Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Predicting osimertinib‐treatment outcomes through EGFR mutant‐fraction monitoring in the circulating tumor DNA of EGFR T790M‐positive patients with non‐small cell lung cancer (WJOG8815L)

The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).

Abbreviations

CIs

confidence intervals

ctDNA

circulating tumor DNA

ddPCR

droplet digital PCR

EGFR

epidermal growth factor receptor

MFs

mutant fractions

NGS

next‐generation sequencing

NSCLC

non‐small cell lung cancer

ORR

overall response rate

OS

overall survival

PD

progressive disease

PFS

progression‐free survival

PR

partial response

SD

stable disease

TKI

tyrosine kinase inhibitor

     

A Model for the Origin of Motion Direction Selectivity in Visual Cortex

Motion perception is a vital part of our sensory repertoire in that it contributes to navigation, awareness of moving objects, and communication. Motion sense in carnivores and primates originates with primary visual cortical neurons selective for motion direction. More than 60 years after the discovery of these neurons, there is still no consensus on the mechanism underlying direction selectivity. This paper describes a model of the cat''s visual system in which direction selectivity results from the well-documented orientation selectivity of inhibitory neurons: inhomogeneities in the orientation preference map for inhibitory neurons leads to spatially asymmetric inhibition, and thus to direction selectivity. Stimulation of the model with a drifting grating shows that direction selectivity results from the relative timing of excitatory and inhibitory inputs to a neuron. Using a stationary contrast-reversing grating reveals that the inhibitory input is spatially displaced in the preferred direction relative to the excitatory input, and that this asymmetry leads to the timing difference. More generally, the model yields physiologically realistic estimates of the direction selectivity index, and it reproduces the critical finding with contrast-reversing gratings that response phase advances with grating spatial phase. It is concluded that a model based on intracortical inhibition can account well for the known properties of direction selectivity in carnivores and primates.SIGNIFICANCE STATEMENT Motion perception is vital for navigation, communication, and the awareness of moving objects. Motion sense depends on cortical neurons that are selective for motion direction, and this paper describes a model for the physiological mechanism underlying cortical direction selectivity. The essence of the model is that intracortical inhibition of a direction-selective cell is spatially inhomogeneous and therefore depends on whether a stimulus generates inhibition before or after reaching the cell''s receptive field: the response is weaker in the former than in the latter case. If the model is correct, it will contribute to the understanding of motion processing in carnivores and primates.     

《邵氏医案》从血辨治痛经浅析

[目的]分析总结浙江近代著名临床医家邵兰荪治疗痛经的经验,以期为临床治疗提供借鉴。[方法]通过研读裘吉生编《邵氏医案》,筛选出其中治疗痛经的医案十余则,并结合邵氏在妇科方面的学术思想,进一步分析其辨证立法遣方特色,从而总结邵氏治疗痛经的临证经验。[结果]邵氏治疗痛经多从血辨治,且分虚实两端,其中属虚者血虚内热用益母胜金丹养血清热、活血止痛,血虚肝风治以养血柔肝、息风止痛;属实者水结血瘀用五苓散利水散瘀、行气止痛,气阻血滞治从行气活血、调经止痛。[结论]在治疗妇人痛经方面,邵氏辨治遣方确有独特经验,这些经验可为中医药治疗此类疾病拓宽诊治思路,有助于提高临床疗效。     

Routine Laboratory Testing Every 4 Versus Every 6 Weeks for Patients on Maintenance Hemodialysis: A Quality Improvement Project

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超声多探头检查在新生儿颅脑疾病诊断中的应用

目的研究超声低频探头和低频探头联合高频探头检查在新生儿颅脑疾病诊断中的准确率和敏感性。 方法选取河源市妇幼保健院自2017年1月至2018年12月收治的有颅脑疾病高危因素(早产、低体质量、多胎妊娠、出生过程有缺氧窒息及产时感染)的新生儿90例作为研究对象。采用随机数字表法将所有新生儿平均分为2组，研究组（45例）给予低频探头联合高频探头进行探查，对照组（45例）仅给予低频探头进行探查。结合CT检查结果和临床治疗，比较2种检测方法的准确率和敏感性。 结果研究组检测新生儿缺氧缺血性脑病、脑室内出血和室管膜下出血诊断准确率分别为87.5%、100%、100%，高于相应对照组（15.38%、12.5%、0%），差异有统计学意义（P<0.05）；研究组和对照组检测脑实质内出血和脑积水的诊断准确率分别为87.5%、100%以及42.85%、66.67%，差异无统计学意义（P>0.05）。研究组检测新生儿颅脑疾病的效率为82.22%，高于对照组（22.22%），差异具有统计学意义（P<0.05）。 结论使用超声低频探头联合高频探头的方法提高了缺氧缺血性脑病、脑室内出血、室管膜下出血等新生儿颅脑疾病诊断的准确率，在诊断新生儿脑实质内出血和脑积水的准确率没有差异，且对颅脑疾病诊断的敏感性较高，因此具有较为重要的临床意义。     

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.     

基于“气道神经源性炎症-TRP通路”探讨慢性咳嗽发病机制及中医治疗

咳嗽临床常见，尤其是胸部影像学无明显异常的慢性咳嗽，病因复杂、易误诊误治，逐渐受到重视，国内外相继颁发相关指南，目前认为咳嗽高敏感性是其重要的病理生理机制。中医将慢性咳嗽归于"久咳""久嗽"范畴，在病因病机、治法方药上积累了丰富的临床经验，史利卿教授团队针对该病开展了专项临床及基础研究15年，根据传统中医理论及其突出临床症状提出"风邪伏肺"病机，应用祛风宣肺法治疗效果显著。文章结合西医学相关咳嗽机制研究进展及既往研究结果，初步探讨祛风宣肺法治疗该病的疗效机制，丰富慢性咳嗽风邪伏肺致咳相关学术理论的科学内涵，有利于提高中医药防治慢性咳嗽学术水平。     

足头向穿刺路径在膈肌下方肝肿瘤消融治疗中的CT模拟测量研究

【摘要】 目的 对足头向穿刺路径进行模拟测量并评价在膈肌下方肝肿瘤热消融治疗中的临床应用价值。方法 重建患者上腹部CT图像，选取有代表性的3个矢状面和1个冠状面作为标准层面，在各层面建立膈下标准病灶模型，并采用足头向穿刺路径进行模拟穿刺。测量各平面上膈肌高度、穿刺路径长度及间距。采用可到达性评价模拟穿刺时穿刺针分布于标准病灶中的最理想的位置情况。结果 纳入86例患者行测量研究，多数患者矢状2、3面的膈肌高度低于2cm，仅分别对平面内1511%的病灶e和813%的病灶f进行了测量。标准病灶a、b、c、d、b’的完全到达比例分别为5243%、6097%、3837%、5294%、6353%，中位路径长度分别为1039cm、1337cm（背侧，腹侧1266cm）、1315cm、888cm、1126cm，中位穿刺路径间距分别为21cm、209cm（背侧，214cm腹侧）、206cm、211cm、2145cm。结论 采用足头向穿刺路径进行穿刺，标准病灶a、b、d、b’有较高的完全到达比例，穿刺宽容度较高，有进一步在临床中应用的价值。标准病灶c的完全到达率不高。标准病灶e、f需要采用该路径穿刺的比例不高。