Electronic clinical records in primary care for estimating disease burden and management. An example of COPD

Chronic obstructive pulmonary disease (COPD) is a significant health problem in developed countries. We aimed to estimate the prevalence of COPD in a single Spanish healthcare area. We also aimed to assess if there are any differences in prevalence and spirometry use among primary care services by utilizing already registered information. We designed a cross-sectional study to determine the prevalence of COPD and the performance of spirometries in each primary care service. A total of 8,444 patients were diagnosed with COPD, with a prevalence of 2.6% for individuals older than 39 years. The prevalence increased with age and was much higher in men. Significant heterogeneity was found in the prevalence of COPD and spirometry use among primary care services. COPD was underdiagnosed and there was wide variability in spirometry use in our area. Greater efforts are needed to diagnose COPD in order to improve its clinical outcomes and to refine registries so that they can be used as reliable sources of information     

Hernias de la incisión de asistencia tras resección colorrectal laparoscópica. Influencia de la localización de la incisión y del uso de una malla profiláctica

Objectives

To determine the incidence of incisional hernia (IH) in the extraction incision (EI) in colorectal resection for cancer. To analyze whether the location of the incision has any relationship with the incidence of hernias and whether mesh could be useful for prevention in high-risk patients.

原发癌灶定位与甲状腺微小癌颈侧区淋巴结转移关系研究

目的 探究原发灶定位与甲状腺乳头状微小癌（PTMC）颈侧区淋巴结转移的关系，评估超声检查预测颈侧区淋巴结转移的准确率。方法 回顾性分析2014年1月至2015年12月天津医科大学肿瘤医院收治的134例PTMC病人的临床资料，均行中央区淋巴结清扫+改良颈侧区淋巴结清扫。依据超声定位分组，分析癌灶位置与颈侧区淋巴结转移的关系。结果 颈侧各分区淋巴结转移发生率分别为：Ⅱ区30.6%、Ⅲ区50.7%、Ⅳ区57.5%、Ⅴ区11.3%。癌灶位于中上极者颈侧区淋巴结转移发生率高于癌灶位于下极者（89.7% vs. 75.7%，P=0.038），靠近外侧者较内侧者更易出现颈侧区淋巴结转移（93.7% vs. 81.4%，P=0.049）。超声检查判定Ⅱ、Ⅲ、Ⅳ、Ⅴ区淋巴结转移的敏感度分别为43.9%、85.3%、85.7%、14.3%；特异度为91.4%、57.6%、35.1%、99.1%。超声预测Ⅲ、Ⅳ区淋巴结转移敏感度较高，Ⅱ、Ⅴ区淋巴结转移特异度较高。结论 癌灶位置与甲状腺微小癌颈侧区淋巴结转移密切相关，超声可为临床确定颈侧区淋巴结的清扫范围提供依据。     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

杨宇飞教授舌癌的中医康复治疗与验案两则＊

舌癌患者手术及放化疗后会出现构音障碍、吞咽困难、口腔黏膜炎、口干、营养不良等并发症，使患者生存质量下降，甚至导致肿瘤的复发转移，影响生存期，单一方法往往顾此失彼。依托于中国中医科学院西苑医院肿瘤康复基地，杨宇飞教授在国内外调研考察基础上，结合中国国情，构建了一种“门诊多学科肿瘤康复模式”，在舌癌康复方面，以患者为中心，以中医肿瘤内科为主导，多学科共同参与，结合康复科、口腔科、营养科、药剂科等各科优势，形成全程个体化规范序贯康复方案，对患者及早进行康复，在放疗前进行预防性干预尤其重要，使患者能够快速缓解手术和放疗的不良反应，患者获益明显。现取两个典型案例总结其舌癌多学科康复的经验，以期为舌癌的康复提供借鉴。     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Long-term follow-up of camouflage effects following resin infiltration of post orthodontic white-spot lesions in vivo

Objectives:To reassess the long-term camouflage effects of resin infiltration (Icon, DMG, Hamburg, Germany) of white spot lesions (WSL) and sound adjacent enamel (SAE) achieved in a previous trial. The null hypothesis was tested that there were no significantly different CIE-L*a*b*-ΔE-values between WSL and SAE areas of assessment after at least 24 months (T24) compared to those at baseline (T0).Materials and Methods:Of twenty subjects who received previous resin infiltration treatment of n_teeth = 111 nonrestored, noncavitated postorthodontic WSL after multibracket treatment during a randomized controlled trial and were contacted 20 months after baseline, eight subjects (trial teeth n_teeth = 40; m/f ratio 1/7; age range (mean; SD) 12–17 [15.25; 2.12] years); response rate: 40%) were available for follow-up after at least 24 months (T24). CIE-L*a*b* differences between summarized color and lightness values (ΔE_WSL/SAE) of WSL and SAE were assessed using a spectrophotometer and compared to baseline data assessed prior to infiltration (T0), and those after 6 (T6), and 12 (T12) months using paired t tests at a significance level of α = 5%.Results:T24 assessments were performed after a mean 33.86 (SD: 8.64; Min: 24; Max: 45) months following T0. Mean (SD) ΔE_WSL/SAE units of available teeth were 8.76 (5.33) at baseline; 5.5 (2.75) at T6; 5.2 (2.41) at T12; and 5.57 (2.6) at T24. Comparisons of T6, T12, and T24 with T0 yielded highly significant differences, whereas T6–T24 and T12–T24 differences were found to be not significant.Conclusions:Assimilation of infiltrated WSL to the color of adjacent enamel by resin infiltration is considered to be suitable for the long-term improvement in the esthetic appearance of postorthodontic WSL.     

Application of metagenomic next-generation sequencing for suspected infected pancreatic necrosis

BackgroundMetagenomic next-generation sequencing (mNGS) is increasingly used for the clinical diagnosis of infectious diseases, but there is a paucity of data regarding the application of mNGS in the early diagnosis of infected pancreatic necrosis (IPN).ObjectiveTo investigate the clinical application value of mNGS in the pathogenic diagnosis of IPN.MethodsForty-two patients with suspected IPN were prospectively and consecutively enrolled from August 2019 to August 2021. Blood samples were collected for mNGS and microbial culture simultaneously during fever (T ≥ 38.5 °C). For patients who had indications of surgical interventions, peri-pancreatic specimens were collected for mNGS and microbial culture simultaneously during the first surgical intervention to confirm IPN. The clinical performance of mNGS and microbial culture were compared.ResultsA total of 21 patients (50.0%) were confirmed to have IPN during hospitalization. The sensitivity of blood mNGS was significantly higher than blood culture (95.2% vs. 23.8%, P < 0.001) in diagnosing IPN. The negative predictive value of blood mNGS was 90.0%. The turnaround time of mNGS was significantly shorter than that of microbial culture [(37.70 ± 1.44) vs. (115.23 ± 8.79) h, P < 0.01] and the average costs of mNGS accounted for 1.7% of the average total cost of hospitalization. The survival analysis demonstrates that the positive blood mNGS result was not associated with increased mortality (P = 0.119).ConclusionsWith more valuable diagnostic performance and shorter turnaround time, clinical mNGS represents a potential step forward in the early diagnosis of IPN.     

小分子抗血管生成药物在非小细胞肺癌中的研究进展

肺癌是世界上发病率最高的癌症之一，且尚无二线进展后的标准治疗方案，而肿瘤血管生成目前已被确定为恶性肿瘤的重要治疗靶点，小分子多靶点血管激酶抑制剂可通过抑制血管生成相关信号通路，抑制肿瘤血管的生成。目前已开展多项小分子抗血管生成药物治疗非小细胞肺癌的临床试验，且已有部分血管内皮生长因子受体酪氨酸激酶抑制剂（vascular endothelial growth factor receptor-tyrosine kinase inhibitors, VEGFR-TKIs）获批治疗晚期非小细胞肺癌，本文基于国内外多项小分子抗血管生成药物治疗非小细胞肺癌的发展现状，归纳了多个VEGFR-TKIs及成纤维细胞生长因子受体（fibroblast growth factor receptor, FGFR）-TKI单药或联合[包括分别与化疗、表皮生长因子受体（epidermal growth factor receptor, EGFR）-TKIs、免疫治疗、放疗等联合）]治疗非小细胞肺癌的疗效与安全性研究，同时探讨了VEGFR-TKIs可能存在的耐药机制及疗效预测指标等，并对未来抗血管治疗非小细胞肺癌的发展趋势以及存在的潜在问题进行展望，同时为肺癌后续的精准治疗及个体化治疗提供新的思路。