40例职业性化学碱灼伤救治体会

[摘要]　目的　评估直接抗病毒药物（direct antivirus agent, DAA）治疗肝移植术后HCV感染复发的有效性和安全性。方法?回顾性分析首都医科大学附属北京佑安医院2011年2月—2018年12月收治的14例肝移植术后HCV感染复发患者的DAA治疗临床数据，比较患者基线与治疗结束后肝肾功能、血常规、凝血功能、病毒学水平以及无创纤维化评分天冬氨酸转氨酶血小板比率指数（aspartate aminotransferase-platelet ratio index, APRI）的差异。利用电子病历系统和电话随访收集患者治疗期间不良反应发生情况。结果?所有患者均在治疗结束时达到病毒学清除，12周、24周持续病毒学应答率均为100%，DAA治疗后随访17～44个月，期间均未见病毒学复发。与基线水平相比，治疗终点时ALT、AST、TBIL、γ-谷氨酰转移酶以及无创纤维化评分APRI显著下降，WBC、HGB、PLT、CRE、肾小球滤过率和血糖等指标均未见显著变化。DAA治疗期间共3例患者发生不良反应，均为轻度，可自然缓解。结论?肝移植术后HCV感染复发的DAA治疗是安全有效的。     

胸段食管癌累及野放疗与扩大野放疗对危及器官的辐射剂量学分析

目的 研究胸段食管癌逆向调强放射治疗（IMRT）中累及野照射与扩大野照射对危及器官（OAR）受照剂量的影响。方法 40例胸段食管癌患者分别行累及野靶区勾画和扩大野靶区勾画并勾画危及器官，制定IMRT计划，评估2个计划的靶区适形指数（CI）和均匀性指数（HI）及危及器官的剂量学参数，剂量学参数比较采用配对t检验。结果 2种计划的PTV均能满足处方剂量要求，PTV在CI、HI上相近（P = 0.317、0.130）。两组间平均肺剂量、两肺V₅、两肺V₂₀、两肺V₃₀、脊髓D_mean、心脏D_mean、心脏D_max、心脏V₃₀、心脏V₄₀、心脏V₆₀差异均存在统计学意义（P < 0.01）。结论 胸段食管癌患者行累及野照射与扩大野比较，可降低正常器官的受照剂量，从而降低放射性损伤风险。     

Validation of the Modena bleeding score in endoscopic sinus surgery

IntroductionThe Modena bleeding score is a categorical rating scale that allows the assessment of the surgical field in relation to bleeding during endoscopic surgery. It has recently been presented and validated in the field of endoscopic ear surgery by the present authors. The Modena bleeding score provides five grades for rating the surgical field during endoscopic procedures (from grade 1 ? no bleeding to grade 5 ? bleeding that prevents every surgical procedure except those dedicated to bleeding control).ObjectiveThe aim of this study was to validate the Modena bleeding score in the setting of endoscopic sinus surgery.MethodsFifteen three-minute videos of endoscopic sinus surgery procedures (each containing three bleeding situations) were evaluated by 15 specialists, using the Modena bleeding score. Intra and inter-rater reliability were assessed, and the clinical validity of the Modena bleeding score was calculated using a referent standard.ResultsThe data analysis showed an intra-rater reliability ranging from 0.6336 to 0.861. The inter-rater reliability ranged from 0.676 to 0.844. The clinical validity was α = 0.70; confidence limits: 0.64 ? 0.75, corresponding to substantial agreement.ConclusionThe Modena bleeding score is an effective method to score bleeding during endoscopic sinus surgery. Its application in future research could facilitate the performance and efficacy assessment of surgical techniques, materials or devices aimed to bleeding control during endoscopic sinus surgery.     

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

Dose optimization with population pharmacokinetics of ritonavir-boosted lopinavir for Thai people living with HIV with and without active tuberculosis

BackgroundPrior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH.MethodsLPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated.ResultsRifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150 mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150 mg twice daily was recommended.ConclusionThe population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH.     

Correlation between cow’s milk protein allergy and otitis media: a systematic review

ObjectivesTo review the evidence pertaining to the association between cow’s milk protein allergy and recurrent acute otitis media and otitis media with effusion.MethodsThe CENTRAL, Web of Science, EMBASE, MEDLINE, LILACS databases, and gray literature were searched.ResultsFour studies were included, identifying the prevalence rates: 0.2% of delayed speech due to chronic otitis media with effusion in 382 children with cow’s milk protein allergy, 10.7% of cow’s milk protein allergy in 242 children who underwent ENT procedures, 40% of cow’s milk protein allergy in 25 children with recurrent otitis media with effusion and higher tendency to otitis media in children with cow’s milk protein allergy of 186 children (1.5 + 0.6 vs. 0.4 + 0.1; p < 0.1).ConclusionConsidering the characteristics and methodological variations of the identified studies, it is not possible to state that there is reliable evidence of an association between cow’s milk protein allergy and otitis media.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

信息化随访干预措施对HBV感染患者依从性影响分析

目的通过信息化随访方式干预慢性乙型病毒性肝炎患者,对比分析其对患者疾病及用药依从性影响。方法收集2014年10月至2017年10月惠州市第六人民医院门诊及住院部诊断为慢性乙型病毒性肝炎、乙肝肝硬化患者,剔除不符合纳入条件患者,共纳入符合条件患者264例,有42例合并肝硬化。对纳入患者采取分层随机抽样方法进行分组,最终微信+电话随访组87例,电话随访组88例,对照组89例。随访并对比三组在2年后肝功能、肝硬化人数及停用恩替卡韦时间等不同差异。结果随访年后三组在失访人数上差异存在统计学意义,其中A组与B组2年后两组在ALT(Z=-3.218,P=0.02)、AST(Z=-2.749,P=0.03)、Alb(Z=1.746,P=0.04)、乙肝病毒DNA(Z=-3.231,P=0.02)指标差异具有统计学意义,而TBil、FIB-4指数、APRI、γ-GT指标差异无统计学意义。A组与C组2年后对比结果显示,两组在ALT(Z=-11.089,P<0.001)、AST(Z=-9.247,P=0.01)、TBil(Z=-7.623,P=0.01)、APRI(Z=-4.834,P=0.01)、γ-GT(Z=-2.867,P=0.03)、Alb(Z=3.187,P=0.02)、乙肝病毒DNA(Z=-10.078,P<0.001)指标差异具有统计学意义,而FIB-4指数指标差异无统计学意义。B组与C组2年后两组对比结果显示,两组在ALT(Z=-1.275,P=0.04)、AST(Z=-2.045,P=0.03)、TBil(Z=-3.762,P=0.02)、APRI(Z=-1.461,P=0.04)、γ-GT(Z=-2.254,P=0.03)、乙肝病毒DNA(Z=-1.782,P=0.04)指标差异具有统计学意义,而Alb、FIB-4指数指标差异无统计学意义。随访2年后A组肝硬化人数为12人,B组为16人,C组为24人。A组与B组(χ²=0.945,P=0.408)、B组与C组肝硬化人数(χ²=2.741,P=0.103)差异无统计学意义,而A、C两组肝硬化人数差异有统计学意义(χ²=6.843,P=0.013)。在2年时间内,A组有15例患者暂停使用恩替卡韦,B组有28例,C组有61例,三组停用恩替卡韦人数差异有统计学意义(χ²=25.061,P<0.001),通过Kaplan-meier分析,结果显示A组使用恩替卡韦时间长于B组(83.0%vs 68.5%,χ²=5.754,P=0.016)及C组(83.0%vs 33.7%,χ²=61.601,P<0.001),而B组使用时间长于C组(63.5%vs 33.7%,χ²=32.451,P<0.001)。结论通过对患者强化信息化干预,可以使患者服用抗乙肝病毒药物依从性提高,降低患者肝功能异常发生及肝硬化发病率。