Exploration of the optimal GS-441524 trough concentration for treating COVID-19.

OBJECTIVES: Remdesivir (RDV) is the cornerstone for treating coronavirus disease 2019 (COVID-19). The active metabolite of RDV, GS-441524 (a nucleoside analogue), has high interindividual variability in plasma concentrations; however, its concentration-response relationship is still unclear. This study investigated the target GS-441524 trough concentration for symptom improvement in COVID-19 pneumonia. METHODS: This single-center, retrospective, observational study included Japanese patients (age ≥15 years) with COVID-19 pneumonia who were administered RDV for ≥3 days from May 2020 to August 2021. To determine the cut-off value of GS-441524 trough concentration on Day 3, achievement of the National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS) ≤3 after RDV administration was evaluated using the cumulative incidence function (CIF) with the Gray test and time-dependent receiver operating characteristic (ROC) analysis. Multivariate logistic regression analysis was performed to determine factors influencing GS-441524 target trough concentrations. RESULTS: The analysis comprised 59 patients. The CIF revealed that GS-441524 trough concentration ≥70 ng/mL was associated with the achievement of NIAID-OS ≤3 (P = 0.047), which was significant based on the time-dependent ROC analysis. Factors influencing GS-441524 trough concentration ≥70 ng/mL included a decrease in estimated glomerular filtration rate (eGFR) [adjusted odds ratio (aOR) = 0.96, 95% confidence interval (CI) 0.92-0.99; P = 0.027] and BMI ≥25 kg/m2 (aOR = 0.26, 95% CI 0.07-0.86; P = 0.031). CONCLUSION: GS-441524 trough concentration ≥70 ng/mL is a predictor of efficacy in COVID-19 pneumonia. The presence of lower eGFR or BMI ≥25 kg/m2 was associated with achieving GS-441524 trough concentration ≥70 ng/mL.

[Primary Lung Cancer Initially Suspected of Pulmonary Extranodal Marginal Zone Lymphoma of Mucosa Associated Lymphoid Tissue(MALT)].

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is associated with pre-existing infections or autoimmune disorders. We report a case of lung cancer initially suspected of MALT lymphoma. The patient was a 73-year-old woman. Complete screening examinations identified a tumor in the right middle lobe. Transbronchial lung biopsy revealed the infiltration of CD20+/CD79a+ lymphocytes invading the structure of the alveolus. MALT lymphoma was suspected, and the middle lobe was resected. The tumor was primarily invasive mucinous carcinoma, and lymphocytic infiltration was observed around the tumor. The monoclonal expansion of B cells and genetic and chromosomal abnormalities which are criteria for the diagnosis of MALT lymphoma were not demonstrated and the lesion was diagnosed as reactive lymphoid infiltrates. Marked lymphocytic infiltration regardless of neoplastic or reactive may suggest the presence of latent lesions.

Prevalence of previously undiagnosed airflow limitation in patients who underwent preoperative pulmonary function test.

Although being a rapidly expanding socioeconomical burden worldwide, chronic obstructive pulmonary disease (COPD) is often overlooked because of its insidious progression. Since spirometry is the primary tool for the diagnosis of COPD, physicians should be aware of the disease in any situation where interpreting spirometry. This study was to estimate the prevalence of undiagnosed COPD among patients who underwent spirometry as a preoperative evaluation for elective surgeries. Patients aged 40 years or older who completed routine spirometry as a preoperative evaluation for elective surgeries between January to December, 2000. Medical records were reviewed for medical history, clinical findings, smoking status, and discharge diagnoses for patients who demonstrated airflow limitation (AL), defined as FEV(1)/FVC<70% on spirometry. Of the 1031 patients who qualified for the study, 263 (26%) presented AL. Sixty-nine of these patients with AL (26%) had underlying conditions that could account for AL, such as asthma and previously diagnosed COPD. The remaining 194 patients with AL (74%) were suspected to have undiagnosed COPD, 90% of which was mild in severity. Only 30 (15%) of these patients appeared to be diagnosed have received a diagnosed as COPD by physician on this occasion. This study testifies that COPD is often unnoticed, and demonstrates that every spirometry, such as in preoperative evaluation, gives a clue to identify affected individuals, for which awareness of the disease is essential.