Automated Computational Detection of Interstitial Fibrosis,Tubular Atrophy,and Glomerulosclerosis

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双侧深低温停循环顺行性脑灌注对主动脉弓替换术患者脑损伤的影响

目的 探讨双侧深低温停循环(Deep hypothermia and circulatory arrest,DHCA)+顺行性脑灌注(Anterograde cerebral perfusion,ACP)对主动脉弓替换术患者脑损伤的影响。方法 选择2018年1月-2020年1月本院实施主动脉弓替换术的DebakeyⅠ型主动脉夹层患者96例,根据不同的脑保护技术将患者分为单侧ACP组和双侧ACP组,各48例; 2组均进行DHCA,单侧ACP组经右侧腋动脉进行单侧ACP,双侧ACP组经右侧腋动脉和左颈总动脉进行双侧ACP。结果 全部患者痊愈出院,出院前CT复查显示主动脉弓和升主动脉的人工血管血流畅通,无人工血管扭曲和造影剂渗漏等状况。双侧ACP组术后短暂性脑损伤发生率为2.08%(1/48),明显低于单侧ACP组的16.67%(8/48)(P<0.05)。双侧ACP组术后苏醒时间为(13.18±3.42)h,明显短于单侧ACP组的(16.98±4.18)h(P<0.05)。体外循环开始后2组血清神经元特异性烯醇化酶(Neuron-specific enolase,NSE)、中枢神经特异性蛋白 100-β亚型(Specific protein 100-β,S100-β)水平均逐渐升高,且在体外循环结束时达到峰值,随后开始降低; 脑灌注5min后双侧ACP组血清NSE,S-100β水平明显低于单侧ACP组(P<0.05)。结论 双侧深低温停循环顺行性脑灌注对主动脉弓替换术患者脑损伤的影响程度更小,其机制可能是通过降低血清NSE,S-100β水平,进而有效保护脑组织。     

Management of patients suffering from hemorrhagic intracranial metastases: Propositions to help the neurosurgeon in emergency situations based on a literature review

IntroductionBrain metastases are the most common intracranial neoplasm in adult patients, and one of the fearsome complications proves to be intratumoral hemorrhage. The neurosurgical management of patients harboring a bleeding brain metastasis is not fully established and there is still today an ongoing debate on the optimal management of these patients. The aim of this article is to provide the neurosurgeons with practical tools to assist in their decision-making process in the management of BMs.MethodsWe conducted a literature review of the relevant Pubmed, Cochrane, and Google scholar-indexed articles published between 2000 and 2019. The following key words were entered in the Pubmed search engine: [metastasis], [metastases], [brain metastases], [brain metastasis], [hemorrhage], [hematoma], [blood clot], [intracerebral hemorrhage], [intracranial hemorrhage]. The review was performed in accordance with the PRISMA recommendations.ResultsBased on PubMed, Cochrane, and Google scholar, 459 articles were retained, 392 were then removed because of their non-adequacy with the topic and, 9 articles were removed because they were not written in English language. So, 58 articles were analyzed. Radiological evaluation is crucial, but few traps exist. The frequency of overall brain tumor-related with intracranial hematoma is 7.2%, with a higher frequency for secondary tumors. The local recurrence rate after resection of a hemorrhagic metastasis seems to be better probably because of an easier “en bloc” resection thanks to the hematoma. An atypical presentation is reported in up to 4% in patients with chronic or acute subdural hematoma. Patients with subarachnoid hemorrhage and epidural hematoma are rare. A clear-cut correlation between the incidence of bleeding event in brain mets and prior stereotactic radiosurgery was not established.ConclusionThe current literature pertaining to the neurosurgical management of acute bleeding in brain metastasis is scant and the level of evidence remains low (experts ‘opinions; class C). Herein we suggest a flowchart to assist in dealing with those difficult patients.     

Immunotherapy as Single Treatment for Patients With NSCLC With Brain Metastases: A Systematic Review and Meta-Analysis—the META-L-BRAIN Study

IntroductionBrain metastases (BMs) occur in 40% of patients with lung cancer. The activity of immunotherapy in these patients, however, remains controversial, as the cornerstone treatment is radiotherapy (RT). Because RT is associated with adverse events that may impair the quality of life, the possibility of substituting it with a single systemic approach is attractive. Therefore, we performed a systematic review and meta-analysis to evaluate the potential benefit of immune checkpoint inhibitors (ICIs) in patients with NSCLC with untreated BM (unBM).MethodsStudies that enrolled patients with NSCLC treated with ICIs and specifically allowed for unBM were identified by searching the EMBASE, PubMed, Cochrane, and other databases. The outcomes evaluated were intracerebral overall response rate (icORR) and intracerebral disease control rate (icDCR) for unBM, and grades 3 and 4 toxicity rate.ResultsWe included 12 studies with a total of 566 individuals in the final analysis. Anti–programmed cell death protein-1 therapy seems to be active in the central nervous system, with an icORR of 16.4% (95% confidence interval [CI]: 9.8%–24%; I² = 33.17%) and an icDCR of 45% (95% CI: 33.4%–56.9%; I² = 46.91%). In the meta-analysis for icORR (risk ratio = 1.26, 95% CI: 0.57–2.79) and icDCR (risk ratio = 0.88, 95% CI: 0.55–1.43) we did not observe any difference among patients with BM who were treated with RT before ICI start and those who were treated with ICI only.ConclusionsICI seems to be effective as a single treatment for active BM in selected patients with advanced NSCLC.     

Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder

Inflammatory processes are implicated in the aetiology of Major Depressive Disorder (MDD); however, the relationship between peripheral inflammation, brain structure and depression remains unclear, partly due to complexities around the use of acute/phasic inflammatory biomarkers.Here, we report the first large-scale study of both serological and methylomic signatures of CRP (considered to represent acute and chronic measures of inflammation respectively) and their associations with depression status/symptoms, and structural neuroimaging phenotypes (T1 and diffusion MRI) in a large community-based sample (Generation Scotland; N_{MDD cases} = 271, N_controls = 609).Serum CRP was associated with overall MDD severity, and specifically with current somatic symptoms- general interest (β = 0.145, P_FDR = 6 × 10⁻⁴) and energy levels (β = 0.101, P_FDR = 0.027), along with reduced entorhinal cortex thickness (β = −0.095, P_FDR = 0.037). DNAm CRP was significantly associated with reduced global grey matter/cortical volume and widespread reductions in integrity of 16/24 white matter tracts (with greatest regional effects in the external and internal capsules, β_FA= −0.12 to −0.14). In general, the methylation-based measures showed stronger associations with imaging metrics than serum-based CRP measures (βaverage = −0.15 versus βaverage = 0.01 respectively).These findings provide evidence for central effects of peripheral inflammation from both serological and epigenetic markers of inflammation, including in brain regions previously implicated in depression. This suggests that these imaging measures may be involved in the relationship between peripheral inflammation and somatic/depressive symptoms. Notably, greater effects on brain morphology were seen for methylation-based rather than serum-based measures of inflammation, indicating the importance of such measures for future studies.     

Intraoperative thalamocortical tract monitoring via direct cortical recordings during craniotomy

ObjectiveNeuromonitoring of primary motor regions allows preservation of motor strength and is frequently employed during cranial procedures. Less is known about protection of sensory function and ability to modulate movements, both of which rely on integrity of thalamocortical afferents (TCA) to fronto-parietal regions. We describe our experience with TCA monitoring and their cortical relays during brain tumor surgery.MethodologyTo study its feasibility and usefulness, continuous somatosensory evoked potentials (SSEP) recording via a subdural electrode was attempted in 32 consecutive patients.ResultsMedian and posterior tibial SSEP were successfully monitored in 31 and 17 patients respectively. SSEP improved lesion localization and prevented unnecessary cortical stimulation in 9 and 16 cases respectively. A threshold of ≥30% SSEP amplitude decrease influenced management in 10 patients while a decrement of ≥50 % had a sensitivity of 0.89 and specificity of 1 in detecting worsening of sensory function. Simultaneous motor evoked potentials (MEP) and SSEP monitoring were performed in 10 cases, 9 of which showed short-lived fluctuations of the former.ConclusionDirect cortical SSEP monitoring is feasible, informs management and predicts outcome.SignificanceEarly intervention prevents sensory deficit. Concomitant MEP fluctuations may reflect modulation of motor activity by TCA.     

An insight into electrical resistivity of white matter and brain tumors

BackgroundThere is a lack of information regarding electrical properties of white matter and brain tumors.ObjectiveTo investigate the feasibility of in-vivo measurement of electrical resistivity during brain surgery and establish a better understanding of the resistivity patterns of brain tumors in correlation to the white matter.MethodsA bipolar probe was used to measure electrical resistivity during surgery in a prospective cohort of patients with brain tumors. For impedance measurement, the probe applied a constant current of 0.7 μA with a frequency of 140 Hz. The measurement was performed in the white matter within and outside peritumoral edema as well as in non-enhancing, enhancing and necrotic tumor areas. Resistivity values expressed in ohmmeter (Ω1m) were compared between different intracranial tissues and brain tumors.ResultsNinety-two patients (gliomas WHO II:16, WHO III:10, WHO IV:33, metastasis:33) were included. White matter outside peritumoral edema had higher resistivity values (13.3 ± 1.7 Ω1m) than within peritumoral edema (8.5 ± 1.6 Ω1m), and both had higher values than brain tumors including non-enhancing (WHO II:6.4 ± 1.3 Ω1m, WHO III:6.3 ± 0.9 Ω1m), enhancing (WHO IV:5 ± 1 Ω1m, metastasis:5.4 ± 1.3 Ω1m) and necrotic tumor areas (WHO IV:3.9 ± 1.1 Ω1m, metastasis:4.3 ± 1.3 Ω1m), p=<0.001. No difference was found between low-grade and anaplastic gliomas, p = 0.808, while resistivity values in both were higher than the highest values found in glioblastomas, p = 0.003 and p = 0.004, respectively.ConclusionsThe technique we applied enabled us to measure electrical resistivity of white matter and brain tumors in-vivo presumably with a significant effect with regard to dielectric polarization. Our results suggest that there are significant differences within different areas and subtypes of brain tumors and that white matter exhibits higher electrical resistivity than brain tumors.     

The association between the decreased expression levels of FOXJ1 and the activation of NF-κB pathway in interstitial lung disease of MRL/Lpr mice

Background: Pulmonary manifestations of systemic lupus erythematosus (SLE) are appearing in 4-5% of patients involving lung in almost half of the cases during the disease course. Objective: We compared the autoimmune pulmonary inflammation in the lung tissue of mice to determine the association between decreased expression levels of Forkhead Box J1 (FOXJ1) and the activation of the NF-κB pathway in autoimmune pulmonary inflammation of MRL/Lpr mice. Methods: The female BALB/c mice (n=6) and MRL/Lpr mice (n=30) were divided into 5 groups including a control group (BALB/c), and five MRL/Lpr mice groups (8W, 12W, 16W, 24W, and 32W). The infiltration of the inflammatory cells was determined in lung tissue by performing the histological analysis. The western blotting was used to examine the expression levels of the age-related FOXJ1, and p50 and p65 proteins in the lungs of MRL/Lpr mice. The expression levels of MMP2 and MMP9 were determined via immunohistochemistry and immunofluorescence. Results: There were severe infiltrates of lung cells with high levels of tracheal damage, perivascular injury and interstitial inflammatory cell infiltration when the MRL/Lpr mice from 16w to 32w comparing to the 8w old healthy MRL/Lpr mice in the control group (p <0.05). Moreover, the reduced expression levels of FOXJ1 were associated with the activation of the NF-κB pathway in interstitial lung disease of MRL/Lpr mice via the modulation of p50 and p65. In addition, the expression levels of MMP2 and MMP9 pro-inflammation factors increased in the lungs of the MRL/Lpr mice from 16w to 32w. Conclusions: The expression level of FOXJ1 might be an indicator of the degree of lung disease in lupus-prone mice.