Background: Tuberculous meningitis (TBM) is one of the most serious types of extrapulmonary tuberculosis. However, low sensitivity of culture of cerebrospinal fluid (CSF) increases the difficulty in clinical diagnosis, leading to diagnostic delay, and misdiagnosis. Xpert MTB/RIF assay is a rapid and simple method to detect tuberculosis. However, the efficacy of this technique in diagnosing TBM remains unclear. Therefore, a meta-analysis was conducted to evaluate the diagnostic efficacy of Xpert MTB/RIF for TBM, which may enhance the development of early diagnosis of TBM. Methods: Relevant studies in the PubMed, Embase, and Web of Science databases were retrieved using the keywords ‘Xpert MTB/RIF’, ‘tuberculous meningitis (TBM)’. The pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, summary receiver operator characteristic curve, and area under the curve (AUC) of Xpert MTB/RIF were determined and analyzed. Results: A total of 162 studies were enrolled and only 14 met the criteria for meta-analysis. The overall pooled sensitivity of Xpert MTB/RIF was 63% [95% confidence interval (CI), 59–66%], while the overall pooled specificity was 98.1% (95% CI, 97.5–98.5%). The pooled values of positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 20.91% (12.71–52.82%), 0.40% (0.32–0.50%), and 71.49% (32.64–156.56%), respectively. The AUC was 0.76. Conclusions: Xpert MTB/RIF exhibited high specificity in diagnosing TBM in CSF samples, but its sensitivity was relatively low. It is necessary to combine other high-sensitive detection methods for the early diagnosis of TBM. Moreover, the centrifugation of CSF samples was found to be beneficial in improving the sensitivity.

No abstract

Portal vein tumor thrombus (PVTT) is a frequent complication in hepatocellular carcinoma (HCC). HCC patients with PVTT have the characteristics of less treatment tolerance and poor prognosis. Immunotherapy, especially combined immunotherapy, has been successfully used in advanced HCC. However, there are no recognized universally indicators that can predict response or resistance to immunotherapy for HCC. Herein, we reported a 58-year-old HCC patient with PVTT, cirrhosis and chronic viral hepatitis, who achieved complete response (CR) after combined immunotherapy (camrelizumab combined with sorafenib or regorafenib), according to his high enrichment of tumor-infiltrating immune cells and tertiary lymphoid structure (TLS). In this case, we revealed the characteristics of the baseline tumor immune microenvironment (TIME) in a HCC patient who responded well to combined immunotherapy, suggesting that TIME can be used to assist in clinical decision making of immunotherapy for HCC.

BackgroundMinimal residual disease (MRD) is considered an essential factor leading to relapse within 2 years (early relapse) after radical surgery, which is challenging to be detected by conventional imaging. Circulating tumor DNA (ctDNA) provides a novel approach for detecting MRD and predicting clinical outcomes. Here, we tried to construct a fixed panel for plasma-only ctDNA NGS to enable tumor-uninformed MRD detection in hepatocellular carcinoma (HCC).MethodsHere, we performed the followings: (i) profiling genomic alteration spectrum of ctDNA from the Chinese HCC cohort consisting of 493 individuals by NGS; (ii) screening of MRD monitoring genes; and (iii) performance evaluation of MRD monitoring genes in predicting early relapse in the ZJZS2020 cohort comprising 20 HCC patients who underwent curative resection.ResultsA total of 493 plasma samples from the Chinese HCC cohort were detected using a 381/733-gene NGS panel to characterize the mutational spectrum of ctDNA. Most patients (94.1%, 464/493) had at least one mutation in ctDNA. The variants fell most frequently in TP53 (45.1%), LRP1B (20.2%), TERT (20.2%), FAT1 (16.2%), and CTNNB1 (13.4%). By customized filtering strategy, 13 MRD monitoring genes were identified, and any plasma sample with one or more MRD monitoring gene mutations was considered MRD-positive. In the ZJZS2020 cohort, MRD positivity presented a sensitivity of 75% (6/8) and a specificity of 100% (6/6) in identifying early postoperative relapse. The Kaplan-Meier analysis revealed a significantly short relapse-free survival (RFS; median RFS, 4.2 months vs. NR, P=0.002) in the MRD-positive patients versus those with MRD negativity. Cox regression analyses revealed MRD positivity as an independent predictor of poor RFS (HR 13.00, 95% CI 2.60-69.00, P=0.002).ConclusionsWe successfully developed a 13-gene panel for plasma-only MRD detection, which was effective and convenient for predicting the risk of early postoperative relapse in HCC.

e16135 Background: Given its clear efficacy and high safety demonstrated in the phase 3 ZGDH3 study, donafenib has been recommended by the Chinese guidelines for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). Recently, combination therapies have shown favorable results. However, triple therapy with donafenib, anti-PD-1 antibodies, and transarterial therapy has not yet been investigated. Thus, we aimed to investigate the efficacy and safety of triple therapy with donafenib, anti-PD-1 antibodies, and transarterial therapy in patients with uHCC. Methods: A single-center, retrospective study was performed based on the medical records of consecutive patients diagnosed with HCC who were not suitable for curative surgery or local ablation at Zhujiang Hospital of Southern Medical University from June 2021 to October 2022. Patients with ≥18 years, Child-Pugh score ≤7, ECOG PS ≤1, no prior systemic therapy, having at least one measurable lesion (per mRECIST) were enrolled. Patients were treated with donafenib 200 mg orally twice daily, anti-PD-1 antibodies intravenously every three weeks, and transarterial therapy until disease progression or unacceptable toxicity. Endpoints include objective response rate (ORR, the proportion of patients with partial or complete response according to mRECIST and RECIST v1.1), surgical conversion rate (the proportion of patients who successfully underwent resection), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Results: A total of 27 patients were enrolled (median age 52 years [range, 29–74], 81% males, 85% with HBV infection, 41% with cirrhosis, 48% with AFP level ≥400 ng/mL, and 67% in BCLC C). All patients received donafenib and anti-PD-1 antibodies with hepatic arterial infusion chemotherapy (HAIC, n = 10), transarterial chemoembolization (TACE, n = 8), or both (n = 9). By the cutoff date of January 6, 2023, the median follow-up duration was 6.8 months (95% confidence interval [CI], 5.9–7.7), and 17 (63.0%) patients were still undergoing treatment. The ORR and DCR were 59.3% and 92.6% by mRECIST, and 18.5% and 88.9% by RECIST v1.1, respectively. The surgical conversion rate was 22.2%, and the median surgical conversion time was 3.4 months (range, 2.2–4.6). The median PFS was 8.3 months (95% CI, 6.8–9.8), and median OS was not reached. The 6-month PFS rate and 12-month OS rate were 74.7% and 72.9%, respectively. Grade 3 treatment-related adverse events (TRAEs) were observed in 5 patients (18.5%), the most common of which was increased total bilirubin (11.1%). No grade 4/5 TRAEs occurred. Conclusions: Donafenib combined with anti-PD-1 antibodies plus transarterial therapy shows promising efficacy and manageable toxicity in patients with initially uHCC. Clinical trial information: NCT05638438 .