Biomarkers for response to immunotherapy in hepatobiliary malignancies

BackgroundThe advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic options of hepatobiliary malignancies. However, the clinical benefit provided by immunotherapy seems limited to a small subgroup of patients with hepatobiliary malignancies. The identification of reliable predictors of the response to immunotherapy is urgently needed.Data sourcesLiterature search was conducted in PubMed for relevant articles published up to May 2022. Information of clinical trials was obtained from https://clinicaltrials.gov/.ResultsBiomarkers for ICI response of hepatobiliary malignancies remain in the exploration stage and lack compelling evidence. Tumor programmed death-ligand 1 (PD-L1) expression is the most widely studied biomarker in hepatocellular carcinoma (HCC) and biliary tract cancers (BTCs), but there are conflicting results on its predictive potential. Tumor mutational burden (TMB) is generally low both in HCC and BTCs, and the clinical trials of TMB are rare in hepatobiliary malignancies. Promisingly, mismatch repair deficiency (dMMR)/high microsatellite instability (MSI-H) may be a predictive biomarker of response to anti-PD-1 therapy in BTCs. Furthermore, some emerging biomarkers, such as gut microbiota, show predictive potential in the preliminary studies. Radiomics and liquid-biopsy biomarkers, including circulating tumor cells, circulating tumor DNA (ctDNA) and exosomal PD-L1 provide a quick and non-invasive approach for monitoring the ICI response, showing a new promising direction.ConclusionsMultiple potential biomarkers for predicting ICI response of hepatobiliary malignancies have been explored and tried to apply in clinic. Yet there is no robust evidence to prove their clinical value in predicting immunotherapeutic response for patients with hepatobiliary malignancies. The identification of predictors for response to ICIs is an urgent need and major challenge. Further studies are warranted to validate the role of emerging biomarkers in predicting immunotherapeutic responses.     

关注特殊人群抗菌药物应用的安全性

婴幼儿、妊娠及哺乳期妇女、肝肾功能不全患者及老年人等特殊人群存在不同程度的免疫功能不全,发生感染的概率高于其他人群,抗菌药物的使用率较高,而因其特殊的生理病理状态和药物代谢特点,发生不良反应的风险更大。因此,抗菌药物在特殊人群中应用的安全性应得到更多的关注。掌握特殊人群的病理生理特点和抗菌药物的药代动力学特点,加强对特殊人群抗菌药物处方的审核和点评,有助于提高抗菌药物合理用药水平,减少抗菌药物对特殊人群的伤害。     

AIDS抗病毒治疗6个月内机会性感染的变化和分布状况

目的 探讨对AIDS患者进行高效抗反转录病毒治疗6个月内机会性感染的变化和分布状况.方法 使用统一的调查表进行回顾性和前瞻性研究.调查表的内容涉及患者编号、性别、年龄、治疗开始时间、治疗方案、开始抗病毒治疗前3个月、治疗后2周内、2周～3个月和3～6个月出现机会性感染的情况及基线、治疗3个月和治疗6个月CD4+T淋巴细...     

D-dimer for assessment of treatment response,and survival to drug-eluting beads transarterial chemoembolization in hepatocellular carcinoma

BackgroundD-dimer exhibits a certain prognostic value in hepatocellular carcinoma (HCC) patients who underwent hepatectomy and microwave ablation, while its value in estimating the clinical benefit of drug-eluting beads transarterial chemoembolization (DEB-TACE) remains unclear. Hence, this study aimed to investigate the correlation of D-dimer with tumor features, response and survival to DEB-TACE in HCC patients.MethodsFifty-one HCC patients treated with DEB-TACE were recruited. Their serum samples at baseline and after DEB-TACE were collected and proposed for D-dimer detection by the immunoturbidimetry method.ResultsElevated D-dimer levels were related to a higher Child?Pugh stage (P = 0.013), tumor nodule number (P = 0.031), largest tumor size (P = 0.004), and portal vein invasion (P = 0.050) in HCC patients. Then, patients were classified by the median value of D-dimer, and it was observed that patients with D-dimer >0.7 mg/L achieved a lower complete response rate (12.0% vs. 46.2%, P = 0.007) but a similar objective response rate (84.0% vs. 84.6%, P = 1.000) compared to those with D-dimer ≤0.7 mg/L. The Kaplan?Meier curve showed that D-dimer >0.7 mg/L (vs. ≤0.7 mg/L) was related to shorter overall survival (OS) (P = 0.013). Further univariate Cox regression analyses showed that D-dimer >0.7 mg/L (vs. ≤0.7 mg/L) was related to unfavorable OS [hazard ratio (HR): 5.524, 95% confidence interval (CI): 1.209–25.229, P = 0.027], but it failed to independently estimate OS (HR: 10.303, 95%CI: 0.640–165.831, P = 0.100) in multivariate Cox regression analyses. Moreover, D-dimer was elevated during DEB-TACE therapy (P<0.001).ConclusionD-dimer may be helpful for monitoring prognosis to DEB-TACE therapy in HCC, while further large-scale-study validation is warranted.     

肝硬化合并肠系膜上静脉栓塞患者2年预后预测模型的构建与验证

目的 探讨肝硬化合并肠系膜上静脉栓塞(superior mesenteric venous thrombosis, SMVT)长期预后的影响因素，构建2年预后预测模型并进行预测效果评价。方法 采集2016年12月至2020年3月确诊的肝硬化合并SMVT患者254人的临床信息，以2019年3月30日为时间节点分为建模组(170例)和验证组(84例)。建模组依据随访2年时的结局分为生存组(148例)和死亡组(22例),运用多因素Logistic回归分析患者预后影响因素，建立模型并绘制列线图；采用受试者工作特征(receiver operating characteristic, ROC)曲线、校准曲线和Hosmer-Lemeshow拟合优度检验评价预测模型的准确性、区分度和校准度；决策曲线分析(decision curve analysis, DCA)评估预测模型的临床有效性。结果 年龄(HR=4.625,95%CI:1.493～14.322,P=0.008)、粒细胞/淋巴细胞比值(neutrophils/lymphocyte ratio, NLR)(HR=4.650,95%CI:1.34...     

肝硬化门静脉高压症合并原发性肝癌患者腹腔镜术后并发症危险因素分析

目的 分析肝硬化门静脉高压症合并原发性肝癌腹腔镜同期联合手术并发症危险因素，为完善围手术期并发症预防护理提供参考。方法 回顾分析105例患者临床资料，记录手术并发症发生情况，采用单因素分析与logistic回归分析手术并发症独立危险因素。结果 手术并发症总体发生率为68.57%。肺部感染、门静脉血栓和胸水发生率分别为25.71%、33.33%和28.57%。术前Child-Pugh分级、MELD评分、血红蛋白、术后卧床时间和腹腔引流管留置时间是总体手术并发症的危险因素(均P<0.05)。吸烟、术前MELD评分、术前腹水、手术方式、术后卧床时间和胃管留置时间是肺部感染的危险因素(均P<0.05)。术前Child-Pugh分级、血小板、术前腹水和手术方式是门静脉血栓的危险因素(均P<0.05)。年龄和术前MELD评分是术后胸水的危险因素(均P<0.05)。结论 肝硬化门静脉高压症合并原发性肝癌腹腔镜同期联合手术面临较高的手术并发症风险，应针对危险因素加强专科护理，以降低手术并发症发生率。     

Wolf in sheep's clothing - Oral proliferative verrucous leukoplakia: Progression with longitudinal molecular insights

BackgroundOral proliferative verrucous leukoplakia (OPVL) is a chronic form of oral leukoplakia that progresses to a multifocal disease with confluent, exophytic and proliferative features. The clinical differential diagnosis for OPVL includes frictional keratosis, leukoplakia, chronic hyperplastic candidiasis, squamous papilloma, verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma. In this study, we aimed to delineate the dynamic changes in molecular signature during OPVL progression. We compare to a cohort of oral cavity keratinizing squamous cell carcinoma (OSCC) patients covering the spectrum of verrucous carcinoma to invasive squamous cell carcinoma including cytologically bland cuniculatum variant.MethodsSamples from a large OPVL lesion that exhibited a histopathologic continuum of OPVL progression.ResultsCanonical hotspot TERT promoter mutations were identified in all patients. TERT C228T was dominant and mutually exclusive with TERT C250T. In patients with TERT C250T, there was concurrent PI3 point mutation. TP53 mutations were also consistently found (8/10). At the protein level, p53 was abnormal, with loss of function and gain of function.ConclusionsOPVL is a pathology that shows proximity to the gene expression profile of OSCC, highlighting signatures in common that can be important targets for drug treatment, as well as in the development of diagnostic and prognostic strategies for this disease.