Preoperative nomogram predicting ventriculoperitoneal shunt longevity after initial shunt failure.

Background and objectives: Initial shunt failure following ventriculoperitoneal (VP) shunt surgery has a significant impact on the working time of the shunt. However, there are few studies regarding factors affecting VP shunt longevity. Hence, in this study, we aimed to build a nomogram to predict the longevity of the replacement VP shunt in patients with initial shunt failure. Methods: From 2011 to 2021, 142 patients with initial VP failure who underwent VP shunt revision were enrolled and relevant clinical and demographic factors were analyzed. Univariate and multivariate Cox proportional hazard regression models were used to choose predictors, and a nomogram was constructed using nine independent prognostic variables: sex, age, hydrocephalus type, intensive care unit admission, tracheostomy, decompressive craniectomy, craniotomy, lumbar cisterna drainage, and ventricular drainage. The prediction models' discrimination, accuracy, calibration, and clinical value were evaluated using Harrell's C-index, a calibration plot, and decision curve analysis. Results: At 1 month, 3 months, and 5 years, the nomogram's C-index was 0.680, 0.708, and 0.694, respectively. The nomogram's calibration plot provided a good fit for the overall prediction over the course of 1 year. Decision curve analysis predicted that 1-3 months after surgery will yield good net benefits between 30 and 50% probability thresholds. Conclusion: A preoperative nomogram may be an effective tool for assessing VP shunt longevity after initial VP shunt placement.

Treatment of Carbapenem-Resistant Multidrug-Resistant Gram-Negative Bacilli with Intracerebroventricular Injection of Polymyxin B: A Retrospective Study.

Purpose: We evaluated the efficacy and administration time of intraventricular (IVT) polymyxin B in the treatment of carbapenem-resistant and multidrug-resistant/extensively drug-resistant (MDR/XDR) Gram-negative bacilli in central nervous system (CNS) infections and investigated prognostic factors. Patients and Methods: This retrospective analysis comprised 41 post-surgical carbapenem-resistant CNS infections from October 2016 to October 2021. All patients were treated with effective intravenous antibiotics and IVT polymyxin B. Patient characteristics, therapeutic procedure, symptoms, cerebrospinal fluid (CSF) examination, laboratory tests, and complications were recorded. The effectiveness of IVT polymyxin B was evaluated using temperature, Glasgow Coma Scale, CSF contents, bacterial clearance rate, cure rate, and mortality. Mortality between early (7 days) and late administration of IVT polymyxin B was compared. Prognostic factors were evaluated using the pupillary light reflex and multiloculated hydrocephalus. Results: The 41 patients acquired carbapenem-resistant MDR/XDR bacteria, including 24 Klebsiella pneumoniae, 15 Acinetobacter baumannii, 3 Pseudomonas aeruginosa, and 1 Enterobacter cloacae. The bacterial clearance rate was 32/41 (78.0%), and 9 patients (22.0%) with uncured bacterial infections died. Adverse events included 1 case of skin pigmentation. Among the 32 cured patients, 31 received a ventriculoperitoneal shunt, and 1 patient had an extraventricular drainage tube removed. Mortality in the late (>7 days) group was higher (39.1% vs 0%, P < 0.05). The group without pupillary light reflex showed a higher death rate (41.2% vs 8.3%; P < 0.05). The multiloculated hydrocephalus group had a higher mortality rate than that of the normal group (34.8% vs 5.6%, P < 0.05). All 32 cured patients were followed up for 9 to 66 months, and all survived without recurrent infections. Conclusion: Intraventricular polymyxin B is an effective treatment for carbapenem-resistant MDR/XDR Gram-negative bacilli, with a 78% cure rate and significant mortality reduction if administered within 7 days of bacterial identification. Multiloculated hydrocephalus and the pupillary light reflex may be used as prognostic indicators of mortality.

Candida central nervous system infection after neurosurgery: a single-institution case series and literature review.

BACKGROUND: Candida central nervous system (CNS) infection is a rare complication following neurosurgery. This disease often occurs during the treatment of bacterial CNS infection, and common bacterial culture results have a high false negative rate, which delays diagnosis and treatment, and seriously affect the prognosis of patients. The purpose of this study was to discuss the diagnosis, treatment process, and results of this disease through a small series of cases, so as to provide data support and a theoretical basis for the timely diagnosis and treatment of Candida CNS infection after neurosurgery. METHODS: A retrospective analysis was conducted on eight patients with confirmed Candida CNS infection following neurosurgery in our department between June 2011 and June 2019. Their clinical symptoms, treatment schemes, outcomes, risk factors, and complications were analyzed. RESULTS: Four patients received intravenous administration of fluconazole and were cured. Three patients received intravenous administration of amphotericin B. Two of them were cured, and the other died. One patient was cured after intravenous administration of voriconazole throughout the treatment. The overall cure rate was 87.5% (7/8), and the death rate was 12.5% (1/8). Among the three patients treated by amphotericin B, one patient suffered vomiting and renal function impairment. After drug discontinuation, this patient gradually improved. Another patient had acute renal failure, and the conditions were not improved after drug discontinuation. The remaining patient suffered from anemia and vomiting, which were relieved after drug discontinuation. One patient had hematuria during voriconazole treatment, and the symptoms were improved after the therapy was changed to fluconazole. Four patients treated with fluconazole did not have apparent adverse reactions. None of the cured patients relapsed during the 3-12 months follow-up after discharge. CONCLUSIONS: Candida CNS infection following neurosurgery is a rare condition; however, it may result in disastrous consequences. Early diagnosis and timely use of antifungal agents are considered the primary treatment principles. Blood culture of cerebrospinal fluid (CSF) is useful for early diagnosis. Fluconazole is the preferred choice for the clinical treatment of Candida CNS infection as it has both good efficacy and safety.

A Clinical Study on the Use of Intraventricular Polymyxin B Supplemented by Continuous External Ventricular Drainage in the Treatment of Drug-Resistant Gram-Negative Bacilli Intracranial Infection.

PURPOSE: To investigate the clinical effect of ventricular polymyxin B supplemented by continuous external ventricular drainage in the treatment of intracranial infection with multidrug-resistant (MDR) or extensively drug-resistant (XDR) Gram-negative (G-) bacilli following neurosurgery. PATIENTS AND METHODS: A retrospective analysis was performed on 28 patients who had G-bacilli intracranial infection following neurosurgery in our department between January 2017 and December 2019. The patients were treated with intraventricular polymyxin B supplemented by continuous external ventricular drainage. The clinical characteristics, treatment process, cerebrospinal-fluid-related indicators, results and prognosis were analysed. RESULTS: All of 28 patients developed an infection subsequent to neurosurgery, and cerebrospinal fluid (CSF) cultures demonstrated MDR/XDR G- bacilli, including Acinetobacter baumannii in 14 cases, Klebsiella pneumoniae in 9 cases, Pseudomonas aeruginosa in 3 cases, and Enterobacter cloacae in 2 cases. The ventricular drainage tube remained unobstructed in all patients during treatment, and intraventricular polymyxin B combined with intravenous antibiotics were administered each day. The duration of treatment with intraventricular polymyxin B was 14.96±4.28 days, and the time required to obtain a negative CSF culture was 8.23±4.02 days. The bacterial clearance rate from cerebrospinal fluid was 92.9% (26/28), and the clinical cure rate was 82.1% (23/28). Among them, 18 patients underwent ventriculoperitoneal shunt insertion for hydrocephalus 82.5 (59.5,114.75) days after the infection was cured, and the mortality rate was 17.6% (5/28). There was no significant change in patient blood creatinine levels before and after treatment. Cured patients were followed up for 4 months to 3 years, and no recurrences were observed. CONCLUSION: Treatment of intracranial infection with MDR/XDR G- bacilli using early intraventricular polymyxin B supplemented by continuous external ventricular drainage treatment may be a safe and effective treatment strategy.

Protective Effects of Transforming Growth Factor-ß1 Knockdown in Human Umbilical Cord Mesenchymal Stem Cells against Subarachnoid Hemorrhage in a Rat Model.

BACKGROUND: Emerging evidence indicates a beneficial effect of mesenchymal stem cell (MSC) transplantation in subarachnoid hemorrhage (SAH). Chronic hydrocephalus is a common complication after SAH, which is associated with subarachnoid fibrosis promoted by transforming growth factor-ß1 (TGF-ß1). This study investigated the effect of human umbilical cord derived MSCs (hUC-MSCs) with TGF-ß1 knockdown on chronic hydrocephalus after SAH. METHODS: About 0.5 mL autologous blood was injected into the cerebellomedullaris cistern of 6-week SD rats to establish SAH model. hUC-MSCs or hUC-MSCs carrying TGF-ß1 knockdown (1 × 105 cells) were intraventricularly transplanted at 1 day before surgery and at P10. Neurological behavior score and water maze test were performed to assess neurological functions. Hydrocephalus was evaluated by Nissl staining. Concentrations of proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. The levels of TGF-ß1, p-Smad2/3, and Smad2/3 were measured using western blotting. RESULTS: Intraventricular hUC-MSCs transplantation significantly attenuated SAH-induced chronic hydrocephalus, upregulation of inflammatory cytokines, and behavioral impairment. Knockdown of TGF-ß1 in hUC-MSCs enhanced these effects. hUC-MSCs also reduced the upregulation of TGF-ß1 levels and Smad2/3 phosphorylation after SAH, and this effect was also enhanced by TGF-ß1 knockdown. CONCLUSION: Transplantation of hUC-MSCs exerts beneficial effect after SAH, possibly be through inhibiting TGF-ß1/Smad2/3 signaling pathway. Knockdown of TGF-ß1 in hUC-MSCs enhanced these effects.

Clinical, radiological features and surgical strategies for 23 NF1 patients with intraorbital meningoencephalocele.

Intraorbital meningoencephalocele is a rare manifestation of neurofibromatosis type 1 (NF1) caused by secondary changes in sphenoid dysplasia, and it seriously affects patients' vision and facial appearance. We retrospectively analyzed the clinical data of 23 patients with NF1 and intraorbital meningoencephalocele, summarized the surgical strategies employed, and evaluated their clinical efficacy in order to better understand its management in clinical practice, establish a reasonable surgical strategy, and assess prognosis. Before surgery, 22 patients had unilateral pulsatile exophthalmos, 18 patients had significant visual impairment, and 13 patients had ptosis associated with an orbital plexiform neurofibroma (PNF). All 23 patients underwent microsurgical craniotomy with skull base reconstruction using a soft titanium mesh. One month after surgery, the degree of exophthalmos in the 22 (95.65%) patients was significantly reduced compared with before surgery (P < 0.001), and ocular pulsation had subsided. The visual acuity did not decrease significantly (P = 0.298) compared with before surgery. Eleven (47.83%) patients received phase-II eyelid PNF resection and/or oculoplastic surgery, and the degree of ptosis was significantly reduced (P < 0.001). There was no recurrence of pulsatile exophthalmos, displacement of titanium mesh, decreased visual acuity, or increased degree of ptosis noted during follow-up. The best strategy is to reconstruct the skull base under microscopy to relieve pulsating exophthalmos and preserve existing visual function. In cases of ptosis caused by an eyelid PNF, surgical resection should be performed as soon as possible to remove the tumor, and/or oculoplastic surgery should be performed to improve the cosmetic outcome.

Extracellular Vesicle lncRNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Released From Glioma Stem Cells Modulates the Inflammatory Response of Microglia After Lipopolysaccharide Stimulation Through Regulating miR-129-5p/High Mobility Group Box-1 Protein Axis.

Glioma stem cell (GSC)-derived extracellular vesicles (EVs) can mediate the communication between GSCs and microglia. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in GSCs, EVs, and supernatant was detected by real-time PCR. The direct targeting between MALAT1 and miR-129-5p, miR-129-5p, and HMGB1 were tested with luciferase reporter analysis. The expression and secretion of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were determined in lipopolysaccharide-stimulated microglia or miR-129-5p inhibitor transferred to microglia exposed to GSC EVs or EVs derived from siMALAT1 pre-transferred GSCs. MALAT1 was enriched in GSC EVs compared with GSCs, and up-regulated MALAT1 was also observed in microglia upon GSC EVs incubation. The relative expression and secretion of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia were up-regulated in the GSC supernatant group, which could be reversed by dimethyl amiloride (DMA) (EV secretion inhibitor) co-administration or si-MALAT1 pre-transfection of GSCs. Luciferase reporter assay testified the direct binding of MALAT1 and miR-129-5p, miR-129-5p, and HMGB1, and si-MALAT1 could up-regulate miR-129-5p expression and down-regulate HMGB1 expression in microglia cells. The concentration of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia exposed to EVs from siMALAT1 transfected GSCs could be up-regulated by miR-129-5p inhibition. EVs lncRNA MALAT1 released from GSCs could modulate the inflammatory response of microglia after lipopolysaccharide stimulation through regulating the miR-129-5p/HMGB1 axis.

Preoperative prediction of cavernous sinus invasion by pituitary adenomas using a radiomics method based on magnetic resonance images.

OBJECTIVES: To predict cavernous sinus (CS) invasion by pituitary adenomas (PAs) pre-operatively using a radiomics method based on contrast-enhanced T1 (CE-T1) and T2-weighted magnetic resonance (MR) imaging. METHODS: A total of 194 patients with Knosp grade two and three PAs (training set: n = 97; test set: n = 97) were enrolled in this retrospective study. From CE-T1 and T2 MR images, 2553 quantitative imaging features were extracted. To select the most informative features, least absolute shrinkage and selection operator (LASSO) was performed. Subsequently, a linear support vector machine (SVM) was used to fit the predictive model. Furthermore, a nomogram was constructed by incorporating clinico-radiological risk factors and radiomics signature, and the clinical usefulness of the nomogram was validated using decision curve analysis (DCA). RESULTS: Three imaging features were selected in the training set, based on which the radiomics model yielded area under the curve (AUC) values of 0.852 and 0.826 for the training and test sets. The nomogram based on the radiomics signature and the clinico-radiological risk factors yielded an AUC of 0.899 in the training set and 0.871 in the test set. CONCLUSIONS: The nomogram developed in this study might aid neurosurgeons in the pre-operative prediction of CS invasion by Knosp grade two and three PAs, which might contribute to creating surgical strategies. KEY POINTS: • Pre-operative diagnosis of CS invasion by PAs might affect creating surgical strategies • MRI might help for diagnosis of CS invasion by PAs before surgery • Radiomics might improve the CS invasion detection by MR images.

Clinical Features and Prognostic Risk Factors of Choroid Plexus Tumors in Children.

BACKGROUND: Decision-making concerning the treatment of choroid plexus tumor (CPT) in pediatric patients remains a topic of considerable debate. The aim of this work was to describe clinical features and prognostic risk factors of CPT in the pediatric population and to provide theoretical opinions regarding clinical decisions for CPT. METHODS: The data of 96 patients with CPT and younger than 14 years were retrospectively analyzed. Clinical characteristics such as pathological type of CPTs, rate and severity of hydrocephalus, treatment and outcome, and recurrence were investigated. For categorical variables, the Pearson's Chi-square test was performed. The Mann-Whitney U-test was used for comparisons between nonnormally distributed parameters. Log-rank test was used for progression-free survival (PFS). RESULTS: The study included 70 choroid plexus papilloma (CPP) cases, 17 atypical choroid plexus papilloma (aCPP) cases, and 9 choroid plexus carcinoma (CPC) cases. Compared with patients with CPP or aCPP, patients with CPC had a shorter disease course (median: CPP, 4 months; aCPP, 2 months; CPC, 1 month; H: 23.5, P < 0.001), higher rate of acute hydrocephalus (CPP, 27.1%; aCPP, 52.9%; CPC, 77.8%; χ2 = 10.9, P < 0.05), and lower incidence of cure rate (CPP, 85.7%; aCPP, 70.5%; CPC, 33.3%; χ2 = 13.5, P < 0.05). The severity of hydrocephalus with tumor in the lateral or third ventricle was significantly higher than that with tumors in the fourth ventricle (severe hydrocephalus: lateral ventricle, 51.7%; third ventricle, 47.0%; fourth ventricle, 11.1%; χ2 = 26.0, P < 0.001). Patients with gross total surgical resection had no better PFS than those with partial resection because of the use of adjuvant therapy in the latter (χ2 = 4.0, P > 0.05). Patients with CPC experienced shorter time for recurrence than those with CPP or aCPP (χ2 = 40.1, P < 0.0001). CONCLUSIONS: Our results indicated that CPP in the fourth ventricle could trigger serious clinical symptoms at an early stage, requiring early intervention. Adjuvant treatment might be necessary for patients with partially resected CPP, aCPP, and CPC to achieve a favorable outcome.

Claudin-5 regulates blood-brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis.

AIMS: To investigate the roles of Claudin-5 (CLDN5) in regulating the permeability of the blood-brain barrier (BBB) during lung cancer brain metastasis. RESULTS: By silencing and overexpressing the CLDN5 gene in human brain vascular endothelial (hCMEC/D3) cells, we demonstrated the attenuation of cell migration ability and CLDN5's significant positive role in cell proliferation in CLDN5-overexpressing hCMEC/D3 cells and observed the opposite result in the CLDN5 knockdown group. The reinforced CLDN5 expression reduced the paracellular permeability of hCMEC/D3 cells and decreased the invasion of lung adenocarcinoma A549 cells. Overall, 1685 genes were found to be differentially expressed between the CLDN5-overexpressing cells and the control cells using the Affymetrix Human Transcriptome Array 2.0 (HTA 2.0), and the function of these genes was determined by Gene Ontology and pathway analyses. The possible biological functions of the 1685 genes include cell proliferation, adhesion molecules, and the Jak-STAT, PI3K-Akt, Wnt, and Notch signaling pathways. The identified sets of mRNAs that were specific to CLDN5-overexpressing hCMEC/D3 cells were verified by a qRT-PCR experiment. CONCLUSION: CLDN5 regulates the permeability of BBB by regulating the proliferation, migration, and permeability of hCMEC/D3 cells, especially through the cell adhesion molecule signaling pathway, to enhance the function of the tight junctions, which was involved in reducing the formation of lung cancer brain metastasis.

Microsurgical Treatment of Meningiomas in the Torcular Herophili Region.

The Torcular Herophili region of the brain is anatomically complex, and surgery in this area requires much skill and care. Retrospective analysis on 35 cases of meningiomas in the Torcular Herophili region treated by microsurgery and confirmed by pathology. Tumor resection range was evaluated using the Simpson grading criteria. Postoperative complications and tumor recurrence were evaluated. Patients were followed up. The Karnofsky performance status was used to evaluate neurologic functions. Magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) revealed the extent of disease in all patients. Simpson level I excision was done in 27 patients, level II in 5 patients, and level IV in 3 patients. Gamma knife treatment after surgery was performed in 3 patients. Symptoms of increased intracranial pressure were relieved after surgery. No patient died, and no patient suffered from any relevant operative complications and disabilities. Pathology reported typical meningioma (World Health Organization [WHO] level I) in 32 patients, and atypical meningioma (WHO level II) in 3 patients. Thirty-two patients were followed up for 0.5 to 5 years: 1 patient relapsed 2 years after operation (Simpson level IV excision), and 2 patients relapsed 3 years after operation (one Simpson level I and one level II). These results indicated that MRV should be performed to confirm the exact relationship between the tumor and venous sinus. The operative approach should be planned according to the MRI results, and the venous sinus should be preserved. Gamma knife might be a beneficial auxiliary treatment of meningioma in the Torcular Herophili region.

Diagnosis and microsurgical treatment of spinal hemangioblastoma.

Spinal cord hemangioblastomas are rare benign tumors, with difficult surgical management and poor prognosis due to high vascularization. We aim to evaluate the diagnostic methods and microsurgical treatment of spinal cord hemangioblastoma. This retrospective study assessed 25 patients treated for spinal hemangioblastoma using microsurgery at Beijing Tiantan Hospital and Department of Neurosurgery, The General Hospital of Chinese People's Armed Police Forces, between October 2008 and October 2013. Clinical, imaging, and treatment data were collected. Meanwhile, efficacy was assessed with the McCormick grading system for spinal cord function. The symptoms lasted 17.0 ± 15.1 months. Sixteen (64 %) patients were suffering from von Hippel-Lindau disease; magnetic resonance imaging revealed the lesions in all patients. Intraoperative fluorescence angiography was helpful in identifying the feeding arteries and draining veins. Total tumor removal was achieved in all subjects. Patients were followed up for 21.3 ± 8.5 months. One week after surgery, neurological symptoms were improved in 22 patients, remained stable in 2 patients, and were aggravated in 1. The latter patient began to recover 7-10 days after surgery and was completely recovered within a month. At the last follow-up, all patients were alive, and all showed a McCormick grade ≤II. Microsurgery seems effective in the treatment of spinal cord hemangioblastoma. Intraoperative fluorescence angiography is helpful in defining the resection scope, to reduce intraoperative bleeding and prevent spinal swelling, which results in improved success rate.

Role of IL-6 in the invasiveness and prognosis of glioma.

IL-6 is a cytokine secreted by glioma cells and plays an important role in the tumor growth. However, the impact of IL-6 on the invasiveness and prognosis of glioma is still unclear. In this study, immunohistochemistry was performed to determine the expression of IL-6 in 86 glioma tissues, and ELISA to measure IL-6 in the serum and cerebrospinal fluid (CSF) of these patients. Results showed, as ccompared with normal controls, the IL-6 in the glioma, CSF and serumincreased remarkably, and increased with the elevation of glioma grade. In addition, IL-6 in the supernatant was also detectable in glioma cell lines U251, U87, A172 and T98G. Transwell invasion assay showed that the invasiveness of glioma U87 cells and U251 cells increased remarkably after exogenous IL-6 treatment. Survival analysis indicated higher IL-6 before surgery and significantly reduction in IL-6 after operation in the serum and CSF predicted a poor prognosis. Thus, we speculate that, the poor prognosis of glioma is related to the IL-6 autocrine in the glioma and the IL-6 induced tumor growth and invasion. IL-6 may serve as a therapeutic target for glioma patients and IL-6 in the CSF and serum of glioma may be used to predict the prognosis of these patients.