注意缺陷多动障碍患儿血清25（OH）D及微量元素表达水平及临床意义

目的 探究注意缺陷多动障碍(ADHD)患儿血清25羟基维生素D[25(OH)D]、微量元素表达水平及临床意义。方法 选取2019年4月至2020年11月本院诊治的84例ADHD患儿进行研究(ADHD组),依据ADHD分型标准将患儿分为注意缺陷为主型组(28例)、多动为主型组(33例)、混合型组(23例),并选取同期84例体检健康儿童进行对照研究(对照组)。采用高效液相色谱-串联质谱法检测所有受试儿童血清25(OH)D水平；检测血清铁(Fe)、磷(P)、镁(Mg)、钙(Ca)、铜(Cu)、锌(Zn)、铅(Pb)水平；Pearson法分析ADHD患儿血清25(OH)D水平与Cu、Zn、Pb水平的相关性；Logistic回归分析ADHD发生的影响因素；受试者工作特征(ROC)曲线分析血清25(OH)D、Zn、Pb水平对ADHD的诊断价值。结果 ADHD组血清25(OH)D、Cu、Zn水平均显著低于对照组(P<0.05),Pb水平显著高于对照组(P<0.05)；注意缺陷为主型组、多动为主型组、混合型组患儿血清25(OH)D、Fe、P、Mg、Ca、Cu、Zn、Pb水平比较,差异无统计学意义(P>0.05)；ADHD患儿血清25(OH)D水平与Cu、Zn水平均呈正相关(P<0.05),与Pb水平呈负相关(P<0.05)；25(OH)D、Zn是影响ADHD发生的保护因素(P＜0.05),Pb是影响ADHD发生的危险因素(P＜0.05)；血清25(OH)D、Zn、Pb水平诊断ADHD的曲线下面积(AUC)分别为0.773、0.770、0.772,截断值分别为21.01 ng/mL、16.05 μmol/L、50.69 μg/L,相应灵敏度分别为82.1%、77.4%、63.1%,特异度分别为67.9%、71.4%、88.1%；三者联合诊断ADHD的AUC为0.883,其灵敏度、特异度分别为81.0%、81.0%。结论 ADHD患儿血清25(OH)D、Cu、Zn水平降低,Pb水平升高,25(OH)D、微量元素水平与ADHD患儿类型无关,25(OH)D、Zn、Pb联合有助于临床筛查ADHD患儿。     

Radiation-Free Thoracic Endovascular Aneurysm Repair with Fiberoptic and Electromagnetic Guidance: A Phantom Study

PurposeTo evaluate the feasibility and accuracy of a radiation-free implantation of a thoracic aortic stent graft employing fiberoptic and electromagnetic tracking in an anthropomorphic phantom.Materials and MethodsAn anthropomorphic phantom was manufactured based on computed tomography (CT) angiography data from a patient. An aortic stent graft application system was equipped with a fiber Bragg gratings and 3 electromagnetic sensors. The stent graft was navigated in the phantom by 3 interventionalists using the tracking data generated by both technologies. One implantation procedure was performed. The technical success of the procedure was evaluated using digital subtraction angiography and CT angiography (before and after the intervention). Tracking accuracy was determined at various anatomical landmarks based on separately acquired fluoroscopic images. The mean/maximum errors were measured for the stent graft application system and the tip/end of the stent graft.ResultsThe procedure resulted in technical success with a mean error below 3 mm for the entire application system and <2 mm for the position of the tip of the stent graft. Navigation/implantation and handling of the device were rated sufficiently accurate and on par with comparable, routinely used stent graft application systems.ConclusionsThe study demonstrates successful stent graft implantation during a thoracic endovascular aortic repair procedure employing advanced guidance techniques and avoiding fluoroscopic imaging. This is an essential step in facilitating the implantation of stent grafts and reducing the health risks associated with ionizing radiation during endovascular procedures.     

Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis

PurposeTo create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE).Materials and MethodsFluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4–6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4–6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75–250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (K_trans) and extracellular volume fraction (v_e) were calculated from DCE-MR imaging along the lateral synovial regions of interest.ResultsThe mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The K_trans/v_e values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed.ConclusionsA nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.     

Interpretation,pitfalls of biomarkers in diagnosis of invasive fungal diseases

BackgroundInvasive Fungal Diseases (IFD), account for high morbidity and mortality in immunocompromised and seriously ill patients worldwide. Early, faster and accurate diagnosis with timely and appropriate patient management is critical for improved patient outcome and antifungal stewardship. Clinical/radiological presentations in IFD are non-specific and microscopy/culture based tests have low sensitivity and long turnaround time. Biomarkers have clinical utility for diagnosing IFD but their interpretation is not straight forward.ObjectivesThis review discusses the salient characteristics, clinical usefulness and limitations of common biomarkers such as Galactomannan (GM), 1–3, β D glucan (βDG), mannan, anti-mannan antibody (Mn/antiMn), Cryptococcal antigen test (CrAg), Nucleic Acid Amplification (NAA) tests and next generation sequencing for diagnosing IFD.ContentsFungal biomarkers are useful adjuncts as screening and diagnostic tools for IFD and are much more suited for ‘ruling out’ rather than ‘ruling in’ disease. GM, NAA tests are promising biomarkers for screening of invasive Aspergillosis in high risk asymptomatic patients who are not on antifungal therapy and for diagnosis of breakthrough infections in symptomatic patients. 1–3, β D glucan has limitations both as a ‘rule in’ and ‘rule out’ test and is useful in only specific clinical settings. Two consecutive positive 1-3-βDG tests or combined positivity with GM increases its specificity. Mn/antiMn, T2Candida nano diagnostic panel are promising candidates for diagnosing invasive candidiasis. Combining two or more biomarkers improves the sensitivity for prompt initiation of antifungal therapy and the negative predictive value for suspension of empirical treatment.Serum CrAg test is a good ‘rule in’ rather than a ‘rule out’ test in immunocompetent patients but has good diagnostic accuracy in immunocompromised patients. Detection of single nucleotide polymorphisms by next generation sequencing is useful for fungal characterization and identification of host determinants responsible for increased susceptibility to fungal infections but is still in experimental stages.     

黄芩素调控 NLRP3 / Caspase-1 通路对牙周炎大鼠牙槽骨吸收的影响

目的 探索黄芩素调控核苷酸结合寡聚化结构域样受体蛋白 3 ( nucleotide-binding oligomerization domain-like receptor protein 3, NLRP3) / 半胱氨酸天冬氨酸蛋白酶 1 ( cysteine aspartate protease 1, Caspase1) 通路对牙周炎大鼠牙槽骨吸收的影响。 方法 将 40 只牙周炎大鼠随机分为模型组、 黄芩素组、 激活剂 组、 黄芩素 + 激活剂组, 另取 10 只正常作为对照组。 检测大鼠釉牙骨质界到牙槽嵴顶 (CEJ-AC) 的距离、 血清中白细胞介素-6 (IL-6)、 转化生长因子-β (TGF-β) 含量以及牙周组织病理变化、 IL-6、 TGF-β 阳性 表达和 NLRP3、 Caspase-1 蛋白表达。 结果 模型组大鼠 CEJ-AC、 NLRP3、 Caspase-1、 IL-6、 TGF-β 水平及 阳性表达水平以及蛋白表达水平均升高 (P< 0. 05); 经黄芩素干预后, 各项指标均降低 (P< 0. 05); 引入 激活剂明显削弱了黄芩素对牙周炎大鼠的抗炎作用。 结论 黄芩素通过抑制 NLRP3 / Caspase-1 通路减轻炎性反应, 控制牙槽骨吸收。     

Diagnostic pitfalls in needle core biopsy of the breast

Breast core biopsies are a standard component of the triple approach that includes clinical examination, imaging and tissue sampling. Conventional cores, diagnostic vacuum assisted biopsy and vacuum assisted excisions are established methods for sampling and managing breast lesions. It is important to be aware of the potential pitfalls in the technical handling and interpretation of the limited core biopsy samples. Here, we present a clinically oriented, well illustrated overview of the common diagnostic pitfalls based on the author's diagnostic and second opinion practice, emphasize the value of clinicopathological correlation and provide histological tips and clues with useful immunohistochemistry to aid the reporting pathologists in their daily interpretation of breast core biopsies.     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

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.     

子宫浆液性癌的分子学特征及靶向治疗研究进展

子宫浆液性癌（uterine serous carcinoma,USC）是一种特殊类型的子宫内膜癌。有别于常见的子宫内膜样腺癌,USC较为少见,且恶性程度高,侵袭转移风险高,临床上预后较差。随着子宫内膜癌分子学研究的不断深入,分子学特征被应用于子宫内膜癌的病理分型诊断、治疗和预后评价中。研究发现USC中存在多种基因的突变,这些相关基因的突变对该病的诊断和预后具有重要的指导意义。同时,特异性的分子学改变为USC的靶向治疗提供了潜在的治疗靶点。目前,多种靶向治疗手段包括人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）抑制剂、免疫检查点抑制剂、抗血管生成治疗、磷脂酰肌醇3激酶（phosphoinositide 3-kinases,PI3K）通路抑制剂和多腺苷二磷酸核糖聚合酶[poly(ADP-ribose) polymerase,PARP]抑制剂等被应用于USC的临床治疗研究中,针对性的靶向治疗有望成为USC治疗的新突破。     

Management of blood pressure disorders in individuals with spinal cord injury

Blood pressure regulation is impacted by a spinal cord injury (SCI) due to impaired descending sympathetic vascular control. Common blood pressure problems in the SCI population include persistently low blood pressure with bouts of orthostatic hypotension and autonomic dysreflexia, which are more prevalent in individuals with lesions above the sixth thoracic vertebral level; however, they may occur regardless of the neurological level of injury. Although blood pressure disorders adversely impact daily function and quality of life, most individuals with SCI do not acknowledge this association. Few pharmacological options have been rigorously tested for safety and efficacy to manage blood pressure disorders in the SCI population. Furthermore, clinical management of any one blood pressure disorder may adversely impact others, as such treatment is complicated and not often prioritized.