Safety and Efficacy of Tocilizumab 4 or 8 mg/kg in Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial.

BACKGROUND: Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with coronavirus disease 2019 (COVID-19) pneumonia, but the optimal dose is unknown. METHODS: Patients hospitalized for moderate to severe COVID-19 pneumonia were randomized 1:1 to receive standard of care treatment and 1-2 doses of intravenous tocilizumab 4 mg/kg or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble interleukin 6 receptor (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60. The secondary end point was safety. Key exploratory efficacy end points included clinical status, time to discharge, mortality rate, and incidence of mechanical ventilation. RESULTS: Of 100 patients randomized, 49 received tocilizumab 4 mg/kg and 48 received 8 mg/kg. In pharmacokinetic and sIL-6R assessments, dose-dependent differences were seen in patients who received 1 or 2 doses of 4 or 8 mg/kg. Serum concentrations of IL-6, ferritin, and CRP and safety outcomes were comparable between groups. Through day 60, serious adverse events were reported in 30.6% and 25.0% of patients in the 4- and 8-mg/kg groups, respectively. Eight patients (16.3%) in the 4-mg/kg group and 6 (12.5%) in the 8-mg/kg group died. Exploratory time-to-event outcomes favored 8 mg/kg within the first 2 weeks. CONCLUSIONS: In patients with moderate to severe COVID-19 pneumonia who received tocilizumab 4 or 8 mg/kg, pharmacokinetic and sIL-6R assessments showed expected dose-dependent effects; pharmacodynamic assessments and safety were comparable, with no new safety signals. Further study is required before a lower dose of tocilizumab can be recommended in patients with COVID-19 pneumonia. CLINICAL TRIALS REGISTRATION: NCT04363736.

Marked Elevation in Serum Procalcitonin Levels Do Not Correlate With Severity of Disease or Mortality in Hospitalized Patients: A Retrospective Study.

BACKGROUND: Bacteremia and sepsis are significant contributors to the morbidity, mortality, and economic burden of health care systems worldwide. Procalcitonin has been identified as a potentially useful marker of disease and severity in sepsis. However, the assumption that greater procalcitonin levels correlate with greater burden of disease has not been adequately studied. METHODS: A retrospective chart review of adult patients admitted to an urban teaching hospital with suspected sepsis was undertaken to test the association of elevated procalcitonin (>30 ng/mL) with other markers of sepsis (lactic acid, white blood cell count, percent bands), severity of disease (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation-II [APACHE II] scores), and mortality. RESULTS: In total, 168 patients were identified over 18 months (42% ward, 11% Stepdown, 44% medical intensive care unit [MICU], 2% surgical intensive care unit (STICU), 1% gynecology [GYN]). The Spearman correlation analysis showed that serum procalcitonin level did not correlate with SOFA (P = .238) or APACHE II (P = .918) scores on admission, and did not correlate with survival (Kruskal-Wallis test, P = .937). However, higher serum procalcitonin levels were associated with patients who had positive blood cultures (Kruskal-Wallis test, P = .0016 for Gram-positive and P = .0007 for Gram-negative bacteria). Lactic acid levels on admission strongly correlated with SOFA APACHE II (the Spearman correlation, P < .0001 for both) and mortality (P = .0001 for both). CONCLUSIONS: Higher serum procalcitonin levels above 30 ng/mL failed to correlate with indicators of sepsis, severity of disease (SOFA and APACHE II scores), and mortality but were associated with positive blood cultures. Lactic acid levels did show correlation to both severity of disease and mortality. Serum procalcitonin levels >30 ng/mL do not appear to correlate with the severity of disease in a sample of patients with markedly elevated initial procalcitonin levels.

Rapidly progressive course of pauci-immune pulmonary capillaritis in a 70-year-old Asian male refractory to immunosuppression and plasma exchange.

A 70-year-old man presented with acute respiratory failure, alveolar infiltrates and haemoptysis requiring supplemental oxygen. Flexible bronchoscopy with bronchoalveolar lavage identifies diffuse alveolar haemorrhage. Clinical and serological evaluations do not identify a precise aetiology and histopathology establishes the diagnosis of isolated pauci-immune pulmonary capillaritis. The patient received induction therapy with high dose methylprednisolone at 1000 mg/day for 5 days and weekly rituximab at 375 mg/m2 scheduled over 4 weeks. Although the patient demonstrated clinical improvement after the first week, he experienced a rapid relapse requiring mechanical ventilation. His induction rituximab regimen was continued and plasma exchange was initiated. Despite these therapies, the patient's condition deteriorated and passed away. Our case adds insight to the management of this rare entity and describes the use of plasma exchange as salvage therapy.

Cavitary Lung Diseases: A Clinical-Radiologic Algorithmic Approach.

Cavities occasionally are encountered on thoracic images. Their differential diagnosis is large and includes, among others, various infections, autoimmune conditions, and primary and metastatic malignancies. We offer an algorithmic approach to their evaluation by initially excluding mimics of cavities and then broadly classifying them according to the duration of clinical symptoms and radiographic abnormalities. An acute or subacute process (< 12 weeks) suggests common bacterial and uncommon nocardial and fungal causes of pulmonary abscesses, necrotizing pneumonias, and septic emboli. A chronic process (≥ 12 weeks) suggests mycobacterial, fungal, viral, or parasitic infections; malignancy (primary lung cancer or metastases); or autoimmune disorders (rheumatoid arthritis and granulomatosis with polyangiitis). Although a number of radiographic features can suggest a diagnosis, their lack of specificity requires that imaging findings be combined with the clinical context to make a confident diagnosis.

Non-Small-Cell Lung Cancer Clinicopathologic Features and Survival Outcomes in Asian Pacific Islanders Residing in the United States: A SEER Analysis.

Background. The objective of our study was to ascertain racial/ethnic disparities in Asian/Pacific Islanders (API) for non-small-cell lung cancer (NSCLC) clinicopathologic features and survival outcomes based on various tumor characteristics and treatment modalities. Method. SEER database identified invasive NSCLC cases from 2004 to 2010. Variables included American Joint Committee on Cancer (AJCC) stage 7, tumor grade, tumor size, histology, age, marital status, radiation, surgery, and reason for no surgery. The Kruskall-Wallis test and the Z test were used to examine differences between races/ethnicities and the referent, non-Hispanic white (NHW). Multivariate Cox proportional analyses were used to establish the weight of the prognostic significance contributing to disease-specific survival (DSS) in each AJCC stage. Result. Improved DSS was seen in API across stage I (HR: 0.78), stage II (HR: 0.79), and stage IV (HR: 0.86), respectively, compared to the referent NHW (P < 0.01). Prognosis was improved by being married, being female gender, AIS histology, and birth outside the US (P < 0.01). Conclusion. We have demonstrated improved survival among API in early stage and stage IV NSCLC. Further research is necessary to clarify the role of lifestyle and tumor biology for these differences.