Improved pairwise kinship analysis using massively parallel sequencing

In the present study, 67 individuals from two families were analyzed to explore the efficacy of the ForenSeq^™ DNA Signature Prep Kit for pairwise kinship analysis. Six types of pairwise relationships including 81 parent-offspring, 60 full siblings, 48 grandparent-grandchildren, 147 uncle/aunt-nephew/nieces, 97 first cousins and 190 non-relatives were generated from these two families and the corresponding likelihood ratio (LR) was calculated using either sequence-based or length-based STR genotype data (i.e., LR_sequence and LR_length). In addition, 10,000 pairs of different relationships were simulated to estimate the system powers of the STRs and SNPs in this panel. The results showed that 54, 9 and 5 additional alleles were observed based on sequence for 27 autosomal STRs, 24 Y-STRs and 7 X-STRs, respectively, compared to those based on length information and 11 novel alleles were identified. Five mutations were found for 58 STRs in 81 parent-offspring but no mutations were observed for SNPs. For 27 autosomal STR loci, the LRs were increased from 9.20, 7.87, 2.01, 2.07, 0.42 for log₁₀LR_length to 11.52, 10.12, 2.61, 2.60, 0.52 for log₁₀LR_sequence for paternity index (PI), full siblings index (FSI), grandparent-grandchild index (GI), uncle/aunt-nephew/niece index (UNI) and first cousins index (FCI), respectively. PI values for 94 SNPs separated more than those of 27 STRs if two individuals were non parent-offspring relatives. For the simulation study, the effectiveness was 1 for the parent-offspring relationship at the thresholds of t₁ = − 4 and t₂ = 4 and was 0.9998 for full siblings (t₁ = − 2, t₂ = 2). With an error rate of 0.42%, 93.02% of second degree relatives could be identified at the thresholds of t₁ = − 1 and t₂ = 1. However, the effectiveness was only 0.4300 for first cousins with a relatively high error rate of 2.68% (t₁ = − 1, t₂ = 1). In conclusion, STR typing according to the sequence information is more polymorphic, which increases the discrimination power for kinship testing. Compared to these 27 STR markers, 94 SNP markers in this panel have advantages in paternity testing especially when mutated STRs are involved or when a relative is an alleged parent. This panel is powerful enough to resolve paternity and full sibling testing. Most of the second degree relationships could be identified with low error rate while more markers are still needed for first cousins testing.     

Neurólise do tronco celíaco com o uso de agulha única versus agulha dupla no manejo da dor abdominal maligna: estudo randômico controlado

BackgroundComputerized tomography‐guided celiac plexus neurolysis has become almost a safe technique to alleviate abdominal malignancy pain. We compared the single needle technique with changing patients’ position and the double needle technique using posterior anterocrural approach.MethodsIn Double Needles Celiac Neurolysis Group (n = 17), we used two needles posterior anterocrural technique injecting 12.5 mL phenol 10% on each side in prone position. In Single Needle Celiac Neurolysis Group (n = 17), we used single needle posterior anterocrural approach. 25 mL of phenol 10% was injected from left side while patients were in left lateral position then turned to right side. The monitoring parameters were failure block rate and duration of patient positioning, technique time, Visual Analog Scale, complications (hypotension, diarrhea, vomiting, hemorrhage, neurological damage and infection) and rescue analgesia.ResultsThe failure block rate and duration of patient positioning significantly increased in double needles celiac neurolysis vs. single needle celiac neurolysis (30.8% vs. 0.13.8±1.2 vs. 8.9 ± 1; p = 0.046, p ≤ 0.001 respectively). Also, the technique time increased significantly in double needles celiac neurolysis than single needle celiac neurolysis (24.5 ± 5.1 vs. 15.4 ± 1.8; p ≤ 0.001). No significant differences existed as regards visual analogue scale: double needles celiac neurolysis = 2 (0‐5), 2 (0‐4), 3 (0‐6), 3 (2‐6) and single needle celiac neurolysis = 3 (0‐5), 2 (0‐5), 2 (0‐4), 4 (2‐6) after 1 day, 1 week, 1 and 3 months respectively. However, visual analogue scale in each group reduced significantly compared with basal values (p ≤ 0.001). There were no statistically significant differences as regards rescue analgesia and complications (p > 0.05).ConclusionSingle needle celiac neurolysis with changing patients’ position has less failure block rate, less procedure time, shorter duration of patient positioning than double needles celiac neurolysis in abdominal malignancy.     

Single-source dual energy CT to assess myocardial extracellular volume fraction in aortic stenosis before transcatheter aortic valve implantation (TAVI)

PurposeTo assess myocardial extracellular volume fraction (ECV) measurement provided by a single-source dual-energy computed tomography (SSDE-CT) acquisition added at the end of a routine CT examination before transcatether aortic valve implantation (TAVI) compared to cardiac magnetic resonance imaging (MRI).Materials and methodsTwenty-one patients (10 men, 11 women; mean age, 86 ± 4.9 years [SD]; age range: 71–92 years) with severe aortic stenosis underwent standard pre-TAVI CT with additional cardiac SSDE-CT acquisition 7 minutes after intravenous administration of iodinated contrast material and myocardial MRI including pre- and post-contrast T1-maps. Myocardial ECV and standard deviation (σECV) were calculated in the 16-segments model. ECV provided by SSDE-CT was compared to ECV provided by MRI, which served as the reference. Analyses were performed on a per-segment basis and on a per-patient involving the mean value of the 16-segments.ResultsECV was slightly overestimated by SSDE-CT (29.9 ± 4.6 [SD] %; range: 20.9%–48.3%) compared to MRI (29.1 ± 3.9 [SD] %; range: 22.0%–50.7%) (P < 0.0001) with a bias and limits of agreement of +2.3% (95%CI: −16.1%– + 20.6%) and +2.5% (95%CI: −2.1%– + 7.1%) for per-segment and per-patient-analyses, respectively. Good (r = 0.81 for per-segment-analysis) to excellent (r = 0.97 for per-patient-analysis) linear relationships (both P < 0.0001) were obtained. The σECV was significantly higher at SSDE-CT (P < 0.0001). Additional radiation dose from CT was 1.89 ± 0.38 (SD) mSv (range: 1.48–2.47 mSv).ConclusionA single additional SSDE-CT acquisition added at the end of a standard pre-TAVI CT protocol can provide ECV measurement with good to excellent linear relationship with MRI.     

猪尾巴导管在单孔胸腔镜肺肿瘤手术中应用的有效性评估:基于倾向性评分匹配法的研究

目的评估猪尾巴导管在单孔胸腔镜肺肿瘤手术中应用的有效性。方法回顾性分析2020年1月至12月上海交通大学医学院附属仁济医院东院接受单孔胸腔镜肺肿瘤手术的患者共441例,根据是否放置猪尾巴导管分为胸管组和猪尾巴管组,通过倾向性评分匹配法进行1∶1匹配,对比两组患者围手术期的各项指标。结果匹配后每组143例配对成功,匹配后两组间基线特征无统计学差异。对比两组围手术期指标发现,猪尾巴管组患者术后3天胸腔引流总量显著多于胸管组(375.49 ml对285.03 ml,P<0.001),术后两周复查CT示胸腔积液量显著少于胸管组(131.77 ml对178.84 ml,P=0.032),两组术后疼痛评分、引流天数及住院天数无明显统计学差异。结论加放猪尾巴导管可有效改善单孔胸腔镜肺肿瘤术后胸腔引流情况,且不增加患者术后疼痛,不延长胸腔引流及住院天数。     

C反应蛋白和白蛋白比值预测单发小肝癌患者微血管侵犯的价值研究

背景 既往对肝癌微血管侵犯病理诊断的重要性重视不够，目前国内外缺乏对微血管侵犯统一的病理诊断标准，也未将微血管侵犯列为病理常规诊断指标。C反应蛋白/白蛋白比值（CAR）作为新型系统性炎性因子，与肝癌的增殖、侵袭转移等恶性生物学行为密切相关。 目的 探讨CAR预测单发小肝癌患者微血管侵犯的价值。 方法 选择2017年6月至2021年6月在新疆医科大学第一附属医院行肝切除术的单个、肿瘤直径≤5 cm的术后病理检查证实为肝癌的患者346例为研究对象。收集患者一般资料，并计算CAR。绘制CAR预测单发小肝癌患者微血管侵犯的受试者工作特征（ROC）曲线，并计算CAR的最佳诊断截点，根据CAR最佳诊断截点将患者进行分组，采用1∶1最近邻居倾向性评分匹配（PSM）法将Logistic模型估计的倾向性评分相近患者进行配对，得到两组间各临床特征比较均衡性较高的样本。比较匹配后两组患者微血管侵犯率，采用Logistic回归分析评估匹配前、后CAR对单发小肝癌患者微血管侵犯的预测价值。 结果 346例患者中微血管侵犯阳性131例（37.9%），微血管侵犯阴性215例（62.1%）。ROC曲线分析结果显示，CAR预测单发小肝癌患者微血管侵犯的灵敏度为82.9%，特异度为76.4%，ROC曲线下面积为0.787〔95%CI（0.697，0.877）〕，最佳诊断截点为0.03。根据CAR最佳诊断截点，将患者分为CAR<0.03组（A组，n=145）和CAR≥0.03组（B组，n=201）。采用1∶1最近邻居PSM法，共92对匹配成功，匹配后两组临床资料均衡。匹配后，B组患者微血管侵犯发生率〔43.5%（40/92）〕高于A组〔13.0%（12/92）〕（χ2=6.314，P=0.013）。采用3种Logistic回归分析结果显示，匹配前、后CAR均为单发小肝癌患者微血管侵犯的独立影响因素（P<0.05）。 结论 CAR作为新型系统性炎症指标，可用于预测单发小肝癌微血管侵犯，当CAR≥0.03时提示单发小肝癌微血管侵犯发生率较高。     

泸州汉族人群MTHFR基因多态性分布及育龄妇女该基因多态性与复发性流产相关性的研究

目的了解泸州市亚甲基四氢叶酸还原酶(MTHFR)基因多态性分布情况以及该单核苷酸多态性与复发性流产的相关性。方法选取2016-2018年在西南医科大学附属医院进行MTHFR基因检测的泸州汉族人群691例为研究对象,利用PCR-微阵列基因芯片法检测其C677T单核苷酸多态性,统计得出3种基因型的频率以及等位基因频率,并与全国其他地区已报道的多态性分布特征进行比较。结果泸州汉族人群CC、CT与TT基因型频率分别为39.2%、46.7%、14.0%,T等位基因频率为37.4%。其中女性T等位基因频率为38.1%,基因分布与纬度相近地区(N25°~31°)差异无统计学意义(P>0.05),与南方的海南、惠州及北方的西安、银川、赤峰、烟台人群差异有统计学意义(P<0.05)。在泸州育龄妇女中,复发性流产与MTHFR C677T基因多态性暂未发现存在直接关联。结论泸州地区汉族人群的MTHFR基因分布具有西南地区的分布特征,T等位基因频率整体呈现出随着纬度升高而升高的趋势。     

Molecular genetic analysis reveals atypical confined placental mosaicism with a small supernumerary marker chromosome derived from chromosome 18: A clinical report of discordant results from three prenatal tests

We present a case with discordant results in three prenatal screening methods, with additional genetic analyses. Non-invasive prenatal testing (NIPT) was performed on a 41-year-old Japanese woman at 10 weeks of gestation, and the result was positive for trisomy 18 with high accuracy. Amniocentesis was performed at 16 weeks of gestation. However, the result showed 47,XX,+mar[16]/47,XX,+18[2]. Fetal examination by ultrasound revealed no malformations. After termination of the pregnancy, we performed additional genetic analyses, and confirmed the presence of confined placental mosaicism (CPM). Furthermore, a small supernumerary marker chromosome (sSMC) was detected in fetal cells, which was derived de novo from the centromere of chromosome 18. Single nucleotide polymorphism array analysis revealed that fetal chromosome 18 was inherited with maternal uniparental disomy, with a relatively large copy-neutral loss of heterozygosity, including its centromere. Our genetic analyses strongly indicated the cause of result discrepancy in prenatal testing as incomplete trisomy 18 rescue leading to atypical CPM with a sSMC. These findings also offer insight into the mechanisms by which chromosomal aberrations form during human oogenesis and embryogenesis.