Effectiveness of MEP and SSEP Monitoring in the Diagnosis of Neurological Dysfunction Immediately After Craniotomy Aneurysm Clipping.

OBJECTIVE: To explore the diagnostic accuracy of motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring in predicting immediate neurological dysfunction after craniotomy aneurysm clipping. METHODS: A total of 184 patients with neurosurgery aneurysms in the Affiliated Hospital of Qingdao University from April 2019 to December 2021 were retrospectively included. All patients underwent craniotomy aneurysm clipping, and MEP and SSEP were used to monitor during the operation. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for early warning of MEP and SSEP amplitude decline and to evaluate the effectiveness of MEP and SSEP changes in predicting immediate postoperative neurological dysfunction. RESULTS: Among the 184 patients with intracranial aneurysms, the incidences of immediate postoperative neurological dysfunction were 44.4% (12/27) and 3.2% (5/157) in patients with intraoperative MEP changes and without changes, respectively. For SSEP, The incidence rates were 52.6% (10/19) and 4.2% (7/165), respectively, and the differences were statistically significant ( P <0.001). Significant changes in intraoperative MEP and SSEP were significantly associated with the development of immediate postoperative neurological deficits ( P <0.05). The critical values for early warning of MEP and SSEP amplitude decrease were: 61.6% ( P < 0.001, area under the curve 0.803) for MEP amplitude decrease and 54.6% ( P <0.001, area under the curve 0.770) for SSEP amplitude decrease. The sensitivity and specificity of MEP amplitude change in predicting immediate postoperative neurological dysfunction were 70.6% and 91.0%, respectively. For SSEP amplitude changes, the sensitivity and specificity were 58.8% and 95.8%, respectively. CONCLUSIONS: Motor-evoked potential and SSEP monitoring have moderate sensitivity and high specificity for immediate postoperative neurological dysfunction after craniotomy aneurysm clipping. Motor-evoked potential is more accurate than SSEP. Patients with changes in MEP and SSEP are at greatly increased risk of immediate postoperative neurologic deficits.

Pentraxin 3 plays a key role in tubular cell senescence and renal fibrosis through inducing ß-catenin signaling.

Renal fibrosis is the common pathological feature of various chronic kidney diseases (CKD). Tubular cell senescence plays a key role in the progression of renal fibrosis. However, the underlying mechanisms are still in mystery. In this study, we identified, Pentraxin 3 (PTX3), belonging to the Pentraxin family, is a new fibrogenic factor. PTX3 was increased in various CKD models. PTX3 was primarily localized in tubular epithelial cells and upregulated, accompanied by mitochondrial dysfunction and cellular senescence. Overexpression of PTX3 aggravated mitochondrial damage and accelerated cell senescence in tubular cells, leading to more severe fibrogenesis in kidneys. However, knockout of PTX3 significantly preserved mitochondrial homeostasis, and blocked cellular senescence in primary cultured tubular cells. Furthermore, KYA1797K, a destabilizer of ß-catenin, greatly inhibited PTX3-induced mitochondrial dysfunction, tubular cell senescence, and renal fibrosis. Overexpression of PTX3 triggered nuclear translocation of ß-catenin, an activating form of ß-catenin. PTX3-induced mitochondrial dysfunction and tubular cell senescence were also significantly inhibited by knockdown of p16INK4A, a senescence-related protein. In a clinical cohort, we found PTX3 was increased in urine and serum in patients with CKD. Urinary PTX3 negatively correlated with eGFR. PTX3 also increased gradually following the severity of diseases, triggering the fibrogenesis. Taken together, our results provide strong evidences that PTX3 is a new fibrogenic factor in the development of renal fibrosis through ß-catenin-induced mitochondrial dysfunction and cell senescence. This study further suggests PTX3 is a new diagnostic factor to renal fibrosis and provides a new therapeutic target against renal fibrosis.

Low BMI and high waist-to-hip ratio are associated with mortality risk among hemodialysis patients: a multicenter prospective cohort study.

Background: Data are limited on the relationship between waist-to-hip ratio (WHR) and mortality risk among maintenance hemodialysis (MHD) patients. Moreover, the combined association of body mass index (BMI) and WHR with mortality remains uncertain. Therefore, we aimed to explore the individual and combined association of BMI and WHR with the all-cause and cardiovascular disease (CVD) mortality. Methods: In this multicenter prospective cohort study, we enrolled 1034 MHD patients. The primary outcome was all-cause mortality and secondary outcome was CVD mortality. Multivariable Cox proportional hazards models were used to evaluate the individual and combined association of BMI and WHR with the risk of mortality. Results: A nonlinear inverse relationship was found between BMI and risk of all-cause mortality (P for nonlinearity <.05). Being underweight (<18.5 kg/m2) was associated with higher all-cause mortality risk (HR 1.45; 95% CI 1.08-1.94) compared with normal weight (18.5-23.9 kg/m2), while being overweight (24-27.9 kg/m2; HR 0.96; 95% CI 0.70-1.31) and obese (≥28 kg/m2; HR 1.19; 95% CI 0.62-2.26) showed no significant differences. Of note, WHR was independently and positively associated with all-cause mortality (per standard deviation increase, HR 1.13; 95% CI 1.00-1.27). When analyzed jointly, patients with low BMI (<18.5 kg/m2) and high WHR (≥0.95) had the highest risk of all-cause mortality. Similar results were obtained for CVD mortality. Conclusions: In patients undergoing hemodialysis from China, low BMI and high WHR were individually and jointly associated with higher risk of mortality. Our results emphasize that BMI and WHR may jointly affect the prognosis of MHD patients.

Nano hydroxyapatite induces glioma cell apoptosis by suppressing NF-κB signaling pathway.

Nano-sized hydroxyapatite (nHA) particles have been demonstrated to exert anti-cancer effects on multiple cancer cell lines and animal models of cancer biology. However, the molecular mechanism underlying the effects of nHA particles on glioma cells remains unclear. The present study aimed to examine the effects of nHA on the behavior of glioma cells and investigate its underlying molecular mechanism. Rat glioma C6 cells and human glioma U87MG ATCC cells were exposed to nHA (20-100 µg/ml), and its effects on cell morphology, viability, apoptosis, cell cycle, invasion and nuclear factor (NF)-κB signaling were analyzed. Exposure of C6 and U87MG ATCC cells to 20 µg/ml nHA for 24 h caused cell detachment. Viability of C6 and U87MG ATCC cells were significantly reduced by nHA in a dose-dependent manner (P<0.05). Nuclear staining with Hoechst 33258 exhibited clear chromatin condensation in C6 cells following 24 h exposure to ≥25 µg/ml nHA. Flow cytometry revealed that nHA (20-100 µg/ml) significantly induced apoptosis and cell cycle G2/M arrest in C6 and U87MG ATCC cells (P<0.05). Transwell invasion assay demonstrated that nHA (20-60 µg/ml) significantly inhibited invasion of U87MG ATCC cells (P<0.05). Furthermore, western blotting and confocal immunofluorescence microscopy revealed that nHA (20-100 µg/ml) decreased NF-κB p65 protein expression and blocked NF-κB p65 nuclear translocation in C6 cells. The protein expression of NF-κB target molecules, such as B cell lymphoma 2, cyclooxygenase-2 and survivin, were also significantly reduced by nHA in a dose-dependent manner in both C6 and U87MG ATCC cells (P<0.05). In conclusion, it was demonstrated that the inhibitory effect of nHA on glioma cells is likely associated with the downregulation of NF-κB signaling.

Liquid Posterior Fossa Epidural Hematoma in Pediatric Trauma: A Single-Center Case Series.

BACKGROUND: Liquid posterior fossa epidural hematoma (LPFEH) following head trauma is uncommon, and very few such cases have been described in the literature. Eight patients with this entity and their treatments are presented here. METHODS: We performed a single-institution retrospective analysis of all patients with diagnosed LPFEH over a 3-year period. Collected data included clinical history, laboratory results, treatment, and review of all imaging studies performed. RESULTS: Eight pediatric cases were identified with imaging findings consistent with LPFEH; no adult case was identified. Enlargement of ventricles appeared on computed tomography (CT) in six cases, and secondary epilepsy onset occurred in three cases with severe dilated ventricles. Routine hematologic and coagulation tests failed to disclose anemia or abnormal coagulation in each case. Five patients underwent burr-hole drainage of the hematoma and recovered completely. Conservative therapy was adopted in three patients for small hematomas, and hematoma enlargement was not observed in the follow-up CT scans. CONCLUSIONS: LPFEH is a rare subtype of traumatic epidural hematoma specifically recognized in the pediatric population. Minimally invasive burr-hole drainage is a feasible procedure for the patient with evident space-occupying effect. Coagulation dysfunction or low hemoglobin as a possible contributing factor and its role in formation of LPFEH was excluded.

Attenuation of EGFL7 Expression Inhibits Growth Hormone-Producing Pituitary Adenomas Growth and Invasion.

Invasiveness of growth hormone-producing pituitary adenomas (GHPAs) causes difficulties in safe and complete adenoma removal during surgery and often leads to high recurrence. Epidermal growth factor-like domain 7 (EGFL7) has been shown to be able to promote tumor angiogenesis, growth, invasiveness, and metastasis through the Notch signaling pathway. It was previously demonstrated that EGFL7 was overexpressed in GHPAs. This study reports that EGFL7 and Notch2 (positive correlation with EGFL7) are overexpressed in invasive GHPA. A long-rank test (Kaplan-Meier method) shows that invasive GHPAs with EGFL7 strong expression results in reduced recurrence-free survival. Multivariate Cox regression analysis reveals that weak EGFL7 expression is an independent prognostic factor for recurrence-free survival. In addition, knockdown of EGFL7 expression suppresses proliferation and invasion of GH3 and GT1-1 cells in vitro. Moreover, attenuation of EGFL7 inhibits human GHPA growth in vivo. The data suggest that as a Notch agonist, EGFL7 may potentially be an appropriate novel molecular target for future development of GHPA medical therapy.

Rapid Clearance of Lateral Ventricular Hematoma via Frontal Eminence Puncture and Aspiration: A Technical Note.

Background Intraventricular extension of a parenchymal hemorrhage is an independent predictor of poor outcome and might be complicated by delayed hydrocephalus. We describe a method for the rapid and effective removal of a lateral ventricular hematoma via catheter-based puncture and aspiration. Methods A catheter-based aspiration of a ventricular hematoma via a frontal eminence (FE) puncture was performed in 10 patients with thalamic and ganglionic hemorrhage perforating into the lateral ventricle. Paralleling the long axis of the lateral ventricle, a flexible silicone catheter was moved anteroposteriorly and rotated simultaneously to facilitate clot aspiration and removal. Computed tomography scans before and after surgery were compared for assessment of ventricular clot volume, Graeb score, and the ventriculocranial ratio (VCR). The Glasgow Coma Scale (GCS) score and Glasgow Outcome Scale (GOS) score were assessed at 14 days and 12 months following surgery, respectively. Results In all 10 patients, catheter-based aspiration resulted in substantial hematoma removal with a clearance rate of 64.9%, a reduced Graeb score by 61.8%, and an elevated GCS score by 52.7%. The procedure was performed safely without occurrence of another hemorrhage, infection, and catheter obstruction in any case. At 12-month follow-up, VCR was reduced by 22.5%, no delayed hydrocephalus occurred, and a favorable outcome with an average GOS of 4.6 was observed in this small cohort of patients. Conclusion Catheter-based aspiration of a ventricular hematoma via FE puncture rapidly, efficiently, and safely reduced the clot in the ventricular system, prevented delayed hydrocephalus sufficiently, and produced a favorable outcome.

Whole-exome sequencing identifies variants in invasive pituitary adenomas.

Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F-actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor-related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of tumorigenesis, and most likely contribute to the development of oncocytic change and to the invasive tumor phenotype.

Adult-Onset Leukoencephalopathy with Calcifications and Cysts: Focusing on Hemorrhagic Propensity and Cysts Development.

BACKGROUND: An uncommon disorder, adult-onset leukoencephalopathy with calcifications and cysts (ALCC) has been recognized clinically for approximately a decade. Its typical radiologic signs and pathologic characteristics have been investigated thoroughly and described fully in a series of cases. However, little attention has focused on the propensity of hemorrhage in this entity, and the etiology of cyst occurrence in ALLC remains uncertain. To the best of our knowledge, there is a lack of relevant articles addressing the relationship between hemorrhage and cyst development in ALCC. CASE DESCRIPTION: A 30-year-old woman presented with headache, diminishing eyesight, and face numbness over the course of 16 months. Repeat radiologic examination showed the formation of a new cyst and the enlargement of former cyst after hemorrhage. She was diagnosed formerly with ALCC with the triad of leukoencephalopathy, calcifications, and cyst in imaging. Staging gross total resections of cyst were achieved with neurologic improvement postoperatively. Histologic examination revealed angiomatous vessels, Rosenthal fiber formation, microcalcification, and deposits of hemosiderin, and ALCC was confirmed pathologically. CONCLUSIONS: After analyzing the clinical data about the hemorrhage and cysts in our case and all 15 reported ALCC cases in the literature, we conclude that intermittent hemorrhage and cysts development are 2 outstanding features for ALCC and that hemorrhage is a probable mechanism for the formation and expansion of cyst.

Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

BACKGROUND: Dopamine agonists (DAs) are the first-line treatment for prolactinomas, which account for 25-30% of functioning pituitary adenomas, and bromocriptine (BRC) is the only commercially available DAs in China. However, tumors are resistant to therapy in 5-18% of patients. METHODS: The exomes of six responsive prolactinomas and six resistant prolactinomas were analyzed by whole-exome sequencing. RESULTS: Using stringent variant calling and filtering parameters, ten somatic variants that were mainly associated with DNA repair or protein metabolic processes were identified. New resistant variants were identified in multiple genes including PRDM2, PRG4, MUC4, DSPP, DPCR1, RP1L1, MX2, POTEF, C1orf170, and KRTAP10-3. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in 12 prolactinomas and 3 normal pituitary glands. The mRNA levels of PRDM2 were approximately five-fold lower in resistant prolactinomas than in responsive tumors (p < 0.05). PRDM2 protein levels were lower in resistant prolactinomas than in responsive tumors, as determined by Western blotting and immunohistochemical analysis (p < 0.05). Overexpression of PRDM2 upregulated dopamine receptor D2 (D2DR) and inhibited the phosphorylation of ERK1/2 in MMQ cells. PRDM2 showed a synergistic effect with BRC on the inhibition of prolactin (PRL) secretion and MMQ cell viability, and low PRDM2 expression was associated with tumor recurrence. CONCLUSIONS: PRDM2 downregulation may play a role in dopamine-agonist resistance and tumor recurrence in prolactinomas.

The role of TGF-ß/Smad signaling in dopamine agonist-resistant prolactinomas.

BACKGROUND: Prolactinomas are the most common secretory pituitary adenomas. The first line of treatment involves dopamine agonists (DAs); however, a subset of patients is resistant to such therapy. Recent studies suggest that dopamine can up-regulate TGF-ß1 synthesis in rat pituitary lactotrophs whereas estradiol down-regulates TGF-ß1. To date, the role of TGF-ß/Smad signaling in DAs-resistant prolactinomas has not been explored. METHODS: High-content screening (HCS) techniques, qRT-PCR, Western blot, immunofluorescence and ELISA, were performed to determine the role of TGF-ß/Smad signaling in DAs-resistant prolactinomas. RESULTS: We reported a significant down-regulation of TGF-ß/Smad signaling cascade in DAs-resistant prolactinomas compared to normal human anterior pituitaries. Following treatment with TGF-ß1, the dopamine agonist, bromocriptine, and the estrogen antagonist (ER), fulvestrant in GH3 cells, we found that TGF-ß1 and fulvestrant caused significant cytotoxicity in a dose- and time-dependent manner and activated Smad3 was detected following exposure to TGF-ß1 and fulvestrant. In addition, treating GH3 cells with fulvestrant increased active TGF-ß1 levels and decreased PRL levels in a dose-dependent manner. CONCLUSION: TGF-ß/Smad signaling pathway may play an important role in DA-resistant prolactinomas and has the potential to be a viable target for the diagnosis and treatment of prolactinomas, particularly in patients who are resistant to DAs.

Primary cerebellar paraganglioma: a pediatric case report and review of the literature.

BACKGROUND: Only four cases of primary intracerebellar paragangliomas have been reported in the literature to date. Because of its rarity, primary intracerebellar paraganglioma still presents a diagnostic challenge for both radiologists and neurosurgeons, and the optimal therapeutic modality is still debatable for its hypervascularity and location. PATIENTS: We report a 16-year-old boy with pathology-proven primary intracerebellar paraganglioma who presented with dull headache, dizziness, and gait disturbance, and underwent gross total resection. Further, we review all reported cases of primary intracerebellar paraganglioma in the English literature and discuss its clinical profile, neuroradiological features, and treatment modalities. RESULTS: His symptoms improved following tumor removal without radiotherapy, and postoperative neuroimaging thirteenth months after surgery showed no recurrence. In the literature, all four patients were stable in the follow-up period including three with complete resection and one with partial resection plus adjuvant radiotherapy. CONCLUSION: Surgical resection is the treatment modality most often used for primary intracerebellar paraganglioma; radiation therapy may be used when there is residual tumor or recurrence. Angiography may help to clarify the vessel architecture for reducing intraoperative bleeding when primary intracerebellar paraganglioma is considered.

Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

Prolactinomas, or prolactin-secreting adenomas, constitute the most common type of hyperfunctioning pituitary adenoma. Dopamine agonists are used as first-line medication for prolactinomas, but the tumors are resistant to the therapy in 5-18 % of patients. To explore potential mechanisms of resistance to bromocriptine (a dopamine agonist), we analyzed six responsive prolactinomas and six resistant prolactinomas by whole-exome sequencing. We identified ten genes with sequence variants that were differentially found in the two groups of tumors. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in the 12 prolactinomas and in six normal pituitary glands. The mRNA levels of one of the genes, PRB3, were about fourfold lower in resistant prolactinomas than in the responsive tumors (p = 0.02). Furthermore, low PRB3 expression was also associated with tumor recurrence. Our results suggest that low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor recurrence of prolactinomas.

Bilateral supratentorial epidural hematomas: a rare complication in adolescent spine surgery.

A 14-year-old girl presented with a rare case of spontaneous bilateral supratentorial epidural hematomas which developed rapidly following cervical surgery. The hematomas presumably resulted from dural dynamics changes secondary to cerebrospinal fluid loss and intracranial hypotension. Intracranial epidural hemorrhage after spinal surgery is extremely uncommon with only one previous case report. Spontaneous intracranial epidural hematoma is an extremely rare complication, but should be considered as a possible complication of spine surgery, especially in adolescents complicated by delayed consciousness and breathing restoration from anesthesia. This case report expands the presently known clinical spectrum of this uncommon complication.