Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Non-antiviral therapeutic options are required for the treatment of hospitalised patients with COVID-19. CD24Fc is an immunomodulator with potential to reduce the exaggerated inflammatory response to tissue injuries. We aimed to evaluate the safety and efficacy of CD24Fc in hospitalised adults with COVID-19 receiving oxygen support. METHODS: We conducted a randomised, double-blind, placebo-controlled, phase 3 study at nine medical centres in the USA. Hospitalised patients (age ≥18 years) with confirmed SARS-CoV-2 infection who were receiving oxygen support and standard of care were randomly assigned (1:1) by site-stratified block randomisation to receive a single intravenous infusion of CD24Fc 480 mg or placebo. The study funder, investigators, and patients were masked to treatment group assignment. The primary endpoint was time to clinical improvement over 28 days, defined as time that elapsed between a baseline National Institute of Allergy and Infectious Diseases ordinal scale score of 2-4 and reaching a score of 5 or higher or hospital discharge. The prespecified primary interim analysis was done when 146 participants reached the time to clinical improvement endpoint. Efficacy was assessed in the intention-to-treat population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT04317040. FINDINGS: Between April 24 and Sept 22, 2020, 243 hospitalised patients were assessed for eligibility and 234 were enrolled and randomly assigned to receive CD24Fc (n=116) or placebo (n=118). The prespecified interim analysis was done when 146 participants reached the time to clinical improvement endpoint among 197 randomised participants. In the interim analysis, the 28-day clinical improvement rate was 82% (81 of 99) for CD24Fc versus 66% (65 of 98) for placebo; median time to clinical improvement was 6·0 days (95% CI 5·0-8·0) in the CD24Fc group versus 10·0 days (7·0-15·0) in the placebo group (hazard ratio [HR] 1·61, 95% CI 1·16-2·23; log-rank p=0·0028, which crossed the prespecified efficacy boundary [α=0·0147]). 37 participants were randomly assigned after the interim analysis data cutoff date; among the 234 randomised participants, median time to clinical improvement was 6·0 days (95% CI 5·0-9·0) in the CD24Fc group versus 10·5 days (7·0-15·0) in the placebo group (HR 1·40, 95% CI 1·02-1·92; log-rank p=0·037). The proportion of participants with disease progression within 28 days was 19% (22 of 116) in the CD24Fc group versus 31% (36 of 118) in the placebo group (HR 0·56, 95% CI 0·33-0·95; unadjusted p=0·031). The incidences of adverse events and serious adverse events were similar in both groups. No treatment-related adverse events were observed. INTERPRETATION: CD24Fc is generally well tolerated and accelerates clinical improvement of hospitalised patients with COVID-19 who are receiving oxygen support. These data suggest that targeting inflammation in response to tissue injuries might provide a therapeutic option for patients hospitalised with COVID-19. FUNDING: Merck & Co, National Cancer Institute, OncoImmune.

Repeat needle biopsies combined with clinical observation are safe and accurate in the management of a solitary pulmonary nodule.

BACKGROUND: Sixty percent of removed solitary pulmonary nodules (SPNs) are benign. An approach that reduces the unnecessary excision of benign nodules is consistent with the oncologic objective of organ preservation. METHODS: A prospective observational study was performed at a lung cancer referral center in which consecutive patients were evaluated who presented with SPNs measuring < 4 cm on computed tomography (CT) scans. Patients underwent transbronchial biopsy (TBB), percutaneous needle aspiration (PCNA), clinical observation, repeat CT scans, and repeat biopsies. Patients were observed clinically and underwent repeat biopsies in an effort to reduce unnecessary surgical intervention. RESULTS: One hundred eighteen patients underwent 194 biopsy sessions, including 137 TBB sessions and 57 PCNA sessions. The mean follow-up was 4 years. The shortest follow-up of a benign lesion was 3 years. The incidence of malignancy was 61%. The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy all were 100%. Five patients had a delayed change in diagnosis from benign to malignant. This delay in diagnosis neither resulted in a change in tumor stage nor had an impact on patient management or survival. CONCLUSIONS: Repeat needle biopsies combined with clinical observation and repeat CT scans can classify an SPN as benign versus malignant with 100% accuracy (95% confidence interval, 96.1-100.0%). An SPN diagnostic approach that includes a TBB, then PCNA, clinical observation, repeat CT scans, and repeat biopsies for continued suspicion of malignancy appears to reduce the unnecessary surgical excision of benign nodules from the current rate of 60% to 5% of SPN resections without affecting the survival of patients who have malignant SPNs.

Diagnosis of primary bone tumors with image-guided percutaneous biopsy: experience with 110 tumors.

PURPOSE: To determine the diagnostic accuracy of image-guided percutaneous biopsy in 110 primary bone tumors of varying internal compositions. MATERIALS AND METHODS: One hundred ten consecutive patients with primary bone tumors underwent biopsy with computed tomography (CT) or fluoroscopy. Ninety-one patients underwent surgical follow-up and 19 received medical treatment and underwent subsequent imaging studies. Final analysis of bone biopsy results included tumor type, malignancy, final tumor grade, biopsy complications, and effect on eventual treatment outcome. RESULTS: Seventy-seven tumors were malignant and 33 were benign. Most common tumors at biopsy were osteosarcoma (n = 20), lymphoma (n = 18), chondrosarcoma (n = 16), and giant cell tumor (n = 16). Correct final diagnosis was attained in 97 (88%) patients. Sixty-three lesions were solid nonsclerotic; 26, sclerotic; and 21, lytic with cystic centers containing internal areas of fluid, hemorrhage, or necrosis. In six of 21 lesions with a predominant cystic internal composition, problems occurred in determining a final diagnosis. In 13 patients, definite correct diagnosis was not obtained with initial percutaneous bone biopsy. Of these patients, benign bone tumors were better defined with surgical specimens in seven, a diagnosis of malignancy was changed to that of another malignancy in four, and the diagnosis was changed from benign to malignant in two. Nine patients underwent open surgical biopsy. Seven of the difficult cases were of cystic tumors with hemorrhagic fluid levels visible at CT or magnetic resonance imaging. The only complication was a small hematoma. CONCLUSION: Percutaneous biopsy of primary bone tumors is safe and accurate for diagnosis and grade of specific tumor. In cases with nondiagnostic biopsy, open-procedure biopsy is likely to be associated with similar diagnostic difficulties.