Objective: To retrospectively analysely the electrophysiological and imaging features of isolated congenital anosmia (ICA) and to assess the clinical phenotypic characteristics and classification of ICA. Methods: Clinical data of 30 ICA patients in Beijing Anzhen Hospital from 2012 to 2019 was retrospectively reviewed, including 13 males and 17 females, aged (35±19) years. The control group consisted of 30 healthy people from medical examination center, including 13 males and 17 females, aged (39±14) years. The clinical characteristics of ICA were analyzed using Sniffin' Sticks test, olfactory event-related potentials (oERPs), trigeminal event-related potentials (tERP) and olfactory pathway MRI. SPSS 17.0 software was used to compare the difference of olfactory function between the two groups. The correlation between olfactory bulb, olfactory sulcus structure and age was observed, and the clinical phenotype characteristics of ICA patients were analyzed. Results: The subjective olfactory function was completely lost in ICA patients. oERP was absent in all of the ICA patients, but showed normal N1 and P2 waves in controls. tERP could be evoked in 63.3% (19/30) of ICA patients, and signals in these patients showed higher amplitude in the N1 ((-10.33±6.93) μV vs (-5.11±2.71) μV, t=-10.113, P 0.05). Conclusions: ICA patients show neurophysiologic deficits and some anatomic differences compared with healthy controls. The absence of oERP combining with a depth of olfactory sulcus less than 8 mm is the important indicator for clinical diagnosis of ICA. The structure of olfactory bulb may be a critical factor for clinical classification of ICA.
Objective: To investigate the white matter integrity in patients with olfactory dysfunction using diffusion tensor imaging (DTI). Methods: Twenty-one patients with olfactory dysfunction and sixteen age, sex and level of education matched normal subjects were recruited in this study. Sniffin' Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired diffusion tensor images with a echo planar imaging (EPI) sequence from all subjects on a 3T scanner. The fractional anisotropy (FA) images were performed using DTI-studio, and bilateral piriform cortex, orbitofrontal cortex, hippocampus and insula cortex adjacent white matter as well as capsula interna were delineated from the FA images as the region of interest associated with olfactory (ROI(awo)) manually. Independent sample t test analysis was used to compare the FA value of all ROI(awo) between the controls and patients. Results: In olfactory dysfunction group, the FA value of adjacent white matter of right piriform cortex and orbitofrontal cortex were significantly lower than those of control group (0.42±0.05 (x±s) vs 0.45±0.05, 0.43±0.06 vs 0.49±0.07, t value was 2.32, 2.79, respectively, all P<0.05). The FA value of adjacent white matter of left piriform cortex and orbitofrontal cortex had no significant difference compared with those of control group (0.43±0.05 vs 0.45±0.04, 0.44±0.04 vs 0.47±0.06, t value was 1.65, 1.37, respectively, all P>0.05). The FA value of the adjacent white matter of bilateral hippocampus, insula cortex and capsula interna had no significant difference compared with those of control group, neither (0.45±0.08 vs 0.44±0.08, 0.45±0.09 vs 0.44±0.10, 0.41±0.08 vs 0.39±0.07, 0.41±0.07 vs 0.38±0.05, 0.64±0.08 vs 0.63±0.08, 0.64±0.07 vs 0.63±0.07, t value was 0.30, 0.15, 0.88, 1.34, 0.14, 0.35, respectively, all P>0.05). Conclusions: The patients with olfactory dysfunction showed abnormal white matter connection in the major primary and secondary olfactory cortex. The reduced white matter integrity in ROI(awo) might contribute to the pathogenesis of olfactory dysfunction.目的： 分析嗅觉障碍患者脑白质的完整性。 方法： 收集2014—2016年就诊于首都医科大学附属北京安贞医院耳鼻咽喉头颈外科的21例嗅觉障碍患者(患者组)与16例年龄、性别、受教育程度相匹配的健康志愿者(对照组)，对其进行Sniffin′ Sticks嗅觉功能测试及脑磁共振弥散张量成像(diffusion tensor imaging，DTI)检查。以DTI－studio软件处理脑DTI图像，得到各向异性分数(fractional anisotropy，FA)参数图，选择双侧梨状皮层、眶额皮层、海马、岛叶邻近脑白质和内囊为嗅觉相关感兴趣区(region of interest associated with olfactory，ROI(awo))，计算每个ROI(awo)的FA值。采用独立样本t检验比较患者组和对照组间ROI(awo)的FA值差异。 结果： 患者组右侧梨状皮层和右侧眶额皮层下脑白质的FA值均显著低于对照组[0.42±0.05(x±s，下同)比0.45±0.05，0.43±0.06比0.49±0.07，t值分别为2.32、2.79，P值均<0.05]。左侧梨状皮层、左侧眶额皮层下的脑白质FA值与对照组之间的差异无统计学意义(0.43±0.05比0.45±0.04，0.44±0.04比0.47±0.06，t值分别为1.65、1.37，P值均>0.05)。左右两侧海马、岛叶下方脑白质FA值与对照组之间的差异均无统计学意义(0.45±0.08比0.44±0.08，0.45±0.09比0.44±0.10，0.41±0.08比0.39±0.07，0.41±0.07比0.38±0.05，t值分别为0.30、0.15、0.88、1.34，P值均>0.05)。左右两侧内囊FA值与对照组之间的差异亦无统计学意义(0.64±0.08比0.63±0.08，0.64±0.07比0.63±0.07，t值分别为0.14、0.35，P值均>0.05)。 结论： 嗅觉障碍患者的初级、次级嗅觉皮层邻近脑白质可能存在结构连接障碍，ROI(awo)脑白质完整性的降低，可能是导致嗅觉障碍的发病机制之一。.
Objective: Using (18)F-fluorodeoxyglucose ((18)F-FDG) and microPET-CT to test the feasibility of (18)F-FDG PET-CT for validation of olfactory function of rats with standard phenethyl alcohol (PEA) and isovaleric acid (IVA) odors stimulation. To verify the possibility of (18)F-FDG PET-CT as a new objective examination method for olfactory function. Methods: Six healthy Sprague-Dawley (SD) male rats were selected with a weight of 250-300 g. First of all, buried food pellet test (BFT) was used to confirm the normal olfactory function of rats. Then in the next 3 days, after the intravenous injection of (18)F-FDG (18 MBq/100 g), awaken rats were placed in a ventilated plexiglas cage for 30 min. Subsequently, pure air (the first day), PEA (the second day) and IVA (the third day) were delivered. After odor stimulation for 30 min, rats were performed by a static PET-CT under anesthesia. Images reconstructed were assessed by SPM method and analyzed by VBM method. Data was analysied by paired t test. Results: Activation regions of rat's brain after PEA stimulation included bed nucleus and insula. Activation regions of rat's brain after IVA stimulation included olfactory bulb, anterior olfactory nucleus, amygdala, entorhinal cortex, olfactory cortex, piriform cortex, insula, prefrontal cortex, cingulate cortex and bed nucleus (P<0.005, Ke>20 voxels). Conclusions: Through microPET-CT, we can observe that olfactory stimulation with different odors can induce metabolic activation in different regions of rat's brain, which was in concordance with olfactory regions. The olfactory related brain regions of rats have strong responses to odor stimulation of IVA.目的： 利用氟代脱氧葡萄糖((18)F－ fluorodeoxyglucose，(18)F－FDG)小动物正电子发射型计算机断层显像(microPET－CT)，研究大鼠嗅觉相关脑区葡萄糖代谢在苯乙醇和异戊酸两种气味刺激下的应激反应，并对大鼠嗅觉中枢及其通路进行功能定位，验证正电子发射型计算机断层显像(PET－CT)作为新型嗅觉客观检查工具的可能性。 方法： 选取健康雄性SD大鼠6只，体重250～300 g，利用食物埋球试验验证大鼠嗅觉功能正常。对6只大鼠进行尾静脉注射(18)F－FDG，然后将清醒的大鼠放置于通风的玻璃笼中分别行洁净空气(第1天)、苯乙醇(第2天)和异戊酸(第3天)刺激30 min后，将大鼠麻醉行microPET－CT扫描，收集图像信息。依托MATLAB、SPM等软件采用逐像素方法分析大鼠脑部影像数据，利用配对t检验统计学方法进行数据分析。 结果： 苯乙醇气味刺激后激活的大鼠脑区为：终纹床核、脑岛；异戊酸气味刺激后激活的大鼠脑区主要为：嗅球、前嗅核、杏仁核、内嗅皮层、嗅觉皮质、梨状皮质、脑岛、前额叶皮质、扣带回和终纹床核(P<0.005，像素个数>20)。 结论： 利用microPET－CT技术，可以观察到不同气味的嗅觉刺激引起大鼠不同嗅觉相关脑区的代谢激活，且大鼠嗅觉相关脑区对异戊酸气味刺激反应更加强烈。.
Objective: To explore the clinical effects and the influence factors of olfactory training in the treatment of olfactory dysfunction. Methods: A total of 86 patients with olfactory dysfunction (49 post-infectious and 37 post-traumatic) in Beijing Anzhen Hospital during Dec 2016 to May 2017 were recruited in this prospective study. The clinical data of patients were analyzed, including gender, age, body mass index (BMI), course of disease, smoking history, drinking history, diabetes history, hypertension history, hyperlipidemia history, and anxiety visual analogue score (VAS). All patients were treated with olfactory training for 16 weeks, and all of them underwent Sniffin' Sticks olfactory test before and after treatment, which was evaluated by composite threshold-discrimination-identification score (TDI). SPSS 23.0 software, paired t test and univariate and multivariate Logistic regression analysis were used to analyze the data. Results: Eighty patients received treatment, including 46 post-infectious olfactory dysfunction and 34 post-traumatic olfactory dysfunction. After olfactory training, the total scores of TDI increased with statistically significant (18.3±8.6 vs 13.6±7.4, t=-6.158, P<0.05). The overall efficacy was 40% (32/80). The effective rate were 45.7% (21/46) in post-infectious olfactory dysfunction and 32.4% (11/34) in post-traumatic olfactory dysfunction respectively, with no statistically significant difference (χ(2)=1.441, P=0.230). Logistic regression analysis showed that the course of disease was an influence factor in the clinical curative effect (OR=0.881, 95%CI: 0.799-0.973, P=0.012). In patients with less than a year of olfactory dysfunction, the olfactory function improved obviously with the efficiency of 50.9% (29/57). Conclusion: Sixteen weeks of olfactory training provides a significant therapeutic effect on the post-infectious and post-traumatic olfactory dysfunction, and the olfactory training can achieve better therapeutic effects at the early stage.目的： 探讨嗅觉训练治疗嗅觉障碍的临床疗效及其影响因素。 方法： 2016年11月至2017年5月就诊于首都医科大学附属北京安贞医院的86例嗅觉障碍患者纳入本前瞻性研究，其中上呼吸道感染后嗅觉障碍患者49例，外伤性嗅觉障碍患者37例。入选时收集患者临床资料，包括性别、年龄、体质量指数(BMI)、病程、烟酒史、2型糖尿病等慢性病史、焦虑视觉模拟量表(VAS)评分。采用嗅觉训练治疗16周，并于治疗前后行Sniffin′ Sticks嗅觉测试，气味察觉阈、气味辨别能力和气味识别能力3项测试的得分总和组成TDI综合评分(composite threshold-discrimination-identification score，TDI)。采用SPSS 23.0软件对结果进行配对t检验、单因素及多因素Logistic回归分析。 结果： 共80例患者完成治疗方案，其中上呼吸道感染后嗅觉障碍患者46例，外伤性嗅觉障碍患者34例。治疗后TDI得分较治疗前升高，差异有统计学意义[(18.3±8.6)分比(13.6±7.4)分，t＝－6.158，P<0.05]。治疗总体有效率40.0%(32/80)。上呼吸道感染后嗅觉障碍治疗有效率45.7%(21/46)，外伤性嗅觉障碍治疗有效率32.4%(11/34)，二者差异无统计学意义(χ(2)＝1.441，P＝0.230)。Logistic回归分析显示，病程是影响嗅觉训练疗效的因素(OR＝0.881，95%CI：0.799～0.973，P＝0.012)，初发症状到开始嗅觉训练时间间隔≤1年的患者治疗有效率为50.9%(29/57)。 结论： 16周的嗅觉训练可有效治疗上呼吸道感染后和外伤性嗅觉障碍；早期进行嗅觉训练可取得更好的治疗效果。.
Objective: Adrenal vein sampling (AVS) is recognized by Endocrine Society guidelines as the only reliable mean to distinguish between aldosterone producing adenomas and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). However, despite being the gold-standard procedure, AVS protocols are not standardized and vary widely between centers. The objective of the present study was to assess whether the presence or absence of contralateral adrenal (CL) suppression has an impact on the postoperative clinical and biochemical parameters in patients who underwent unilateral adrenalectomy for PA. Design and method: The study was retrospectively carried out in eight referral hypertension centers in Italy, Germany and Japan. Case detection and subtype differentiation were performed according to the Japan Endocrine Society and The Endocrine Society guidelines and a total of 234 AVS procedures were included in the study. CL suppression was defined as aldosterone/cortisol non dominant adrenal vein/aldosterone/cortisol peripheral vein less than 1. Results: Overall, 82% of patients displayed CL suppression at AVS, with no statistically significant differences among centers. This percentage was significantly higher in ACTH-stimulated compared with basal procedures (90% vs 77%). The contralateral ratio was inversely correlated with the aldosterone level at diagnosis and, among AVS parameters, with the lateralization index (P < 0.02 and P < 0.01, respectively). To investigate whether the presence of CL suppression was correlated with response to adrenalectomy, we analyzed the CL suppression status with regard to the patient's clinical and biochemical postoperative parameters. No differences were observed between the two groups for the main clinical and biochemical parameters (systolic and diastolic blood pressure, aldosterone, PRA, PRC, K+, number of drugs, reduction of blood pressure levels, and the number of classes of drugs assumed), but patients with CL suppression underwent a significantly larger reduction in aldosterone levels after adrenalectomy. Conclusions: For patients with lateralization indices of greater than 4 (which comprised the great majority of subjects in this study), contralateral suppression should not be required to refer patients to adrenalectomy because it is not associated with a larger blood pressure reduction and might exclude patients from curative surgery.
Background Hierarchical management of sports risk is highly critical to ensure the safety of sports rehabilitation. Early identification, timely prevention and control of sports-related risk factors, and enhanced supervision and guidance can provide a basis for the formulation of sports programmes and the setting of sports monitoring levels. Objective This study aimed to retrieve, evaluate, and integrate evidence for the stratified management of motor risk in patients with a cardiac implantable electronic device (CIED). Methods We searched for evidence according to the “6S” model of evidence-based resources. CNKI, VIP, Wanfang Data, CBM, PubMed, Cochrane Iibrary, CINAHL, EMbase, Web of Science, BMJ Best Practice, Up To Date, and International Guidelines Collaboration Network were searched from inception to February 2024. To search for evidence on stratified management of motor risk in patients with CIEDs, this research includes guidelines, systematic reviews, meta-analyses, expert consensus, clinical decision-making, and randomized controlled trials. After methodological quality evaluation, the evidence was extracted and summarized accordingly. Results According to the inclusion and exclusion criteria, 16 pieces of evidence were screened, including 5 guidelines, 1 clinical decision-making, 5 systematic reviews, 4 expert consensus, and 1 randomized controlled trial. After reading, extracting, and categorizing, 34 pieces of evidence in 4 areas were identified, namely, screening and assessment of exercise risk in CIEDs, exercise monitoring, implementation of exercise prescriptions, and prevention and management of exercise-related risks. Conclusions This study provides the best evidence for the prevention and management of exercise risk in patients with CIEDs, clarifies the role of nurses in evaluating, monitoring, and educating patients undergoing motor rehabilitation, and provides a basis for the formulation of clinically feasible rehabilitation programs. Systematic Review Registration PROSPERO, identifier (CRD2024509622).
Schwannomatosis (SWN) is a genetic disorder characterized by multiple non-malignant schwannomas growing on the spine and peripheral nerves. Patients with SWN overwhelmingly present with intractable, debilitating chronic pain, severe enough to cause permanent disability. The etiology of pain in SWN is not clear, and the development of novel treatments for SWN and related pain has been extremely slow and inefficient. Treatment for SWN is limited to invasive surgery, which carries significant risks of further nerve damage. No drug is currently FDA-approved to halt SWN tumor growth or ameliorate SWN-associated pain. The drivers of pain response and tumor progression in SWN are not clear - the pain is not proportionally linked to tumor size and is not always relieved by tumor resection, suggesting that mechanisms other than mechanical nerve compression exist to cause pain. SWN research is limited by the lack of clinically-relevant models.
Methods
We established novel patient-derived xenograft (PDX) models and dorsal root ganglia (DRG) imaging models. Combined with single-cell resolution intravital imaging and RNASeq to study the mechanisms cause pain.
Results
We discovered: i) schwannomas on the peripheral nerve cause macrophage influx into the DRG, via secreting HMGB1 to directly stimulate DRG neurons to express CCL2, the key macrophage chemokine, ii) once recruited to the DRG, macrophages cause pain response via overproduction of IL-6, iii) IL-6 blockade in a therapeutic setting significantly reduces pain but has modest efficacy on tumor growth, iv) EGF signaling is a potential driver of schwannoma growth and escape mechanism from anti-IL6 treatment, and v) combined IL-6 and EGFR blockade simultaneously controlled pain and tumor growth in SWN models.
Conclusions
In summary, we deciphered the cellular and molecular crosstalk between schwannoma (HMGB1)-neuron (CCL2)-macrophage (IL-6) in driving pain response, and identified EGF pathway as driver of SWN tumor progression. Our findings prompted the initiation of phase II clinical trial (NCT05684692) for pain relief in patients with SWN.
Ethics Approval
This study was approved by Massachusetts General Hospital's Ethics Board; approval number is A3596-0.
For the diagnosis of primary aldosteronism (PA), confirmatory testing is mandatory and different function tests can be employed. There are, however, sparse data comparing the fludrocortisone suppression test (FST) and the saline infusion test (SIT). Patients with PA (n=90) or essential hypertension (n=65) were studied. They underwent one or the other test or both of them. Using the DPC Siemens aldosterone radioimmunoassay, we found that the SIT led to a stronger suppression of aldosterone than the FST. Post-test aldosterone-to-renin ratios (ARRs) and the percentage of suppression of aldosterone serum concentrations performed worse. The same results were observed in patients who underwent both FST and SIT. Some patients had divergent results in both tests. For the SIT, a lower cutoff value should be used than for the FST for the adequate identification of patients with unilateral PA. Long-term prospective studies are needed to address the question at what cutoff values patients benefit from subtype differentiation of PA. We discuss here possible explanations for divergent results obtained with both tests.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
