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Patients with cancer have been prioritized for vaccination against severe acute respiratory syndrome coronavirus 2. Nevertheless, there are limited data regarding the safety, efficacy, and risk of developing immune-related adverse events (irAEs) associated with mRNA vaccines in patients with lung cancer, especially those being actively treated with immune checkpoint inhibitors.This multicenter observational study was conducted at nine hospitals in Japan. Patients with lung cancer (≥20 y) actively treated with immune checkpoint inhibitors between 4 weeks prefirst vaccination and 4 weeks postsecond vaccination were enrolled. The primary end point was the incidence of irAEs of any grade on the basis of an assumed incidence without vaccination rate of 35%. Immunogenicity was assessed by measuring anti-spike (S)-IgG antibody levels against severe acute respiratory syndrome coronavirus 2.A total of 126 patients with lung cancer (median age, 71 y; interquartile range, 65-74) were enrolled from May to November 2021 and followed up until December 2021. There were 26 patients (20.6%, 95% confidence interval: 13.9%-28.8%) and seven patients (5.6%, 95% confidence interval: 2.3%-11.1%) who developed irAEs of any grade pre- and postvaccination, respectively, which was lower than the predicted incidence without vaccination. None of the patients experienced exacerbation of preexisting irAE postvaccination. S-IgG antibodies were seroconverted in 96.7% and 100% of the patients with lung cancer and controls, respectively, but antibody levels were significantly lower in patients with lung cancer (p0.001).Patients with lung cancer who were actively treated with ICIs were safely vaccinated without an increased incidence of irAEs; however, their vaccine immunogenicity was lower. This requires further evaluation.

Acetaminophen (APAP)-induced liver injury (AILI) is the most common cause of acute liver failure. Although the mechanisms that trigger AILI are well known, it is less understood how to halt AILI progression and facilitate liver recovery. Therefore, it is necessary to understand the pathophysiology of APAP hepatotoxicity in patients and to examine predictive/preventive markers. In a clinical study, we had a case in which aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels increased in a patient with a low ratio of APAP glucuronide concentration (AP-G)/APAP plasma concentration. Then a reverse translational study was conducted for clarifying this clinical question. The relationship between plasma AP-G/APAP concentration ratio and the levels of AST and ALT was examined by in vivo and in vitro experiments. In in vivo experiments, 10-week-old rats showed lower UGT activity, lower AP-G/APAP concentration ratios, and higher AST and ALT levels than 5-week-old rats. This suggests an inverse correlation between the AP-G/APAP concentration ratio and the AST, ALT levels in APAP-treated rats. Furthermore, as a result of the in vitro experiment, it was confirmed that the cell viability decreased when the AP-G/APAP concentration ratio in the culture medium decreased. Since the decrease in the plasma AP-G/APAP concentration ratio appears earlier than the increase of AST and ALT levels, the ratio might be a presymptomatic marker of AILI. When APAP is used for a long time, it is recommended to perform therapeutic drug monitoring of the AP-G/APAP concentration ratio, which is a predictive/preventive marker of AILI.

We aimed to assess the efficacy and safety of synbiotics, including live microorganisms and non-digestible food ingredients, in patients undergoing high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT). This prospective, randomized, double-blind study, included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomized to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo including dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). The secondary endpoint was safety. A total of 12 patients were included and randomized. The median duration of TPN was 15 days (range, 12–33 days) in the synbiotic group and 17.5 days (range, 0–32 days) in the placebo group, with no clear difference between the two groups. The median duration of grade 3 or higher diarrhea was shorter in the synbiotic group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). Oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Synbiotics may reduce gastrointestinal toxicity leading to nutritional problems and improve the quality of life of patients undergoing auto-HSCT, without severe adverse events. (The Japan Registry of Clinical Trials, No. jRCTs051180026.)

Chemoimmunotherapy improved overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage small cell lung cancer (ES-SCLC) in two phase III trials. They set the age-stratified subgroup analyses at 65 years; however, over half of the patients with lung cancer were newly diagnosed at ≥75 years in Japan. Therefore, treatment efficacy and safety in elderly patients ≥ 75 years with ES-SCLC should be evaluated through real-world Japanese evidence. Consecutive Japanese patients with untreated ES-SCLC or limited-stage SCLC unfit for chemoradiotherapy between 5 August 2019 and 28 February 2022 were evaluated. Patients treated with chemoimmunotherapy were divided into the non-elderly (