with biologics for the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease severity during the COVID-19 pandemic. METHODS: Physicians from centers treating patients with severe asthma all over Greece provided demographic and medical data regarding their patients treated with biologics. Physicians were also asked to follow up patients during the pandemic and to perform a polymerase chain reaction test in case of a suspected SARS-Cov-2 infection. RESULTS: Among the 591 severe asthmatics (63.5% female) included in the study, 219 (37.1%) were treated with omalizumab, 358 (60.6%) with mepolizumab, and 14 (2.4%) with benralizumab. In total, 26 patients (4.4%) had a confirmed SARS-CoV-2 infection, 9 (34.6%) of whom were admitted to the hospital because of severe COVID-19, and 1 required mechanical ventilation and died 19 days after admission. Of the 26 infected patients, 5 (19.2%) experienced asthma control deterioration, characterized as exacerbation that required treatment with systemic corticosteroids. The scheduled administration of the biological therapy was performed timely in all patients with the exception of 2, in whom it was postponed for 1 week according to their doctors' suggestion. CONCLUSION: Our study confirms that despite the initial concerns, SARS-CoV-2 infection is not more common in asthmatics treated with biologics compared with the general population, whereas the use of biologic treatments for severe asthma during the COVID-19 pandemic does not seem to be related to adverse outcomes from severe COVID-19.

Mortality Among Hospitalized Patients With Pleural Effusions. A Multicenter, Observational, Prospective Study.

Background: Data regarding the prognostic significance of pleural effusion (PE) are scarce. Objective: Explore the impact of PE on mortality among hospitalized patients. Methods: Multicenter prospective observational study. Patients that underwent computed tomography (thorax and/or abdomen) and in which PE was detected, were admitted to the study. PE was classified by size on CT, anatomical distribution, diagnosis, and Light's criteria. Charlson comorbidity index (CCI), APACHE II, and SOFA score were calculated. Mortality at 1 month and 1 year were recorded. Results: Five hundred and eight subjects, mean age 78 years. Overall mortality was 22.6% at 1 month and 49.4% at 1 year. Bilateral effusions were associated with higher mortality than unilateral effusions at 1 month (32 vs. 13.3%, p = 0.005) and large effusions with higher mortality than small effusions at 1 year (66.6 vs. 43.3%, p < 0.01). On multivariate analysis age, CCI, APACHE II, SOFA score, and bilateral distribution were associated with short-term mortality, while long-term significant predictors were CCI, APACHE II, SOFA, and malignant etiology. Exudates (excluding MPE) exhibited a survival benefit at both 1 month and 1 year but due to the smaller sample, fluid characteristics were not included in the multivariate analysis. Conclusions: Pleural effusion is a marker of advanced disease. Mortality is higher within the first month in patients with PEs related to organ failure, while patients with MPE have the worst long-term outcome. Independent predictors of mortality, apart from CCI, APACHE II, and SOFA scores, are age and bilateral distribution in the short-term, and malignancy in the long-term.

Cardiac sarcoidosis: diagnosis and management.

Sarcoidosis is a chronic inflammatory disease of unknown etiology characterized by multi-organ involvement. End-organ disease consists of granulomatous inflammation, which if left untreated or not resolved spontaneously, leads to permanent fibrosis and end-organ dysfunction. Cardiac involvement and fibrosis in sarcoidosis occur in 5-10% of cases and is becoming increasingly diagnosed. This is due to increased clinical awareness among clinicians and new diagnostic modalities, since magnetic resonance imaging and positron-emission tomography are emerging as "gold standard" tools replacing endomyocardial biopsy. Despite this progress, isolated cardiac sarcoidosis is difficult to differentiate from other causes of arrhythmogenic cardiomyopathy. Cardiac fibrosis leads to congestive heart failure, arrhythmias and sudden cardiac death. Immunosuppressives (mostly corticosteroids) are used for the treatment of cardiac sarcoidosis. Implantable devices like a cardioverter-defibrillator may be warranted in order to prevent sudden cardiac death. In this article current trends in the pathophysiology, diagnosis and management of cardiac sarcoidosis will be reviewed focusing on published research and latest guidelines. Lastly, a management algorithm is proposed.

Immune status in sarcoidosis: one size does not fit all.

B-cell immunity and immunoglobulins are less commonly affected in sarcoidosis. We aimed to evaluate immune status in sarcoidosis patients. Retrospective chart review of sarcoidosis patients attending a out-patient clinic over 3 months period. Immunoglobulins levels were recorded (A, M, G, E) along with clinical and serological data. They were divided in group A (normal IgG), group B (increased IgG), group C (decreased IgG) and group D (decreased IgG and IgM and/or IgA). Of 50 subjects, 68% were females and 62% of Caucasian origin. 22 (44%) had normal IgG levels, 16 (32%) had increased IgG levels, 10 (20%) had hypogammaglobulinemia and 2 (4%) had combined hypogammaglobulinemia, diagnosed with combined sarcoidosis and common variable immunodeficiency. Decreased IgA values was found in groups C and D. IgE was high in group B. Globulin was increased in group B and decreased in groups C and D. Decreased neutrophils were found in group D (all statistically significant). Correlation analysis showed significant association of angiotensin converting enzyme with IgA and IgM, inverse correlation of IgG with white blood cells and neutrophils, of IgA with globulin and inverse with albumin and of calcium with albumin. Most sarcoidosis patients have normal or increased immunoglobulin levels, that correlate with serum biomarkers of disease activity. Hypogammaglobulinemia may reflect treatment side effects and accompanied by blood leukocytosis. Combined severe immunodeficiency occurs in sarcoidosis.

An unusual disease with an interesting sign.

Acute interstitial pneumonias mimic infectious pneumonias. Radiology signs point to, but usually don't establish, diagnosis. http://bit.ly/3b3P1iK.

Integrating multi-disciplinary discussion in clinical practice.

Interstitial lung diseases are very heterogeneous. We present a case of usual interstitial pneumonia pattern on high resolution computed tomography of the chest that was diagnosed successfully after multi-disciplinary discussion. Pulmonologists should be aware of the pitfalls in the diagnostic management of interstitial lung diseases, especially in cases with atypical clinical presentation and systemic signs and symptoms.