Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal–Wallis tests were used to compare staining scores (intensity × percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (ρ) in all cases, and stratified by HPV status. HPV-negative HNSCC over-expressed EGFR [median (range): 30 (0–300)] relative to HPV-positive HNSCC [7.5 (0–200)] (P = 0.006). VEGF and NOTCH1 were unrelated to HPV status (P > 0.05). EGFR was associated with VEGF in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive HNSCC (ρ = 0.25, P = 0.20). NOTCH1 and VEGF were associated in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive tumors (ρ = −0.12, P = 0.57). NOTCH1 was not associated with EGFR (P > 0.05). Our results are suggestive of heterogeneity in HNSCC angiogenesis. Future studies should explore angiogenesis mechanisms in HPV-positive and HPV-negative HNSCC.

Electronic supplementary material

The online version of this article (doi:10.1007/s12105-013-0447-y) contains supplementary material, which is available to authorized users.     

Traumatic experiences and posttraumatic stress reactions in children and their parents from Kurdistan and Sweden

This study was conducted to assess trauma scores and posttraumatic stress symptoms among Kurdistanian refugee children and their parents in Sweden and a comparable group of Swedish children and their parents. Comparative Kurdistanian and Swedish samples composed of 32 children each and their parents were interviewed by means of a specially devised trauma instrument (HUTQ-C), to identify traumatic events and to measure trauma scores, and with (PTSS-C) and (HTQ) to diagnose posttraumatic stress syndrome (PTSD) among children and adults, respectively. Although Kurdistanian parents reported considerably more traumatic events than Swedish parents, children in both samples showed more similarities than differences, both with regard to types and levels of traumatic events. Kurdistanian parents showed higher PTSD frequencies than Swedish parents. However, these differences proved to be significant with regard to both the mother's and the father's lifetime and current PTSD symptom scores. Kurdistanian parents have experienced more war traumas and differ with regard to trauma exposure and its consequences when compared with Swedish parents. Children from the two samples showed more similarities than differences with regard to reported trauma and PTSD-related symptoms. These results underline the significance of child-specific factors in trauma and PTSD.     

血浆同型半胱氨酸和血清神经元特异性烯醇化酶对轻度血管性认知障碍的预测价值

目的探讨血浆同型半胱氨酸(Hcy)和血清神经元特异性烯醇化酶(NSE)对轻度血管性认知障碍(VMCI)的预测价值。方法选取VMCI患者51例,正常对照组45例,完成神经心理学评估,头颅MRI或CT检查,测定血浆Hcy和血清NSE水平。结果 (1)两组间年龄、性别、受教育程度差异无统计学意义(P>0.05)。与正常对照组比较,VMCI患者Hcy和NSE水平明显升高,差异有统计学意义(P<0.05);(2)VMCI患者中,LA-VMCI(23例)和LI-VMCI(28例),两组间Hcy和NSE水平差异无统计学意义(P>0.05);(3)相关性分析显示,血浆Hcy与血清NSE呈正相关(r=0.657,P=0.008);(4)以Hcy来预测VMCI,其曲线下AUC为0.871(P=0.000,95%CI 0.753～0.948),OPP=15.89μmol.L-1,敏感性为86.5%,特异性为87.1%,阳性预测值86.7%,阴性预测值71.3%。以NSE来预测VMCI,其曲线下AUC为0.866(P=0.000,95%CI 0.756～0.930),OPP=17.82μg.L-1,敏感性为87.8%,特异性为85.3%,阳性预测值91.5%,阴性预测值为78.7%。结论血浆Hcy和血清NSE对VMCI有一定预测价值。     

Growth hormone combined with child-specific motor training improves motor development in infants with Prader-Willi syndrome: A randomized controlled trial

Although severe motor problems in infants with Prader-Willi syndrome (PWS) are striking, motor development has never been studied longitudinally and the results of growth hormone (GH) treatment on motor development are contradictory. The authors studied whether GH treatment can enhance the effect of physical training on motor development in infants with PWS. Twenty-two infants were followed for two years during a randomized controlled trial. The treatment and control groups began GH after baseline or following a control period, respectively. Both groups followed a child-specific physical training program. Motor performance was measured every three months. Multi-level regression analysis revealed that motor development differed significantly between infants (p < .001), and this could be partially explained by baseline motor developmental level (p < .01). GH treatment enhanced the effects of child-specific physical training on both motor developmental rate and motor developmental potential. Moreover, this effect was more pronounced when GH treatment was initiated at a younger age.     

人工合成E-选择素对兔颈总动脉动脉瘤壁平滑肌细胞增殖活性的影响

目的 探讨人工合成E-选择素对兔颈总动脉动脉瘤壁平滑肌细胞增殖活性的影响.方法 新西兰白兔54只,雌雄各半,随机分成9组(每组6只),对照组;实验1、2、3、4周组;治疗l、2、3、4周组.用弹性蛋白酶(EA)滴注法建立兔右颈总动脉瘤模型,并用CTA和HE染色观察模型动脉瘤的形态学改变和病理变化,免疫组化分析基质金属蛋白酶-2(MMP-2)、细胞增殖核抗原(PCNA)和平滑肌α肌动蛋白(α-SMA)表达,Real-time PCR检测骨桥蛋白(OPN)和MMP-2 mRNA表达.结果 大体测量和CTA结果显示:治疗组与实验组相比,其动脉瘤高度和宽度均有不同程度减小;免疫组化结果显示:治疗组动脉瘤壁MMP-2蛋白表达与同期实验组相比均有减少,治疗1、2周组动脉瘤壁PCNA蛋白表达低于同期实验组,而治疗3、4周组动脉瘤壁PCNA蛋白表达与同期实验组比较表达升高;治疗组动脉瘤壁α-SMA蛋白表达低于同期实验组.Real-time PCR结果显示:治疗组动脉瘤壁OPN mRNA表达与同期实验组相比均有增加,而治疗组动脉瘤壁MMP-2 mRNA表达分别低于同期实验组.结论 人工合成E-选择素可以抑制兔颈总动脉瘤壁平滑肌细胞数目和层数的减少,有效促进兔颈总动脉瘤壁平滑肌细胞的增殖,使血管平滑肌细胞由收缩型向合成型转化,进而对动脉瘤壁起到一定的修复作用.     

Natural Language Processing of Radiology Reports in Patients With Hepatocellular Carcinoma to Predict Radiology Resource Utilization

ObjectiveRadiology is a finite health care resource in high demand at most health centers. However, anticipating fluctuations in demand is a challenge because of the inherent uncertainty in disease prognosis. The aim of this study was to explore the potential of natural language processing (NLP) to predict downstream radiology resource utilization in patients undergoing surveillance for hepatocellular carcinoma (HCC).Materials and MethodsAll HCC surveillance CT examinations performed at our institution from January 1, 2010, to October 31, 2017 were selected from our departmental radiology information system. We used open source NLP and machine learning software to parse radiology report text into bag-of-words and term frequency–inverse document frequency (TF-IDF) representations. Three machine learning models—logistic regression, support vector machine (SVM), and random forest—were used to predict future utilization of radiology department resources. A test data set was used to calculate accuracy, sensitivity, and specificity in addition to the area under the curve (AUC).ResultsAs a group, the bag-of-word models were slightly inferior to the TF-IDF feature extraction approach. The TF-IDF + SVM model outperformed all other models with an accuracy of 92%, a sensitivity of 83%, and a specificity of 96%, with an AUC of 0.971.ConclusionsNLP-based models can accurately predict downstream radiology resource utilization from narrative HCC surveillance reports and has potential for translation to health care management where it may improve decision making, reduce costs, and broaden access to care.     

Growth and differentiation factor-15 as a potential prognostic biomarker for status-epilepticus-associated-with-fever: A pilot study

ObjectiveBiomarkers predicting poor outcomes of status-epilepticus-associated-with-fever (SEF) at an early stage may contribute to treatment guidance. However, none have been reported thus far. We investigated the dynamics of serum growth and differentiation factor (GDF)-15 after seizure onset in patients with SEF and determined whether GDF-15 can predict poor outcomes, particularly in the first 6 h after seizure onset.MethodsWe enrolled 37 pediatric patients with SEF and eight patients with simple febrile seizures (SFS) and collected their blood samples within 24 h of seizure onset and eight febrile control patients between March 1, 2017 and September 30, 2020. All patients were aged ≤15 years.ResultsIn the SEF group, the median post-seizure serum GDF-15 values were 1,065 (<6h), 2,720 (6–12 h), and 2,411 (12–24 h) pg/mL. The median serum GDF-15 in the first 6 h was measured in patients with SEF without a significant past medical history (n = 21) and was found to be statistically significantly higher (1,587 pg/mL) than in the febrile control (551 pg/mL) and SFS (411 pg/mL) groups. The median serum GDF-15 was statistically significantly higher in patients with SEF with sequelae (n = 5) and patients with acute encephalopathy with biphasic seizures/reduced diffusion/hemorrhagic shock and encephalopathy syndrome (n = 6) than in patients with SEF without sequelae (n = 16) (15,898 vs 756 pg/mL) and patients with prolonged FS (n = 15) (9,448 vs 796 pg/mL).ConclusionsThis study demonstrates the dynamics of serum GDF-15 in patients with SEF and indicates the potential of GDF-15 as an early predictor of poor outcomes.     

小儿化脓性脑膜炎脑脊液中HBP和VE-cadherin的水平变化及其对预后的预测价值

目的 探讨小儿化脓性脑膜炎脑脊液肝素结合蛋白(Heparin-binding protein,HBP)和血管内皮细胞钙黏蛋白(Vascular endothelial-cadherin,VE-cadherin)的水平变化及其对预后的预测价值。方法 选取2019年2月-2021年本院收治的化脓性脑膜炎患儿106例[(Purulent meningitis,PM)组]和病毒性脑炎患儿75例[(Vascular endothelial,VE)组],同时选取60例在本院就诊的非感染性疾病患儿作为对照组; 比较3组患儿脑脊液HBP,VE-cadherin水平变化; 将PM组患儿依据出院时格拉斯哥预后评分(Glasgow outcome scale,GOS)标准分为预后良好组和预后不良组,对比预后良好组和预后不良组患儿脑脊液HBP,VE-cadherin水平以及其他可能的影响因素; 采用Logistic回归分析法明确影响化脓性脑膜炎患儿预后不良的危险因素; 绘制受试者工作特征(ROC)曲线,分析脑脊液HBP,VE-cadherin水平对化脓性脑膜炎患儿预后不良的预测价值。结果 入院第1 d PM组、VE组患儿脑脊液HBP,VE-cadherin水平均高于对照组(P<0.05); PM组患儿脑脊液HBP,VE-cadherin水平均高于VE组(P<0.05)。治疗后PM组与VE组患儿脑脊液HBP,VE-cadherin水平均低于入院第1 d(P<0.05),但2组治疗7 d后比较无明显差异(P>0.05)。单因素分析显示,预后不良组休克、意识障碍、脑脊液细菌培养阳性的占比、脑脊液白细胞计数(White blood cell,WBC)、C-反应蛋白(C-reactive protein,CRP)、降钙素原(Procalcitonin,PCT)、HBP(入院第1 d与治疗7 d后)、VE-cadherin(入院第1 d与治疗7 d后)水平高于预后良好组(P<0.05)。经Logistic回归分析显示,休克、意识障碍、HBP(入院第1 d与治疗7 d后)、VE-cadherin(入院第1 d与治疗7 d后)水平均是化脓性脑膜炎患儿预后不良的危险因素(P<0.05)。受试者工作特征(Receiver operating characteristic,ROC)曲线分析显示,入院第1 d脑脊液HBP联合VE-cadherin水平预测化脓性脑膜炎患儿预后不良的灵敏度、准确度、曲线下面积(Areaunder the curve,AUC)分别为93.57%、92.16%、0.915,均高于脑脊液HBP,VE-cadherin单独预测; 治疗7 d后脑脊液HBP联合VE-cadherin水平预测化脓性脑膜炎患儿预后不良的灵敏度、准确度、曲线下面积(AUC)分别为96.89%、95.71%、0.931,均高于脑脊液HBP,VE-cadherin单独预测。结论 在化脓性脑膜炎患儿中脑脊液HBP,VE-cadherin水平异常升高,且是导致化脓性脑膜炎患儿预后不良的危险因素,对小儿化脓性脑膜炎的预后具有较高的预测价值。