No abstract

Objective: The influence of continuous renal replacement therapy (CRRT) on the steady-state plasma concentration of high-dose tigecycline was investigated in septic shock patients to provide references for drug dosing.Methods: In this prospective observational study, 17 septic shock patients presenting with severe infections needing a broad-spectrum antibiotic therapy with high-dose tigecycline (100 mg per 12 h) in the intensive care unit were included and divided into CRRT group (n = 6) or non-CRRT group (n = 11). The blood samples were collected and plasma drug concentration was determined by SHIMADZU LC-20A and SHIMADZU LCMS 8040. The steady-state plasma concentration was compared between groups using unpaired t-test. Furthermore, between-groups comparisons adjusted for baseline value was also done using multivariate linear regression model.Results: Peak concentration (Cmax) of tigecycline was increased in CRRT group compared to non-CRRT group, but there were no statistical differences (505.11 ± 143.84 vs. 406.29 ± 108.00 ng/mL, p-value: 0.129). Trough concentration (Cmin) of tigecycline was significantly higher in CRRT group than in non-CRRT group, with statistical differences (287.92 ± 41.91 vs. 174.79 ± 33.15 ng/mL, p-value: 0.000, adjusted p-value: 0.000). In safety, Cmin was reported to be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL. In our studies, Cmin of all patients in CRRT group was lower than 474.8 ng/mL.Conclusion: The plasma concentration of tigecycline was increased in septic shock patients with CRRT treatment and only Cmin shown statistical differences. No dose adjustment seems needed in the view of hepatotoxicity.Clinical Trial Registration:https://www.chictr.org.cn/, identifier ChiCTR2000037475.

Pancreatic carcinoma is the leading cause of death among digestive malignancies in China. In particular, there is no breakthrough in prolonging the survival of pancreatic cancer patients with chemical and targeted therapies. Tumor immunotherapy brings opportunities and progress for the treatment of pancreatic cancer. Sintilimab is an innovative PD-1 inhibitor which was reported certain clinical benefits in multi-line treatments of advanced pancreatic cancer with gemcitabine. The combination therapy of PD-1 with gemcitabine plus high-intensity focused ultrasound (HIFU) in pancreatic cancer has not been reported. Here we report a case of a Chinese old patient diagnosed with metastatic pancreatic cancer. Two months after sintilimab treatment, the patient occurred severe immune colitis. The patient was diagnosed with immune ureteritis after 8 months of treatment. The immue-related adverse events (irAEs) refined after timely recognition and correct intervention by the clinician and clinical pharmacist. After first-line treatment of sintilimab plus gemcitabine combined with pancreatic HIFU, the patient achieved a remarkable benefit of 11-month progression-free survival (PFS) and 20-month overall survival (OS). The first-line treatment of sintilimab plus gemcitabine combined with HIFU demonstrates a potential therapeutic effect on metastatic pancreatic carcinoma with tolerable adverse reactions.