Paradigm shift in hydrocephalus research in legacy of Dandy’s pioneering work: rationale for third ventriculostomy in communicating hydrocephalus

Objective This study aims to question the generally accepted cerebrospinal fluid (CSF) bulk flow theory suggesting that the CSF is exclusively absorbed by the arachnoid villi and that the cause of hydrocephalus is a CSF absorption deficit. In addition, this study aims to briefly describe the new hydrodynamic concept of hydrocephalus and the rationale for endoscopic third ventriculostomy (ETV) in communicating hydrocephalus. Critique The bulk flow theory has proven incapable of explaining the pivotal mechanisms behind communicating hydrocephalus. Thus, the theory is unable to explain why the ventricles enlarge, why the CSF pressure remains normal and why some patients improve after ETV. Hydrodynamic concept of hydrocephalus Communicating hydrocephalus is caused by decreased intracranial compliance increasing the systolic pressure transmission into the brain parenchyma. The increased systolic pressure in the brain distends the brain towards the skull and simultaneously compresses the periventricular region of the brain against the ventricles. The final result is the predominant enlargement of the ventricles and narrowing of the subarachnoid space. The ETV reduces the increased systolic pressure in the brain simply by venting ventricular CSF through the stoma. The patent aqueduct in communicating hydrocephalus is too narrow to vent the CSF sufficiently.     

Diagnosis and treatment for pure aqueductal tumor

Pure aqueductal tumor (PAT) typically originates from pure aqueductal region and is extremely rare. It is radiographically similar to tectal glioma. We examined two patients with PATs who were diagnosed with pilocytic astrocytoma and rosette-forming glioneuronal tumor. Both cases showed a progressive clinical course. It is important to distinguish between PAT and tectal glioma by radiographic imaging because the treatment strategy is different. While observation is common for tectal gliomas, a biopsy is recommended at the same time of endoscopic third ventriculostomy for PAT with hydrocephalus. Low-grade PATs show an aggressive clinical course in some cases. Our two cases also showed aggressive course in spite of no genetic aggressive mutations. Sagittal view by constructive interference in steady state (CISS) imaging was helpful to make an accurate diagnosis of PAT. Close observation is needed if PAT is diagnosed as low-grade tumor.     

恩替卡韦联合阿德福韦酯治疗耐拉米夫定慢性乙型肝炎患者48周的疗效分析

目的：观察恩替卡韦（ETV）联合阿德福韦酯（ADV）治疗耐拉米夫定（LAM）慢性乙型肝炎的疗效。方法选取 LAM 耐药患者66例,随机分成两组,治疗组36例应用 ETV 联合 ADV 挽救治疗,对照组30例应用 LAM 联合 ADV 挽救治疗,观察两组治疗前及治疗后12周、48周谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）、乙型肝炎病毒 DNA（HBV-DNA）、乙型肝炎 e 抗原（HBeAg）含量变化以及治疗48周时非 rtM204I 位点变异发生率。结果治疗组挽救治疗后12周 ALT 和 AST 分别降至（36．5±13．23）U／L 和（50．2±11．66）U／L,显著低于同期对照组 ALT[（60．3±12．28）U／L,P ＜0．01]及 AST [（69．7±13．56）U／L,P ＜0．01]含量;治疗后48周治疗组 ALT 和 AST 降至（27．9±10．58）U／L 和（26．7±10．95）U／L,低于同期对照组 ALT[（50．4±11．53）U／L,P ＜0．01]及 AST[（44．9±15．33）,P ＜0．05]含量。治疗12周及48周,治疗组 HBV-DNA 转阴率分别为85．5％及91．7％,显著高于同期对照组转阴率（53．3％和73．3％,P 均＜0．05）。治疗组48周后出现1例新的非 rtM204I 位点变异,而对照组非 rtM204I位点变异情况为6例,两组相比差异有统计学意义（χ2＝5．12,P ＝0．024）。结论ETV 联合 ADV 用于既往 LAM 耐药的慢性乙型肝炎患者的挽救治疗疗效明显,值得临床推广。     

Infantile Fibrosarcoma With NTRK3–ETV6 Fusion Successfully Treated With the Tropomyosin‐Related Kinase Inhibitor LOXO‐101

Infantile fibrosarcoma (IFS) is a rare pediatric cancer typically presenting in the first 2 years of life. Surgical resection is usually curative and chemotherapy is active against gross residual disease. However, when recurrences occur, therapeutic options are limited. We report a case of refractory IFS with constitutive activation of the tropomyosin‐related kinase (TRK) signaling pathway from an ETS variant gene 6–neurotrophin 3 receptor gene (ETV6–NTRK3) gene fusion. The patient enrolled in a pediatric Phase 1 trial of LOXO‐101, an experimental, highly selective inhibitor of TRK. The patient experienced a rapid, radiographic response, demonstrating the potential for LOXO‐101 to provide benefit for IFS harboring NTRK gene fusions.     

Comparison of 48‐week efficacy of tenofovir vs entecavir for patients with chronic hepatitis B: A network meta‐analysis

Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are accepted as first‐line treatments for chronic hepatitis B (CHB). However, there are few randomized studies comparing their efficacy. The primary aim of this study was to compare the efficacy of TDF and ETV using a network meta‐analysis of randomized trials. The secondary aim was to additionally include propensity‐matched cohort studies in a conventional meta‐analysis. We systematically searched PubMed, EMBASE, Cochrane Library and Web of Science for published English‐language randomized and propensity‐matched studies between 1/1/2000 and 4/2/2020. Outcomes included undetectable HBV DNA, ALT normalization and HBeAg seroconversion at 48 weeks. We excluded patients who had co‐infection or significant prior treatment with antivirals. 13 517 participants from 16 studies (11 RCTs, n = 2675; five propensity‐matched cohort studies, n = 10 842) were included. Virological response at 48 weeks was higher in patients receiving TDF compared to ETV using both the network meta‐analytic approach (OR 1.69, P < .001) and the conventional meta‐analysis including propensity‐matched cohort studies (OR 1.40, P < .001). On subgroup analysis, this difference was only significant in HBeAg‐positive patients (OR 1.81, P = .037). There was limited evidence to suggest a higher rate of ALT normalization with ETV (OR 0.74, P = .07). There was no difference in rates of HBeAg seroconversion between the two antivirals. TDF is more likely than ETV to induce virological response at 48 weeks in treatment‐naïve CHB patients. Future studies should focus on elucidating associations between early and sustained virological response with adverse patient outcomes including development of HCC or cirrhosis.