Access to Care: End-to-End Digital Response for COVID-19 Care Delivery

The coronavirus disease 2019 pandemic disrupted health care, requiring organizational leaders to act quickly to manage the health-related concerns of individuals and communities. The ability to offer a variety of digitally enabled telehealth services with 24/7 access to nurse practitioners and physician assistants allowed us to care for patients in their homes. It reduced the spread of the virus, protected our employees from further disease spread, and provided early interventions to those in need. The roles of nurse practitioner leaders, the enacted strategies, and patient outcomes demonstrate the impact of an innovative digital care delivery model on care across the continuum.     

基于规律成簇的间隔短回文重复序列及其相关蛋白技术检测乙型肝炎病毒共价闭合环状DNA方法的建立

目的建立一种基于规律成簇的间隔短回文重复序列及其相关蛋白(CRISPR/Cas13a)的乙型肝炎病毒(HBV)共价闭合环状DNA(HBV cccDNA)检测方法。方法提取2017年6月至2020年10月于首都医科大学附属北京佑安医院就诊的4例乙型肝炎患者肝脏总DNA后,使用HindⅢ内切酶和质粒安全性ATP依赖DNA酶(PSAD)分别进行酶切;根据松弛环状DNA(rcDNA)和cccDNA的结构差异,设计特异性扩增HBV cccDNA的引物,对酶切后的产物进行滚环扩增(RCA)和PCR扩增;并筛选crRNA,建立基于CRISPR/Cas13a技术的HBV cccDNA检测新方法。结果利用α-1-抗胰蛋白酶(A1AT)和HBV表面抗原(HBsAg)引物对双重酶切后的产物进行扩增,验证产物中HBV基因组的存在;利用HBV cccDNA和HBV rcDNA引物对PSDA酶切后的产物扩增,验证了产物中只存在HBV cccDNA;利用RCA后的阳性样本作为模板梯度稀释,然后进行PCR扩增转录后使用CRISPR/Cas13a检测,计算出检测下限为10拷贝/μl。结论本研究建立了RCA-PCR-CRISPR-Cas13a的新型检测方法,可对HBV cccDNA进行高灵敏度和高特异性检测,为乙型肝炎患者抗病毒治疗评估、治疗终点的确定以及调整治疗方案提供了有效的监测手段。     

Predicting osimertinib‐treatment outcomes through EGFR mutant‐fraction monitoring in the circulating tumor DNA of EGFR T790M‐positive patients with non‐small cell lung cancer (WJOG8815L)

The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).

Abbreviations

CIs

confidence intervals

ctDNA

circulating tumor DNA

ddPCR

droplet digital PCR

EGFR

epidermal growth factor receptor

MFs

mutant fractions

NGS

next‐generation sequencing

NSCLC

non‐small cell lung cancer

ORR

overall response rate

OS

overall survival

PD

progressive disease

PFS

progression‐free survival

PR

partial response

SD

stable disease

TKI

tyrosine kinase inhibitor

     

Effect of orbital wall resection areas in the treatment of patients with endocrine orbitopathy

In patients treated by orbital wall decompression for endocrine orbitopathy (EO) there is limited evidence on the effect of orbital wall resections. Thus, the aim of this study was to evaluate the effect of one, two, and three-wall resections on orbital parameters to determine if any such correlations exist. Preoperative and postoperative data from all patients at a tertiary care centre who underwent decompression surgery from 2010 - 2020 were digitally analysed. The effect of the number and area of resected walls on orbital area, orbital volume, and Hertel value, and the effect of lateral rim advancement (LARA) were determined. A total of 131 orbital areas showed an increase from a mean (SD) preoperative area of 42.0 (4.6) cm² to 47.3 (6.1) cm² postoperatively (p<0.001). In total, the mean (SD) area of osseous wall removed in all patients was 6.2 (1.7) cm² at the lateral orbit (n = 129), 6.7 (2.3) cm² at the orbital floor (n = 123), and 5.8 (1.8) cm² at the medial orbital wall (n =30). The mean (SD) orbital volume increased by 6.0 (3.0) cm³ after decompression. There was also a significant reduction in exophthalmos of 7.3 (3.2) mm (from 25.2 (3.9) to 17.9 (3.5), p<0.001). LARA was performed in 50 patients. Changes in volume and area, and reduction in exophthalmos were not significantly different with or without LARA. The postoperative effects of orbital wall resection are predictable and exhibit a relation with six units of change. Two-wall resection is the most common intervention.     

肿瘤的数字治疗北大核心

肿瘤治疗已经进入数字治疗时代。数字治疗是数字健康的重要部分,它是应用数字技术预防、控制和治疗疾病。人工智能分析由生物传感器发来的数据资料,远距离控制肿瘤患者进行虚拟治疗和数字临床试验,模拟现实在线治疗帮助肿瘤患者采取健康行为,这些技术正在改变现有的医学模式。     

The Viral Load of Epstein-Barr Virus in Blood of Children after Hematopoietic Stem Cell Transplantation

ObjectiveTo detect the Epstein-Barr virus (EBV) viral load of children after hematopoietic stem cell transplantation (HSCT) using chip digital PCR (cdPCR).MethodsThe sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain. The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses (herpes simplex virus 1, herpes simplex virus 2, varicella zoster virus, human cytomegalovirus, human herpesvirus 6, and human herpesvirus 7). From May 2019 to September 2020, 64 serum samples of children following HSCT were collected. EBV infection and the viral load of serum samples were detected by cdPCR. The epidemiological characteristics of EBV infections were analyzed in HSCT patients.ResultsThe limit of detection of EBV cdPCR was 110 copies/mL, and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid. The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain, and both were more sensitive than that of quantitative PCR. Using cdPCR, the incidence of EBV infection was 18.75% in 64 children after HSCT. The minimum EBV viral load was 140 copies/mL, and the maximum viral load was 3,209 copies/mL using cdPCR. The average hospital stay of children with EBV infection (184 ± 91 days) was longer than that of children without EBV infection (125 ± 79 days), P = 0.026.ConclusionEBV cdPCR had good sensitivity and specificity. The incidence of EBV infection was 18.75% in 64 children after HSCT from May 2019 to September 2020. EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.