Noninvasive detection of brain gliomas using plasma cell-free DNA 5-hydroxymethylcytosine sequencing.

Liquid biopsy techniques based on deep sequencing of plasma cell-free DNA (cfDNA) could detect the low-frequency somatic mutations and provide an accurate diagnosis for many cancers. However, for brain gliomas, reliable performance of these techniques currently requires obtaining cfDNA from patients' cerebral spinal fluid, which is cumbersome and risky. Here we report a liquid biopsy method based on sequencing of plasma cfDNA fragments carrying 5-hydroxymethylcytosine (5hmC) using selective chemical labeling (hMe-Seal). We first constructed a dataset including 180 glioma patients and 229 non-glioma controls. We found marked concordance between cfDNA hydroxymethylome and the aberrant transcriptome of the underlying gliomas. Functional analysis also revealed overrepresentation of the differentially hydroxymethylated genes (DhmGs) in oncogenic and neural pathways. After splitting our dataset into training and test cohort, we showed that a penalized logistic model constructed with training set DhmGs could distinguish glioma patients from healthy controls in both our test set (AUC = 0.962) and an independent dataset (AUC = 0.930) consisting of 111 gliomas and 111 controls. Additionally, the DhmGs between gliomas with mutant and wild-type isocitrate dehydrogenase (IDH) could be used to train a cfDNA predictor of the IDH mutation status of the underlying tumor (AUC = 0.816), and patients with predicted IDH mutant gliomas had significantly better outcome (P = .01). These results indicate that our plasma cfDNA 5hmC sequencing method could obtain glioma-specific signals, which may be used to noninvasively detect these patients and predict the aggressiveness of their tumors.

Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling.

BACKGROUND: PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated. METHODS: By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes. RESULTS: PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell-cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs. CONCLUSIONS: Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.

Targeting CXCR4 to suppress glioma-initiating cells and chemoresistance in glioma.

Glioma initiating cells (GICs), also known as glioma stem cells, display the capacity to recapitulate the functional diversity within the tumor. Despite the great progress achieved over the last decades, defining the key molecular regulators of GICs has represented a major obstacle in this field. In our study, data from The Cancer Genome Atlas database illustrated a relationship between C-X-C motif chemokine receptor 4 (CXCR4) expression and the survival of glioma patients. Mechanistically, we further indicated that CXCR4 mediated the upregulation of Kruppel like factor 5 (KLF5), a zinc-finger-containing transcription factor, to facilitate the proliferation of GICs. What's more, CXCR4 also enhanced the chemoresistance through KLF5/Bcl2-like 12 (BCl2L12) in glioma. The elevated expression of KLF5 and BCL2L12 induced by CXCR4 was dependent on phosphoinositide 3-kinases (PI3K)/serine/threonine kinase (AKT) signaling. Importantly, combined application of temozolomide and a CXCR4 inhibitor efficiently reversed CXCR4 mediated drugs resistance and improved anticancer effects in vivo. Collectively, our findings confirmed that CXCR4 promoted GICs proliferation via the KLF5/BCL2L12 dependent pathway, which may enrich the understanding of GICs and help drive the design of efficacious therapeutic strategies.

The outcome of microvascular decompression for hemifacial spasm: a systematic review and meta-analysis.

Microvascular decompression (MVD) is the first choice of surgery for hemifacial spasm (HFS). MVD surgery for vertebral artery (VA)-associated HFS is more difficult than for non-VA-associated HFS. There is controversy about the cure rate and complication of MVD for HFS in previous studies. We searched PubMed, Web of Science, and Embase for relevant publications. Based on the search results, we compared the outcomes of MVD for VA-associated HFS and non-VA-associated HFS. At the same time, we analyzed spasm-free rates and the complications and assessed the relationship between VA-associated HFS and gender, left side, and age. For analysis, six studies that included 2952 patients in the VA-associated group and 604 in the non-VA-associated group were selected. The effective rate of MVD was not significantly different between both groups (OR = 1.16, 95% CI 0.81-1.67, P = 0.42). Compared to non-VA-associated group, the transient complications (OR = 0.64, 95% CI 0.46-0.89, P = 0.008) and permanent complications (OR = 0.28, 95% CI 0.15-0.54, P = 0.0001) occurred more frequently in VA-associated group. The rate of hearing loss was significantly higher in VA-associated HFS than non-VA-associated HFS (OR = 0.35, 95% CI 0.19-0.64, P = 0.0007); the facial paralysis after operation was not significantly different between both groups (OR = 1.25, 95% CI 0.91-1.72, P = 0.17). There were older patients (WMD = 3.67, 95% CI 3.29-4.05, P < 0.00001) and more left-sided HFS (OR = 0.23, 95% CI 0.19 - 0.29, P < 0.0002) in the VA-associated HFS group than non-VA-associated HFS group, while the non-VA-associated HFS group was female-dominated (OR = 1.58, 95% CI 1.32 - 1.89, P < 0.00001). Both groups achieved good results in MVD cure rates. In VA-associated HFS, the complication rate of decompression and the rate of hearing loss after operation were higher than in non-VA-associated HFS, but the facial paralysis after operation was similar in both groups, and most complications were transient and disappeared during follow-up. VA-associated HFS is more prevalent in older adults, less prevalent in women, and more predominantly left-sided. More clinical studies are needed to better compare the efficacy and complication of MVD between both groups.

Clinical outcomes in central nervous system solitary-fibrous tumor/hemangiopericytoma: a STROBE-compliant single-center analysis.

BACKGROUND: Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare mesenchymal tumors in the central nervous system with a high tendency to relapse, having a significant impact on quality of life (QoL). Due to the rarity of intracranial SFT/HPC, the prognostic factors and optimal treatment remain to be elucidated. Meanwhile, quality of life in patients with intracranial SFT/HPC is seldomly concerned. Thus, we aim to survey about the quality of life and underline some aspects demanding concern in intracranial SFT/HPC treatment through summarizing our case series in recent ten years. METHODS: Patients with intracranial SFT/HPC who underwent surgical resection from January 2009 to June 2019 were included in the study. Clinical features, such as age, gender, and resection extent, were collected. The EuroQol Five Dimensions Questionnaire (EQ-5D) was used to assess the patients' quality of life (QoL). Prognosis factors related to progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: Thirty-six patients with a mean follow-up period of 61.6 months (range 13-123 months) were included in this study. Sixteen (44.4%) patients achieved gross total resection (GTR). Fourteen patients (38.9%) with tumor progression experienced adjuvant radiotherapy (11.1%) or Gamma Knife surgery (GKS, 27.8%). According to the 2016 WHO classification, there were 6 (16.7%) grade I SFT/HPC, 11 (30.5%) grade II SFT/HPC, and 19 (52.8%) grade III SFT/HPC. The PFS and OS were 29 months (range 4-96 months) and 38 months (range 4-125 months). The median EQ5D-3 L tariff with or without progression was 0.617 (95% CI 0.470-0.756) and 0.939 (95% CI 0.772-0.977) respectively. Gross total resection (GTR, p = 0.024) and grade I SFT/HPC (p = 0.017) were significantly associated with longer PFS. In multivariate analysis, GTR (HR 0.378, 95% CI 0.154-0.927) and adjuvant therapy (HR 0.336, 95% CI 0.118-0.956) result in significantly longer PFS in patients with SFT/HPC. CONCLUSIONS: Patients underwent GTR and adjuvant therapy had longer PFS. Similarly, patients with lower WHO grade had relatively longer PFS. Therefore, GTR is advocated for the treatment of SFT/HPC. And adjuvant therapy such as GKS could be an alternative treatment for patients who underwent STR or with tumor progression. Further, the QoL decreased in patients with tumor progression and metastasis, and more attention is demanded to the QoL of intracranial SFT/HPC patients.

Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 µM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 µM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

Primary spinal pilocytic astrocytoma: clinical study with long-term follow-up in 16 patients and a literature review.

Primary pilocytic astrocytoma (PA) of the spine is extremely rare and most published case series only include only a few patients. We attempted to explore the clinical features, radiological findings, and treatment outcomes of patients with spinal PA. Sixteen spinal PA patients who were surgically treated in our hospital between April 2008 and June 2018 were included in this retrospective study. An integrative analysis was performed regarding spinal PA patients by extracting from published studies on PubMed. The 16 patients with spinal PA included eight male and eight female patients with a mean age of 29.1 years. Ten cases (62.5%) had masses located in the cervical segments, five (31.3%) had masses in the thoracic segments, and one (6.2%) had masses in the sacral canal. All the patients were treated surgically with 13 gross total resections (GTRs, 81.3%) and three subtotal resections (STRs). The mean follow-up period was 40.4 months. These tumors accounted for a recurrence rate of 37.5% (6 of 16 patients) and no death during the follow-up periods. The influencing factors of recurrence were mainly STR, gene mutation (NF-1 and H2-K27M), and the number of segments involved. The mean recurrence-free survival duration was 19 months. The imaging features of spinal PA are heterogeneous, and the definitive diagnosis requires pathological support. GTR is the standard therapy for spinal PAs, although patients with GTR are still likely to relapse. The regular spinal magnetic resonance imaging follow-ups are required regardless of the resection status. Reoperation is feasible for patients with recurrence.

Improved Macaca fascicularis gene annotation reveals evolution of gene expression profiles in multiple tissues.

BACKGROUNDS: Macaca fascicularis (M. fascicularis) is a primate model organism that played important role in studying human health. It is vital to better understand the similarity and differences of gene regulation between M. fascicularis and human. Current comparative study of gene regulation between the two species are limited by low quality of gene annotation and lack of regulatory element data on M. fascicularis genome. RESULTS: In this study, we improved the M. fascicularis gene annotation with 57 gene expression data from multiple tissues and, more importantly, a manual curation procedure. The new annotation enabled us to map gene expression and identify gene location more accurately. CONCLUSIONS: Comparing with human gene expression data from the same cell types, we characterized the evolution of expression patterns of homologous genes.

Perventricular device closure of congenital ventricular septal defects.

Ventricular septal defect (VSD) is a common congenital heart disease. Open surgical repair with cardiopulmonary bypass (CPB) and sternotomy is the classic treatment. Percutaneous device closure is a minimally invasive alternative in treating selected VSDs, but it is limited by vascular access as well as radiation exposure especially in pediatric patients. Hybrid perventricular device closure of VSDs was designed to combine the advantages of both approaches allowing direct access to the defect without CPB and has gained wider acceptance in recent years. Under transesophageal echocardiography guidance, it could effectively close muscular, perimembranous, and even doubly committed defects. It is a safe and effective option for selected patients with congenital VSDs. In this article, we reviewed the application and results of this technique.

Three risk factors for WHO grade II and III meningiomas: A study of 1737 cases from a single center.

BACKGROUND: Meningiomas account for 35.5% of central nervous system (CNS) tumors, of which 21-37.8% are atypical or anaplastic/malignant. High-grade meningiomas have higher rates of recurrence and worse outcome than grade I/II meningiomas. Thus, it is of importance to assess the tumor biology before treatment initiation. MATERIALS AND METHODS: This study reviewed 1737 patients with histologically confirmed meningioma at a single institution. Meningiomas were classified according to World Health Organization (WHO) 2007 grading and the location of the tumor was confirmed from the operation records and preoperative imaging. Univariate and multivariate logistic regression were used to analyze the potential risk factors for high-grade pathology. RESULTS: Young men and pediatric patients were less likely to have meningioma, but they had high-grade meningioma. Tumors originated from non-skull base and lateral intracranial are more likely to be grade II/III meningioma. CONCLUSIONS: Lateral and non-skull base location, male sex, and the younger patients increase the risk for grade II and III pathology. These factors should be considered while deciding treatment choice, surgical resection, and prognosis as well.

[Pituitary functional recovery and hormone replacement therapy of patients with pituitary adenoma surgery].

OBJECTIVE: To study the pituitary functional recovery of patients with pituitary adenoma surgery and to identify appropriate dosages of hormone replacement for those patients. METHODS: Serum hormone levels of 187 patients with pituitary adenoma were detected before and after surgery. RESULTS: The lowest serum hormone levels were detected on the 3rd day after surgery (P < 0.05). The hormone levels were partly recovered on the 30th day (P < 0.05) and continued to rise to a relatively high level on the 90th day and one year after surgery (P < 0.05). Patients with older ages were more likely to suffer from hypopituitarism and had less satisfying recovery (P < 0.05) than their younger counterparts. The dosages of Euthyrox and Prednisone that were needed for hormone replacement therapy reached a relatively stable level on the 90th day after surgery (P < 0.05). CONCLUSION: Most patients with pituitary adenoma experienced hypopituitarism shortly after surgery, especially for the elderly who recovered more slowly. Low dosage of hormone replacement therapy based on their symptoms can help the patients reach a stable level of hormone within three months. As a result, the 90th day after surgery can be regarded as a cut-off time for measuring functional recovery of glandula pituitaria.

[Effects of bromocriptine on the treatment of prolactinomas in male patients and its influences on their sexual function].

OBJECTIVE: To explore the effect of bromocriptine in the treatment of male patients with prolactinoma and its impacts on their sexual function. METHODS: The clinical data of 29 male patients with prolactinomas treated with Bromocriptine were analysed, International Index of Erectile Function-5 (IIEF-5) was used to assess the sexual function of married patients before and after the treatment of Bromocriptine. RESULTS: The main clinical symptoms of male patients with prolactinomas were sexual dysfunction, headache and hypopsia, which were released significantly at 6 months after Bromocriptine therapy, with the decrease of serum prolactin (PRL) level (P < 0.05) and the improvement of basal testosterone (T) level (P < 0.05). The total normalization rate of PRL was 82.8%, and total effective rate of Bromocriptine therapy was 100%. According to the assessment of IIEF-5, all the male patients had their sexual function improved in various degree. CONCLUSION: Bromocriptine can improve the clinical symptoms of male patients with prolactinoma and their sexual function.

Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder.

OBJECTIVE: Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD. METHODS: Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAc-ALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG. RESULTS: The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude. CONCLUSIONS: These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD. Clinical trial registration no.: NCT02398318 (ClinicalTrials.gov).

Clivus-involved immunoglobulin G4 related hypertrophic pachymeningitis mimicking meningioma: A case report.

BACKGROUND: Immunoglobulin G4 related disease (IgG4-RD) is a fibroinflammatory disease with markedly elevated serum IgG4 levels and fibrous tissue proliferation, accompanied by numerous plasma cells. IgG4 related hypertrophic pachymeningitis (IgG4-RHP) is relatively rare and indistinguishable from other phymatoid diseases before the operation. The risk of long-term immunosuppression needs to be balanced with disease activity. CASE SUMMARY: A 40-year-old man presented with headache and bilateral abducent paralysis. He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same. Before the operation and steroid therapy, the patient was suspected of having tubercular meningitis at a local hospital. A clivus lesion was found via brain magnetic resonance imaging (MRI) at this presentation. He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery. Transnasal endoscopic resection was performed to treat deterioration of nerve function. Postoperative pathologic examination suggested IgG4-RD. Moreover, the serum IgG4 was elevated at 1.90 g/L (reference range: 0.035-1.500 g/L). After steroid therapy for 2 mo, the lesion size diminished on MRI, and the function of bilateral abducent nerves recovered. CONCLUSION: IgG4-RHP is relatively rare and indistinguishable before the operation. Elevated serum IgG4 levels and imaging examination help in the diagnosis of IgG4-RHP. Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.

TDO2 and tryptophan metabolites promote kynurenine/AhR signals to facilitate glioma progression and immunosuppression.

Tumor cells exhibit enhanced uptake and processing of nutrients to fulfill the demands of rapid growth of tumor tissues. Tryptophan metabolizing dioxygenases are frequently up-regulated in several tumor types, which has been recognized as a crucial determinant in accelerated tumor progression. In our study, we explored the specific role of tryptophan 2,3-dioxygenase 2 (TDO2) in glioma progression. Analysis of mRNA profiles in 325 glioma patients based on the rich set of CCGA database was performed, which revealed that high TDO2 expression was tightly correlated with poor prognosis in glioma patients. TDO2 increased intracellular levels of tryptophan metabolism in the kynurenine (Kyn) pathway in vitro and in vivo, resulting in sustained glioma cell proliferation. Mechanistically, overexpression of TDO2 promoted the secretion of Kyn, which in turn stimulated the activation of the aryl hydrocarbon receptor (AhR)/AKT signaling pathway, resulting in heightened proliferative properties and tumorigenic potential in glioma cells. Meanwhile, Kyn produced by tumor cells further suppressed the proliferation of functional T cells, thereby resulting in immunosuppression and enhanced tumor growth in glioma. Our study showed that TDO2-induced increase in tryptophan metabolite Kyn played a pivotal role in glioma development via the AhR/AKT pro-survival signals and immunosuppressive effects, suggesting that the use of TDO2 inhibitors in combination with chemotherapy may be a novel strategy to effectively and synergistically eliminate glioma cells.

Incidence, demographics, and survival of patients with primary pituitary tumors: a SEER database study in 2004-2016.

Comprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Extensive clinical and demographic characteristics were extracted and submitted to group comparisons. The standardized incidence rate was calculated and stratified by year at diagnosis, age/sex and age/treatment groups. The Kaplan-Meier analysis and multivariable regressions were performed to identify the factors associated with overall survival. A total of 47,180 pituitary tumors were identified, including 47,030 typical adenomas, 111 uncertain behavior pituitary adenomas, and 39 pituitary carcinomas. The overall standardized incidence rate was 4.8 cases per 100,000 person-years and the annual incidence rate continually trended upwards, with a peak seen in 2015. We noticed a bimodal age-related distribution in females and a unimodal distribution in males. In the multivariate regression analysis, the factors associated with prolonged survival included typical adenoma, younger age, and smaller tumor size. Whereas, black and male patients had worse overall survival. Our study provides a reliable estimate on the incidence of pituitary adenoma and confirms that the annual standardized incidence rate is increasing. Pituitary adenomas have a satisfactory long-term prognosis and age, tumor size, and tumor subtypes are related to overall survival. Though statistically significant, our inferential findings should be constrained within the limitations of SEER database.

Exosomal miRNA Profiling is a Potential Screening Route for Non-Functional Pituitary Adenoma.

Non-functional pituitary adenomas (NFPAs) are one of the most prevalent pituitary adenoma subtypes. The lack of reliable screening approach for NFPAs for the insidious clinical course usually leads to delays in medical therapy and consequently worse prognosis. Hence, we employed a sequence cohort (patient: control, 6:2) and a validation cohort (patient: control, 22:8) to develop a serum exosomal miRNA profile-based method for NFPA screening and prognosis prediction. We found that a total of 1,395 kinds of human miRNA were detected. Compared with healthy donors, 18 up-regulated and 36 down-regulated miRNAs showed significant expression alterations in NFPA patients. Target genes of differentially expressed miRNAs are mainly enriched in axonogenesis and cancer-associated terms. After validation, hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p were promising biomarkers for NFPA, in which miR-486-5p was the most competent one. After a median of 33 months of prospective follow-up, exosomal hsa-miR-486-5p also was an efficient predictive biomarker for progression or relapse of NFPAs. By protein-protein interaction network construction of hsa-miR-486-5p targeted genes, the core modules revealed a high possibility that exosomal hsa-miR-486-5p regulated tumor progression by epigenetic regulation of MAPK signaling pathways. In conclusion, exosomal hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p are candidate biomarkers for diagnosis and screening of NFPAs. More importantly, prospective follow-up reveals that hsa-miR-486-5p can be regarded as a significant predictor for prognosis of NFPAs.

Clinical Significance of Preoperative Fibrinogen to Albumin Ratio in Patients with Glioblastoma: A Singe Center Experience.

OBJECTIVE: To explore the prognostic value of preoperative fibrinogen to albumin ratio (FAR) in patients with glioblastoma (GBM) and its association with clinical characteristics. PATIENTS AND METHODS: A retrospective analysis was carried out on patients with newly diagnosed GBM who had undergone operation at the Department of Neurosurgery at West China Hospital between June 1st 2015 to June 31st 2018. Receiver operating characteristic (ROC) curves were performed to determine the optimal cut-off values for fibrinogen, albumin, neutrophil to lymphocyte ratio (NLR), and FAR by calculating the maximum Youden index. Kaplan-Meier curves and Cox regression analyses were applied to evaluate the prognostic value of FAR in GBM. Harrell concordance index (C-index) and Akaike information criterion (AIC) were calculated to compare different prognostic models. RESULTS: A total of 206 GBM patients were included in this research. The optimal cut-off value for fibrinogen, albumin, NLR, and FAR were 2.57, 42.4, 2.28, and 0.068 respectively. High FAR was significantly related to older age, KPS≤80, IDH-1 wildtype, presence of preoperative seizures, higher NLR, and tumor location. In Cox regression analyses, high FAR was significantly associated with poor prognosis. Prognostic models including FAR had the largest C-index and lowest AIC. CONCLUSION: FAR was determined to be an independent risk factor of prognosis in patients with newly-diagnosed GBM. And the prognostic predictive ability of FAR is stronger than fibrinogen and albumin.

Clinical characteristics and treatment outcomes of pigmented tumors in central nervous system: Focusing on melanocytic tumors.

Pigmented tumors are rare neoplasm of central nervous system. Melanocytic tumor, including primary and metastatic lesions, is the most common type. Owing to the rarity, the differential diagnosis of pigmented tumors and clinical management of melanocytic tumor remain challenge. Therefore, focusing on melanocytic tumors, the clinical, radiological, histopathological features and treatment outcomes were presented and analyzed in this study. We identified 22 melanocytic tumors, 2 melanotic medulloblastomas, 2 melanotic ependymomas and 1 melanotic schwannoma. Compared with metastatic melanocytic tumors (MMTs), primary melanocytic tumors (PMTs) were characterized by younger age (36.11 ± 17.96 vs. 51.69 ± 12.58 years, p = 0.0262), lower possibility to be multiple lesions (11.1%vs. 61.5%, p = 0.0306), higher proportion of hypointensity on T2-weighted images (66.7% vs. 15.4%, p = 0.0260) and higher frequency in black appearance (77.8% vs. 23.1%, p = 0.0247). During the follow-up, 4 PMTs and 11 MMTs (71.4%) experienced tumor progression. PMTs had better prognosis than MMTs that progression-free survival (PFS) rate of PMT was 50.0% but decreased to 23.1% for MMTs at 12 months (p = 0.0123). Cox proportional hazards regression revealed that multiplicity of tumor was an independent predictor for PFS. None of patient with multiple tumors was in PFS after 12 months' follow-up whereas PFS rate was 40.5% for single tumor (p = 0.0002). In conclusion, radiological appearances, especially hypointensity on T2-weighted images, might be an indication for PMT. MMTs are more likely to be multiple intraparenchymal masses in elder patients located in supratentorial region. Current treatments included operation, radiotherapy and chemotherapy are not competent to control tumor progression and other therapeutic modalities are urgently needed.

Hyperprolactinemia in clinical non-functional pituitary macroadenomas: A STROBE-compliant study.

Hyperprolactinemia is a prevalent endocrine disorder presented in patients with non-functional pituitary adenomas (NFPAs). However, the mechanism involved in hyperprolactinemia in NFPA is not fully illustrated. The current study aims to investigate predictors for hyperprolactinemia in NFPA via analyzing relevant clinical features. Thus, in this study, a cohort of 214 cases with integrated medical records was retrospectively analyzed concerning clinical, pathological, and endocrinological studies before and after surgery.Hyperprolactinemia happened in 93 cases (43.5%). Women (adjust odds ratio [OR] = 3.093; P < .01), age of patients (adjust OR = 0.951; P < .01), and serum free tetraiodothyronine (FT4) level (adjust OR = 0.882; P = .02) were independent predictors for developing preoperative hyperprolactinemia. Tumor size and hypopituitarism had no impact on hyperprolactinemia. During a median follow-up of 43.5 (range, 22-80) months, 83.9% patients with preoperative hyperprolactinemia experienced prolactin (PRL) normalization. Preoperative PRL level (adjusted OR = 1.741, P = .03) was the exclusive predictor for PRL normalization after adjusting for tumor volume, preoperative serum FT4 concentration, and postoperative residual. The PRL normalization rate of patients with lower PRL level (<2.35-fold upper limit of normal range) was 95.2% and decreased to 65.5% for patients with higher PRL level.In conclusion, our results suggest existence of potentially alternative mechanisms underlying hyperprolactinemia in NFPAs, like the discrepancy of sex and age and the negative feedback of FT4. Preoperative PRL is a predictor for postoperative PRL normalization, which is of clinically relevant for postoperative management of NFPAs.