Cerebrospinal fluid hypotension following fall in a child: Case report

CSF hypotension arises in the context of a leak of CSF which causes negative intracranial pressure. Sacral fractures result from high-energy trauma which are frequently underdiagnosed. A ten-year-old boy presented with hip pain, after a fall. He mobilized both lower limbs, reported no leg pain, irradiation nor lack of sphincter control. The neurological examination was normal. When asked to stand, he began biparietal headache, nausea and vomiting, which improved laying down. CT scan showed an occult intrasacral meningocele; the MRI revealed collections of CSF along the spine, a S3 fracture with potential laceration of the meningocele and opening of a CSF fistula. Our diagnosis was the CSF hypotension, secondary to the fistula opening. The diagnosis was challenging. The child first presented with symptoms of CSF hypotension without evident cause. The discovery of the meningocele led us to hypothesize the opening of a fistula, a rare diagnosis, later confirmed by MRI.     

限制液体复苏在创伤失血性休克患者急救中的应用效果

目的观察限制液体复苏在创伤失血性休克患者急救中的应用效果。方法选取福建医科大学附属南平市第一医院收治的76例创伤失血性休克患者作为研究对象,依据入院前后顺序将其分为对照组(n=38)和观察组(n=38),对照组接受积极液体复苏方案,观察组接受限制液体复苏方案,比较两组治愈率、治疗后各指标水平、液体输入量及并发症发生情况。结果观察组治愈率明显高于对照组,液体输入量明显低于对照组,差异有统计学意义(P<0.05);治疗后观察组乳酸、凝血酶原时间、平均动脉压及血红蛋白水平均明显优于对照组,差异均有统计学意义(P<0.05);观察组并发症发生率为15.8%,明显低于对照组的36.8%,差异有统计学意义(P<0.05)。结论限制液体复苏应用在创伤失血性休克患者急救中,可提高患者的治愈率,改善乳酸、凝血酶原时间等指标水平,降低并发症发生率的效果优于积极液体复苏应用效果。     

槽型鞘脑穿刺针的设计及动物实验初步结果

目的测试槽型鞘脑穿刺针用于实验动物脑组织穿刺的可操作性和安全性。 方法新西兰兔6只，麻醉后骨窗开颅显露双侧大脑半球，左侧大脑半球以传统脑穿刺针进行穿刺，右侧以槽型鞘脑穿刺针穿刺，完成穿刺、拔出穿刺针留置槽形鞘、置管后拔出槽形鞘等步骤。拔出穿刺针后穿刺道以苏木素染色，观察30 min后处死实验动物，提取脑组织，沿脑组织穿刺道制3 μm厚切片，常规HE染色，显微镜下观察脑组织穿刺道病理解剖学变化（脑组织破损及出血情况），评估损伤程度。 结果2种穿刺针穿刺操作后均会造成穿刺道局灶性脑挫裂伤，表现为穿刺道组织缺损、脑组织淤血、水肿。光镜下可见穿刺道脑组织破碎、细胞排列不规则、水肿的细胞体增大和细胞核固缩，穿刺道外围细胞结构正常。2种穿刺针针道脑组织病理特征差别不明显。 结论槽型鞘脑穿刺针穿刺操作简便，通过槽型鞘置入引流管方便，脑组织损伤程度与传统脑穿刺针无明显差别。     

Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR‐neurography were performed. All the patients complained of progressive upper or lower limbs sensory‐motor symptoms, with heterogeneous disease duration (1‐34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.     

Plasma matrix metalloproteinase 7, CC-chemokine ligand 18, and periostin as markers for pulmonary sarcoidosis

BackgroundSome patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis.MethodsPlasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics.ResultsPlasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function.ConclusionAmong these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.     

Corynebacterium species as one of the major causative pathogens of bacterial pneumonia

Recent advances using molecular methods, matrix-assisted laser desorption ionization time of flightmass spectrometry, and next-generation sequencers enable rapid and precise detection of bacterial species in the clinical samples, revealing bacterial diversities in the human body. Corynebacterium species are Gram-positive bacilli, which can cause pneumonia and have been reported as causative pathogens of lower respiratory tract infections since the 1970's. However, Corynebacterium spp. may be recognized and sorted as part of normal respiratory flora on Gram staining and culture, resulting in clinical under-recognition as pathogenic bacteria.The results of the clone library method using bacterial 16S ribosomal RNA gene sequence analysis in Japanese patients with hospital-acquired pneumonia revealed that bronchoalveolar lavage fluid obtained from the lung lesions contained 11.8% Corynebacterium spp., which was the second most predominant bacterial phylotype. Additionally, among patients in whom Corynebacterium spp. were detected, C. simulans was most commonly detected followed by C. striatum. In addition, almost half of the patients in whom C. simulans was detected was monophylotypic infection and/or co-detection of C. simulansand C. striatum. Further clinical information is expected on corynebacteria as pathogens of lower respiratory tract infection.     

帕金森病患者和健康对照者的纵向CSF生物标志物对比研究

目的 探讨帕金森病(Parkinson's disease,PD)患者脑脊液(CSF)生物标志物的水平变化及其临床意义。方法 选取本院2018年3月-2019年3月收治的70例PD患者,并根据改良PD综合评分量表(UPDRS量表)及Hoehn-Yahr评分标准将患者分为轻度组(n=38)、中度组(n=18)和重度组(n=14)。另选择同期于本院接受体检健康人员70例作为对照组,检测并比较4组研究对象CSF生物标志物蛋白α-突触核蛋白(α-syn)、磷酸化Tau蛋白(P-Tau)及总Tau蛋白(T-Tau),微小RNA133 b(miR-133b)及C反应蛋白(CRP)、白细胞介素-8(IL-8)水平。结果 各组性别、年龄比较无明显差异(P>0.05); 不同病情严重程度PD患者UPDRS评分比较有明显差异,且均显著高于对照组(P<0.05); PD患者轻度组、中度组及重度组H-Y评分比较有明显差异(P<0.05)。各组α-syn、P-Tau、T-Tau、miR-133b、CRP及IL-8水平比较有明显差异(P<0.05),且随着PD患者病情严重程度加重,α-syn水平显著降低,P-Tau、T-Tau、miR-133b、CRP及IL-8水平显著升高(P<0.05)。Pearson相关分析显示,α-syn与UPDRS评分呈显著正相关,P-Tau、T-Tau、miR-133b、CRP及IL-8与UPDRS呈显著负相关(P<0.05)。受试者工作曲线(ROC)显示α-syn、P-Tau、T-Tau、miR-133b、CRP及IL-8水平诊断PD的曲线下面积(AUC)分别为0.755、0.785、0.742、0.746、0.779、0.755,联合诊断的AUC为0.905。结论 脑脊液生物标志物的水平变化是PD发生与发展的重要参考指标,其对于PD的诊断和病情严重程度判断具有重要价值     

万古霉素脑室内注射治疗成人中枢神经系统感染的研究进展

中枢神经系统(CNS)周围的屏障以及多重耐药菌的出现对有效治疗CNS感染提出了治疗挑战。万古霉素是一种糖肽类抗生素，用于治疗和预防由革兰阳性菌引起的各种细菌感染，包括耐甲氧西林金黄色葡萄球菌(MRSA)。它也用于肠球菌、链球菌和甲氧西林敏感的金黄色葡萄球菌(MSSA)等引起的感染。万古霉素被推荐作为颅内感染的一线治疗药物。然而，通过静脉(IV)输注给药时，万古霉素在脑脊液(CSF)中的渗透是有限的。万古霉素通过脑室内(IVT)给药可绕过血脑屏障直接到达目标部位，实现高浓度以获得更好的杀菌作用。万古霉素IVT给药的适应症主要包括对IV抗生素反应较差的脑膜炎、脑室炎、颅内装置感染和脑脓肿。本文综述了成人万古霉素IVT给药的研究现状，旨在为临床实践提供参考。根据现有证据，使用万古霉素IVT给药治疗CNS感染是安全有效的。万古霉素IVT给药的最佳给药方案需要考虑到不同患者CNS的病理生理学特点并根据具体情况进行临床判断。     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.